Genomic epidemiology of severe acute respiratory syndrome coronavirus 2 from Theni, Tamil Nadu.

Introduction: The coronavirus disease 2019 (COVID-19) is a viral infection characterized by respiratory and gastrointestinal symptoms. The causative agent of this infection is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genomic study helps in understanding the pathogenesis, epidemiology, and the development of therapeutic and preventive strategies in the combat against COVID-19. Materials and Methods: Nasopharyngeal and oropharyngeal swab samples were collected from asymptomatic and symptomatic patients during the time period of 2021-2022 for the detection of SARS-CoV-2 by employing real-time reverse transcriptase, cDNA synthesis, whole-genome sequencing by next-genome sequencing, analysis of SARS-CoV-2 sequence data and lineage and variant of concern assignment along with phylogenetic analysis. Results: Lineages BA.2.10 and BA.4.1.1 clustered with genomes from Senegal suggested the spread of infections. Similarly, high clustering among delta samples during the second wave showed possible importation and subsequent spread via local transmission. Conclusions: Studies like these are important to understand the characteristics and origins of locally circulating SARS-CoV-2 diversity in order to prevent further spread.

The Asymptomatic Proportion of SARS-CoV-2 Omicron Variant Infections in Households: A Systematic Review.

Understanding the clinical spectrum of SARS-CoV-2 infection, including the asymptomatic fraction, is important as asymptomatic individuals are still able to infect other individuals and contribute to ongoing transmission. The WHO Unity Household transmission investigation (HHTI) protocol provides a platform for the prospective and systematic collection of high-quality clinical, epidemiological, serological and virological data from SARS-CoV-2 confirmed cases and their household contacts. These data can be used to understand key severity and transmissibility parameters-including the asymptomatic proportion-in relation to local epidemic context and help inform public health response. We aimed to estimate the asymptomatic proportion of SARS-CoV-2 Omicron variant infections in Unity-aligned HHTIs. We conducted a systematic review and meta-analysis in alignment with the PRISMA 2020 guidelines and registered our systematic review on PROSPERO (CRD42022378648). We searched EMBASE, Web of Science, MEDLINE and bioRxiv and medRxiv from 1 November 2021 to 22 August 2023. We identified 8368 records, of which 98 underwent full text review. We identified only three studies for data extraction, with substantial variation in study design and corresponding estimates of the asymptomatic proportion. As a result, we did not generate a pooled estimate or I2 metric. The limited number of quality studies that we identified highlights the need for improved preparedness and response capabilities to facilitate robust HHTI implementation, analysis and reporting, to better inform national, regional and global risk assessments and policymaking.

Molecular mimicry of SARS-COV-2 antigens as a possible natural anti-cancer preventive immunization.

Background: In the present study we investigated whether peptides derived from the entire SARS-CoV-2 proteome share homology to TAAs (tumor-associated antigens) and cross-reactive CD8+ T cell can be elicited by the BNT162b2 preventive vaccine or the SARS-CoV-2 natural infection. Methods and results: Viral epitopes with high affinity (<100nM) to the HLA-A*02:01 allele were predicted. Shared and variant-specific epitopes were identified. Significant homologies in amino acidic sequence have been found between SARS-CoV-2 peptides and multiple TAAs, mainly associated with breast, liver, melanoma and colon cancers. The molecular mimicry of the viral epitopes and the TAAs was found in all viral proteins, mostly the Orf 1ab and the Spike, which is included in the BNT162b2 vaccine. Predicted structural similarities confirmed the sequence homology and comparable patterns of contact with both HLA and TCR α and ß chains were observed. CD8+ T cell clones cross-reactive with the paired peptides have been found by MHC class l-dextramer staining. Conclusions: Our results show for the first time that several SARS-COV-2 antigens are highly homologous to TAAs and cross-reactive T cells are identified in infected and BNT162b2 preventive vaccinated individuals. The implication would be that the SARS-Cov-2 pandemic could represent a natural preventive immunization for breast, liver, melanoma and colon cancers. In the coming years, real-world evidences will provide the final proof for such immunological experimental evidence. Moreover, such SARS-CoV-2 epitopes can be used to develop "multi-cancer" off-the-shelf preventive/therapeutic vaccine formulations, with higher antigenicity and immunogenicity than over-expressed tumor self-antigens, for the potential valuable benefit of thousands of cancer patients around the World.

