(1) Background: Immunosuppressed patients, especially those receiving B-cells depleting therapies (BCDT), are at major risk to develop reduced vaccine seroconversion and contract severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. The aim of our study is to assess safety and efficacy of the pre-exposure prophylactic combination of Tixagevimab and Cilgavimab (TGM-CGM) in a cohort of rheumatic patients diagnosed with Autoimmune Rheumatic Diseases; (2) Methods: We performed a prospective study using the clinical medical charts of 25 patients treated with Rituximab and received a single injection of TGM/CGM. The cohort was followed for 6 months from the injection and compared to a control group of 25 immunosuppressed patients who did not receive TGM-CGM. We assessed the incidence and the severity of Covid-19 in both groups, as well as early and late adverse events; (3) Results: Despite the small sample, we noticed a downward trend in the incidence and severity of symptomatic infection in the group treated with TGM/CGM. In the experimental cohort, one patient was completely asymptomatic, four patients were oligosymptomatic infection, and just one had mild-moderate infection versus 4 oligosymptomatic and 5 mild-moderate infection in the control group. We observed also a reduction in time to nasopharyngeal swab negativization. No adverse events were reported in our data. We collected the dosage of anti-Receptor-Binding Domain (RBD) SARS-CoV2 spike protein for 21 patients, revealing adequate seroconversion in 12 patients out of 21; (4) Conclusions: Even though the study was conducted during the Omicron wave, notably known to be less responsive to monoclonal antibodies, we proved that TGM-CGM could be a risk-free additional tool to prevent SARS-Cov2 infection in rheumatic immunosuppressed patients.

The coronavirus disease 2019 (COVID-19) is now a global pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unlike other known coronaviruses, such as the Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 reveals new clinical, immunological, and pathologic features. The lymphocyte depletion, macrophage and neutrophil hyperactivation, cytokine dysregulation, thrombophilia, delayed antiviral response, and immune exhaustion are key immunological findings linked to the clinical progression of this disease. Understanding and identifying the underlying immunological basis of COVID-19 is crucial to designing effective therapies. Here, we provide an overview of immunopathogenesis driven by SARS-CoV-2 after its interactions with the immune system.

Tixagevimab/cilgavimab (TIXA/CILGA) was introduced in early 2022 as a promising new drug for pre-exposure prophylaxis against COVID-19 in immunocompromised patients. The aim of our study was to evaluate the efficacy and safety of TIXA/CILGA in a Slovenian national cohort of kidney transplant recipients as pre-exposure prophylaxis in the Omicron era. Demographic, clinical, laboratory, and therapeutic data were collected from electronic and paper medical rec-ords. Of the 106 patients who received TIXA/CILGA, 6 patients (5.7%) subsequently acquired SARS-CoV-2 breakthrough infection. The incidence of SARS-CoV-2 infection was only slightly lower compared with patients who did not receive TIXA/CILGA (7.0%). All patients who re-ceived TIXA/CILGA had a mild disease course, whereas 20% of patients who did not receive TIXA/CILGA required hospitalization and two patients died. Adverse effects most likely related to TIXA/CILGA occurred in 12% of patients, one of whom experienced deep vein thrombosis. None of the patients suffered acute myocardial infarction or cerebrovascular insult. Overall, the benefit of added protection for kidney transplant patients appears to outweigh the potential risk of adverse events and provide additional protection against severe COVID-19 protection.

Tixagevimab–cilgavimab are effective for treatment of early COVID-19 among outpatients with risk factors for progression to severe illness, as well as for primary prevention and post-exposure prophylaxis. We aimed to retrospectively evaluate the hospital stay (expressed in days), prognosis, and negativity rate for COVID-19 after treatment with tixagevimab–cilgavimab. We enrolled 42 patients who were nasal swab positive for SARS-CoV-2 (antigenic and molecular), both vaccinated and not vaccinated for COVID-19, hospitalized at the first division of the Cotugno Hospital in Naples and who received intramuscular single dose of tixagevimab-cilgavimab (300 mg / 300 mg). All patients candidates for tixagevimab-cilgavimab had immunocompromised immune system either for chronic degenerative disorders (Group A: 27 patients) or onco-hematological diseases (Group B: 15patients). Patients enrolled in group A came to our observation after 10 days from the detection of positivity to COVID-19 unlike the other types of patients enrolled in this study. The mean stay in hospital of patients in Group A was 21±5 days vs 25±5 days in Group B. Twenty patients resulted negative after a median of hospitalization stay of 16 days (IQR: 18-15.25), of them 5 (25%) patients belonged to group B. Therefore, patients with active hematological malignancy had the lower negativization rate.

In this paper we first provide a primer on SARS-CoV-2 and Covid-19 delineating the etiopathogenesis, epidemiology, clinical manifestations and the natural history of the disease. We then trace the evolution of the Covid-19 pandemic highlighting the characteristics of the epidemic in China where the pandemic originated, select countries of Europe which peaked during April, and Brazil, US and India where the pandemic has taken serious turns recently. We also project some possible trajectories for the mega cities of India based on the demographic characteristics of these cities in comparison to New York city. This is an updated version of the article from mid-April published online.

The greatest pandemic of the century, COVID-19, is an ongoing global public health problem. With a clinically approved treatment available only for those who are acutely ill and are hospitalized, the control of this disease in the general population is still largely dependent on the preventive measures issued by the World Health Organization. Among the general control measures other than immunization with the COVID-19 vaccines, handwashing with soap and water has been emphasized the most because it is cost-effective and easily accessible to the general public. Studies have reported that soaps offer unique chemical properties that can completely destroy enveloped viruses. However, the general public seems to be still uncertain about whether soaps can shield us from a highly contagious disease such as COVID-19. In an attempt to help eliminate the uncertainty, we analyzed the mechanisms underlying the efficacy of soap and its prospect for preventing the spread of COVID-19. In this paper, we provide an overview of the history and characteristics of the SARS-CoV-2 virus, the current global COVID-19 situation, the possible mechanisms of the deactivation of viruses by soaps, and the potential effectiveness of soap in eliminating coronaviruses including SARS-CoV-2.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic which has been a topic of major concern to global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7, B.1.351, P1 and, B.1.617., which show in-creased transmissibility and resistance towards vaccines and therapies. Importantly, the likelihood of susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response or comorbidities needs greater attention. Herein, we provide a comprehensive perspective regarding ongoing vaccine (mRNA, protein-based, viral vector based etc.) and therapeutic (mono-clonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress and fatality. At present, the global case fatality rate of COVID-19 laboratory confirmed cases is ~4.7% ranging from ~0.3-0.4% in Chile and Israel to ~10.8% in Italy. To address this global crisis, up-to-date information on the viral genomics and transcriptomics is crucial for understanding the origins and global dispersal of the virus, providing insight into viral pathogenicity, transmission and epidemiology, and enabling strategies for therapeutic interventions, drug discovery and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.

Cardiac complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been well-identified since the beginning of the current coronavirus disease 2019 (COVID-19) pandemic. Such conditions can occur of various etiologies, such as respiratory failure and hypoxemia, direct cardiac tissue damage due to viral replication, indirect myocarditis as systemic inflammation, and the interaction of different medications. Recently, with the start of the COVID-19 vaccination programs, COVID-19 vaccine-associated cardiac adverse events (AEs) have emerged and are increasingly being reported. Although these AEs are usually mild and self-limited, they can sometimes cause severe, catastrophic outcomes. This review compares the pathophysiology, diagnosis, and treatment of the de novo SARS-CoV-2 infection-related and COVID-19 vaccine-related myocarditis and pericarditis.

ABSTRACT Two years after first patients approached the emergency rooms of hospitals in Wuhan becouse of respiratory distress,thousend of SARS-CoV-2 infected persons continue to die every day worldwide.SARS-CoV-2-infected patients undergo a process of dehydration and malnutrition before they develop respiratory problems and approach the emergency room of a hospital.This is,in many cases, the consequence of high fever which causes massive loss of fluids. In addition loss of appetite, is responsible for the deficit of protein intake.Most of the virus-infected patients admitted to the emergency room are therefore hypovolemic and hypoproteinemic and suffer of respiratory distress accompanied by ground grass opacities at CT-scan of the lungs.Critically ill patients are treated following the guidelines for treatment of septic shock but with „conservative“ fluid replacement and administration of diuretics to assure sufficient hourly urine production. The combination of conservative fluid administration with reduced protein content in the enterally administered diet, together with administration of diuretics, has severe hemodynamic consequenses in mostly aged,dehydrated,critically ill patients. Many of them will develop acute kidney injury in the next 24 hours.In most of the cases, patients continue to loose weight by loosing skeletal muscle mass. Ischemic damage in the lung capillaries is responsible for the acute respiratory distreass syndrome (ARDS) and for the hallmark of autoptic findings,diffuse alveolar damage (DAD) characterized by hyaline membrane formation,fluid invasion of the alveoli recruitment of some inflammatory cells and progressive arrest of blood flow in the pulmonary vessels.The consequence is progressive congestion , increase of lung weight and progressive hypoxia (progressive severity of ARDS).Sequestration of blood in the lungs worsen hypovolemia and ischemia in different organs.This is most probably responsible for recruitment of inflammatory cells and for persistance of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autoptic studies have been performed mostly in patients who died in the ICU after SARS-CoV-2-infection because of progessive ARDS.In those patients, tubulus epithelium necrosis in the kidney is a frequent finding as it has been the case in the first SARS-CoV-1 pandemic.In the death certification charts, many times weeks after first symptoms have started ,cardiac arrest is the cause of death after respitatory insufficiency.Replacement therapy with sufficient amount of fluid and albumin should be part of the early individualized life-saving supportive measures avoiding mechanical ventilation.

The novel coronavirus named by WHO and Coronavirus Study Group (CSG) as SARS-COV-2 is the etiological agent of the newly emerged Coronavirus disease (COVID-19). COVID-19 has become a pandemic threat as the WHO declared it a public health emergency of international concern. Early and precise detection of the virus is important for effective diagnosis and treatment. Various testing kits and assays, including real-time reverse Transcriptase PCR, thermal screening guns, ELISA-based immunoassays, and Point-of-Care (POC), have been implemented or are being explored to detect the virus and/or characterise cellular and antibody responses to the infection. However, these approaches have inherent limitations such as non-specificity, high cost, characterize by long turnaround times for test results, and can be labour intensive. Aptamers, which are single-stranded oligonucleotides, generated artificially by SELEX (Evolution of Ligands by Exponential Enrichment) may offer the capacity to generate high affinity bioprobes for monitoring relevant SARS-COV 2 and COVID-19 biomarkers. This article discusses the prospects of implementing aptasensing technologies for rapid point-of-care detection of SARS-COV-2.

Many people in the USA have lost their lives or become addicted to opioids via prescription opioids given for chronic pain. The chronic pain epidemic has emerged due to a convergence of factors, including the medicalization of pain as well as injuries happening in the workplace, in the home, or during recreation. Opioid prescriptions rose precipitously from the late 1990’s through to approximately 2020, and despite public awareness, still are increasing. This review examines literature on integrative approaches to chronic pain as delineated by pain type. The review is organized by the most common causes of chronic pain, and randomized controlled trials, meta-analyses and systematic reviews are extracted for each cause of chronic pain. Several promising interventions may alleviate chronic pain of some causes, and some interventions may work across pain causes. Lowering inflammation through dietary or lifestyle regimens may be a general way of reducing pain. Pain can be alleviated through several adjunctive and integrative treatment approaches, which may serve to lower the need for opioid medication.

Since the beginning of the coronavirus disease 2019 (Covid-19) pandemic, there have been multiple peaks of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus virus 2) infection, mainly due to the emergence of new variants, each with a new set of mutations in the viral genome, which have led to changes in the pathogenicity, transmissibility, and morbidity. The Omicron variant is the most recent variant of concern (VOC) to emerge and was recognized by the World Health Organization (WHO) on November 26, 2021. The Omicron lineage is phylogenetically distinct from earlier variants, including the previously dominant Delta SARS-CoV-2 variant. Previous research has reported the most common clinical manifestations of the Omicron variant to be fever, runny nose, sore throat, severe headache, and fatigue. The reverse transcription-polymerase chain reaction (RT-PCR) test, rapid antigen assays, and chest computed tomography (CT) scans can help diagnose those with the Omicron variant. Furthermore, many agents are expected to have therapeutic benefits for those infected with the Omicron variant, including TriSb92, molnupiravir, nirmatrelvir, and their combination, corticosteroids, and interleukin-6 (IL-6) receptor blockers. Despite being milder than previous variants, the Omicron variant threatens many lives, particularly among the unvaccinated, due to its higher transmissibility, pathogenicity, and infectivity. This review summarizes the essential features of the Omicron variant, including its history, genome, transmissibility, clinical manifestations, diagnosis, management, and the effectiveness of existing vaccines against this VOC.

The scientific, private and industrial sectors use a wide variety of technological platforms available to achieve protection against SARS-CoV-2, including vaccines. However, the virus evolves continually into new highly virulent variants, which might overcome the protection provided by vaccines and may re-expose the population to infections. Mass vaccinations should be continued in combination with more or less obligation mandatory non-pharmaceutical interventions. Therefore, the key questions to be answered are: (i) How to identify the primary and secondary infections of SARS-CoV-2? (ii) Why are neutralizing antibodies not long-lasting in both the cases of natural infections and post-vaccinations? (iii) Which are the factors responsible for this decay in neutralizing antibodies? (iv) What strategy could be adapted to develop long-term herd immunity? (v) Is the Spike the only vaccine candidate or a vaccine cocktail is better?

The COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide in recent decades, and it is infecting and killing increasing numbers of people every day. In this paper, we discuss the possible relationships among lysosomotropism, increasing lysosomal pH, and the SARS-CoV-2 infection and disease process, and we deduce a possible approach for treatment and prophylaxis. Lysosomotropism is a biological characteristic of small molecules, such as (hydroxyl)chloroquine, amitriptyline, NB 06, or sertraline, which is present in addition to intrinsic receptor-mediated or enzymatic pharmacological effects. Lysosomotropic compounds affect prominent inflammatory messengers, such as IL1B, CCL4, CCL20, and IL6, as well as cathepsin L dependent viral entry (fusion) into host cells. Therefore, this heterogeneous group of compounds is a promising candidate for the prevention and treatment of SARS-CoV-2 infections, as well as influenza A infections and cytokine release syndrome (CRS) triggered by bacterial or viral infections. Patients who have already taken medications with lysosomotropic compounds for other pre-existing conditions may benefit from this treatment in the COVID-19 pandemic. Increased lysosomal pH levels play an important role in the disease process in common skin disorders, such as psoriasis and atopic dermatitis, thus suggesting that affected individuals might benefit from their particular conditions in the COVID-19 pandemic. We suggest data analysis of patients with these diseases, and who are treated with lysosomotropic compounds, and, if the results are promising, subsequent clinical testing of off-label therapy with clinically approved lysosomotropic compounds in the current COVID-19 pandemic and future influenza A pandemics.

Background and Objectives: Most individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are asymptomatic or have mild symptoms of COVID-19, which usually resolve after few days. Regardless of symptoms, infected people can transmit the virus to others especially on the first days of infection. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is used to confirm SARS-CoV-2 infection; some individuals show persistent PCR-positivity after recovering from COVID-19. In this study, 12 individuals who showed persistence of COVID-19 symptoms and of SARS-CoV-2 PCR-positivity were followed-up. Methods: nasopharyngeal samples were collected for SARS-CoV-2 detection by RT-qPCR; clinical and epidemiological data were analyzed. Results: that persistence of SARS-CoV-2 PCR positivity was associated with duration of symptoms (r_s 0.81338), which varied between one and 49 days, with 75% of the individuals reporting symptoms for more than two weeks; 83.33% of cases remained positive after two weeks of onset of symptoms, despite decreases in viral load. Conclusion: neither RT-qPCR test nor a symptom-based approach alone are sufficient to evaluate discontinuation of patient isolation; other factors such as viral loads and symptom severity should also be considered. Additional studies are needed to understand how RT-PCR-positivity is related to symptoms and the risk of viral transmission, and to better support isolation guidelines.

Objectives: Monoclonal antibodies (mAbs) have proven to be a valuable tool against COVID-19, mostly among subjects with risk factors for progression to severe illness. Tixagevimab/cilgavimab (TIX/CIL), a combination of two Fc-modified human monoclonal antibodies, has been recently approved to be employed as early treatment. Methods: Two groups of immunocompromised patients exposed to different early treatments (i.e., TIX/CIL vs. other mAbs [casirivimab/imdevimab, bamlanivimab/etesevimab, sotrovimab]) were compared in terms of clinical outcomes (hospitalization and mortality within 14 days from administration) and time to the negativity of nasal swabs. We used either Pearson’s chi-square or Fisher’s exact test for categorical variables, whereas the Wilcoxon rank–sum test was employed for continuous ones. Kaplan–Meier curves were produced to compare the time to nasopharyngeal swab negativity. Results: Early treatment with TIX/CIL was administered to 19 immunocompromised patients, while 89 patients received other mAbs. Most of them were solid organ transplant recipients or suffering from hematologic or solid malignancies. Overall, no significant difference was observed between the two groups in terms of clinical outcomes. In the TIX/CIL group, one patient (1/19, 5.3%), who was admitted to the emergency room within the first 14 days from treatment and was hospitalised due to COVID-19 progression, died. Regarding the time to nasal swab negativity, no significant difference (p=0.088) emerged. Conclusions: Early treatment of SARS-CoV-2 infection with TIX/CIL shows favourable outcomes in a small group of immunocompromised patients, reporting no significant difference when compared to similar patients treated with other mAbs.

Long COVID-19 syndrom appears after Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection with acute damages to microcapillaries, microthombi and endotheliitis. However, the mech-anisms involved in these processes remain to be identified. All blood vessels are lined with a monolayer of endothelial cells called vascular endothelium of which one of the major properties is to prevent coagulation. VE cadherin is a component of endothelial cell junctions responsible for maintenance of the integrity of the vessels through homophilic interaction of its Ca++- dependent adhesive extracellular domain. We first provide evidence that VE-cadherin is a target in vitro for ACE2 cleavage because its extracellular domain (hrVE-ED) contains two amino acid sequences for ACE2 substrate recognition at the po-sitions 256P-F257 and 321PMKP-325L. Indeed, incubation of hrVE-ED with the active ecto-peptidase hrACE2 for 16 hrs in the presence of 10M ZnCl2 showed a dose-dependent (from 0.2 ng/ul to 2 ng/ul) decrease of the VE-cadherin immunoreactive band. In vivo, in the blood from patients having severe COVID-19, a circulating form of ACE2 was detected with an apparent molecular mass of 70 kDa while it was barely detectable in patients with mild infection. Of importance, in the patients with severe COVID-19 disease, the presence of three soluble fragments of VE-cadherin (70, 62, 54 kDa) were detected using the antiEC1 antibody while only the 54 kDa fragment was present in patients with mild disease. Altogether, these data clearly support a role for ACE2 on VE-cadherin cleavage leading to potential biomarkers in SARS-CoV2 infection related with the vascular disease in “Long COVID-19”.

The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) Omicron variant of concern has been the dominant cause of worldwide COVID-19 cases since 2022. All the Omicron sublineage viruses have demonstrated high transmissibility and an ability to escape vaccine-induced immunity. While first-generation vaccines, including monovalent vaccines, continue to provide protection against severe disease, hospitalization and mortality, their efficacy against Omicron sub variants remains sparse. These vaccines have also been associated with rapidly waning protection against primary COVID-19 and COVID-19 reinfections conferred by evolving Omicron sublineages.. This led to the development and deployment of updated vaccines and the introduction of the bivalent booster. Through this review, we highlight the brief journey of the variants of concern leading to the dominance of Omicron and the effectiveness of the key vaccines against these variants, including the updated (bivalent) boosters.

Background: The COVID-19 pandemic has hit the Spanish economy hard. The result is an unprecedented economic and social crisis due to uncertainty about the remedy, and due to the socio-economic effects on people’s lives. Methods: We performed a retrospective analysis of the macro-economic impact of COVID-19 in 2020, using the principal indicators of the Spanish economic and productive model. National statistics were examined in the search for impacts or anomalies occurring since the beginning of the pandemic. To estimate the strength of the impact on each of the indicators analysed, we used Bayesian structural time series. Results: In 2020, the cumulative impact on the Gross Domestic Product was of -11.41% [95% credible interval: -13.46; -9.29]. The indicator for Business Turnover fell by -9.37% [-12.71; -6.07]. The reduction in business activity was related to the sharp fall in demand. The Spanish employment market was strongly affected; our estimates showed a cumulative increase of 11.9% [4.27; 19.45] in the rate of unemployment during 2020. The autonomous communities which are economically the most heavily dependent on the services sector were those which recorded the worst indicators. Conclusions: Our estimates portray a dramatic situation in our country, and show all too clearly the fragility of a productive system which has to make the behavioural changes that are necessary to confront the COVID-19 pandemic.

Our first modern global pandemic is caused by a nanosized lipid vesicle, called SARS-CoV-2. Its molecular structure and biogenesis have remarkable similarities with Extracellular Vesicles (EVs, most notably exosomes) that are constantly shed by all cells during their life. Their resemblance may not be a coincidence. Growing body of evidence has shown that EVs have significant roles in various biological processes, including viral infection, transmission and anti-viral response. Drawing comparison with the virus might shed light on how we could fight the COVID-19 disease. This may include novel EV research and diagnostics technologies as well as novel EV-based treatments.

The potential for transmission of the SARS-CoV-2 virus during minimally invasive gynaecological procedures, such as hysteroscopy or laparoscopy, on the reproductive tract of patients with COVID-19 is not known. We examined existing data for prevalence of virus in the reproductive tract and other bodily fluids.

The 2019 novel coronavirus (previously 2019-nCoV) or coronavirus infectious disease 2019 (COVID-19) outbreak has been summarized as on March 29, 2020. COVID-19 is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SERS-CoV-2). The disease was first seen during an outbreak in Wuhan, China and continuous spreading from human to human around the sphere. The disease is uncontrolled and increasing the death toll through. The world is facing a global challenge to protect human lives caused by coronavirus outbreak. The number of infected patients is increasing day by day due to COVID-19 as a pandemic. The world health organization (WHO) has declared global public health emergency on January 30, 2020. The disease has been spread around 201 countries with total confirmed cases 634835 and death cases 29891 as on March 29, 2020. The goal of this review to summaries and update the clinical/medical features and suggestions for diagnosis of the COVID-19 as a pandemic. The discussion of the various therapeutic algorithms, risk, prevention and control based on the latest reports has been provided.

Systemic capillary leak syndrome (SCLS) is an uncommon, potentially life-threatening disorder defined as recurrent attacks of pseudo-shock. This syndrome occurs due to the disruption of endothelial cells, which leads to increased vascular permeability, causing intravascular fluid to leak into the extravascular space and albumin to be retained in the interstitial space. SCLS can lead to hypovolemia, peripheral hypoperfusion, and acute renal insufficiency. The syndrome is presented with fever, generalized edema, pleural effusions, dyspnea, hypovolemia, hemoconcentration, prerenal azotemia, shock, and syncope. After ruling out other causes of hypovolemic shock, the diagnosis of SCLS can be considered on the presence of the classical triad of hypotension, hemoconcentration, and hypoalbuminemia. Eliminating the precipitating factors is the cornerstone of SCLS management. It is advisable to be very cautious and weigh the risks and benefits of vaccination of people with a history of this condition. This review will discuss and compare different aspects of SLCS after SARS-CoV-2 infection and COVID-19 vaccination.

COVID-19 pandemic event requires a rapid response from various organizations at the international and national levels. One important response is the provision of information sharing facilities and monitoring of the spread of cases around the world, JHU CSSE developed the Dashboard in January 2020 and followed by WHO the same month for the WHO COVID-19 dashboard. Both dashboards have distributed information as expected by the user with their respective pros and cons. JHU CSSE Dashboard provides faster information with good access to mobile device users even though the display and color selection are less attractive. Information on the WHO COVID-19 Dashboard is often late but more data appearances and variations and comparisons between countries can be made. In the Indonesian context, ESSC for COVID-19 Geoportal as Esri Indonesia initiative has been developed with the support of data and information from various parties and developed with the principles of big data management which are fully supported by adequate spatial portal developer software from Esri. Particularly in Indonesia, there is not yet an adequate system to support spatial based decision making at the local level, therefore the development of a GIS dashboard to support provincial and district governments is highly recommended.

SARS-CoV-2 is a newly emerging, highly transmissible, and pathogenic coronavirus in humans, which has caused global public health emergency and economic crisis. To date, millions of infections and thousands of deaths have been reported worldwide, and the numbers continue to rise. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism through which this virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor binding domain of the spike glycoprotein (S) to recognize ACE2 receptors on the human cells; this initiates host cell entry by promoting viral-host cell membrane fusion through large scale conformational changes in the S protein. Receptor recognition and fusion are critical and essential steps of viral infections and are key determinants of the viral host range and cross-species transmission. In this review, we summarize the current knowledge on the origin and evolution of SARS-CoV-2 and the roles of key viral factors. We discuss the RNA dependent RNA polymerase structure of SARS-CoV-2, its significance in drug discovery, and explain the receptor recognition mechanisms of coronaviruses. We provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins, receptor-binding specificity, and discuss the differences in their antigenicity based on biophysical and structural characteristics.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to the coronavirus disease 2019 (COVID-19) pandemic. The main protease of SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from the viral RNA, making it a validated target for the development of SARS-CoV-2 therapeutics. New chemical phenotypes are frequently discovered in natural goods. In the current study, we used a fluorogenic assay to test a variety of natural products for their ability to inhibit SARS-CoV-2 Mpro. Several compounds were discovered to inhibit the Mpro at low micromolar concentrations. It was possible to crystallize robinetin together with SARS-CoV-2 Mpro, and the X-ray structure revealed covalent interaction with the protease's catalytic Cys145 site. Selected potent molecules also exhibited antiviral properties without cytotoxicity. Some of these powerful inhibitors might be utilized as lead compounds for COVID-19 research.

