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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, China, in 2019 and rapidly spread worldwide. Over 750 million people were infected and close to 7 million were killed from 2019 to July 2023 according to the World Health Organization. Early in the pandemic, it was suggested that serological tests can confirm atypical or remote cases and assist in clinical diagnosis when molecular testing was limited. Although clinical uses of serological testing are limited, testing remains useful to: 1) assess and differentiate vaccine from infection related immune responses (when whole cell killed vaccines are not used), 2) enable population-level vaccination/infection and/or hybrid immune response surveillance, 3) understand at the population-level how serological markers correlate with the subsequent risk of infection based on the vaccine product used and the circulating variant, and 4) understand how different types of immunosuppression or other clinical factors impact the immune response. Seroprevalence assessments for infection/vaccination and hybrid immunity was helpful to assist in early phase pandemic modeling and when integrated with vaccine status and epidemiological outcomes enabled assessment of near- and long-term vaccine efficacy. This article will provide an overview of SARS-CoV-2 immunity over time, serology testing technologies, and appropriate SARS-CoV-2 serology test utilization and interpretation. [ABSTRACT FROM AUTHOR]

Background: Fatigue is a common symptom of long COVID syndrome. Compared to male survivors, females have a higher incidence of post-COVID fatigue. Therefore, long-term follow-up is necessary to understand which groups of females are more vulnerable to post-COVID fatigue. Methods: This is a nested case–control study of female COVID-19 survivors who were discharged from two designated hospitals in Wuhan, China in 2020, and received 2-year follow-up from March 1 to April 6, 2022. All patients completed the Checklist Individual Strength-subscale subjective fatigue (CIS-fatigue), a chronic obstructive pulmonary disease (COPD) assessment test (CAT), and the Hospital Anxiety and Depression Scale (HADS; including the HADS-Anxiety [HADS-A] and the HADS-Depression [HADS-D]). Individuals with CIS-fatigue scores of 27 or higher were classified as cases. The risk factors for fatigue was analysed with multivariable logistic regression analysis. Results: A total of 899 female COVID-19 survivors were enrolled for analysis, including 47 cases and 852 controls. Compared with controls, cases had higher CAT, HADS-A and HADS-D scores, and showed a higher prevalence of symptoms, including anxiety (cases vs. controls, 44.7% vs. 4.0%, p < 0.001), chest tightness (21.2% vs. 2.3%, p < 0.001), dyspnoea (19.1% vs. 0.8%, p < 0.001) and so on. In multivariable logistic regression analysis, age (OR, 1.03; 95% CI, 1.01–1.06; p = 0.02) and cerebrovascular disease (OR, 11.32; 95% CI, 2.87–43.00; p < 0.001) were risk factors for fatigue. Fatigue had a statistically significant moderate correlation with depression (r = 0.44, p < 0.001), but not with CAT ≥ 10. Conclusion: Female COVID-19 patients who had cerebrovascular disease and older age have higher risk of fatigue. Patients with fatigue have higher CAT scores, and are more likely to have concurrent depression. [ABSTRACT FROM AUTHOR]

The current global pandemic of COVID-19 is characterized by waves of infection due to the emergence of new SARS-CoV-2 variants carrying mutations on the Spike (S) protein gene. Since autumn 2020 many Variants of Concern (VOC) have been reported: Alpha/B.1.1.7, Beta/B.1.351, Gamma/P.1, Delta/B.1.617.2, Omicron/B.1.1.529, and sublineages. Surveillance of genomic variants is currently based on whole-genome sequencing (WGS) of viral genomes on a random fraction of samples positive to molecular tests. WGS involves high costs, extended analysis time, specialized staff, and expensive instruments compared to a PCR-based test. To rapidly identify the VOCs in positive samples, six assays based on real-time PCR and high-resolution melting (HRM) were designed on the S gene and applied to 120 oro/nasopharyngeal swab samples collected from October 2020 to June 2022 (106 positive and 14 negative samples). Overall, the assays showed 100% specificity and sensitivity compared with commercial PCR tests for COVID-19. Moreover, 104 samples out of 106 (98.1%) were correctly identified as follows: 8 Wuhan (wild type), 12 Alpha, 23 Delta, 46 Omicron BA.1/BA.1.1, 15 Omicron BA.2/BA.4/BA.5. With our lab equipment, about 10 samples can be processed every 3 h at the cost of less than € 10 ($ 10.60) per sample, including RNA extraction. The implementation of this approach could help local epidemiological surveillance and clinical decision-making. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human virus that burst at Wuhan in China and spread quickly over the world, leading to millions of deaths globally. The journey of this deadly virus to different mutant strains is still ongoing. The plethora of drugs and vaccines have been tested to cope up this pandemic. The herbal plants and different spices have received great attention during pandemic, because of their anti-inflammatory, and immunomodulatory properties in treating viruses and their symptoms. Also, it has been shown that nano-formulation of phytochemicals has potential therapeutic effect against COVID-19. Furthermore, the plant derived compound nano-formulation specifically increases its antiviral property by enhancing its bioavailability, solubility, and target-specific delivery system. This review highlights the potentiality of herbal plants and their phytochemical against SARS-CoV-2 utilizing different mechanisms such as blocking the ACE-2 receptors, inhibiting the main proteases, binding spike proteins and reducing the cytokine storms. [ABSTRACT FROM AUTHOR]

RAD51 is an important factor involved in the homologous recombination and repair of DNA breaks, which has also been implicated in various virus replication processes. We have previously reported that hepatitis C virus (HCV) exploits cellular RAD51 to promote viral propagation. Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also an RNA virus, we interrogated whether SARS-CoV-2 could coopt RAD51 for its propagation. Here, we showed that silencing of RAD51 impaired SARS-CoV-2 propagation. We further demonstrated that RAD51 colocalized with SARS-CoV-2 RNA in Vero E6 cells. Interestingly, RAD51 interacted with SARS-CoV-2 3CL protease. This suggests that RAD51 inhibitors may block SARS-CoV-2 propagation. Hence, we evaluated multiple RAD51 inhibitors as potential drug candidates for coronavirus disease 2019 (COVID-19). Among these, B02, 4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), IBR2, and RI(dl)-2 significantly decreased RNA, protein, and infectious virion levels of Wuhan and variants of SARS-CoV-2. Antiviral activity of DIDS was further confirmed in the Syrian hamster model. Molecular docking model showed that these chemicals interfered with RAD51 through dimerization interface. These data suggest that SARS-CoV-2 exploits host RAD51 to facilitate viral propagation, and hence, RAD51 inhibitor may serve as a putative novel therapeutic agent for the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Serological diagnosis of COVID-19 is complex due to the emergence of different SARS-CoV-2 variants. Methods: 164 serum samples from (I) patients who recovered from COVID-19 (n = 62) as well as (II) vaccinated individuals (n = 52) and (III) vaccinated individuals who were infected with different SARS-CoV-2 variants after vaccination (n = 50) were included. All samples were tested using EIA (binding antibodies) and a virus neutralization test (VNT) using the Wuhan strain (NT antibodies). Group III was further tested with a VNT using the Alpha/Delta/Omicron strains. Results: The highest antibody index (AI) was observed in vaccinated individuals infected with COVID-19 (median AI = 50, IQR = 27–71) and the lowest in vaccinated individuals (median AI = 19, IQR = 8–48). Similarly, NT antibody titer was highest in vaccinated individuals infected with COVID-19 (median 128; IQR = 32–256) compared to vaccinated individuals (median 32, IQR = 4–128) and patients with COVID-19 (median 32, IQR = 8–64). The correlation between AI and NT titer was strongly positive in vaccinated individuals and moderately positive in patients with COVID-19. No significant correlation was observed in vaccinated individuals infected with COVID-19. In patients infected with Alpha and Delta, the lowest VNT positivity rate was for the Omicron variant (85.0%/83.3%). Patients infected with the Alpha variant showed the lowest NT titer for the Omicron variant (median titer 32) compared to the Wuhan/Delta variants (64/128). Patients infected with the Delta variant had the lowest NT titer to the Omicron variant (median 32), compared to the Wuhan/Alpha variants (64/128). Patients infected with the Omicron variant showed similar titers to the Delta/Wuhan variants (128) and higher to the Alpha variant (256). Conclusions: The cross-immunity to SARS-CoV-2 is lowest for the Omicron variant compared to the Alpha/Delta variants. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease of 2019 (COVID-19), has caused havoc around the world. While several COVID-19 vaccines and drugs have been authorized for use, these antiviral drugs remain beyond the reach of most low- and middle-income countries. Rapid viral evolution is reducing the efficacy of vaccines and monoclonal antibodies and contributing to the deaths of some fully vaccinated persons. Others with normal immunity may have chosen not to be vaccinated and remain at risk if they contract the infection. Vaccines may not protect some immunodeficient patients from SARS-CoV-2, who are also at increased risk of chronic COVID-19 infection, a dangerous stalemate between the virus and a suboptimal immune response. Intra-host viral evolution could rapidly lead to the selection and dominance of vaccine and monoclonal antibody-resistant clades of SARS-CoV-2. There is thus an urgent need to develop new treatments for COVID-19. The NZACE2-Pātari project, comprising modified soluble angiotensin-converting enzyme 2 (ACE2) molecules, seeks to intercept and block SARS-CoV-2 infection of the respiratory mucosa. In vitro data presented here show that soluble wild-type ACE2 molecules retain the ability to effectively block the Spike (S) glycoprotein of SARS-CoV-2 variants including the ancestral Wuhan, delta (B.1.617.2) and omicron (B.1.1.529) strains. This therapeutic strategy may prove effective if implemented early during the nasal phase of the infection and may act synergistically with other antiviral drugs such as Paxlovid to further mitigate disease severity. This article shows that soluble wild-type ACE2 receptors can block the binding of the SARS-CoV-2 to ACE2. This is an antiviral strategy that is resistant to viral evolution. In the future, it may be used against new variants of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19), instigated by the zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), rapidly transformed from an outbreak in Wuhan, China, into a widespread global pandemic. A significant post-infection condition, known as 'long- COVID-19′ (or simply 'long- COVID'), emerges in a substantial subset of patients, manifesting with a constellation of over 200 reported symptoms that span multiple organ systems. This condition, also known as 'post-acute sequelae of SARS-CoV-2 infection' (PASC), presents a perplexing clinical picture with far-reaching implications, often persisting long after the acute phase. While initial research focused on the immediate pulmonary impact of the virus, the recognition of COVID-19 as a multiorgan disruptor has unveiled a gamut of protracted and severe health issues. This review summarizes the primary effects of long COVID on the respiratory, cardiovascular, and nervous systems. It also delves into the mechanisms underlying these impacts and underscores the critical need for a comprehensive understanding of long COVID's pathogenesis. [ABSTRACT FROM AUTHOR]