A retrospective analysis of the influencing factors of nucleic acid CT value fluctuation in COVID-19 patients infected with Omicron variant virus in Changchun city.

Objective: This study aimed to determine the risk factors associated with fluctuations in nucleic acid CT values in patients infected with the Omicron variant during an outbreak at a hospital in Changchun city. Methods: A retrospective analysis was conducted on general information, medical history, vaccination history, and laboratory test data of COVID-19 patients infected with the Omicron variant and admitted to the hospital in Changchun from March 2022 to April 2022. The study aimed to explore the factors influencing nucleic acid CT value fluctuations in COVID-19 patients infected with the Omicron variant in Changchun city. Results: Fluctuations in nucleic acid CT values were significantly correlated with occupation composition (p = 0.030), hospital stay duration (p = 0.000), heart rate (p = 0.026), creatinine (p = 0.011), platelet count (p = 0.000), glutamic-pyruvic transaminase (p = 0.045), and glutamic oxaloacetic transaminase (p = 0.017). Binary logistic regression analysis revealed significant correlations between hospital stay duration (p = 0.000), platelet count (p = 0.019), heart rate (p = 0.036), and nucleic acid CT value fluctuations (p < 0.05), indicating that they were independent risk factors. Red blood cell count was identified as a factor influencing nucleic acid CT value fluctuations in Group A patients. Occupation composition, direct bilirubin, and platelet count were identified as factors influencing nucleic acid CT value fluctuations in Group B patients. Further binary logistic regression analysis indicated that occupational composition and direct bilirubin are significant independent factors for nucleic acid CT value fluctuations in Group B patients, positively correlated with occupational risk and negatively correlated with direct bilirubin. Conclusion: Therefore, enhancing patients' immunity, increasing physical exercise to improve myocardial oxygen consumption, reducing the length of hospital stays, and closely monitoring liver function at the onset of hospitalization to prevent liver function abnormalities are effective measures to control fluctuations in nucleic acid CT values.

Epidemiology, risk factors, and vaccine effectiveness for SARS-CoV-2 infection among healthcare workers during the omicron pandemic in Shanghai, China.

Background: The COVID-19 pandemic has exposed healthcare workers (HCWs) to serious risk of infection. The aims of our study were to investigate the epidemiological characteristics and risk factors of SARS-CoV-2 infection among HCWs, and evaluate the vaccine effectiveness (VE) during the Omicron pandemic in Shanghai, China. Methods: Active surveillance of COVID-19 was performed among HCWs who worked in Shanghai General Hospital from December 2022 to January 2023. A case-control study was conducted by questionnaire survey to analyse the infection-related risk factors. A retrospective cohort study was explored to evaluate VE against primary infection. Results: During the Omicron outbreak, 2,008 of 2,460 (81.6%) HCWs were infected with SARS-CoV-2. The infection rate was higher in women, younger age groups, nurses and medical technicians. Among the 1,742 participants in the questionnaire, 1,463 (84.0%) were tested positive, and 95.1% of them developed symptoms. Most of the infections (53.0%) were acquired outside the hospital. The risk factors associated with higher odds of infection were working in the emergency department (aOR 3.77, 95% CI 1.69-8.38) and medical examination area (aOR 2.47, 95% CI 1.10-5.51). The protective factors associated with lower odds of infection were previous infection with SARS-CoV-2 (aOR 0.01, 95% CI 0-0.07) and receiving four doses of vaccines (aOR 0.40, 95% CI 0.17-0.97). For frontline HCWs, those who had oral-nasal exposure to coworkers were more likely to be infected (aOR 1.74, 95% CI 1.21-2.51). In VE analysis, the risk of primary infection was lower in HCWs who received the emergency heterologous booster (the fourth dose) during the epidemic (aHR 0.25, 95% CI 0.15-0.40), resulting in an adjusted-VE of 75.1%. Conclusions: In response to future pandemic, it is important for public health policies to aim at protecting HCWs through risk-differentiated infection control measures, strengthening personal protection and recommending vaccination to vulnerable individuals before the arrival of Omicron wave.

Vital Signs as Predictors of Oxygen Requirements in COVID-19 Outpatients: The Development of a Streamlined Risk Score.