Background: to analyze the impact of COVID-19 pandemic on characteristics and management of uveal melanoma (UM) in National Referral Center in Poland. Materials and Methods: the retrospective analysis of 1336 patients who were newly diagnosed with UM at Department of Ophthalmology and Ophthalmic Oncology, Jagiellonian University Collegium Medicum Krakow, Poland between January 1, 2018 and December 31, 2021. The demographic and clinical data were compiled including localization, size and treatment methods of tumors. Results: In total, 728 patients with UM were included before COVID-19 pandemic in years 2018-2019 and 608 were included during COVID-19 pandemic in years 2020-2021. Fixed-base dynamics indicators for the incidence of uveal melanoma (base year 2018) in the national referral center in Poland were 80.22% and 86.81% in year 2020 and 2021, respectively. UMs were statistically significantly larger and more frequently localized anterior to the equator of the eye globe in year 2021 than in year 2018 (Chi^2 Pearson test p= 0.0001 and p= 0.0077, respectively). The rate of patients treated with enucleation increased from 15.94% in year 2018 to 26.90% in year 2021 (Chi^2 Pearson test p=0.0005). Conclusions: statistically significant differences were found in the management of uveal melanoma in National Referral Center in Poland during COVID-19 pandemic with tumors being larger, more frequently localized anterior to the equator of the eye globe and more often enucleated.

Coronavirus is a disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged as a global pandemic in 2019 from Wuhan, China. Since its emergence, it has caused immense suffering to human life, 6.27 million lives have been lost, movement curtailed and social dynamics disrupted. The golden standard for getting samples for SARS-CoV-2 detection is through oral- nasopharyngeal swab, this method of sample collection is invasive and uncomfortable, thus stigmatized the general population, and thereby impeded the progress of controlling the spread through mass testing. Being a contact disease, mechanisms to encourage mass testing is key to reduce the spread. This study thus developed a complimentary sample type to test for SARS-CoV-2, the use of human feces. Fecal samples were collected from 100 asym-symptomatic individuals suspected to be infected with COVID-19, virus RNA was then extracted and profiled through Real Time Polymerase Chain Reaction (RT-qPCR). The antigen rapid diagnostic test revealed high positivity rate of 44%, but the real time polymerase chain reaction results on nasopharyngeal and fecal samples revealed a significant variation, high number of the patients tested positive with stool samples compared to the nasopharyngeal swabs, with 43 and 37%, respectively. SARS-CoV-2 virus was detected in both symptomatic and asymptomatic individuals; however, the symptomatic registered a higher positivity of 25% compared to 20% among the asymptomatic patients. Vaccination only lowered the risk of infection, fully and partially vaccinated lowered the infection level to 10% compared to 20% among the unvaccinated. Finally, gender parity in relation to COVID19 was evaluated, more females (56%) compared to males were recruited in this study, out of which (20; 43.4%) were positive, and 26 (56.6%) were negative based on fecal RT-qPCR outcomes. Based on the outcome of this study, rapid diagnostic test (Ag-RDT) however cheap and or fast does not provide accurate information, moreover, the virus does not stay longer within the Oro-nasopharyngeal region, thus the invalid or negative results, thus use of feces should be adopted as a confirmatory test to ascertain the COVID19 status of an individual.

Postural orthostatic tachycardia syndrome (POTS) and its related symptoms have been identified as a possible complication of COVID-19 infection and vaccination and have recently gained attention. The diagnosis and management of POTS require great care and attention, even under normal circumstances, due to its complex nature. However, the COVID-19 pandemic and its complications have further complicated the diagnosis and management of this syndrome in COVID-19-related settings. The objective of this study is to enhance our comprehension of POTS and POTS-like symptoms in the context of COVID-19. To achieve this, we provide a concise overview of the POTS concept, its potential underlying mechanisms, available clinical reports of POTS following COVID-19 infection and vaccination, as well as the clinical manifestations of this syndrome in COVID-19-related scenarios with a brief overview of its management.

The purpose of this work was to longitudinally investigate the dynamic evolution of vaccine hesitancy towards both COVID-19 and influenza. We followed a cohort of 479 adult patients at Udine Hospital (Italy) having in common a medical history of SARS-CoV-2 infection in 2020, during the first and most impactful pandemic wave. Vaccine attitude was assessed through standardized telephone interviews performed at 12 and 18 months after the acute illness. The background of the survey was represented by COVID-19 vaccination campaign, started with the approval of the first vaccine in December 2020 and bolstered by the introduction of Green Pass in July 2021, in a context where anti-vaccination beliefs and mistrust in healthcare system were rising. The first interview reported the success of the 2020/21 seasonal influenza immunization with 46.8% (224/479) of the participants showing a positive attitude, especially the elderly and people with comorbidities (p< 0.001). The investigation conducted at 18 months showed a drastic drop in flu shot acceptance (30/166, 18.1%), the reluctance being justified by the feeling of protection regardless of prevention (55.8%) and by concerns regarding vaccines safety and efficacy (23.3%). In parallel, a great increase in vaccinations against SARS-CoV2 occurred after the introduction of Green Pass (72.9% vs 26.7%), although only a minority of the participants identified in the restrictions induced by the certification the leading incentive to get immunized (22.3%). Vaccine hesitancy remains a dynamic and complex phenomenon, which is difficult to overcome with incentive or obligatory strategies alone. The purpose of achieving vaccine compliance should always take into account the social and political context, as well as the role of personal opinions and emotions.

Background: Given the potential for additional development to clarify a better knowledge of the overall impact of COVID-19 on the pediatric population, the clinical symptoms of SARS-CoV-2 infection in children and adolescents are still being explored. Morbidity in children is characterized by a variable clinical course. Our study's goal was to compare clinical aspects of 230 pediatric patients who tested positive for SARS-CoV-2 and were hospitalized between April 2020 and March 2022. Methods: In a retrospective analysis, we compared two groups hospitalized in the infectious diseases clinical ward IX at the National Institute for Infectious Diseases "Prof. Dr. Matei Bals," Bucharest, Romania. The first group of 88 patients was admitted between (April–December 2020) and their clinical manifestations were compared with the second group of 142 children followed between July 2021 and March 2022. Results: Of 230 children, the median age was 4.5 (interquartile range 0.6-17) years, 53.9% were male. 88 (36.21%) patients (first group) were admitted during the second wave in Romania, mostly aged < 5 years old, and experienced digestive manifestations like fever (p=0.001), and diarrhoea (p=0.004). The second group experienced different clinical signs when compared with the first group, with higher temperature and increased respiratory symptoms analogous to those of acute respiratory viral infections. The proportion in the second group increased, and 64.5% had symptoms for a median interval of 5 days; age (0-4 -years old) and length of stay were both proportionally inversely (p<0.01) and with correlation with hospital admission (p = 0.04). We report two Paediatric Inflammatory Multisystem Syndrome (PIMS) in the second group, with favourable evolution under treatment. Comorbidities were risk factors for complications appear (p < 0.001) in both groups. All paediatric cases admitted to our clinic evolved favourably and no death was recorded. Conclusions: In the first group children experienced digestive symptoms, whereas the second group experienced mild and moderate respiratory symptoms. We confirmed risk factors for severe cases as manifestations across the age spectrum, 0-4 (digestive symptoms) and 5-12 years old (for respiratory symptoms), associated comorbidities, fever, and male gender. The potential effects of COVID-19 infection in children older than 5 years should encourage caregivers to vaccinate and improve the prognosis among pediatric patients at risk.

It is known for decades that viruses from the Coronoviridae family can adapt to human-to-human transmission. In 2020, SARS-CoV-2 caused a global pandemic of unprecedented scale imposing the loss of millions of human lives and being at the heart of a global economic crisis. Thus, we overviewed key research advances generated from the identification of the etiological agent to a better understanding of its origin, evolution and factors underlying global spread. Furthermore, we analyze the scientific productivity using the PubMed database. We found that the total number of publications increased more than 8% in 2020 when compared with 2019 or the average publications per year in the previous quinquennial. Remarkably, 86,638 publications related with COVID-19 and SARS-CoV-2 were published in 2020. Furthermore, there was also an increase in 2020 of publications in other major infectious diseases, such as AIDS, tuberculosis, or malaria. This success is likely the result from the vigorous, international, collaborative, and multidisciplinary response by the research community. During 2020 it was demonstrated, that with adequate support, it is possible to boost the rate of scientific progress in infectious diseases. Sustained investment in science will be key to address existing and future pandemics as the human population increases.

COVID-19 manifests regarding extreme acute respiratory conditions caused by a novel beta coronavirus (SARS-CoV-2) which is reported to be the seventh coronavirus to infect humans. Like other SARS-CoVs it has a large positive-stranded RNA genome. But specific furin site in the spike protein, mutation prone and phylogenetically mess Orf1ab separates SARS-CoV-2 from other RNA viruses. Since, the outbreak (February - March 2020) which originated in China, researchers, scientists, and medical professionals are inspecting all possible facts from every possible aspect including its replication, detection, and prevention strategies. This led to the prompt identification of its basic biology, genome characterization, structural based functional information of proteins, and strategies to prevent its spread. Due to the rapid mutation rate, the functional characterization of a few proteins is still lagging. This review summarizes the recent updates on the basic molecular biology of SARS-CoV-2 and prevention strategies undertaken worldwide to tackle COVID-19. This recent information can be implemented for the development and designing of therapeutics against SARS-CoV-2.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need for fast detection, understanding, and treatment of COVID-19. To control the ongoing COVID-19 pandemic, it is of utmost importance to get insight into the evolution and pathogenesis of the virus. In this review, we cover bioinformatics workflows and tools for the routine detection of SARS-CoV-2 infection, the reliable analysis of sequencing data, the tracking of the COVID-19 pandemic and evaluation of containment measures, the study of coronavirus evolution, the discovery of potential drug targets and development of therapeutic strategies. For each tool, we briefly describe its use case and how it advances research specifically for SARS-CoV-2. All tools are freely available online, either through web applications or public code repositories.

Our goal was to determine the cellular immune response (CIR) among a random sample of the Borriana COVID-19 cohort (Spain) to identify its associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals age 18 and older, including 36 individual naïve to SARS-CoV-2 infection, and 189 infected patients. We employed flow cytometry-based immunoassays for intracellular cytokine staining, utilizing Wuhan and BA.2 antigens and chemoluminescence microparticle immunoassay for detection SARS-CoV-2 antibodies. Logistic regression models were used. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3% respectively. No difference in CIR was found for naïve and infected patients. Patients who experienced sequelae exhibited higher CIR than those without. A positive correlation was observed between TCR and Anti-Spike IgG levels. Factors positive associated with TCR included A-blood group, number of SARS-CoV-2 vaccine doses received, and Anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and B-blood group. These findings contribute valuable insights into the nuance immune landscape shaped by SARS-CoV-2 infection and vaccination.

The COVID-19 pandemic has had a major impact on health systems around the globe and Romania is no exception. The impact on healthcare expense for pregnant women has been considerable, especially in COVID-only tertiary centers, where specialized care is being provided .The aim of this study is to analyze the impact of SARS-CoV-2 infection on healthcare costs, in particular by managing cases in COVID-only maternity. Material and Methods: The objective of the study was to analyze if the model adopted by the health system consisting in complete separation of delivering obstetrical care for covid and non-covid patients was efficient. We conducted an observational study in which we compared a group of pregnant women infected with SARS-CoV-2 (study group) with a control group in which we included uninfected pregnant women. The patients were recruited from Bucur Maternity Hospital, declared a COVID-only center in march 2020. We compared the two groups in terms of expenses over the entire period of hospitalization, i.e. expense on hospitalization, medicines, medical supplies, and medical investigations.

There is a rising global concern for the ongoing outbreak of SARS-CoV-2 due to its high transmission rate and unavailability of treatment. Through the binding of its spike glycoprotein with angiotensin type 2 (ACE2), SARS-CoV-2 can efficiently get in the cells of patients and start its pandemic cycle. Herein, the biological diversity of SARS-CoV-2 infection was assessed in Babylon province of Iraq by investigating the possible genetic variations of the spike glycoprotein. A specific coding region of 795 bp within the viral spike (S) gene was amplified from 19 patients who suffered from obvious symptoms of SARS-CoV-2 infection. Sequencing results identified fifteen novel nucleic acid variations with a variety of distributions within the investigated samples. The electropherograms of all the identified variations showed obvious co-infections with at least two different viral strains per sample. Within these co-infections, the majority of samples exhibited three nonsense single nucleotide polymorphism (SNP)s, p.301Cdel, p.380Ydel, and p.436del, which yielded three truncated SARS-CoV-2 spike glycoproteins of 301, 380, and 436 amino acids length, respectively. The network and phylogenetic analyses indicated that for all viral infections were derived from multi-ancestral origins. Results inferred from the specific clade-based tree entailed that some viral strains were derived from European G-clade sequences. In conclusion, our data demonstrated the absence of any single strain infection among all investigated viral samples in the studied area, which may entail a higher risk of SARS-CoV-2 in this country. Through the identified high frequency of truncated spike proteins, we suggest that defective SARS-CoV-2 may depend on helper strains having intact spikes in its infection. Alternatively, another putative ACE2-independent route of viral infection way also suggested. To the best of our knowledge, this is the first report to describe the co-infection of multiple strains of SARS-CoV-2 in patients with COVID-19.

The aging populations observed across numerous countries worldwide necessitate a thorough exploration of interventions aimed at promoting healthy aging. As individuals age, they undergo significant physiological changes that impact their functional capacity and often necessitate increased reliance on external support systems. Enhancing the autonomy and well-being of elderly individuals emerges as a critical imperative, serving not only individual interests but also broader societal goals. This review investigates various interventions designed to optimize the health and independence of aging populations, offering insights into effective strategies for promoting healthy aging and mitigating the societal burdens associated with an aging demographic.