Background: The outbreak of Coronavirus Disease 2019 (COVID-19) has originated from Wuhan, China and rapidly spread all over the world. This disease is caused by a coronavirus termed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) that mainly infects the human respiratory tract. Herbal agents including Atractylodes lancea, Ephedra, Curcumin, and Echinacea purpurea had immunomodulatory effects and antiviral activities on other respiratory viruses including Influenza virus. They strengthen the innate immunity through increasing the phagocytic activity and anti-inflammatory activity. These herbs could be used as a complementary therapy to prevent entry of COVID-19 and improve immune system. This review delves into the role and therapeutic compounds of various herbal agents in relation to immunity, their effectiveness in treating other viral respiratory illnesses, and their potential influence on COVID-19 disease. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by SARS CoV-2 that emerged in Wuhan, China, and has rapidly spread worldwide. The mortality rate of critically ill COVID-19 patients is high. The objective of the study was to assess the COVID-19 disease severity and outcome among COVID-19 positive patients admitted before and after vaccination. Methodology: A prospective observational study conducted among all patients aged more than 18 years were included in the study. The patients who were positive before vaccination and received at least one dose of vaccine and positive after receiving two doses of vaccination included in the study. Disease severity was assessed in terms of high-resolution computed tomography (HRCT) score, intensive care unit (ICU) admission, SpO2 maintained, oxygen, plasma exchange, steroids received and on mechanical ventilation, and outcome was assessed on prognosis and stabilized/discharged to home. Results: A total of 172 were participated in the study with 101 (58.7%) males and 71 (41.3) females, respectively. Amongst them, 92 were affected before vaccination and 80 were affected before vaccination. The patients admitted in the ICU were 56 (32.6%) and 116 (67.4%) were not admitted in the ICU; among the patient admitted in ICU 42 (45.7%) before vaccination, and 14 (17.5%) were after vaccination, and difference was statistically significant with P- value <0.001. SPO2, steroids given, plasma exchange, oxygen >10 litres given and mechanical ventilation were positively associated with the vaccine received and disease severity with P- value <0.05. Conclusion: The severe COVID-19 had the worst outcome in the unvaccinated patients in terms of severity. Most partially vaccinated patients got infected before developing immunity; receiving at least one vaccination dose significantly reduced illness severity. [ABSTRACT FROM AUTHOR]

Vaccination remains crucial for protection against severe SARS-CoV-2 infection, especially for people of advanced age, however, optimal dosing regimens are as yet lacking. EU-COVAT-1-AGED Part A is a randomised controlled, adaptive, multicentre phase II trial evaluating safety and immunogenicity of a 3rd vaccination (1st booster) in individuals ≥75 years. Fifty-three participants were randomised to full-doses of either mRNA-1273 (Spikevax®, 100 µg) or BNT162b2 (Comirnaty®, 30 µg). The primary endpoint was the rate of 2-fold circulating antibody titre increase 14 days post-vaccination measured by quantitative electrochemiluminescence (ECL) immunoassay, targeting RBD region of Wuhan wild-type SARS-CoV-2. Secondary endpoints included the changes in neutralising capacity against wild-type and 25 variants of concern at 14 days and up to 12 months. Safety was assessed by monitoring of solicited adverse events (AEs) for seven days after on-study vaccination. Unsolicited AEs were collected until the end of follow-up at 12 months, SAEs were pursued for a further 30 days. Between 08th of November 2021 and 04th of January 2022, 53 participants ≥75 years received a COVID-19 vaccine as 1st booster. Fifty subjects (BNT162b2 n = 25/mRNA-1273 n = 25) were included in the analyses for immunogenicity at day 14. The primary endpoint of a 2-fold anti-RBD IgG titre increase 14 days after vaccination was reached for all subjects. A 3rd vaccination of full-dose mRNA-1273 provided higher anti-RBD IgG titres (Geometric mean titre) D14 mRNA-127310711 IU/mL (95 %-CI: 8003;14336) vs. BNT162b2: 7090 IU/mL (95 %-CI: 5688;8837). We detected a pattern showing higher neutralising capacity of full-dose mRNA-1273 against wild-type as well as for 23 out of 25 tested variants. Third doses of either BNT162b2 or mRNA-1273 provide substantial circulating antibody increase 14 days after vaccination. Full-dose mRNA-1273 provides higher antibody levels with an overall similar safety profile for people ≥75 years. This trial was funded by the European Commission (Framework Program HORIZON 2020). [ABSTRACT FROM AUTHOR]