BACKGROUND: With COVID-19 becoming a common disease, primary care facilities such as clinics are required to efficiently triage patients at high risk of severe illness within the constraints of limited medical resources. However, existing COVID-19 severity risk scores require detailed medical history assessments, such as evaluating the severity of pneumonia via chest CT and accounting for past and comorbid conditions. Therefore, they may not be suitable for practical use in clinical settings with limited medical resources, including personnel and equipment. PURPOSE:  The goal is to identify key variables that predict the need for oxygen therapy in COVID-19 patients and develop a simplified clinical risk score based solely on vital signs to predict oxygen requirements. PATIENTS AND METHODS: A retrospective observational study of 584 outpatients with COVID-19 confirmed by polymerase chain reaction test visited Sasebo Chuo Hospital between April 28, 2022, and August 18, 2022. Analyses were conducted after adjustment for background factors of age and sex with propensity score matching. We used the Fisher test for nominal variables and the Kruskal-Wallis test for continuous variables. RESULTS: After adjusting for age and sex, several factors significantly correlated with the need for oxygen within seven days including body temperature (p < 0.001), respiratory rate (p = 0.007), SpO2 (p < 0.001), and the detection of pneumonia on CT scans (p = 0.032). The area under the receiver-operating characteristic curve for the risk score based on these vital signs and CT was 0.947 (95% confidence interval: 0.911-0.982). The risk score based solely on vital signs was 0.937 (0.900-0.974), demonstrating the ability to predict oxygen administration with no significant differences. CONCLUSIONS: Body temperature, advanced age, increased respiratory rate, decreased SpO2, and the presence of pneumonia on CT scans were significant predictors of oxygen need within seven days among the study participants. The risk score, based solely on vital signs, effectively and simply assesses the likelihood of requiring oxygen therapy within seven days with high accuracy. The risk score, which utilizes only age and vital signs and does not require a detailed patient history or CT scans, could streamline hospital referral processes for admissions.

Comparative analysis of prognostic scoring systems in predicting severity and outcomes of Omicron variant COVID-19 pneumonia.

Background: The global spread of Coronavirus Disease 2019 (COVID-19) underscores the urgent need for reliable methods to forecast the disease's severity and outcome, thereby facilitating timely interventions and reducing mortality rates. This study focuses on evaluating the clinical and laboratory profiles of patients with Omicron variant-induced COVID-19 pneumonia and assessing the efficacy of various scoring systems in prognosticating disease severity and mortality. Methods: In this retrospective analysis, we examined the clinical records of 409 individuals diagnosed with Omicron variant COVID-19 pneumonia. We documented the Pneumonia Severity Index, CURB-65, and MuLBSTA scores within the first 24 h and analyzed the sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve for each scoring system to ascertain their predictive accuracy for disease severity and fatality risk. Results: The cohort's median age was 78 years, predominantly presenting with fever, cough, expectoration, fatigue, and gastrointestinal symptoms. Factors such as expectoration, fatigue, Glasgow Coma Scale score, lactate dehydrogenase levels, procalcitonin, creatinine levels, and co-occurrence of acute respiratory distress syndrome were identified as independent predictors of disease severity. Furthermore, age, oxygenation index, glucose levels, lactate dehydrogenase, and septic shock were independently associated with mortality. For severe disease prediction, the CURB-65, PSI, and MuLBSTA scores demonstrated sensitivities of 65.9%, 63.8%, and 79.7%, respectively, with specificities of 63.8%, 76.8%, and 60.9%, and AUROCs of 0.707, 0.750, and 0.728. To predict mortality risk, these scores at cutoffs of 1.5, 102.5, and 12.5 exhibited sensitivities of 83.3%, 96.3%, and 70.4%, specificities of 59.4%, 60.8%, and 65.4%, and AUROCs of 0.787, 0.850, and 0.736, respectively. Conclusion: The study cohort predominantly comprised elderly individuals with pre-existing health conditions. Elevated lactate dehydrogenase emerged as a significant marker for both disease severity and prognosis, sputum production, gastrointestinal symptoms, GCS score, creatinine, PCT, and ARDS as independent predictors of disease severity, and age, oxygenation index, glucose levels, and septic shock as independent mortality predictors in COVID-19 pneumonia patients. Among the scoring systems evaluated, Pneumonia Severity Index demonstrated superior predictive capability for both disease severity and mortality, suggesting its utility in forecasting the clinical outcomes of Omicron variant COVID-19 pneumonia.

Exploring the binding dynamics of covalent inhibitors within active site of PLpro in SARS-CoV-2.