Coronavirus disease (COVID-19) is a new discovered strain where WHO officially declares the disease as COVID-19 while the virus responsible for it called Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. The incubation period of this disease is between 14 days. Ordinary clinical symptoms that reported around the world include fever, cough, fatigue, diarrhoea and vomiting as well as asymptomatic for certain people. Infection is spread mainly through broad droplets. In early March 2020, WHO again has announced that COVID-19 is a pandemic with currently no specific treatment. The potential use of SARS-COV-2 proteome as a vaccine candidate by analysing through B-cell and T-cell antigenicity by using a immunoinformatics approach as a vaccine development early stage. In this study, we used consensus sequence for SARS-COV-2 proteome that was retrieved from NCBI database. VaxiJen 2.0 was mainly used to identify the antigenic property of SARS-COV-2 proteins. IEDB then used to analyse the B-cell epitope, the presence of T cell immunogenic epitope in SARS-COV-2 proteins was obtained by using compromise method of MHC class I and II tools that accessible respectively using ProPred-1 server and MHC II Binding Prediction in IEDB database. The best epitopes of B and T-cell epitopes were predicted with high antigencity and the information is disseminated through web-based database resource (https://covid-19.omicstutorials.com/epitopes/). This study will be useful to find a new epitope-based candidate for SARS-COV-2. However, further study needs to be done for the next stages of vaccine development.

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. SARS-CoV-2 nucleic acid, peripheral lymphocyte count, and functionality were assessed. SARS-CoV-2-specific and neutralization antibodies were detected, followed by virus isolation and genome sequencing. The median age of the studied cohort was 59.83±12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. Interferon gamma (IFN-ƴ)-generated CD4+ and CD8+ cells were normal as 24.68±9.60% and 66.41±14.87%. However, the number of IFN-ƴ-generated NK cells diminished (58.03±11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (ID50=157.2, P=0.05). SARS-CoV-2 was not isolated, and a cytopathic effect was lacking. Only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity was observed in COVID-19 patients with long-term SARS-CoV-2 infection.

The global COVID-19 pandemic claiming global spread continues to evolve, now to the verge of a third wave of outbreak possibly caused by the novel variants of concern of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). The test positivity rate (TPR) and case fatal-ity rate (CFR) have increased steeply in the second wave of COVID-19 compared to the first. From the example of Kerala, a state in southern India, positivity increased from 1.33% at the peak of wave one in 10th June 2020 to 13.45% during 10th June 2021 in the second wave of pandemic. SARS-CoV-2 is an enveloped single-stranded RNA virus. Angiotensin-Converting Enzyme-2 (ACE-2) is a trans membrane surface protein present on multiple types of cells in the human body to which the viral spike protein attaches. Genetic variations in the SARS-CoV-2 and ACE2 receptor can affect the transmission, clinical manifestations, mortality and the efficacy of drugs and vaccines for COVID-19. Mutations are the primary cause of genetic variations. Given the high TPR and CFR, it is necessary to understand the variations of SARS-CoV-2 and cellular receptors of SARS-CoV-2 at the molecular level. In this review, we summarize the impact of genetic and ep-igenetic variations in determining COVID-19 pathogenesis and disease outcome.

Measures in the SARS-CoV-2 pandemic were based on rough ideas regarding transmission routes of pathogens. Quantified models of physical transmission routes are mostly lacking, a gap to be filled. Vaccines and medicines, important, are not studied here. We first survey main routes, from primary production in the alveoli and intestines to emissions, environmental routes, to exposure and alveolar infection. Next, specific routes are modelled, mostly at a preliminary state, open to systematic improvement. Starting from a standardized emitter, modelling results show extreme differences in potential exposure, in a range covering up to 4 orders of magnitude. The outcomes are pathogen-specific, already different between SARS-CoV-2 and influenza. Extreme exposures may result in smaller spaces; with lower ventilation rates; with a high density of emitting persons per m3; who stay there for several hours; and visitors staying more than a few minutes. In spaces where a build-up of concentrations is low, exposures are low, lowest in open air situations. A main conclusion for the next pandemic is that a quantified model can give strong guidance on where measures are primarily due. For SARS-CoV-2, ventilation can be improved short-term. Longer-term, effective ventilation rules and adaptation of buildings may reduce high exposures substantially.

Acute kidney infection (AKI) occurred by tubular necrosis and glomerular dysfunction caused by many factors. SARS CoV-2 infection identified to cause fatal AKI. This paper aims to review the effect of covid-19 infection on the failure of the kidney and its mechanism. It identified that the SARS-CoV-2 received by the targeted cell by Angiotensin-converting enzyme 2 (ACE2). After the virus received by the target cells, it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and interferons (IFN) by immune cells and causes cytokine storm. The pro-inflammatory cytokines are again responsible to induce the secretion of cyclooxygenase‑2 (COX‑2), which causes inflammation and pain as well it stimulates the iNOS enzyme to produce NO which allows the vasodilation of renal arteries. The increased production of NO by iNO enhanced the vasodilation of arteries, and allows the adhesion of neutrophils to the artery, and causes damage to glomerulus and tubules. Hence, the most likely sustainable intervention could be the application of angiotensin-converting enzyme 2 (ACE2) inhibition by the receptors of the target cells in these vital organs to reduce sever destruction during treatment at the early stage of infection.

In comparison to the general population, lung cancer patients are more likely to suffer from severe Coronavirus disease (COVID-19) and mortality associated with it. Considering this increased risk, and in order to prevent symptoms and severe disease, patients with lung cancer have been prioritized for COVID-19 vaccinations, primary and booster doses. Despite this, the pivotal clinical trials did not include these patients, which leaves open questions regarding vaccine efficacy and humoral immune response. This review outlines the findings of recent investigations into the humoral responses of lung cancer patients to COVID-19 vaccination, particularly the primary doses and first boost.

Citizen Science has come up to perform analytics over the SARS-CoV-2 genome. Public GALAXY servers provide an automated platform for genomics analysis. Study includes design of GALAXY workflows for RNASEQ assembly and annotation as well as genomic variant discovery and perform analysis across four samples of SARS-CoV-2 infected humans obtained from the local population of Wuhan, China. It provides information about transcriptomics and genomic variants across the SARS-CoV-2 genome. Study can be extended to perform evolutionary and comparative study across each species of coronaviruses. Augmented and integrated study with cheminformatics and immunoinformatics will be a way forward for drug discovery and vaccine development.

To control the COVID-19 pandemic, many countries implemented vaccination and imposed societal restrictions both at the national level and for international travel. As a check of the corona status, a COVID pass has been issued. A COVID pass could be obtained when fully vaccinated against COVID-19, having recovered from a documented COVID-19 episode, or a recent (24-48 hours) negative SARS-CoV-2 antigen test. A global analysis of SARS-CoV-2 immune status (determined by past infection and/or vaccination), vaccination rates, as well as societal restrictions in controlling the COVID-19 pandemic is presented.

We determined the levels of neutralizing antibodies against the SARS-CoV-2 ancestral strain, Delta and Omicron variants of concern (VOCs) in 125 healthcare workers, who received Coro-naVac as their primary vaccination and later received either a single ChAdOx1 or a combination of two consecutive boosters using either two ChAdOx1 doses or a ChAdOx1 or BNT162b2 as the primary and second boosters, respectively, or 2 doses of BNT162b2. The titers 12 weeks after primary vaccination were inadequate to neutralize the all strains. After a single ChAdOx1 boost-er, the levels of neutralization at Day 30 varied significantly, only a small proportion of partici-pants developing neutralizing titers against Omicron at Day 7 and 30. The two doses of ChA-dOx1 as the booster induced lowest activity. A combination ChAdOx1 and BNT162b2 induced greater neutralization than by two doses of ChAdOx1. Two doses of BNT162b2 as the booster had the maximal activity against Omicron VOC.

SARS-CoV-2 was empirically and computationally found to be of a specific but peculiar evolution. Shell disorder models found that the outer shell (M protein) of SARS-CoV-2 to be among the hardest in its CoV family. The hard outer shell (low M percentage of disorder (PID)) is likely to be related to the SARS-CoV-2 resistance to the antimicrobial enzymes in saliva and mucus, and be responsible for the high-level of viral shedding which has been observed clinically. Experimental studies have also shown that SARS-CoV-2 is more resilient in the environment than many other CoVs, including SARS-CoV-1. Another aspect of the shell disorder models predicts that SARS-CoV-1 is more virulent than SARS-CoV-2 because of higher inner shell disorder (N PID) that helps SARS-CoV-1 replicate faster in vital organs despite being of lesser viral loads in the saliva and mucus, unlike SARS-CoV-2. This has been reaffirmed experimentally, where higher levels (50 folds) of infectious particles were detected in the SARS-CoV-1 samples in comparison with those of SARS-CoV-2. The hard outer shell of SARS-CoV-2 has been found to be associated with burrowing animals, particularly pangolins, which are often in contact with buried feces. For these reasons, the M protein is highly conserved among close relatives of SARS-CoV-2. The phylogenetic tree using M, unlike the genome-wide one, shows that pangolin-CoVs are more closely related to SARS-CoV-2 than bat-RaTG13. Previous phylogenetic studies may have been confused by recombinations that are usually poorly handled. According to the shell disorder models based on the N PID, an attenuated COVID-19 strain is likely to have entered humans via pangolins in 2017 or before, which provides the virus enough time to adapt to humans. This could explain why the SARS-CoV-2 S protein is highly adapted to the human ACE-2. The specific but peculiar evolution has a wide range of clinical, immunological, and epidemiological implications.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and Long-COVID.

To assess if SARS-CoV-2 infection induces changes in the urinary volatilomic fingerprint able to be used in the non-invasive COVID-19 diagnosis and management, urine samples of SARS-CoV-2 infected patients (62), recovered COVID-19 patients (30), and non-infected individuals (41) were analysed using solid-phase microextraction technique in headspace mode, combined with gas chromatography hyphenated with mass spectrometry (HS-SPME/GC-MS). In total, 101 volatile organic metabolites (VOMs) from 13 chemical families were identified, being terpenes, phenolic compounds, norisoprenoids, and ketones the most represented groups. Overall, a decrease in the levels of terpenes and phenolic compounds was observed in the control group, whereas norisoprenoids and ketones showed a significant increase. In turn, a remarkable increase was noticed in norisoprenoids and ketones and a milder increase in alcohols, furanic, and sulfur compounds in the recovery group than in the COVID-19 group. Multivariate statistical analysis identified sets of VOMs with the potential to constitute volatile signatures for COVID-19 development and progression. These signatures are composed of D-carvone, 3-methoxy-5-(trifluoromethyl)aniline (MTA), 1,1,6-trimethyl-dihydronaphthalene (TDN), 2-heptanone, and 2,5,5,8a-tetramethyl-1,2,3,5,6,7,8,8-octahydro-1-naphthalenyl ester acetate (TONEA) for COVID-19 infection and nonanoic acid, α-terpinene, β-damascenone, α-isophorone, and trans-furan linalool for patients recovering from the disease. This study provides evidence that changes in the urinary volatilomic profile triggered by SARS-CoV-2 infection constitute a promising and valuable screening and/or diagnostic and management tool for COVID-19 in clinical environment.

Antidepressants are among the most used medications in the US, with significant deleterious effects on people’s well-being. At any given time, depression impacts approximately 1 in 10 Americans, causing wide and broad societal costs. Interest is developing for non-pharmacological treatments and preventative measures. We summarize the literature on non-invasive dietary and lifestyle approaches for treating depression, including recent work with the psychedelic treatment of depression. This review aims to inform future research and treatment programs for depression. This review provides an evidentiary summary of integrative therapeutic approaches for depression.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in people in the city of Wuhan at the end of December 2019, and it has since spread to all continents. Global interest has been focused on discovering a treatment and developing a successful coronavirus vaccine as a result of the emergence of this new coronavirus. In this research, we sequenced the whole genome of the SARS-COV-2 virus that were isolated from 40 patients in Duhok, Iraq. 95 different mutations were identified in our isolation when such the whole genome sequence of the SARS-COV-2 isolated from the city of Wuhan, China (Accession number: NC 045512.2) was matched to the virus's sequence using Sequencing technology (Illumina , USA ) and Assembly method (iVar 1.3.1). Sequence analysis revealed that 38 mutations were found at spike glycoprotein (S), 30 of which were found in the ORF1b , 11 mutations were found in ORF1b ,7,3,2,1 mutations were found in ( N,M,ORF6 ,ORF9 /E ) genes which had been linked to structural changes at various places. The conclusion that the cases in Iraq were of different origins of infections and had a close relationship with the isolates from different country and state were further confirmed by phylogenetic analysis and transmission. The whole genome sequence of the SARS-CoV-2 , which were identified from the Iraqi Kurdistan region, and reported as a first study in Kurdistan region.