• Advax-CpG55.2 adjuvanted spike protein vaccine protected hamsters against challenges with Beta or Delta viruses with the trivalent formulation performing best. • In naïve animals, the Beta variant caused higher virus loads in the upper respiratory tract whereas Delta variant caused greater transmission and more severe disease. • Hamsters immunized with Gamma spike vaccine had higher virus loads than unvaccinated infected animals suggesting the possibility of VAERD and/or ADE. • The spike protein vaccines reduced the risk of transmission to naïve co-housed animals. • Virus transmission to naïve animals correlated best with nasal turbinate virus load. The ongoing evolution of SARS-CoV-2 variants emphasizes the need for vaccines providing broad cross-protective immunity. This study was undertaken to assess the ability of Advax-CpG55.2 adjuvanted monovalent recombinant spike protein (Wuhan, Beta, Gamma) vaccines or a trivalent formulation to protect hamsters against Beta or Delta virus infection. The ability of vaccines to block virus transmission to naïve co-housed animals was also assessed. In naïve hosts, the Beta variant induced higher virus loads than the Delta variant, and conversely the Delta variant caused more severe disease and was more likely to be associated with virus transmission. The trivalent vaccine formulation provided the best protection against both Beta and Delta infection and also completely prevented virus transmission. The next best performing vaccine was the original monovalent Wuhan-based vaccine. Notably, hamsters that received the monovalent Gamma spike vaccine had the highest viral loads and clinical disease of all the vaccine groups, a potential signal of antibody dependent-enhancement (ADE). These hamsters were also the most likely to transmit Delta virus to naïve recipients. In murine studies, the Gamma spike vaccine induced the highest total spike protein to RBD IgG ratio and the lowest levels of neutralizing antibody, a context that could predispose to ADE. Overall, the study results confirmed that the current SpikoGen® vaccine based on Wuhan spike protein was still able to protect against clinical disease caused by either the Beta or Delta virus variants but suggested additional protection may be obtained by combining it with extra variant spike proteins to make a multivalent formulation. This study highlights the complexity of optimizing vaccine protection against multiple SARS-CoV-2 variants and stresses the need to continue to pursue new and improved COVID-19 vaccines able to provide robust, long-lasting, and broadly cross-protective immunity against constantly evolving SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Although the Covid-19 pandemic is officially over and the spread of coronavirus infection is no longer considered an international emergency, the virus continues to persist in the population, supporting the process of mutagenesis, which may lead to the emergence of more dangerous variants that can cause new outbreaks in the future. Therefore, the search for new effective drugs against the SARS-CoV-2 virus and other coronaviruses with a wide spectrum of activity remains an urgent task of medicinal chemistry. We synthesized a set of thiazolo-hydrazones based on (+)- and (−)-usnic acid and studied their ability to inhibit the main viral protease of the SARS-CoV-2 virus. It was shown that 9 out of 36 agents exhibit antiprotease activity in the range from 13 to 27 μM. The kinetic parameters of the four most active compounds were studied and molecular modeling of the possible interaction of these compounds with the active site of the main protease was carried out. Using six different strains (Wuhan, Delta, and four Omicron lines) of the SARS-CoV-2 virus, the antiviral activity of selected leader compounds was studied and it was shown that agent (+)-7a with a furan fragment has a pronounced antiviral activity against all strains. Additionally, the ability of the leading compounds to influence the stage of virus entry was studied, for which the activity of the compounds against the pseudoviral system with S glycoprotein on its surface was studied, as well as the ability to inhibit the interaction of recombinant ACE2 receptors with the RBD domain of the S protein by ELISA testing. It was found that the leading compounds are able to effectively inhibit pseudoviral particles without affecting the interaction of ACE2 and RBD. In order to search for a possible binding site for the leading compounds on the surface of the S-protein, molecular modeling was carried out. The N-terminal domain of the S protein was considered as a potential biological target, and it was found that the agents probably bind to the biliverdin site of the surface glycoprotein. Thus, we have identified new usnic acid derivatives that are active against a wide range of strains of the SARS-CoV-2 virus and have multi-targeting effects. [ABSTRACT FROM AUTHOR]

Background: We know turnaround time for the complete blood count is much faster than that of various inflammatory markers like LDH, CRP, interleukins like IL-6, D-dimer. Thus using cell counts as a marker of severity and the prognosis is need of the hour. This will reduce the burden of the health care facilities. Complete blood count including the variation in RBC, WBC and platelets changes has been thoroughly studied. Various retrospective studies have shown that the absolute lymphocyte count can be taken as a marker of severity in COVID 19 patients. In December 2019, several cases of new corona virus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARSCoV-2) have been emerged from Wuhan, China, which was later declared as a global pandemic by World Health Organisation (WHO) on March 11th 2020. Aim: In our study, we analyse and assess the severity of Covid-19 Vs d-NLR and RDW, PLR at our centre. Method and materials: This is the retrospective observational study. We actually collected the data of 300 cases but out of 300 cases only 268 laboratory confirmed COVID-19 cases, Age, neutrophil to lymphocyte ratio (NLR), derived-NLR (d-NLR), platelet to lymphocyte ratio (PLR) and red cell distribution width (RDW) of 268 laboratory confirmed COVID-19 patients, at the time of admission, belonging to clinical category B and C were recorded and compared in this single-center, retrospective observational study. The receiver operating characteristic (ROC) curve was applied to determine the thresholds for bio-markers and their prognostic values were assessed. Results and Observations: A statistically significant elevated NLR (P=0.001), d-NLR ( P=0.001), PLR (P=0.001) and RDW (P=0.026) were noticed in Category C (severe) group when compared to Category B group. From the ROC curve, it was established that d-NLR, NLR and WBC count proved to be a fair distinguisher (area under the curve between 0.7- 0.8) in predicting the clinical severity in COVID-19 patients. NLR and WBC count was found to be having the highest sensitivity of 82%, while d-NLR proved to be highly specific. Elevated age was also significantly associated with illness severity (P=0.001). Conclusion: COVID-19 is giving rise to tremendous challenges in the entire world and over pressurised the health care system and as of yet, efforts have been devoted to artificial intelligence based analysis of HRCT and x-rays have been used to indicate severity in the patients of SARSCoV2. Elevated age, WBC count, NLR, d-NLR, RDW and PLR may be considered as useful prognostic biomarkers for predicting the severity of COVID-19 infection and adverse outcome, with NLR and WBC count showing the highest sensitivity and d-NLR with the highest specificity. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovered in December 2019 in Wuhan, China, caused the coronavirus disease 2019 (COVID-19). Due to the rate of spread of this virus, the World Health Organization, in March 2020, recognised COVID-19 as a worldwide pandemic. The disease is multisystemic with varying degrees of severity. Unfortunately, despite intensive research, the molecular changes caused by SARS-CoV-2 remain unclear. Mechanisms affected by the virus infection include endothelial dysfunction and angiogenesis. Similarly, the vaccines developed so far affect the process of angiogenesis, contributing to the development of undesirable effects on part of the cardiovascular system. The presented research aimed to investigate the impact of the SARS-CoV-2 infection and the Pfizer Comirnaty vaccine (BNT162b2) on the molecular aspect of angiogenesis. We found that convalescents vaccinated with one dose of BNT162b2 were characterised by higher MMP-7 (metalloproteinases 7) expression than non-vaccinated convalescents and healthy volunteers vaccinated with one dose of BNT162b2. Moreover, non-vaccinated convalescents showed increased mRNA expression of ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif 1) compared to healthy volunteers vaccinated with one dose of BNT162b2. In addition, we showed significant sex differences in the expression of MMP-7. In conclusion, the results of our study suggest a significant impact of SARS-CoV-2 infection and vaccination on the course of angiogenesis at the molecular level. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), emerged in Wuhan, China, in December 2019. As of September 2023, there have been over 770 million confirmed cases of COVID-19, including over 6.9 million deaths. Epidemiologic studies have indicated that comorbidities of obesity and diabetes mellitus are associated with increased morbidity and mortality following SARS-CoV-2 infection. We determined how the comorbidities of obesity and diabetes affect morbidity and mortality following SARS-CoV-2 infection in unvaccinated and adjuvanted spike nanoparticle (NVXCoV2373) vaccinated mice. We find that obese/diabetic mice infected with SARS-CoV-2 have increased morbidity and mortality compared to age-matched normal mice. Mice that were fed a high-fat diet (HFD) and then vaccinated with NVX-CoV2373 produce equivalent neutralizing antibody titers compared to those fed a normal diet (ND). However, the HFD mice have reduced viral clearance early in infection. Analysis of the inflammatory immune response in HFD mice demonstrates a recruitment of neutrophils that was correlated with increased mortality and reduced clearance of the virus. Depletion of neutrophils in diabetic/obese vaccinated mice reduced disease severity and protected mice from lethality. This model recapitulates the increased disease severity associated with obesity and diabetes in humans with COVID-19 and is an important comorbidity to study with increasing obesity and diabetes across the world. [ABSTRACT FROM AUTHOR]

Throughout the COVID-19 pandemic, several variants of concern (VoC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have evolved, affecting the efficacy of the approved COVID-19 vaccines. To address the need for vaccines that induce strong and persistent cross-reactive neutralizing antibodies and T cell responses, we developed a prophylactic SARS-CoV-2 vaccine candidate based on our easily and rapidly adaptable plasmid DNA vaccine platform. The vaccine candidate, referred to here as VB2129, encodes a protein homodimer consisting of the receptor binding domain (RBD) from lineage B.1.351 (Beta) of SARS-CoV-2, a VoC with a severe immune profile, linked to a targeting unit (human LD78β/CCL3L1) that binds chemokine receptors on antigen-presenting cells (APCs) and a dimerization unit (derived from the hinge and CH3 exons of human IgG3). Immunogenicity studies in mice demonstrated that the APC-targeted vaccine induced strong antibody responses to both homologous Beta RBD and heterologous RBDs derived from Wuhan, Alpha, Gamma, Delta, and Omicron BA.1 variants, as well as cross-neutralizing antibodies against these VoC. Overall, preclinical data justify the exploration of VB2129 as a potential booster vaccine that induces broader antibody- and T cell-based protection against current and future SARS-CoV-2 VoC. [ABSTRACT FROM AUTHOR]