In the global fight against the COVID-19 pandemic caused by the highly transmissible SARS-CoV-2 virus, the search for potent medications is paramount. With a focused investigation on the SARS-CoV-2 papain-like protease (PLpro) as a promising therapeutic target due to its pivotal role in viral replication and immune modulation, the catalytic triad of PLpro comprising Cys111, His272, and Asp286, highlights Cys111 as an intriguing nucleophilic center for potential covalent bonds with ligands. The detailed analysis of the binding site unveils crucial interactions with both hydrophobic and polar residues, demonstrating the structural insights of the cavity and deepening our understanding of its molecular landscape. The sequence of PLpro among variants of concern (Alpha, Beta, Gamma, Delta and Omicron) and the recent variant of interest, JN.1, remains conserved with no mutations at the active site. Moreover, a thorough exploration of apo, non-covalently bound, and covalently bound PLpro conformations exposes significant conformational changes in loop regions, offering invaluable insights into the intricate dynamics of ligand-protein complex formation. Employing strategic in silico medication repurposing, this study swiftly identifies potential molecules for target inhibition. Within the domain of covalent docking studies and molecular dynamics, using reported inhibitors and clinically tested molecules elucidate the formation of stable covalent bonds with the cysteine residue, laying a robust foundation for potential therapeutic applications. These details not only deepen our comprehension of PLpro inhibition but also play a pivotal role in shaping the dynamic landscape of COVID-19 treatment strategies.

Emergence and fixation of SARS-CoV-2 minority variants in a chronically infected patient receiving therapy in Denmark.

SARS-CoV-2 variants of concern (VOC), such as Delta and Omicron have harbored mutations, which increased viral infectivity or ability to evade neutralizing antibodies. Immunocompromised patients might be a source of some of these emerging variants. In this study, we sequenced 17 consecutive samples from an immunocompromised patient with a long-term SARS-CoV-2 infection with the pre-VOC era lineage B.1.177.35. We here describe the emergence of 73 nonsynonymous minority variants in this patient and show that 10 of these mutations became dominant in the viral population during the treatment period. Four of these were seen throughout the infection period and had a very low global prevalence, although three of them were also observed later in the Alpha, Delta, and Omicron lineages. We also found that two adjacent nsp12 variants (M785I and S786P) belonged to different quasi-species and competed during the early stages of infection and remdesivir administration. This emphasizes the importance of ongoing genome surveillance of SARS-CoV-2 among immunocpromised patients.

Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant.

In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.

Dengue virus (DV) non-cross-reactive Omicron wave COVID-19 serums enhanced DV3 infectivity in vitro.

Introduction. In India, the SARS-CoV-2 Delta wave (2020-2021) faded away with the advent of the Omicron variants (2021-present). Dengue incidences were observed to be less in Southeast Asia during the active years of the pandemic (2020-2021). However, dengue virus type 3 (DV3) cases were increasingly reported in this region (including India) concurrent with the progression of the Omicron waves since 2022.Hypothesis. What could be the reason(s) behind this unusual DV3 surge after an overall dip in dengue incidences in many parts of Southeast Asia?Aim. We, therefore, investigated the current state of cross-reactivity of prevalent (Omicron era) SARS-CoV-2 serums with different DV serotypes and evaluated the impact of such serums on DV neutralization in cell culture.Methodology. Fifty-five COVID-19 serum samples (January-September 2022) and three pre-pandemic archived serum samples from apparently healthy individuals were tested for DV or SARS-CoV-2 IgM/IgG using the lateral flow immunoassays. DV1-4 virus neutralization tests (VNTs) were done with the SARS-CoV-2 antibody (Ab)-positive serums in Huh7 cells. DV3 envelope (env) gene was PCR amplified and sequenced for three archived DV isolates, one from 2017 and two from 2021.Results. SARS-CoV-2 Ab-positive samples constituted 74.5 % of the serums. Of these, 41.5 % were DV cross-reactive and 58.5 % were not. The DV cross-reactive serums neutralized all DV serotypes (DV1-4), as per previous results and this study. The DV non-cross-reactive serums (58.5 %) also cross-neutralized DV1, 2 and 4 but increased DV3 infectivity by means of antibody-dependent enhancement of infection as evident from significantly higher DV3 titres in VNT compared to control serums. The DV3 envelope was identical among the three isolates, including isolate 1 used in VNTs. Our results suggest that DV cross-reactivity of SARS-CoV-2 serums diminished with the shift from Delta to Omicron prevalence. Such COVID-19 serums (DV non-cross-reactive) might have played a major role in causing DV3 surge during the Omicron waves.Conclusion. Patients suspected of dengue or COVID-19 should be subjected to virus/antigen tests and serological tests for both the diseases for definitive diagnosis, prognosis and disease management.