On the 9th March 2020, the first patient with COVID-19 was admitted to ICU in the Royal Gwent Hospital, Newport, Wales. We prospectively recorded the rate of ICU admissions of 52 patients with COVID-19 over 60 days, focusing on the epidemiology of ethnicity and deprivation. Patients were 65% (34 of 52) male and had a median (IQR) age of 55 (48-62) years. Prevalent comorbidities included obesity (52%); diabetes (33%), and asthma (23%). COVID-19 hospital and ICU inpatient numbers peaked on days 23 and 39, respectively – a lag of 16 days. The ICU mortality rate was 33% (17 of 52). Black, Asian and Minority Ethnics (BAME) population represented 35% of ICU COVID-19 admissions (18 of 52) and 35% of deaths (6 of 17). Within the BAME group, 72% (13 of 18) were found to reside in geographical areas representing the 20% most deprived in Wales, versus 27% of Caucasians (9 of 33). Less than 5% of the population within the hospital catchment area are of BAME descent, yet they represent a disproportionately high proportion of patients with ICU admission and mortality suffering from COVID-19. The interplay between ethnicity and deprivation, which is complex, may be a factor in our findings. This in turn could be related to an increased prevalence of co-morbidities; higher community exposure; or genetic polymorphisms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) continues to wreak havoc threatening the public health services and imposing economic collapse worldwide. Tailoring public health responses to the SARS-CoV-2 pandemic depends on understanding the mechanism of viral replication, disease pathogenesis, and accurately identifying acute infections and mapping the spreading risk of hotspots across the globe. However, effective identification and isolation of persons with asymptomatic and mild SARS-CoV-2 infections remain the major obstacles to efforts in controlling the SARS-CoV-2 spread and hence the pandemic. Understanding the mechanism of persistent viral shedding, reinfection, and the post-acute sequalae of SARS-CoV-2 infection (PASC) is crucial in our efforts to combat the pandemic and provide better care and rehabilitation to survivors. Here we present a living literature review on SARS-CoV-2 viral persistence, reinfection and PASC. We also highlight potential areas of research to uncover putative links between viral persistence, intra-host evolution, host immune status, and protective immunity to guide and direct future basic science and clinical research priorities.

A distinctive feature of the SARS-CoV-2 spike protein is its ability to efficiently fuse cells, thus producing syncytia found in COVID-19 patients. This commentary proposes how this ability enables spike to cause COVID-19 complications as well as side effects of COVID-19 vaccines, and suggests how these effects can be prevented..

We investigated humoral immune responses in 222 unvaccinated Japanese people after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2021. Anti-spike protein IgG antibody levels and neutralizing antibody titers were measured in serum samples obtained within 20–180 days after diagnosis. The geometric mean of antibody titers was 1555 ELU/mL (95% confidence interval [CI] = 1257-1923), and the neutralizing activities (50% inhibitory dilution) was 253 (95% CI = 204-313). The antibody titer and neutralizing activity both increased with increasing disease severity, and both values were approximately 4-fold higher for hospitalized patients than for non-hospitalized patients. However, these differences were smaller in older patients. The humoral immune response, which increased with increasing disease severity, gradually decreased over time after SARS-CoV-2 infection. Most patients with mild or moderate symptoms sustained neutralizing activity for up to 180 days after the infection, the decay of the neutralizing activity in the patients with asymptomatic was rather faster than other groups. 11.7% (26/222) of patients had very low neutralizing activity, and half of these were in the age of 20s. Our study results show the importance of measuring the neutralizing activity to confirm the immune status and also estimate the timing of vaccine.

Background: Comorbidities have been frequently reported in COVID-19 patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 receptor and host proteases, namely FURIN and TMPRSS2 that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia (hereafter, referred as leukemia). The expression of ACE2 was also increased in psoriasis, lung cancer, Non-alcoholic fatty liver disease (NAFLD), breast cancer, and pulmonary arterial hypertension patients. The expression of FURIN was higher in psoriasis, NAFLD, lung cancer, and in type II diabetic liver, whereas it was lowered in breast cancer. Similarly, the expression of TMPRSS2 was increased during lung cancer and type II diabetes; it was decreased during psoriasis, NAFLD, lung cancer, breast cancer, and cervical cancer.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia patients, as shown by the higher expression of IFNA2, IFNA8, IFNA10, IFNA14, IFNA16, IFNA21, IFNB1, CXCL10, and IL6. The expression of JAK1, STAT1, IL6, and CXCL10 was higher in NAFLD. Besides, JAK1 and STAT1 were upregulated in type II diabetic muscles. In addition, most of the upregulated genes in COVID-19 patients showed a similar trend in leukemia, NAFLD, and psoriasis. Furthermore, SARS-CoV-2, SARS-CoV and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection are mostly upregulated in leukemia patients; hence, leukemia patients are relatively more susceptible to develop COVID-19, followed by other chronic disorders, such as, NAFLD, type II diabetes, psoriasis, and hypertension. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 and underlie COVID-19 associated comorbidities.

The current coronavirus disease 2019 (COVID-19) pandemic is largely driven by community transmission, after 2019 novel Coronavirus (2019-nCoV or SARS-CoV-2) crosses the borders. To stop the spread, rapid testing is required at community clinics and hospitals. These rapid tests should be comparable with the standard PCR technology. Isothermal amplification technology provides an excellent alternative that is highly amenable to resource limited settings, where expertise and infrastructure to support PCR are not available. In this review, we provide a brief description of isothermal amplification technology, its potential and the gaps that need to be considered for SARS-CoV-2 detection. Among this emerging technology, loop mediated amplification (LAMP) and recombinase polymerase amplification (RPA) technologies have been identified as potential platforms that could be implemented at community level, without samples referral to a centralised laboratory and prolonged turn-around-time associated with the standard COVID-19 RT-PCR test. LAMP, for example, has recently been shown to be comparable with PCR and could be performed in less than 30 min by non-laboratory staff, without RNA extractions commonly associated with PCR. More so, it is cost effective and could easily be scaled up to resource limited settings. Diagnostics developers, scientific community and commercial companies could consider this alternative method to help stop the spread of COVID-19.

COVID-19 pandemic in first seven months has led to more than 15 million confirmed infected cases and 600,000 deaths. SARS-CoV-2, the causative agent for COVID-19 has proved a great challenge for its ability to spread in asymptomatic stages and a diverse disease spectrum it has generated. This has created a challenge of unimaginable magnitude not only affecting human health and life but also potentially generating a long-lasting socioeconomic impact. Both medical sciences and biomedical research have also been challenged consequently leading to a large number of clinical trials and vaccine initiatives. While known proteins of pathobiological importance are targets for these therapeutic approaches, it is imperative to explore other factors of viral significance. Accessory proteins are one such trait that have diverse roles in coronavirus pathobiology. Here we analyze certain genomic characteristics of SARS-CoV-2 accessory protein ORF8, predict upon its protein features and review current available literature regarding its function. We have also undertaken review of ORF8 homolog ORF8ab from SARS-CoV with a purpose of developing holistic understanding of these proteins for reason that coronaviruses have been infecting humans repeatedly and might continue to do so. Despite low nucleotide and protein identity and differentiating genome level characteristics, there appears to be significant structural integrity and functional proximity between these proteins pointing towards their high significance. There is further need for comprehensive genomics and structural-functional studies to lead towards definitive conclusions regarding their criticality and that can eventually define their relevance to therapeutics development.

This study aims to determine the seroprevalence of SARS-CoV-2 in pregnant women attending antenatal consultations (ANC) in Senegal. A non-redundant consecutive recruitment of participants was carried out between, March and July 2021 during the Delta wave of COVID-19. The plasma samples biobanked at -80°C were subjected to an enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of IgG and IgM antibodies of SARS-CoV-2 using the WANTAI SARS-CoV-2 Ab ELISA (Wantai Biological Pharmacy Enterprise, Beijing). To assess factors associated with seropositivity, bivariate analysis was per-formed with JMP® Pro Version 15.0.0 software (SAS Institute Inc., Cary, NC, 1989–2021). For frequencies below 5%, chi2 or Fischer tests were performed. In all cases, significant statistical threshold was set at p-values considered to be less than 0.05. A total of 1,227 pregnant women were recruited in five health facil-ities, including two in Dakar (n=166) and one in each of the following regional capitals: Saint-Louis (n=400), Ziguinchor (n=264) and Kédougou (n=397). The median age among was 25 years [18 - 50]. The overall sero-prevalence observed was 64.9% (797/1227), with higher exposure rates in Dakar with 71.6% (119/166) and Ziguinchor with 68.1% (180/264). Kédougou and Saint-Louis reported 62.9% (250/397) and 62% (248/400), respectively. According to age group, the seroprevalence was 62.6% (331/528), 66.6% (238/357), 63.5% (148/223) and 67.2% (80/119) respectively for [18-23], [24-29], [30-35] and ≥36 years old. This variability in the seroprevalence of SARS-CoV-2 according to the localities was not statistically significant (p=0.7024). We found no association between factors such as recruitment period, age, level of education, marital and pro-fessional status.

Patients with COVID-19 may develop pneumonia, severe symptoms of acute respiratory distress syndrome, and multiple organ failure. Nevertheless, the variety of forms of this disease, requires further research on the pathogenesis of this disease. Based on the analysis of published data on the concentrations of SARS-CoV-2 in biological fluids of the nasopharynx, lungs and intestines and using a developed modular model of the virus distribution in human tissue and organs, an assessment of the SARS-CoV-2 reproduction in various compartments of the body is presented. Most of viral particles can enter into the esophagus from nasopharynx. Entering viral particles into the gastrointestinal tract will obviously be accompanied by infection of the intestinal epithelium and accumulation of the virus in the intestinal lumen in an amount proportional their secretory and protein-synthetic activities. The relatively low concentration of SARS-CoV-2 in tissues implies an essential role of transport processes and redistribution of the virus from nasopharynx and intestines to lungs. The model simulations also supposes that sanitation of the nasopharynx mucosa at the initial stage of the infectious process considering inhibition of the virus accumulation by means of cellular and humoral responses has prospects for the use in medicine practice.

Community-level wastewater monitoring for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has demonstrated useful correlation with both coronavirus disease 2019 (COVID-19) case numbers and clinical testing positivity. Wastewater monitoring on college campuses has demonstrated promising predictive capacity for the presence and absence of COVID-19 cases. However, to date, such monitoring has largely relied upon composite or grab samples and reverse transcription quantitative PCR (RT-qPCR) techniques, which limits the accessibility and scalability of wastewater monitoring. In this study, we piloted a workflow that uses tampons as passive swabs for collection and reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect SARS-CoV-2 RNA in wastewater. Results for the developed workflow were available same day, with a time to result following tampon swab collection of approximately three hours. The RT-LAMP 95% limit of detection (76 gene copies reaction-1) was greater than RT-droplet digital PCR (ddPCR; 3.3 gene copies reaction-1). Nonetheless, during a building-level wastewater monitoring campaign conducted in the midst of weekly clinical testing of all students, the workflow demonstrated a same-day positive predictive value (PPV) of 33% and negative predictive value (NPV) of 80% for incident COVID-19 cases. The NPV is comparable to that reported by wastewater monitoring using RT-qPCR. These observations suggest that even with lower analytical sensitivity the tampon swab and RT-LAMP workflow offers a cost-effective and rapid approach that could be leveraged for scalable same-day building-level wastewater monitoring for COVID-19.

The severity of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), greatly varies from patient to patient. In the present study, we explored and compared mutation profiles of SARS-CoV-2 isolated from mildly affected and severely affected COVID-19 patients in order to explore any relationship between mutation profile and disease severity. Genomic sequences of SARS-CoV-2 were downloaded from GISAID database. With the help of Genome Detective Coronavirus Typing Tool, genomic sequences were aligned with the Wuhan seafood market pneumonia virus reference sequence and all the mutations were identified. Distribution of mutant variants was then compared between mildly and severely affected groups. Among the numerous mutations detected, 14,408C>T and 23,403A>G mutations resulting in RNA-dependent RNA polymerase (RdRp) P323L and spike protein D614G mutations, respectively, were found predominantly in severely affected group (>82%) compared with mildly affected group (<46%, p<0.001). The 241C>T mutation in the non-coding region of the genome was also found predominantly in severely affected group. The 3,037C>T, a silent mutation, also appeared in relatively high frequency in severely affected group. We concluded that RdRp P323L and spike protein D614G mutations predominate in severely affected COVID-19 patients. Further studies will be required to explore whether these mutations have any impact on the severity of COVID-19.

Aims: In late December 2019, early reports predicted the onset of a potential Coronavirus outbreak in china, given the estimate of a reproduction number for the 2019 Novel Coronavirus (COVID-19). Because of high ability of transmission and widespread prevalence, the mortality of COVID-19 infection is growing fast worldwide. Absent of an anti-COVID-19 has put scientists on the urge to repurpose already approved therapeutics or to find new active compounds against coronavirus. Here in this study, a set of computational approaches were performed in order to repurpose antivirals for dual inhibition of the frontier proteases involved in virus replication, papain-like protease (PLpro; corresponding to nsp3) and a main protease (Mpro), 3C‑like protease (3CLpro; corresponding to nsp5). Materials and Methods: In this regard, a rational virtual screening procedure including exhaustive docking techniques was performed for a database of 160 antiviral agents over 3CLpro and PLpro active sites of SARS-CoV-2. The compounds binding energies and interaction modes over 3CLpro and PLpro active sites were analyzed and ranked with the aid of free Gibbs binding energy. The most potent compounds, based on our filtering process, are then proposed as dual inhibitors of SARSC-CoV-2 proteases. Key findings: Accordingly, seven antiviral agents including two FDA approved (Nelfinavir, Valaganciclovir) and five investigational compounds (Merimepodib, Inarigivir, Remdesivir, Taribavirine and TAS106-106) are proposed as potential dual inhibitors of the enzymes necessary for RNA replication in which Remdesivir as well as Inagrivir have the highest binding affinity for both of the active sites. Significance: The mentioned drug proposed to inhibit both PLpro and 3CLpro enzymes with the aim of finding dual inhibitors of SARSC-CoV-2 proteases.