Objective: The aim of this work was to analyze the metadata of the SARS-CoV-2 sequences obtained from samples collected in Mexico from 2020 to 2022. Materials and Methods: Metadata of SARS-CoV-2 sequences from samples collected in Mexico up to 31 December 2022 was retrieved from GISAID and manually cured for interpretation. Results: As of December 2022, Mexican health authorities and the scientific community have sequenced up to 81,983 SARS-CoV-2 viral genomes deposited in GISAID, representing 1.1% of confirmed cases. The number of sequences obtained per state corresponded to the gross domestic product (GDP) of each state for the first (Mexico City) and the last (Tlaxcala). Approximately 25% of the sequences were obtained from CoViGen-Mex, an interdisciplinary initiative of health and scientific institutions to collect and sequence samples nationwide. The metadata showed a clear dominance of sequences retrieved by women. A similar variant distribution over time was found in Mexico and overseas, with the Omicron variant predominating. Finally, the age group with the highest representation in the sequences was adults aged 21 to 50 years, accounting for more than 50% of the total. Conclusions: Mexico presents diverse sociodemographic and economic characteristics. The COVID-19 pandemic has been and continues to be a challenge for collaboration across the country and around the world. [ABSTRACT FROM AUTHOR]

Background: Humans have become the witnessed of three deadly pandemics so far in the twenty-first century which are associated with novel corona viruses. All of these viruses, which are responsible for causing acute respiratory tract infections. Since the emergence of the 2019 novel corona virus (2019-nCoV) infection in Wuhan, China, in December 2019. Objective: 1. To assess the sociodemographic profile of the population. 2. To assess the public response about the covid-19 vaccine demand. 3. The various causes of hesitancy against vaccine acceptance. Method: A cross-sectional study was conducted in urban shivpuri population of above 18 year who are eligible for COVID-19 vaccination after applying inclusion and exclusion criteria during the February 2020-to April 2020. Data was collected by subordinate staff after giving offline training to them by face to face interview to each participant on predesigned and pretested close ended questionnaire. Result: In the present study we found that most common age group was 41-60 year male education middle class. We found that age, sex and religion not have any significance effect on their willingness for taking the vaccine but we found that education and people who have any co-morbidity was play the significance difference about their willingness to wards the acceptance of vaccine against COVID. Conclusion: We concluded that the people have hesitance about the acceptance of the COVID-19 vaccine in which most common reason was Not sure about its effectiveness on the other strain of the Covid-19 virus followed by they felt that after taking the vaccine we were not protect by it 100%.Conclusion: We concluded that the people have hesitance about the acceptance of the COVID-19 vaccine in which most common reason was Not sure about its effectiveness on the other strain of the Covid-19 virus followed by they felt that after taking the vaccine we were not protect by it 100%. [ABSTRACT FROM AUTHOR]

Background Understanding severity of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is crucial to inform public health measures. Here we used coronavirus disease 2019 (COVID-19) patient data from Hong Kong to characterize the severity profile of COVID-19. Methods Time-varying and age-specific effective severity measured by case hospitalization risk and hospitalization fatality risk was estimated with all individual COVID-19 case data collected in Hong Kong from 23 January 2020 through 26 October 2022 over 6 epidemic waves. The intrinsic severity of Omicron BA.2 was compared with the estimate for the ancestral strain with the data from unvaccinated patients without previous infections. Results With 32 222 COVID-19 hospitalizations and 9669 deaths confirmed over 6 epidemic waves, the time-varying hospitalization fatality risk dramatically increased from <10% before the largest fifth wave of Omicron BA.2 to 41% during the peak of the fifth wave when hospital resources were severely constrained. The age-specific fatality risk in unvaccinated hospitalized Omicron cases was comparable to the estimates for unvaccinated cases with the ancestral strain. During epidemics predominated by Omicron BA.2, fatality risk was highest among older unvaccinated patients. Conclusions Omicron has comparable intrinsic severity to the ancestral Wuhan strain, although the effective severity is substantially lower in Omicron cases due to vaccination. [ABSTRACT FROM AUTHOR]

Announced on December 31, 2019, the novel coronavirus arising in Wuhan City, Hubei Province resulted in millions of cases and lives lost. Following intense tracking, coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) in 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the cause of COVID-19 and the continuous evolution of the virus has given rise to several variants. In this review, a comprehensive analysis of the response to the pandemic over the first three-year period is provided, focusing on disease management, development of vaccines and therapeutics, and identification of variants. The transmissibility and pathogenicity of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron are compared. The binding characteristics of the SARS-CoV-2 spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor and reproduction numbers are evaluated. The effects of major variants on disease severity, hospitalisation, and case-fatality rates are outlined. In addition to the spike protein, open reading frames mutations are investigated. We also compare the pathogenicity of SARS-CoV-2 with SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Overall, this study highlights the strengths and weaknesses of the global response to the pandemic, as well as the importance of prevention and preparedness. Monitoring the evolution of SARS-CoV-2 is critical in identifying and potentially predicting the health outcomes of concerning variants as they emerge. The ultimate goal would be a position in which existing vaccines and therapeutics could be adapted to suit new variants in as close to real-time as possible. [ABSTRACT FROM AUTHOR]

The identification of deleterious mutations in different variants of SARS-CoV-2 and their roles in the morbidity of COVID-19 patients has yet to be thoroughly investigated. To unravel the spectrum of mutations and their effects within SARS-CoV-2 genomes, we analyzed 5,724 complete genomes from deceased COVID-19 patients sourced from the GISAID database. This analysis was conducted using the Nextstrain platform, applying a generalized time-reversible model for evolutionary phylogeny. These genomes were compared to the reference strain (hCoV-19/Wuhan/WIV04/2019) using MAFFT v7.470. Our findings revealed that SARS-CoV-2 genomes from deceased individuals belonged to 21 Nextstrain clades, with clade 20I (Alpha variant) being the most predominant, followed by clade 20H (Beta variant) and clade 20J (Gamma variant). The majority of SARS-CoV-2 genomes from deceased patients (33.4%) were sequenced in North America, while the lowest percentage (0.98%) came from Africa. The 'G' clade was dominant in the SARS-CoV-2 genomes of Asian, African, and North American regions, while the 'GRY' clade prevailed in Europe. In our analysis, we identified 35,799 nucleotide (NT) mutations throughout the genome, with the highest frequency (11,402 occurrences) found in the spike protein. Notably, we observed 4150 point-specific amino acid (AA) mutations in SARS-CoV-2 genomes, with D614G (20%) and N501Y (14%) identified as the top two deleterious mutations in the spike protein on a global scale. Furthermore, we detected five common deleterious AA mutations, including G18V, W45S, I33T, P30L, and Q418H, which play a key role in defining each clade of SARS-CoV-2. Our novel findings hold potential value for genomic surveillance, enabling the monitoring of the evolving pattern of SARS-CoV-2 infection, its emerging variants, and their impact on the development of effective vaccination and control strategies. [ABSTRACT FROM AUTHOR]

The identification of deleterious mutations in different variants of SARS-CoV-2 and their roles in the morbidity of COVID-19 patients has yet to be thoroughly investigated. To unravel the spectrum of mutations and their effects within SARS-CoV-2 genomes, we analyzed 5,724 complete genomes from deceased COVID-19 patients sourced from the GISAID database. This analysis was conducted using the Nextstrain platform, applying a generalized time-reversible model for evolutionary phylogeny. These genomes were compared to the reference strain (hCoV-19/Wuhan/WIV04/2019) using MAFFT v7.470. Our findings revealed that SARS-CoV-2 genomes from deceased individuals belonged to 21 Nextstrain clades, with clade 20I (Alpha variant) being the most predominant, followed by clade 20H (Beta variant) and clade 20J (Gamma variant). The majority of SARS-CoV-2 genomes from deceased patients (33.4%) were sequenced in North America, while the lowest percentage (0.98%) came from Africa. The 'G' clade was dominant in the SARS-CoV-2 genomes of Asian, African, and North American regions, while the 'GRY' clade prevailed in Europe. In our analysis, we identified 35,799 nucleotide (NT) mutations throughout the genome, with the highest frequency (11,402 occurrences) found in the spike protein. Notably, we observed 4150 point-specific amino acid (AA) mutations in SARS-CoV-2 genomes, with D614G (20%) and N501Y (14%) identified as the top two deleterious mutations in the spike protein on a global scale. Furthermore, we detected five common deleterious AA mutations, including G18V, W45S, I33T, P30L, and Q418H, which play a key role in defining each clade of SARS-CoV-2. Our novel findings hold potential value for genomic surveillance, enabling the monitoring of the evolving pattern of SARS-CoV-2 infection, its emerging variants, and their impact on the development of effective vaccination and control strategies. [ABSTRACT FROM AUTHOR]

Objective: We aimed to compare the adaptive immune response in individuals with or without prior SARS-CoV-2 infections following the administration of mRNA-based COVID-19 vaccines. Methods: A total of 54 participants with ages ranging from 37 to 56 years old, consisting of 23 individuals without a history of SARS-CoV-2 infection (uninfected group) and 31 individuals with prior infection of SARS-CoV-2 (infected group) who have received two doses of mRNA SARS-CoV-2 vaccines were enrolled in this study. We measured the IFN-γ level upon administration of BNT162b2 (PF) or mRNA-1273 (MO) by QuantiFERON SARS-CoV-2. The production of neutralizing antibodies was evaluated by a surrogate virus neutralization assay, and the neutralizing capacity was assessed by a plaque reduction neutralization test (PRNT50). The immune response was compared between the two groups. Results: A significantly higher level of IFN-γ (p < 0.001) and neutralization antibodies (p < 0.001) were observed in the infected group than those in the uninfected group following the first administration of vaccines. The infected group demonstrated a significantly higher PRNT50 titer than the uninfected group against the Wuhan strain (p < 0.0001). Still, the two groups were not significantly different against Delta (p = 0.07) and Omicron (p = 0.14) variants. Following the second vaccine dose, T- and B-cell levels were not significantly increased in the infected group. Conclusion: A single dose of mRNA-based COVID-19 vaccines would boost immune responses in individuals who had previously contracted SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 19 (COVID-19) is the disease caused by SARS-CoV-2, a highly infectious member of the coronavirus family, which emerged in December 2019 in "Wuhan, China". It induces respiratory illness ranging from mild symptoms to severe disease. It was declared a "pandemic" by the World Health Organization (WHO) in March 2020. Since then, a vast number of clinical and experimental studies have been conducted to identify effective approaches for its prevention and treatment. Main body: The pathophysiology of COVID-19 represents an unprecedented challenge; it triggers a strong immune response, which may be exacerbated by "a cytokine storm syndrome". It also induces thrombogenesis and may trigger multi-organ injury. Therefore, different drug classes have been proposed for its treatment and prevention, such as antivirals, anti-SARS-CoV-2 antibody agents (monoclonal antibodies, convalescent plasma, and immunoglobulins), anti-inflammatory drugs, immunomodulators, and anticoagulant drugs. To the best of our knowledge, this review is the first to present, discuss, and summarize the current knowledge about the different drug classes used for the treatment of COVID-19, with special emphasis on their targets, mechanisms of action, and important adverse effects and drug interactions. Additionally, we spotlight the latest "October 2023" important guidelines (NIH, IDSA, and NICE) and FDA approval or authorization regarding the use of these agents in the management of COVID-19. Conclusion: Despite the wide array of therapeutic strategies introduced for the treatment of COVID-19, one of the most prominent therapeutic challenges is SARS-CoV-2 mutations and emerging new variants and subvariants. Currently, the anti-COVID-19 drug pipeline is continuously affording novel treatments to face this growing challenge. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection, discovered and isolated in Wuhan City, Hubei Province, China, causes acute atypical respiratory symptoms and has led to profound changes in our lives. COVID-19 is characterized by a wide range of complications, which include pulmonary embolism, thromboembolism and arterial clot formation, arrhythmias, cardiomyopathy, multiorgan failure, and more. The disease has caused a worldwide pandemic, and despite various measures such as social distancing, various preventive strategies, and therapeutic approaches, and the creation of vaccines, the novel coronavirus infection (COVID-19) still hides many mysteries for the scientific community. Oxidative stress has been suggested to play an essential role in the pathogenesis of COVID-19, and determining free radical levels in patients with coronavirus infection may provide an insight into disease severity. The generation of abnormal levels of oxidants under a COVID-19-induced cytokine storm causes the irreversible oxidation of a wide range of macromolecules and subsequent damage to cells, tissues, and organs. Clinical studies have shown that oxidative stress initiates endothelial damage, which increases the risk of complications in COVID-19 and post-COVID-19 or long-COVID-19 cases. This review describes the role of oxidative stress and free radicals in the mediation of COVID-19-induced mitochondrial and endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Coronavirus Disease 2019 (COVID-19) is an infectious respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease, first identified in the Chinese city of Wuhan in November 2019, has since spread worldwide, is the latest human pandemic and has officially infected over 800 million people and has caused nearly seven million deaths to date. Although SARS-CoV-2 belongs to the large family of coronaviruses, it has some unique biological characteristics in its interplay with the human host. Therefore, this narrative review aims to provide an up-to-date overview of the structure of the virus, incubation and shedding in the human host, infectivity and biological evolution over time, as well as the main mechanisms for invading human host cells and replicating within. We also proffer that ongoing epidemiological surveillance of newly emerged variants must always be accompanied by biological studies aimed at deciphering new advantageous traits that may contribute to increasing virulence and pathogenicity, such that the most appropriate strategies for establishing a (relatively) safe coexistence with the human host can be implemented. [ABSTRACT FROM AUTHOR]

A novel coronavirus, SARS-CoV-2, first identified in Wuhan, China, in late 2019, caused a global pandemic resulting in significant morbidity and mortality in humans worldwide. Disease presentations in humans range from asymptomatic virus carriers to fatal systemic disease. A historic effort is underway to develop therapeutics and vaccines to slow or stop virus spread and treat those infected with coronavirus disease (COVID-19). Animal models play vital roles in understanding the pathogenesis of SARS-CoV-2 and evaluating therapeutics and vaccines. We compare the pathologic findings, including macroscopic, microscopic, and molecular findings, in three nonhuman primate species (cynomolgus macaques, rhesus macaques, and African green monkeys), ferrets, guinea pigs, hamsters, and mice following experimental exposure to SARS-CoV-2 by the intranasal, intratracheal or small particle aerosol routes to the disease as it occurs in humans who died during the current pandemic. [ABSTRACT FROM AUTHOR]

Key clinical message: In SARS‐CoV‐2 pandemic different disorders in coagulation pathways in COVID‐19 patients were reported. We described a 44‐year‐old female with COVID‐19 and protein C deficiency history. She did not show any coagulation disorder during her disease course. Complete genome sequencing of SARS‐CoV‐2 was performed and some mutations identified and compared with Wuhan strain. Besides hospitalized patients, in COVID‐19 outpatients with low concentration of protein C, early prescription of an anticoagulant such as heparin could be helpful in prevention of venous thromboembolism or pulmonary embolism. [ABSTRACT FROM AUTHOR]

Mucormycosis (Zygomycosis) is an invasive fungal infection, often acute and extremely severe caused by opportunist and ubiquitous fungi belonging to the class Phygomycetes, subclass Zygomycetes, order Mucorales, family Mucoraceae. COVID-19 is an infection caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Since the first case was detected, in December 2019 in Wuhan, China. COVID-19 has been found to have many systemic manifestations. Of these, ocular presentations associated with COVID-19 have been identified. It is acquired by the implantation of the fungal spores in the oral, nasal, and conjunctival mucosa (rhino-orbito-cerebral), by inhalation (pulmonary), or by the ingestion of contaminated food (digestive). The field of neuro-ophthalmology has been affected, due to both neuro-ophthalmic manifestations of COVID-19, as well as adaptations in the delivery of health care and treatment of pre-existing conditions. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has had a devastating impact on global health, highlighting the need to understand how the SARS‐CoV‐2 virus damages the lungs in order to develop effective treatments. Recent research has shown that patients with COVID‐19 experience severe oxidative damage to various biomolecules. We propose that the overproduction of reactive oxygen species (ROS) in SARS‐CoV‐2 infection involves an interaction between copper ions and the virus's spike protein. We tested two peptide fragments, Ac‐ELDKYFKNH‐NH2 (L1) and Ac‐WSHPQFEK‐NH2 (L2), derived from the spike protein of the Wuhan strain and the β variant, respectively, and found that they bind Cu(II) ions and form a three‐nitrogen complexes at lung pH. Our research demonstrates that these complexes trigger the overproduction of ROS, which can break both DNA strands and transform DNA into its linear form. Using A549 cells, we demonstrated that ROS overproduction occurs in the mitochondria, not in the cytoplasm. Our findings highlight the importance of the interaction between copper ions and the virus's spike protein in the development of lung damage and may aid in the development of therapeutic procedures. [ABSTRACT FROM AUTHOR]