Abstract: The emergence of the COVID-19 pandemic has led to the rapid and worldwide devel-opment and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aims to explore the current knowledge on potential endocrine adverse effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pi-tuitary, adrenal, diabetes, and gonadal events will also be reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. A PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar research were performed. Case reports case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines is accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of endocrine disorders linked to COVID-19 vac-cines.

A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China has resulted in an outbreak in China which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 175 countries while affecting nearly 500,000 persons and causing more than 22,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. Till date, no clinically proclaimed, proven therapeutic antibodies or specific drugs and therapeutics, and vaccines have turned up. Several molecular diagnostic tests such as Real Time-PCR, isothermal loop-mediated amplification of coronavirus (i-LACO), full genome analysis by next-generation sequencing (NGS), multiplex nucleic acid amplification, and microarray-based assays are in use currently for the laboratory confirmation of this CoV infection. In this review article, we describe the basic molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.

Objectives: This paper presents a statistical review of modelling simulations for frequency and sensitivity of COVID-19 testing paradigms. Methods: We performed a review of preprints and published articles on PubMed from January 1, 2020 – March 1, 2021 using the search terms “COVID screening testing”, “COVID testing frequency”, “COVID testing frequency screening” and “SARS-CoV-2 testing frequency”.Results: Several authors’ conclusions support the claim that test frequency and test sensitivity both play a role in reducing SARS-CoV-2 transmission. We highlight the interplay between frequency of testing, test sensitivity and the speed at which test results are available in our review. Conclusions: Evidence suggests that sensitivity and frequency of testing both play a part in decreasing transmission of disease. We conclude that, overall, test sensitivity plays less of a role in reducing disease transmission in a population compared to the frequency of testing and how quickly test results are available.

COVID-19 differential spread and impacts across regions is a major focus for researchers and policy makers. Africa has attracted tremendous attention due to predictions of catastrophic impacts that have not yet materialized. Early in the pandemic, the seemingly low African case count was largely attributed to low testing and case reporting. However, there is also reason to consider that many African countries got out ahead of the virus early on. Factors explaining low spread include early government mandated lockdowns, community-wide actions, population distribution, social contacts, and ecology of human habitation. While recent data from seroprevalence studies posit more extensive circulation of the virus, continuing low COVID-19 burden may be explained by the demographic pyramid, prevalence of pre-existing conditions, trained immunity, genetics, and broader sociocultural dynamics. Though all these prongs contribute to the observed profile of COVID-19 in Africa, some provide stronger evidence than others. This review is important to expand what is known about the differential impacts of pandemics enhancing scientific understanding and gearing appropriate public health responses. Also, highlighting potential lessons the world may draw from Africa for global health on assumptions regarding deadly viral pandemics given its long experience with infectious diseases.

Background: Flow-through dot-blot assay (FT-DBA) for SARS-CoV-2 specific IgG detection will provide a reliable and affordable immunoassay for the rapid serosurveillance against COVID-19. Method: SARS-CoV-2 antigens were immobilized on nitrocellulose membrane to capture IgG immunoglobulins, which were then detected with AuNP anti-human IgG. A total of 181 samples were characterized with in-house and commercial immunoassay. The positive panel consisted of RT-PCR positive samples from patients with both <14 days and >14 days from the onset of symptoms, while the negative panel contained samples collected either from the pre-pandemic era dengue patients from healthy donors during the pandemic period. Results: In-house ELISA selected a total of 79 true seropositive and 100 seronegative samples. The sensitivity of samples with <14 days using FT-DBA was 94.7% which increased to 100% for samples >14 days. The overall detection sensitivity and specificity were 98.8% and 98%, respectively, whereas the overall PPV and NPV were 97.6% and 99%. Moreover, comparative analysis between ELISA and FT-DBA revealed clinical agreement of Cohen’s Kappa value of 0.944. Conclusion: The assay can confirm past SARS-CoV-2 infection with high accuracy within 2 minutes compared to ELISA. It can help track SARS-CoV-2 disease progression, population screening, and vaccination response.

In Wuhan city of China, an episode of novel coronavirus (COVID-19) happened. during late December and it has quickly spread to all places in the world. Until May 29, 2020, cases were high in the USA with 1.7 Million, Russia with approximately 387 thousand, the UK with 271 thousand confirmed cases. Everybody on the planet is anxious to know when the coronavirus pandemic will end. In this scourge, most nations force extreme medication measures to contain the spread of COVID-19. Modeling has been utilized broadly by every national government and the World Health Organization in choosing the best procedures to seek after in relieving the impacts of COVID-19. Many epidemiological models are studied to understand the spread of the illness and its prediction to find maximum capacity for human-to-human transmission so that control techniques can be adopted. Also, arrangements for the medical facilities required such as hospital beds and medical supplies can be made in advance. Many models are used to anticipate the results keeping in view the present scenario. There is an urgent need to study the various models and their impacts. In this study, we present a systematic literature review on epidemiological models for the outbreak of novel coronavirus in India. The epidemiological dynamics of COVID-19 is also studied. Here, In addition, an attempt to take out the results from the exploration and comparing it with the real data. The study helps to choose the models that are progressive and dependable to predict and give legitimate methods for various strategies.

This paper surveys estimates of the transmission features of the novel coronavirus, and then proposes a model to address sample-selection bias in estimated determinants of infection. Containment assumptions of the infection forecasting models depend on assumed effects of policies and self-regulating behavior. In the commons dilemma of the pandemic, the perceived ‘low risks’ of unregulated marginal choices do not reflect the full social cost, implying non-pharmaceutical interventions (NPI) to reduce mortality can enhance social welfare. As more economic activity renews with liftings of restrictive NPI (RNPI), a critical question concerns the ability of milder NPI (MNPI) and voluntary precautions to mitigate the risk of greater infections and deaths while also limiting the pandemic’s economic damage and its social costs. Ineffective NPI could lead to continued COVID-19 waves and new types of crises, worsened expectations and delayed economic recoveries. From the central range of surveyed estimates of transmission and alternative herd-immunity-threshold estimates, a ‘worst-case’ virus guidepost suggests eventual deaths of around 25 to 41 million worldwide and 1.1 to 1.7 million in the U.S. needed to reach herd immunity with no vaccine or treatment. The most optimistic study surveyed (theoretical model from a non-reviewed preprint study) combined with the low end of the range of the estimated mortality rate suggests 6 to 9 million deaths worldwide and 250 to 370 thousand in the U.S. to reach herd immunity. Successes in the mix of NPI, treatments, and vaccine can limit the eventual global death toll of the virus. Improved estimation models for forecasting and decision making may assist in better targeting the local timings and mix of NPI. Diagnostic tests for the virus have been largely limited to symptomatic cases, causing possible sample selection bias. A recursive bivariate probit model of infection and testing is proposed along with several possible applications from cross-section or panel-data estimation. Multiple potential explanatory variables, data sources, and estimation needs are specified and discussed.

Background: So far, vaccination has been considered the most crucial defense against viral infection, including SARS-CoV-2. Numerous reports have demonstrated the effectiveness of the above vaccines in oncology patients. It has also been proven that, apart from vaccinations and oncological therapy, the course of the cancer process itself influences the magnitude of the humoral response, especially in people after infection with SARS-CoV-2. Objective: This study aimed to answer the question about the impact of the cancer process on the humoral response in oncological patients vaccinated against SARS-CoV-2 infection and in patients after COVID-19. Material and methods: 1,668 people were observed. Over two years, 5,082 SARS-CoV-2 IgG and IgM antibody samples were determined. The concentration of antibodies was assessed in three groups of oncological patients: those undergoing anticancer therapy after contracting COVID-19 and those after vaccination against the SARS-CoV-2 infection. Results: The obtained results indicate a naturally more significant humoral response in oncological patients who have not been vaccinated and have not undergone anticancer therapy, such as radiotherapy, chemotherapy, or surgical intervention. The above observation applies to patients with breast, lung, and colon cancer, although the response varies significantly depending on the type of cancer. Summary: The size of the humoral response and the presence of specific antibodies directed against the SARS-CoV-2, IgM, and IgG, in response to the supply of the vaccine antigen or assessed after COVID-19, is an indicator of adequate immune protection against reinfection. This study highlights for the first time the phenomenon of increased humoral response in response to a viral infection in patients with certain types of cancer that are assumed to be sensitive to oncological therapy, the initiation of which, according to generally accepted principles, was blocked by infection with the SARS-CoV-2. The phenomenon we observe seems to confirm the presence of a "natural" defence potential in a cancer patient's body, in this case, directed against infection with a viral pathogen. A "stronger" antiviral response also seems to explain the asymptomatic course of SARS-CoV-2 infection in some of the above patients. It remains an open question to what extent the SARS-CoV-2 infection weakened the "natural" potential of the anticancer response in these patients.

The new coronavirus SARS-CoV-2 is the cause of the COVID-19 pandemic, which has created an incomparable global health problem. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. The review begins by elucidating the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Employing homology modeling, a tertiary structure model of PLpro is constructed, laying the groundwork for subsequent investigations. To expedite the search for potential therapeutic candidates, the study harnesses computational methodologies. Molecular docking techniques are employed to explore binding sites for antiviral drugs within the catalytic region of PLpro. This computational approach not only aids in drug development but also provides crucial preliminary data before experimental research commences. The stability of drug-PLpro complexes is assessed through comprehensive all-atom molecular dynamics (MD) simulations, affording dynamic insights into drug-PLpro interactions. By evaluating binding energy estimates from MD simulations, stable drug-PLpro complexes with potential antiviral properties are identified. However, it is emphasized that experimental validation is imperative to confirm these computational findings, necessitating in vitro and in vivo tests to assess safety and efficacy. This pivotal stage bridges the computational realm with real-world clinical applications. The review emphasizes the imperative need for enhancements in the existing PLpro-targeting drugs currently on the market. Their actions are insufficient for clinical use and necessitate thorough characterization and improvement. The Supervised Molecular Dynamics (SuMD) simulation technique reveals critical information about drug unbinding pathways, shedding light on opportunities for refinement. In addition to optimizing existing drugs, the investigation of sub-structurally similar molecules emerges as a promising avenue for drug development. In conclusion, the review underscores the pivotal role of targeting SARS-CoV-2 PLpro in the ongoing battle against COVID-19. By integrating molecular dynamics simulations, structural modeling, and computational insights, a robust foundation is established for identifying promising antiviral drug candidates. The continual need for improvement in existing drugs and the exploration of novel compounds remain paramount in the global effort to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, illustrating the interdisciplinary synergy crucial to this endeavor.

Abstract: The objective of this meta-analysis was to evaluate the factors associated with mortality of elderly Italians diagnosed with the new coronavirus who resided in institutions or who were hospitalized as a result of the disease. Methods: A systematic review following the recommenda-tions of The Joanna Briggs Institute (JBI), where the PEO strategy was utilized - Population, Exposure and Outcome. P, being the elderly over 65 years old. E, the SARS-CoV_2 pandemic. O, mortality. The NCBI / PubMed, LILACS, EMBASE and CINAHL databases were used until July 31, 2020.; Results: Five Italian studies were included in the meta-analysis, with the number of elderly people varying between 18 and 1591 patients. The main morbidities presented by the elderly in the studies were: dementia, diabetes, chronic kidney disease and hypertension. Conclusions: The factors as-sociated with the mortality of elderly Italian people diagnosed with SARS-CoV-2 who lived in in-stitutions or who were hospitalized because of the disease were evaluated. It was found that de-mentia, diabetes, chronic kidney disease and hypertension are the main the main diagnosed dis-eases for mortality in elderly people with Covid-19.

Background: The novel Coronavirus SARS-CoV-2 (COVID-19) is a global pandemic with an increasing public health concern. Due to the non-availability of a vaccine against the disease, non-pharmaceutical interventions constitute major preventive and control measures. However, inadequate knowledge about the disease and poor perception might limit compliance. Aim: This study examined COVID-19-related knowledge, practices, perceptions and associated factors amongst undergraduate veterinary medical students in Nigeria. Methods: A cross-sectional web survey was employed to collect data from 437 consenting respondents using pre-tested self-administered questionnaire (August 2020). Demographic factors associated with the knowledge and adoption of recommended preventive practices towards COVID-19 were explored using multivariate logistic regression at P ≤ 0.05.Results: The respondents’ mean knowledge and practice scores were 22.7 (SD ± 3.0) and 24.1 (SD ± 2.9), respectively with overall 63.4% and 88.8% displaying good knowledge and satisfactory practice levels. However, relatively lower proportions showed adherence to avoid touching face or nose (19.5%), face mask-wearing (58.1%), and social distancing (57.4%). Being in the 6^th year of study (OR = 3.18, 95%CI: 1.62-6.26, P = 0.001) and female (OR = 2.22, 95% CI = 1.11-4.41, P = 0.024) were significant positive predictors of good knowledge and satisfactory practices, respectively. While only 30% of the respondents perceived the pandemic as a scam or a disease of the elites (24.0%), the respondents were worried about their academics being affected negatively (55.6%). Conclusion: The study revealed good knowledge and satisfactory preventive practices towards COVID-19 among Nigerian Veterinary students; albeit with essential gaps in the key non-pharmaceutical preventive measures recommended by the WHO. Therefore, there is a need to step up enlightenment and targeted campaigns about COVID-19 pandemic.