SpikoGen® vaccine is a subunit COVID‐19 vaccine expressed in insect cells comprising recombinant spike protein extracellular domain formulated with Advax‐CpG55.2™ adjuvant. A Phase 2 trial was conducted in 400 adult participants randomised 3:1 to receive two intramuscular doses of SpikoGen® vaccine or saline placebo 3 weeks apart. Some Phase 2 trial participants later enrolled in a separate booster study and received a third dose of SpikoGen® vaccine. This stored serum was used to assess the ability of SpikoGen® vaccine to induce cross‐neutralising antibodies against SARS‐CoV‐2 variants of concern. Sera taken at baseline and 2 weeks after the second vaccine dose from baseline seronegative Phase 2 subjects was evaluated using a panel of spike pseudotype lentivirus neutralisation assays for the ability to cross‐neutralise a wide range of SARS‐CoV‐2 variants, including Omicron BA.1, BA.2 and BA.4/5. Stored samples of subjects who participated in both the 2‐dose Phase 2 trial and a third dose booster trial 6 months later were also analysed for changes in cross‐neutralising antibodies over time and dose. Two weeks after the second dose, sera broadly cross‐neutralised most variants of concern, albeit with titres against Omicron variants being ~10‐fold lower. While Omicron titres fell to low levels 6 months after the second vaccine dose in most subjects, they showed a ~20‐fold rise after the third dose booster, after which there was only a ~2‐3‐fold difference in neutralisation of Omicron and the ancestral strains. Despite being based on the ancestral Wuhan sequence, after two doses, SpikoGen® vaccine induced broadly cross‐neutralising serum antibodies. Titres then reduced over time but were rapidly restored by a third dose booster. This resulted in high neutralisation including against the Omicron variants. This data supports ongoing use of SpikoGen® vaccine for protection against recent SARS‐CoV‐2 Omicron variants. [ABSTRACT FROM AUTHOR]

The Omicron variant of concern (VOC) replaced the delta variant rapidly and became the predominant strain due to more mutations in spike protein and receptor-binding domain (RBD) enhancing its infectivity and binding affinity. The severity of the illness is less than that of the delta variant. Omicron is nonsusceptible to REGEN-COV™ and bamlanivimab with etesevimab. Drugs that are effective against the Omicron variant are oral antiviral drugs such as Paxlovid (nirmatrelvir/ritonavir), remdesivir, sotrovimab, and molnupiravir. The potency of sotrovimab is reduced to 3-fold against Omicron, and 8-fold reduction in potency with sotrovimab is found in a particular variant of Omicron with a R346K substitution in spike protein. There are neither clinical trials comparing the efficacy of these 4 therapies with each other nor any data on a combination of two or more therapies. The current recommendation for mild-moderate, nonhospitalized patients who are at a high risk of disease progression is to use Paxlovid as the first-line option. If Paxlovid is not available or cannot be administered due to drug interactions, then the next best choice is sotrovimab. The third choice is remdesivir if sotrovimab is also not available and molnupiravir is to be given if the other three options are not available or cannot be administered. For prevention, 2130 (cilgavimab) in combination with COV2-2196 (tixagevimab) has been effective against BA.2 only. LY-CoV1404 (bebtelovimab) is recently authorized as it is effective against all sublineages of the Omicron variant. Regarding vaccine efficacy (VE), the 3-dose VE with mRNA vaccines at 14–60 days was found to be 71.6%, and after 60 days, it is 47.4%. There is a 34–38-fold reduction of neutralizing activity with prebooster sera and a 19-fold reduction with booster sera for the Omicron variant. This probably explains the reason for worldwide breakthrough infections with the Omicron variant with waning immunity. The neutralizing antibody response against Omicron elicited by the bivalent vaccine is superior to that of the ancestral Wuhan strain, without any safety concerns. For future advances, the ribosome display technology can be applied for the generation of human single-chain fragment variable (scFv) antibodies from B cells of recovered patients against Omicron and other Coronavirus variants as they are easier and faster to produce and have high affinity and high specificity. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis is characterized by extracellular deposition in the lung primarily collagen but also other ECM molecules. The primary cell type responsible for this is the myofibroblast, and this can be induced by various stressors and signals. Infections be they bacterial or viral can cause pulmonary fibrosis (PF). In 2019, severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) originated in Wuhan, China, has led to a worldwide pandemic and can lead to acute respiratory distress and lung fibrosis. The virus itself can be cleared, but patients may develop long-term PF, which can be debilitating and life-limiting. There is a significantly perturbed immune response that shapes the fibrotic response leading to fibrosis. Given the importance of PF irrespective of cause, understanding the similarities and differences in pathogenesis caused by SARS-CoV-2-induced PF may yield new therapeutic targets. This review examines the pathology associated with the disease and discusses possible targets. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to have a zoonotic origin with bats suspected as a natural host. In this work, we individually express the ACE2 of seven bat species including, little brown, great roundleaf, Pearson's horseshoe, greater horseshoe, Brazilian free-tailed, Egyptian rousette, and Chinese rufous horseshoe in DF1 cells and determine their ability to support attachment and replication of SARS-CoV-2 viruses. We demonstrate that the ACE2 receptor of all seven species made DF1 cells permissible to SARS-CoV-2. The level of virus replication differed between bat species and variants tested. The Wuhan lineage SARS-CoV-2 virus replicated to higher titers than either variant virus tested. All viruses tested grew to higher titers in cells expressing the human ACE2 gene compared to a bat ACE2. This study provides a practical in vitro method for further testing of animal species for potential susceptibility to current and emerging SARS-CoV-2 viruses. • Here we demonstrate that SARS2-CoV-2 and its variants can bind to bat ACE2 for entry and replication in avian DF1 cells. • This work examines the ability of SARS-CoV-2 to attach to bat ACE2 and replicate in a non-permissive avian cell line. • Identification of bat species susceptible to SARS-CoV-2 providing data on zoonotic reservoirs and transmission potential. • Results positively correlate with other studies enhancing the predicative capability of the ACE2 expression model. [ABSTRACT FROM AUTHOR]

The coronavirus pandemic is an unending global epidemic of coronavirus disease 2019 (commonly known as, COVID-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2) that was first reported in Wuhan city of China at the end of the year 2019. Unfortunately, there was no oral antiviral drug for the treatment of this pandemic, which was urgently needed. Recently, after the phase 3 trial, researchers have reported the tolerability, safety profile and antiviral efficacy of Molnupiravir in the treatment of COVID-19. Topological indices are used to determine different physico-chemical, pharmaceutical and biological attributes of a molecular graph. In the current study, we depict the two-dimensional graph structure of the hydrogen-suppressed Molnupiravir. We calculate the values of some well-known degree-based topological indices for Molnupiravir drug by their standard definitions and alternatively by using M-polynomial approach which is more compact and appropriate. Among these indices, we obtain that the augmented Zagreb and modified second Zagreb indices have maximum and minimum values, respectively. Additionally, we geometrically represent the topological indices in increasing order and surface nature of the M-polynomial. The results obtained can help the researchers to study the pharmacokinetic properties of the newly developed drugs used in the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Background: The outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has posed a great threat to human health. Some severe COVID‐19 patients still carried detectable levels of SARS‐CoV‐2 even after prolonged intensive care unit treatment. However, the immunological features of these COVID‐19 patients with delayed virus clearance (CDVC) are still unclear. Methods: We retrospectively reviewed the clinical and immunological data of 13 CDVC cases, who were admitted into one hospital in Wuhan from February to April 2020. These data were also compared to those of perished (n = 9) and recovered (n = 52) cases. The expression of the exhaustion marker PD‐1 on circulating T cells of these patients was measured by flow cytometry. Results: High levels of serum interleukin‐6 (IL‐6), IL‐1β, IL‐8, as well as other inflammatory mediators, were seen in CDVC cases. Severe lymphopenia was observed in CDVC patients with the counts of total lymphocytes (0.9 × 109/L), CD4+ T cells (0.35 × 109/L), and CD8+ T cells (0.28 × 109/L) below their corresponding lower limits of normal range. Similar to the perished group, CDVC cases have higher percentages of CD25+Foxp3+ regulatory T cells (Treg) in circulation. Moreover, enhanced expression of the exhaustion marker PD‐1 on CCR7−CD45RA+ effector, CCR7+CD45RA− central memory, and CCR7−CD45RA− effector memory CD4+ and CD8+ T cells were also observed in CDVC cases. Conclusion: CDVC patients still have SARS‐CoV‐2 and these cases manifest with severe clinical symptoms due to persistent inflammation. Augmentation of the frequency of circulating Treg, severe lymphopenia, and functional exhaustion of T cells might lead to inefficient clearance of SARS‐CoV‐2. Therefore, enhancing lymphocyte counts and reversing T‐cell exhaustion might be key methods to boost immune responses and eliminate SARS‐CoV‐2 in CDVC patients. [ABSTRACT FROM AUTHOR]