During December 2019, a novel coronavirus named SARS-CoV-2 has emerged in Wuhan, China. The human to human transmission of this virus has also been established. The virus has so far infected more than 2 million people and spread over 200 countries. The World Health Organization (WHO) has declared COVID-19 a global health emergency due to its spread well beyond China. It has been established that this virus originates from bats and uses an intermediate host for transfer to humans. The knowledge about the intermediate host is important to find the virus shuttle mechanism to stop future outbreaks. For this, the genetic and structural analysis of coronaviruses spike proteins was performed using a computer-assisted approach.To conduct the In silico analysis, 43 sequences of spike protein belong to different species were retrieved from the NCBI nucleotide database. Pairwise and multiple sequence alignments were performed to check the similarities and differences of the retrieved sequences. Moreover, to highlight relationships among different species, phylogenetics analysis was performed using the MEGA software tool. In the end, protein structure alignment (superimposition) was performed against the reference structure by UCSF Chimera software. The results highlighted that the maximum similarity of human protein was found against Bat and Pangolinsequences. Moreover, among Bat and Pangolin, the highest similarity was found against pangolin based on phylogenetics analysis. These results suggest that SARS-CoV-2 transfers from bats to humans through pangolins.

The current outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 in Wuhan, China has killed more than 2600 people since December 2019. Currently there is no effective treatment for this epidemic. Drug for anti SARS-CoV-2 are urgently needed. In this study we evaluated two compound libraries containing launched drugs and compounds from 300 kinds of Traditional Chinese Medicine in order to find anti SARS-CoV-2 drugs. Docking and then calculating binding free energy were performed as workflow against four key anti-SARS-CoV-2 drug targets, 3CLpro, PLpro and RdRp from SARSCoV-2, and AAK1 from human as well. As a result, drugs launched with potential for antiviral usage were selected in the hope of providing some knowledge for future drug discovery.

Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

The gut microbiota plays a crucial role in maintaining host health and has a significant impact on human health and disease. In this study, we investigated the alpha diversity of gut microbiota in COVID-19 patients and analyzed the impact of COVID-19 variants, antibiotic treatment, type 2 diabetes (T2D), and metformin therapy on gut microbiota composition and diversity. We used a culture-based method to analyze the gut microbiota and calculated alpha-diversity using the Shannon H' and Simpson 1/D indices. We collected clinical data, such as length of hospital stay (LoS), C-reactive protein (CRP) levels, and neutrophil-to-lymphocyte ratio (NLR). We found that patients with T2D had significantly lower alpha-diversity than those without T2D. Antibiotic use was associated with a reduction in alpha-diversity, while metformin therapy was associated with an increase. We did not find significant differences in alpha-diversity between the Delta and Omicron groups. Length of hospital stay, CRP levels, and NLR showed weak to moderate correlations with alpha diversity. Our findings suggest that maintaining a diverse gut microbiota may benefit COVID-19 patients with T2D. Interventions aimed at preserving or restoring gut microbiota diversity, such as avoiding unnecessary antibiotic use and promoting metformin therapy, may improve patient outcomes.

In this study, the analysis of the changes of SARS-CoV-2 Orf3a protein during pandemic is reported. Orf3a, a conserved protein in the Coronaviruses, is involved in virus replication and release. A software workflow able to carry out a quick, systematic and repeatable screening of the SARS-CoV-2 genome isolates to detect protein mutations, was utilized to scan 70,752 high-quality SARS-CoV-2 genomes available in GISAID databank at the end of August 2020. All ORF3a mutations in the virus genomes were grouped according to the collection date interval and over the entire data set. The considered intervals were start of collection-February, March, April, May, June, July and August 2020. The top five most frequent variants were examined within each collection interval. Overall, seventeen variants have been isolated. Ten of the seventeen mutant sites occur within the transmembrane (TM) domain of ORF3a and are in contact with the central pore or side tunnels. The other variant sites are in different places of the Orf3a structure. Within the entire sample, the five most frequent mutations are V13L, Q57H, Q57H+A99V, G196V and G252V. The same analysis identified 28 sites identically conserved in all the genome isolates. These sites are possibly involved in stabilization of monomer, dimer, tetramerization and interaction with other cellular components. The results here reported can be helpful to understand virus biology and to design new therapeutic strategies.

As the coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2, continues to spread rapidly around the world, there is a need for well validated serological assays that allow the detection of viral specific antibody responses in COVID-19 patients or recovered individuals. In this study, we established and used multiple indirect Enzyme Linked Immunosorbent Assay (ELISA)-based serological assays to study the antibody response in COVID-19 patients. In order to validate the assays we determined the cut off values, sensitivity and specificity of the assays using sera collected from pre-pandemic healthy controls, COVID-19 patients at different time points after disease-onset, and seropositive sera to other human coronaviruses. The developed SARS-CoV-2 S1 subunit of the spike glycoprotein and nucleocapsid (N)-based ELISAs not only showed high specificity and sensitivity but also did not show any cross-reactivity with other CoVs. We also show that all RT-PCR confirmed COVID-19 patients tested in our study developed both virus specific IgM and IgG antibodies as early as week one after disease onset. Our data also suggest that the inclusion of both S1 and N in serological testing would capture as many potential SARS-CoV-2 positive cases as possible than using any of them alone. This is specifically important for tracing contacts and cases and conducting large-scale epidemiological studies to understand the true extent of virus spread in populations.

Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is sufficient experimental evidence to confirm that SARS-CoV-2 infection produces states of ciliary and flagellar dysfunction. However, these studies are unable to explain the observed effects molecularly, because they lack a sufficient understanding of the interaction between human proteins and virus proteins. Using the physical-chemical study of the human interactome in interaction with the SARS-CoV-2 proteome, we found evidence of interactions to explain the experimental effects from a molecular perspective. We found that ten viral proteins interact with key components in the maintenance of the molecular structure of axoneme. Additionally, we evaluated the pulmonary and extrapulmonary pathogenesis of COVID-19 from the point of view of ciliary dysfunction, and warned about other possible complications such as episodes of transient infertility that, due to the limitations of our work, would need verification.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

The SARS-CoV-2-induced acute COVID-19 pandemic disorder seems to have begun all of the sudden in 2020, with very little data available regarding prior times in which people experienced mysterious flu-like illness symptoms characteristic of the pandemic disease. The scientific community seems to be divided into a few parts with regards to the belief of the kind of viral origins. A significant number of scientists believe that the virus solely has natural origins and that it underwent a thorough process of zoonosis, independent of laboratory research-based research that would only catalyse zoonosis due to helping the virus gain additional function of transmission and virulence. Many other scientists believe that the virus has wide origins characteristic of “gain-of-function” laboratory research, whilst many other scientists believe that most of the viral genome has natural origins, with the zoonotic process having been artificially catalysed only in its latter part of transmission to humans. Considerable extent of scientific evidence suggests that the virus underwent a restricted, but considerable extent of “gain-of-function” research, prior to having been accidentally leaked into the nearby environment, whilst its process of zoonotic spillover into humans was influenced by such events, given for example the multidimensional pathogenetic process displayed by the virus and its main antigen of action, the spike glycoprotein, causing all kinds of immune pathophysiology - including transient immunosuppression. Investigations into the origins of the novel coronavirus have been lasting for years, seemingly with no concrete end in sight, and the available molecular testing methods to detect SARS-CoV-2 infection displaying less than perfect results have not significantly helped the process. Evidence even started pointing toward the existence of artificial, laboratory research-based viral origins, exposing a probable accidentally-induced artificial process of “accelerated viral evolution”, which could be particularly dangerous because of the nature of the SARS-CoV-2 pathogenic agent. Likewise, it is possible that the prevention of distribution of scientific data regarding scenarios as such in fact constitutes censorship, rather than regulation of data that may be considered not to be significantly evidence based. Simultaneously, it is important not to regard all hypotheses and preliminary reports of scientific research as evidence-based, but to ensure that due diligence is performed in all cases. The integrity of scientific research and ultimately of the innovation process of medical solutions depends on the integrity of democracy and the rule of law, as well as on regulating partnerships with scientific companies from world nations where autocracy rules their society.

Immune escape is observed with SARS-CoV-2 Omicron (Pango lineage B.1.1.529), the predominant circulating strain worldwide. Booster dose was shown to restore immunity against Omicron infection, however, real world data comparing mRNA (BNT162b2; Comirnaty) and inactivated vaccine (CoronaVac; Sinovac) homologous and heterologous boosting is lacking. A retrospective study was performed to compare the rate and outcome of COVID-19 in healthcare workers (HCWs) with various vaccination regime during a territory-wide Omicron outbreak in Hong Kong. During the study period 1 Feb – 31 Mar 2022, 3167 HCWs were recruited, 871 HCWs reported 746 and 183 episodes of significant household and non-household close contact. 737 HCWs acquired COVID-19 which were all clinically mild. Time dependent Cox regression showed that, comparing with 2-dose vaccination, 3-dose vaccination reduced infection risk by 31.7% and 89.3% in household contact and non-household close contact respectively. Using 2-dose BNT162b2 as reference, 2-dose CoronaVac recipient had significantly higher risk of being infected (HR 1.69 P<0.0001). Three-dose BNT162b2 (HR 0.4778 P<0.0001) and 2-dose CoronaVac + BNT162b2 booster (HR 0.4862 P=0.0157) were associated with lower risk of infection. Three-dose CoronaVac and 2-dose BNT162b2 + CoronaVac booster were not significantly different from 2-dose BNT162b2. The mean time to achieve negative RT-PCR or E gene cycle threshold 31 or above was not affected by age, number of vaccine dose taken, vaccine type and timing of the last dose. In summary, we have demonstrated lower risk of breakthrough SARS-CoV-2 infection in HCWs given BNT162b2 as booster after 2 doses of BNT162b2 or CoronaVac.

Risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not well-defined in resident physicians and fellows (trainees). We aimed to identify sociodemographic, occupational and community factors associated with SARS-CoV-2 infection among trainees during the first wave of the coronavirus disease 2019 (COVID-19) pandemic in New York City (NYC). In this retrospective cohort study, we administered an electronic survey between June 26 and August 31, 2020 to trainees at the Mount Sinai Health System in NYC to assess risk factors for SARS-CoV-2 infection between February 1 and June 30, 2020. We used Bayesian generalized linear mixed effect regression and structural equation models to examine associations. SAR-CoV-2 infection was determined by self-reported IgG antibody and reverse transcriptase-polymerase chain reaction results and confirmed with laboratory results. Among 2354 trainees invited to participate, 328 (14%) completed the survey and reported test results. The cumulative incidence of SARS-CoV-2 infection was 20.1%. Assignment to medical-surgical units (odds ratio [OR], 2.51; 95% CI, 1.18-5.34), and training in emergency medicine, critical care and anesthesiology (OR, 2.93; 95% CI, 1.24-6.92) were independently associated with infection. Deployment to care for unfamiliar patient populations was protective against infection (OR, 0.16; 95% CI, 0.03-0.73). Community factors were not significantly associated with infection after adjustment for occupational factors. Our findings may inform tailored infection prevention strategies for trainees responding to the COVID-19 pandemic.

SARS-CoV-2 virus infections in humans were first reported in December 2019, the boreal winter. The resulting COVID-19 pandemic was declared by the WHO in March 2020. By July 2020 COVID-19 is present in 213 countries and territories, with over 12 million confirmed cases and over half a million attributed deaths. Knowledge of other viral respiratory diseases suggests that the transmission of SARS-CoV-2 could be modulated by seasonally-varying environmental factors such as temperature and humidity. Many studies on the environmental sensitivity of COVID-19 are appearing online, and some have been published in peer-reviewed journals. Initially, these studies raised the hypothesis that climatic conditions would subdue the viral transmission rate in places entering the boreal summer and that southern hemisphere countries would experience enhanced disease. For the latter, the COVID-19 peak would coincide with the peak of the influenza season, increasing misdiagnosis and placing an additional burden on health systems. In this review, we assess the evidence that environmental drivers are a significant factor in the trajectory of the COVID-19 pandemic, globally and regionally. We critically assessed 42 peer-reviewed and 80 preprint publications that met qualifying criteria. Since the disease has been prevalent for only half a year in the northern, and a quarter of a year in the southern hemisphere, datasets capturing a full seasonal cycle in one locality are not yet available. Analyses based on space-for-time substitutions, i.e. using data from climatically distinct locations as a surrogate for seasonal progression, have been inconclusive. The reported studies present a strong northern bias. Socio-economic conditions peculiar to the ‘Global South’ have been omitted as confounding variables, thereby weakening evidence of environmental signals. We explore why research to date has failed to show convincing evidence for environmental modulation of COVID-19, and discuss directions for future research. We conclude that the evidence thus far suggests a weak modulation effect, currently overwhelmed by the scale and rate of the spread of COVID-19. Seasonally-modulated transmission, if it exists, will be more evident in 2021 and subsequent years.