SARS COV-2, the etiology of the ongoing COVID-19 pandemic, is a positive single-stranded RNA virus which was first identified in the city of Wuhan in 2019. Since its first discovery, several variants of the virus have been reported around the world. Identifying the emerged SARS-CoV-2 variants overtime is important since this could alter the pathogenicity and transmissibility of the virus as well as the efficacy of the vaccine. Here, 34 genome sequence of SARS COV-2 samples, which were collected between Feb. 2021 to Dec. 2021 in Kurdistan Region of Iraq (KRG), were compared and analyzed in the spike (S) protein region. The nucleotide sequences were collected from the GISAID database (https://gisaid.org/), and the SARS-COV-2 variants were determined based on the mutations that they carry. Additionally, the frequency of each mutation was determined in the S protein region of the isolates. Overall, 29 mutations were detected in the sequence samples; the majority (44.8%) were located in the Nterminal domain (NTD) of the protein, whereas only 10.3% located in the ribosomal binding domain (RBD). D614G was found in all sequenced strains, followed by 67.6% mutation of P681H. Moreover, seven deletions were found in the NTD of the S protein, with 61.8% of the deletions was occurred at the position Y144. Alpha variants (B.1.1.7) were found to be dominant lineage during the period of this study, accounted for 65% of the sequence samples. Overall, our data support the speedy increase of the SARSCOV-2 genome diversity. Based on our knowledge, this is the first mega sequence analyses of different SARS-COV-2 strains from KRG of Iraq. [ABSTRACT FROM AUTHOR]

Because SARS-CoV-2 constantly mutates to escape from the immune response, there is a reduction of neutralizing capacity of antibodies initially targeting the historical strain against emerging Variants of Concerns (VoC)s. That is why the measure of the protection conferred by vaccination cannot solely rely on the antibody levels, but also requires to measure their neutralization capacity. Here we used a mathematical model to follow the humoral response in 26 individuals that received up to three vaccination doses of Bnt162b2 vaccine, and for whom both anti-S IgG and neutralization capacity was measured longitudinally against all main VoCs. Our model could identify two independent mechanisms that led to a marked increase in measured humoral response over the successive vaccination doses. In addition to the already known increase in IgG levels after each dose, we identified that the neutralization capacity was significantly increased after the third vaccine administration against all VoCs, despite large inter-individual variability. Consequently, the model projects that the mean duration of detectable neutralizing capacity against non-Omicron VoC is between 348 days (Beta variant, 95% Prediction Intervals PI [307; 389]) and 587 days (Alpha variant, 95% PI [537; 636]). Despite the low neutralization levels after three doses, the mean duration of detectable neutralizing capacity against Omicron variants varies between 173 days (BA.5 variant, 95% PI [142; 200]) and 256 days (BA.1 variant, 95% PI [227; 286]). Our model shows the benefit of incorporating the neutralization capacity in the follow-up of patients to better inform on their level of protection against the different SARS-CoV-2 variants. Trial registration: This clinical trial is registered with ClinicalTrials.gov, Trial IDs NCT04750720 and NCT05315583. Author summary: Developed vaccines against SARS-CoV-2 have been a turning point against the ongoing Covid-19 pandemic. When the Wuhan virus was dominant, they help to dramatically reduce the number of severe cases as well as infection and transmission rates. For mRNA vaccines, it was in great part explained by the high level of induced antibodies a few weeks/months after injection and linked to high neutralizing capacity, the ability to prevent viruses to enter and infect target cells. However, decreasing antibody concentration over time and apparition of variants escaping their neutralizing action dramatically reduced the initial vaccine efficacy. As a countermeasure, additional injections were used to re-establish significant antibody population and ensure a long-term neutralizing activity against emerging variants. To infer if this multi-dose strategy fulfills such task, we construct a model of the evolution of the induced antibodies and their neutralizing capacity against different variants. This model helps us to quantify the gain brought by each new injection on both antibody population and their neutralizing ability against all tested variants as well as the dramatic differences between them. We also predict the long-term evolution of neutralizing activity, years after last injection, and thus discuss the longevity of the induced protection by vaccine. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is a zoonotic betacoronavirus that was first reported at the dawn of 2019 in Wuhan, China and has since spread globally, causing an ongoing pandemic. Anthroponotic transmission was reported early, with confirmed infections reported in 26 species to date, including dogs and cats. However, there is a paucity of reports on the transmission of SARS-CoV-2 to companion animals, and thus, we aimed to estimate the seroprevalence of SARS-CoV-2 in dogs and cats in Sarawak, Malaysia. From August 2022 to 2023, we screened plasma samples of 172 companion animals in Sarawak, Malaysia, using a species-independent surrogate virus neutralization test. Our findings revealed the presence of neutralizing antibodies of SARS-CoV-2 in 24.5% (27/110) of dogs and 24.2% (15/62) of cats. To the best of our knowledge, this is the first report of the seroprevalence of SARS-CoV-2 in companion animals in Malaysia. Our findings emphasize the need for pet owners to distance themselves from their pets when unwell, and a strategy must be in place to monitor SARS-CoV-2 in companion animals to assess the potential impact of the virus on companion animals. [ABSTRACT FROM AUTHOR]

Airborne SARS‐CoV‐2 virus surveillance faces challenges in complicated biomarker enrichment, interferences from various non‐specific matters and extremely low viral load in the urban ambient air, leading to difficulties in detecting SARS‐CoV‐2 bioaerosols. This work reports a highly specific bioanalysis platform, with an exceptionally low limit‐of‐detection (≤1 copy m−3) and good analytical accordance with RT‐qPCR, relying on surface‐mediated electrochemical signaling and enzyme‐assisted signal amplification, enabling gene and signal amplification for accurate identification and quantitation of low doses human coronavirus 229E (HCoV‐229E) and SARS‐CoV‐2 viruses in urban ambient air. This work provides a laboratory test using cultivated coronavirus to simulate the airborne spread of SARS‐CoV‐2, and validate that the platform could reliably detect airborne coronavirus and reveal the transmission characteristics. This bioassay conducts the quantitation of real‐world HCoV‐229E and SARS‐CoV‐2 in airborne particulate matters collected from road‐side and residential areas in Bern and Zurich (Switzerland) and Wuhan (China), with resultant concentrations verified by RT‐qPCR. [ABSTRACT FROM AUTHOR]

The appearance of mutations in the genes encoding the surface proteins of the new type of coronavirus SARS-CoV-2, when it circulates in the host population, makes it difficult to use monoclonal antibodies for its species identification. In such cases, the choice of conservative genetic targets allows identification by molecular biological methods. In this work, previously developed primers specific to the E-gene fragment were tested to detect a new type of coronavirus on six isolates belonging to different genetic variants (the original Wuhan strain, delta and omicron). The choice of a conservative site of the E gene encoding the small transmembrane protein E as a target for reverse transcription with subsequent amplification (RT-PCR) made it possible to detect coronavirus regardless of its subtypes characterized by antigenic heterogeneity in N- and S-proteins. The possibility of species-level identification of the COVID-19 pathogen circulating in Russia is shown, both in the total reaction volume (in a single test tube) and on biological microarrays. [ABSTRACT FROM AUTHOR]

Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin β1, only some integrin β7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients. During an infection, plasmablasts circulating in blood represent ongoing formation of antibody-producing cells from activated B cells. Here we study the early plasmablasts in previously naïve COVID-19 patients arriving at hospital. We find extensive cross-reactivity to circulating and non-circulating beta-coronaviruses, that IgA1 responses dominate, and that the cells express markers suggesting mucosal homing. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic erupted from Wuhan/China, has impacted the whole world in many ways drastically. Understanding such a pandemic, taking necessary precautions, and controlling a potential epidemic is essential. Modules and communities are typically and frequently represented in networks and analyzed with specific methods. Epidemic network analysis is a powerful method that provides us different information to interpret and make accurate decisions for pandemic events. The randomness of epidemic networks is considerably high; hence, it is essential to obtain consistent information from such networks. In this study, we proposed the network-based community detection of the early-stage COVID-19 associated with the basic reproduction number and the geographical distance between country locations. Worldwide confirmed cases between 22/01/2020 and 08/06/2020 had been analyzed for tenday periods. For this purpose, the Community Detection method was used. Therefore, (i) the community regions, (ii) the change of these regions and weighted nodal degrees of confirmed cases during the COVID-19, (iii) the relations between locations, and (iv) locations or regions which played an important role during the spread of this disease were obtained. The results of this study may help to reduce the reproduction number by lowering the average rate of contact in the early stage of a new pandemic. [ABSTRACT FROM AUTHOR]