Smoking is a risk factor for respiratory infections and there is reasonable concern that it may affect COVID-19 susceptibility and severity. Recent studies have focused on the interaction between smoking (and nicotine) and ACE2 expression, suggesting that ACE2 up-regulation could contribute to enhanced viral cell entry. However, case series have shown that there is an unexpectedly low prevalence of smoking among hospitalized COVID-19 cases. Since early April, we were the first to hypothesize that dysfunction of the nicotinic cholinergic system (NCS) may be implicated in the pathophysiology of severe COVID-19. We recently reported that many of the clinical manifestations of severe COVID-19 could be explained by dysregulation of the NCS. In this study, we present an amino acid sequence in the receptor binding domain of the SARS-CoV-2 Spike glycoprotein which is homologous to a sequence of a snake venom toxin. We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein. These findings suggest that SARS-CoV-2 could potentially interact with acetylcholine receptors causing dysregulation of the NCS and the cholinergic anti-inflammatory pathway.

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus named Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2), emerged in early December 2019 in China and attained a pandemic situation worldwide by its rapid spread to nearly 167 countries with 287.239 confirmed cases and 11.921 human deaths with a case fatality rate (CFR) of around 4 per cent. Bats were considered as the reservoir host, and the search of a probable intermediate host is still going on. Animals have anticipated culprit of SARS-CoV-2 as of now. The disease is mainly manifested by pneumonia and related respiratory signs and symptoms, but the involvement of the gastrointestinal system and nervous system is also suggested. The severe form of the disease associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with rampant inflammation in response to SARS-CoV-2 infection is considered as the leading killer of COVID-19 patients. COVID-19 patients were reported with higher levels of many pro-inflammatory cytokines and chemokines like IFN-g, IL-1b, IP-10, and MCP-1. Furthermore, severe cases of COVID-19 revealed higher levels of TNF-α, G-CSF, and MIP-1A. Blood profile of the COVID-19 patients exhibits lymphopenia, leucopenia, thrombocytopenia and RNAaemia along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortalities unlike other zoonotic coronaviruses like SARS-CoV and MERS-CoV, with no evidence of intrauterine transmission to neonates. Rapid and confirmatory diagnostics have been developed, and high efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapeutic, internationally health care authorities are recommending adoption of effective prevention and control measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-COV-2 / COVID-19 clinical pathology, pathogenesis and immunopathology along with a few recent research developments.

Background. We aimed to assess the validity of the Mat-O-Covid Job Exposure Matrix (JEM) on SARS-CoV2 using compensation data from the French National Health Insurance compensation system for occupational-related COVID-19. Methods. Deidentified compensation data for occupational COVID-19 in France were obtained between August 2020 and August 2021. The acceptance was considered as the reference. Mat-O-Covid is an expert based French JEM on workplace exposure to SARS-CoV2. Bivariate and multivariate models were used to study the association between the exposure assessed by Mat-O-Covid and the reference, as well as the Area Under Curves (AUC), sensitivity, specificity, predictive values, and likelihood ratios. Results. In the 1140 cases included, there was a close association between the Mat-O-Covid index and the reference (p&lt;0.0001). The overall predictivity was good, with an AUC of 0.78 and an optimal threshold at 13 per thousand. Using Youden’s J statistic resulted in 0.67 sensitivity and 0.87 specificity. Both positive and negative likelihood ratios were significant: respectively 4.9 [2.4-6.4] and 0.4 [0.3-0.4]. Discussion. It was possible to assess Mat-O-Covid’s validity using data from the national compensation system for occupational COVID-19. Though further studies are needed, Mat-O-Covid exposure assessment appears to be accurate enough to be used in research.

Introduction- The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods- We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested by RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results- A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.

SARS-CoV-2 or COVID-19, a new seventh human corona virus, has out-broken in Wuhan, China since 31^st December 2019, and quickly escalated to take the form of pandemic which killed many human beings throughout almost all countries across continents. The rapidity of its transmission from human to human is far greater than all previous human corona viruses which came into existence like SARS-CoV, MERS-CoV, etc. The nucleotide sequence of SARS-CoV-2 (isolates Wuhan-Hu-1) is 29,875 bp in ss-RNA. Symptoms of SARS-CoV-2 infected pneumonia include from asymptomatic to high fever and/or respiratory illnesses. Coronavirus virion (spherical/round /elliptical in shape) consists of three parts- outer membrane or envelope, nucleocapsid and genome (RNA). SARS-CoV-2 was shown to use receptor, angiotensin converting enzyme 2 (ACE2) for attachment to the cells through its surface spike (S) protein (S1), and the virion enters into the host cell through two routes- direct membrane fusion and endocytotic pathway. The RNA of SARS-CoV acts directly as mRNA and here minus(-) 1 programmed ribosomal frameshift (-1PRF) is being operated by slippery sequence and pseudoknot, so it translates 16 nonstructural proteins including RNA dependent RNA replicase. Then genomic RNA replicated continuously on – strand RNA template and subgenomic RNA transcribed discontinuously on –RNA template to sgmRNA. Subgenomic RNAs/sgmRNAs synthesize all structural proteins. This article takes into consideration the details of established theories of viral structure, viral attachment, mode of entry into human cells, different models of replication and transcription of virus genome proposed by eminent scientists over the years, and makes an in depth examination highlighting meaningful points or important target cites of viral propagation or synthesis, which are conserved, for prompt development of potent drugs or vaccine to counter COVID-19 for which human race is anxiously and eagerly waiting.

The recent detection of SARS-CoV-2 RNA in feces has led to speculation that it can be transmitted via the fecal-oral/ocular route. This review aims to critically evaluate the incidence of gastrointestinal (GI) symptoms, the quantity and infectivity of SARS-CoV-2 in feces and urine, and whether these pose an infection risk in sanitary settings, sewage networks, wastewater treatment plants, and the wider environment (e.g. rivers, lakes and marine waters). Overall, severe GI dysfunction is only evident in a small number of COVID-19 cases, with 11 ± 2% exhibiting diarrhea and 12 ± 3% exhibiting vomiting and nausea. In addition to these cases, SARS-CoV-2 RNA can be detected in feces from some asymptomatic, mildly- and pre-symptomatic individuals. Fecal shedding of the virus peaks in the symptomatic period and can persist for several weeks, but with declining abundances in the post-symptomatic phase. SARS-CoV-2 RNA is occasionally detected in urine, but reports in fecal samples are more frequent. The abundance of the virus genetic material in both urine (ca. 10²-10⁵ gc/ml) and feces (ca. 10²-10⁷ gc/ml) is much lower than in nasopharyngeal fluids (ca. 10⁵-10¹¹ gc/ml). There is strong evidence of multiplication of SARS-CoV-2 in the GI tract and infectious virus has occasionally been recovered from both urine and stool samples. The level and infectious capability of SARS-CoV-2 in vomit remain unknown. In comparison to enteric viruses transmitted via the fecal-oral route (e.g. norovirus, adenovirus), the likelihood of SARS-CoV-2 being transmitted via feces or urine appears lower due to the lower relative amounts of virus present in feces/urine. The biggest risk of transmission will occur in clinical and care home settings where secondary handling of people and urine/fecal matter occurs. In addition, while SARS-CoV-2 RNA genetic material can be detected by in wastewater, this signal is greatly reduced by conventional treatment. Our analysis also suggests the likelihood of infection due to contact with sewage-contaminated water (e.g. swimming, surfing, angling) or food (e.g. salads, shellfish) is extremely low or negligible based on very low predicted abundances and limited environmental survival of SARS-CoV-2. These conclusions are corroborated by the fact that over eight million global cases of COVID-19 have occurred, but exposure to feces or wastewater has never been implicated as a transmission vector.

A model that predicts levels of coronavirus (CoV) respiratory/fecal-oral transmission potentials based on the outer shell hardness has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Based mainly on the PID of N, SARS-CoV-2 is categorized as having intermediate levels of both respiratory and fecal oral transmission potential. Related to this, other studies have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and are characterized by case-fatality rates of 7.1% and 10.9%, respectively. The link between levels of respiratory transmission and virulence lies in viral load of body fluids and organ respectively. A virus can be infectious via respiratory modes only if the viral loads in saliva and mucus exceed certain minima. Likewise, a person may die, if the viral load is too high especially in viral organs. Inner shell proteins of viruses play important roles in the replication of viruses, and structural disorder enhances these roles by providing greater efficiency in protein-protein/DNA/RNA/lipid binding. This paper outlines a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed.

Both SARS-CoV-2 (COVID-19) and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2, protein sequences from sarbecoviruses were analyzed to identify highly-specific molecular markers consisting of conserved inserts or deletions (termed CSIs) in the spike (S) and nucleocapsid (N) proteins that are specific for either particular clusters/lineages of these viruses or are commonly shared by specific lineages. Three novel CSIs in the N-terminal domain of the spike protein S1-subunit (S1-NTD) are uniquely shared by the SARS-CoV-2, BatCoV-RaTG13 and most pangolin CoVs, distinguishing this cluster of viruses (SARS-CoV-2r) from all others. In the same positions, where these CSIs are found, related CSIs are also present in two other sarbecoviruses (viz. CoVZXC21 and CoVZC45 forming CoVZC cluster), which form an out group of the SARS-CoV-2r cluster. These three CSIs are not found in the SARS-CoVs. However, both SARS and SARS-CoV-2r CoVs contain two large CSIs in the C-terminal domain of S1 (S1-CTD), which binds the human ACE-2 receptor, that are absent in the CoVZC cluster of CoVs. These results indicate that while the S1-NTD of the SARS-CoV-2r viruses possesses the sequence characteristics of the CoVZC cluster of CoVs, their S1-CTD resembles the SARS viruses. Thus, the spike protein of SARS-CoV-2r viruses has likely originated from a recombination event between the S1-NTD of the CoVZC viruses and the S1-CTD of SARS viruses. This inference is also supported by the amino acid sequence similarity of the S1-NTD and S1-CTD from SARS-CoV-2 compared to the CoVZC and SARS CoVs. We also present evidence that one of the pangolin-CoV_MP789, whose receptor-binding domain is most similar to the SARS-CoV-2, is also derived by a recent recombination between the S1-NTD of the CoVZC CoVs and the S1-CTD of a SARS-CoV-2 related virus. Several other identified CSIs are specific for others clusters of sarbecoviruses including a clade consisting of bat SARS-CoVs (BM48-31/BGR/2008 and SARS_BtKY72). Structural mappings studies show that the identified CSIs are located within surface-exposed loops and form distinct patches on the surface of the spike protein. These surface loops/patches are predicted to interact with other host components and play important role in the biology/pathology of SARS-CoV-2 virus. Lastly, the CSIs specific for the SARS-CoV-2r clade provide novel means for development of new diagnostic and therapeutic targets for these viruses.

With arrival of highly transmissible Omicron variants in global pandemic, dentistry is facing another challenge to preserve biosafety of dental care. With a mission to protect both patients and healthcare workers, adaptability to the changing epidemiologic situation is required from dental professionals. This work presents a prospective sustainable biosafety setting for routine orthodontic care. The protocol is composed from combination of available technologies focused on the air-borne part of a virus pathway. Introduced biosafety protocol has been clinically evaluated after 18 months of application in the real clinical environment. The protocol has three fundamental pillars: (1) UVC air disinfection; (2) air saturation with certified virucidal oils through nebulizing diffusers; (3) complementary solutions. As a method of evaluation pseudonymous on-line smart form was used. Protocol operates with premise that everybody as a hypothetical asymptomatic carrier. Results from 115 patient feedbacks imply that with this protocol in place, there was no observed or reported translation of virus from patient to another patient or from patient to doctor or nurse and vice versa, albeit nine patients have retrospectively admitted visiting the clinic as probably infectious. Despite promising results, a larger clinical sample and exposition to current mutated strains is necessary for reliable conclusions about protocol virucidal efficiency.

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, has been confirmed in over 10,000,000 individuals worldwide and has resulted in more than 500,000 deaths in a few months since it first surfaced. With such a rapid spread it is no surprise that there has been a massive effort around the world to collectively elucidate the mechanism by which the virus is transmitted. Despite this, there is still no definitive consensus regarding droplet versus airborne transmission of SARS-CoV-2. Public health officials around the world have introduced guidelines within the scope of droplet transmission. However, increasing evidence and comparative analysis with similar coronaviruses, such as severe acute respiratory syndrome (SARS-CoV-1) and middle eastern respiratory syndrome (MERS), suggest that airborne transmission of SARS-CoV-2 cannot be effectively ruled out. As the data supporting COVID-19 airborne transmission grows, there needs to be an increased effort in terms of technical and policy measures to mitigate the spread of viral aerosols. These measures can be in the form of broader social distancing and facial covering guidelines, exploration of thermal inactivation in clinical settings, low-dose UV-C light implementation, and greater attention to ventilation and airflow control systems. This review summarizes the current evidence available about airborne transmission of SARS-CoV-2, available literature about airborne transmission of similar viruses, and finally the methods that are already available or can be easily adapted to deal with a virus capable of airborne transmission.

SARS-CoV-2 causes severe pneumonia epidemics and probably originated in horseshoe bats, but the intermediate host is unknown. The interaction of SARS-CoV-2 spike protein and its acceptor protein ACE2 is an important issue in determining viral host range and cross-species infection, while the binding capacity of Spike protein to ACE2 of different species is unknown. Here, we used the atomic structure model of SARS-CoV-2 and human ACE2 to assess the receptor utilization capacity of ACE2s from different species including cats, chimpanzees, dogs, cattles. Our results show, domestic cats (Felis catusc) and dogs (Canis lupus familiaris) are more susceptible to infection by SARS-CoV-2 and that they can efficiently transmit the virus to previously uninfected animals that are housed with them. Especially, cats could be a choice of animal model for screening antiviral drugs or vaccine candidates against SARS-CoV-2.