Artificial intelligence plays a very prominent role in many fields, and of late, this term has been gaining much more popularity due to recent advances in machine learning. Machine learning is a sphere of artificial intelligence where machines are responsible for doing daily chores and are believed to be more intelligent than humans. Furthermore, artificial intelligence is significant in behavioral, social, physical, and biological engineering, biomathematical sciences, and many more disciplines. Fractional-order modeling of a real-world problem is a powerful tool for understanding the dynamics of the problem. In this study, an investigation into a fractional-order epidemic model of the novel coronavirus (COVID-19) is presented using intelligent computing through Bayesian-regularization backpropagation networks (BRBFNs). The designed BRBFNs are exploited to predict the transmission dynamics of COVID-19 disease by taking the dataset from a fractional numerical method based on the Grünwald–Letnikov backward finite difference. The datasets for the fractional-order mathematical model of COVID-19 for Wuhan and Karachi metropolitan cities are trained with BRBFNs for biased and unbiased input and target values. The proposed technique (BRBFNs) is implemented to estimate the integer and fractional-order COVID-19 spread dynamics. Its reliability, effectiveness, and validation are verified through consistently achieved accuracy metrics that depend on error histograms, regression studies, and mean squared error. [ABSTRACT FROM AUTHOR]

COVID-19, an acute respiratory syndrome caused by the SARS-CoV-2 virus, was first reported in late 2019 in Wuhan, China, and rapidly escalated into a global pandemic. The condition can lead to organ dysfunction and, ultimately, death through acute respiratory distress syndrome (ARDS). Disease severity has been linked to proinflammatory cytokines, which activate the NF-κB and STAT transcription factors in infected cells. It has been proven that lncRNAs play an essential role in reducing or increasing inflammatory factors. This makes them potentially valuable in recognizing pathogenesis pathways and therapeutic targets in COVID-19. Nanocurcumin is known as an antioxidant, tumor suppressor, and anti-inflammatory substance, and it can be effective in reducing inflammation caused by the disease of COVID-19. This study analyzed Sequence Read Archive data from COVID-19 patients with acute versus milder symptoms, identifying dysregulated genes and noncoding RNAs. To verify this correlation, the expression of the candidate gene was evaluated with quantitative polymerase chain reaction (qPCR) in mouse models, while immunoglobulin (Ig) G titer was measured using enzyme-linked immunosorbent assay (ELISA) in mouse serum samples. Here, we introduced a novel lncRNA called HSD17B3-AS1, suggested as a therapeutic target in COVID-19 patients with acute symptoms. Furthermore, we revealed that nanocurcumin reduces the expression of HSD17B3-AS1, which leads to reduced inflammation in mice. These results suggest that HSD17B3-AS1 plays a significant regulatory role in managing COVID-19, and the downregulation of HSD17B3-AS1 by Nanocurcumin presents a promising treatment option for minimizing complications in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Purpose: Patients with antibody deficiencies often receive maintenance treatment with donor plasma-derived immunoglobulin (Ig) preparations to decrease the incidence and severity of infections. We have previously shown that IgG antibodies to the original SARS-CoV-2 strain were not consistently present in off-the-shelf Ig batches produced up to approximately 18 months after the first identified case of COVID-19 in the USA and that Ig batches with anti-SARS-CoV-2 IgG primarily contained vaccine-induced spike specific antibodies. This study aimed to investigate the degree of cross-reactivity between vaccine-induced anti-SARS-CoV-2 antibodies against Wuhan strain and subsequent viral variants. Methods: Samples were collected from 74 Ig batches supplied by three different commercial manufacturers. All batches were used at the Immunodeficiency Unit at the Karolinska University Hospital from the start of the SARS-CoV-2 pandemic until September 2022. Antibody quantity and potential to neutralize virus entry into host cells were assessed against the original SARS-CoV-2 Wuhan strain and the following nine variants: Alpha, Beta, Delta, IHU, and the Omicron BA.1, BA.1.1, BA.1 with spike mutation L452R, BA.2, and BA.3. Results: Ig batches produced approximately 18 months after the SARS-CoV-2 outbreak (from around July 2021) and later consistently contained high quantities of antibodies that bind the Wuhan strain. The Ig batches had overall low reactivity to the SARS-CoV-2 nucleocapsid, which implies that plasma donor spike IgG essentially is the result of vaccination. We assessed the degree of cross-reactivity towards each virus variant by plotting the variant/Wuhan strain ratio, which was consistent regardless of production date, suggesting cross-reactivity with vaccine-induced antibodies rather than virus exposure in the plasma donor population. Viral variants that emerged later during the pandemic systematically had a lower reactivity ratio, except for the Delta and IHU variants. The Ig batches displayed markedly low neutralizing potential towards the Beta variant and all tested Omicron variants. Conclusion: Commercial Ig batches currently contain large quantities of SARS-CoV-2 vaccine-induced antibodies. Cross-reactivity with variant strains is evident but varies, with markedly low neutralizing potential observed against Omicron variants. [ABSTRACT FROM AUTHOR]

• SARS-CoV-2 has a specific effect on blood pressure during and after the acute phase of infection. • Incidence of new-onset hypertension in patients with COVID-19 is higher than contemporary controls (9 % vs. 5 %). • The interaction between spike proteins and ACE 2 remains a plausible mechanism underlying the raise in blood pressure. • Variants develop mutations that may promote adhesivity to ACE 2 and increase the risk of new onset hypertension. Several reports documented a specific effect of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on blood pressure (BP), during and after the acute phase of infection. Clinical studies demonstrated that coronavirus disease 2019 (COVID-19) is associated with an increased risk of a persistent increase in BP requiring a new or intensified anti-hypertensive treatment during hospitalization. The picture is further complicated by the evidence from large databases showing an increased risk of new-onset hypertension in COVID-19 survivors on the long term. To further elucidate the epidemiological burden of this phenomenon, we performed a pooled analysis of 4 studies reporting crude incidence rates of new-onset hypertension among COVID-19 patients and contemporary controls. Overall, COVID-19 was associated with a 65% increased risk of new-onset hypertension when compared with controls (p<0.0001); furthermore, incidence of new-onset hypertension was 9% and 5% among COVID-19 patients and controls, respectively. In both the acute phase and recovery from infection, the interaction between spike proteins of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE 2) receptors remain the most plausible mechanism explaining the raise in BP (ranking new onset hypertension as one of the most prevalent cardiovascular sequelae of COVID-19). In this area of research, it is worth to mention that new variants of SARS-CoV-2 exhibit specific mutations in the spike protein that promotes entry into viral cells via ACE 2. Thus, the enhanced spike affinity for ACE 2 of new variants has the potential to increase the risk of new-onset hypertension when compared with the original Wuhan strain. [ABSTRACT FROM AUTHOR]

First case of severe acute respiratory syndrome coronavirus-2 was detected in Wuhan province of china. Within a year, the vaccine development process accelerated and emergency approval was rolled out for vaccines. Covishield, an adenovirus vector-based vaccine manufactured by Serum Institute of India, was granted emergency use approval by the subject expert committee under Drug Controller General of India in India in the month of January. Numerous adverse effects are still under study following vaccination. Among them, a very rare complication reported is Guillain-Barre syndrome (GBS). The relation between coronavirus disease 19 (COVID-19) vaccine and GBS is still not clear. Here, we present a case of a 32-year-old female with no comorbidities, presented with complaints of bilateral weakness in lower limbs which gradually progressed to upper limbs along with bilateral facial palsy. She had taken her first shot of Covishield vaccine last month. She has no risk factors for GBS, which suggests that it was caused by the vaccine. She was admitted to intensive care unit for further management. This report might help physicians to be more vigilant in evaluating GBS cases especially in the current COVID-19 pandemic era. [ABSTRACT FROM AUTHOR]

The 2019 novel coronavirus (SARS-CoV-2 / COVID-19), with a point of origin in Wuhan, China, has spread rapidly all over the world. It turned into a raging pandemic wrecking havoc on health care facilities, world economy and affecting everyone's life to date. With every new variant, rate of transmission, spread of infections and the number of cases continues to rise at an international level and scale. There are limited reliable researches that study microdroplets spread and transmissions from human sneeze or cough in the airborne space. In this paper, we propose an intelligent technique to visualize, detect, measure the distance of spread in a real-world settings of microdroplet transmissions in airborne space, called "COVNET45". In this paper, we investigate the microdroplet transmission and validate the measurements accuracy compared to published researches, by examining several microscopic and visual images taken to investigate the novel coronavirus (SARS-CoV-2 / COVID-19). The ultimate contribution is to calculate the spread of the microdroplets, measure it precisely and provide a graphical presentation. Additionally, the work employs machine learning and five algorithms for image optimization, detection and measurement. [ABSTRACT FROM AUTHOR]