Reduction in ACE2 expression in peripheral blood mononuclear cells during COVID-19 - implications for post COVID-19 conditions.

BACKGROUND: Severe COVID-19 is uncommon, restricted to 19% of the total population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether a biomarker indicated severity of disease and, in particular, if variable expression of angiotensin converting enzyme 2 (ACE2) in blood might clarify this difference in risk and of post COVID -19 conditions (PCC). METHODS: The IRB-approved study compared patients hospitalized with severe COVID-19 to healthy controls. Severe infection was defined requiring oxygen or increased oxygen need from baseline at admission with positive COVID-19 PCR. A single blood sample was obtained from patients within a day of admission. ACE2 RNA expression in blood cells was measured by an RT-PCR assay. Plasma ACE1 and ACE2 enzyme activities were quantified by fluorescent peptides. Plasma TIMP-1, PIIINP and MMP-9 antigens were quantified by ELISA. Data were entered into REDCap and analyzed using STATA v 14 and GraphPad Prism v 10. RESULTS: Forty-eight patients and 72 healthy controls were recruited during the pandemic. ACE2 RNA expression in peripheral blood mononuclear cells (PBMC) was rarely detected acutely during severe COVID-19 but common in controls (OR for undetected ACE2: 12.4 [95% CI: 2.62-76.1]). ACE2 RNA expression in PBMC did not determine plasma ACE1 and ACE2 activity, suggesting alternative cell-signaling pathways. Markers of fibrosis (TIMP-1 and PIIINP) and vasculopathy (MMP-9) were additionally elevated. ACE2 RNA expression during severe COVID-19 often responded within hours to convalescent plasma. Analogous to oncogenesis, we speculate that potent, persistent, cryptic processes following COVID-19 (the renin-angiotensin system (RAS), fibrosis and vasculopathy) initiate or promote post-COVID-19 conditions (PCC) in susceptible individuals. CONCLUSIONS: This work elucidates biological and temporal plausibility for ACE2, TIMP1, PIIINP and MMP-9 in the pathogenesis of PCC. Intersection of these independent systems is uncommon and may in part explain the rarity of PCC.

Safety and efficacy of COVID-19 vaccination in the Chinese population with pulmonary lymphangioleiomyomatosis: a single-center retrospective study.

BACKGROUND: The safety and efficacy of vaccination against coronavirus disease 2019 (COVID-19) in patients with lymphangioleiomyomatosis (LAM) is still unclear. This study investigates COVID-19 vaccine hesitancy, vaccine safety and efficacy, and COVID-19 symptoms in LAM patients. RESULTS: In total, 181 LAM patients and 143 healthy individuals responded to the questionnaire. The vaccination rate of LAM patients was 77.34%, and 15.7% of vaccinated LAM patients experienced adverse events. Vaccination decreased the risk of LAM patients developing anorexia [OR: 0.17, 95% CI: (0.07, 0.43)], myalgia [OR: 0.34, 95% CI: (0.13, 0.84)], and ageusia [OR: 0.34, 95% CI: (0.14, 0.84)]. In LAM patients, a use of mTOR inhibitors reduced the risk of developing symptoms during COVID-19, including fatigue [OR: 0.18, 95% CI: (0.03, 0.95)], anorexia [OR: 0.30, 95% CI: (0.09, 0.96)], and ageusia [OR: 0.20, 95% CI: (0.06, 0.67)]. CONCLUSIONS: Vaccination rates in the LAM population were lower than those in the general population, as 22.7% (41/181) of LAM patients had hesitations regarding the COVID-19 vaccine. However, the safety of COVID-19 vaccination in the LAM cohort was comparable to the healthy population, and COVID-19 vaccination decreased the incidence of COVID-19 symptoms in LAM patients. In addition, mTOR inhibitors seem not to determine a greater risk of complications in patients with LAM during COVID-19.

Development and validation of a scoring system to predict the mortality of hospitalized patients with SARS-CoV-2 Omicron: a nationwide, multicentre study.

BACKGROUND: The Omicron variant broke out in China at the end of 2022, causing a considerable number of severe cases and even deaths. The study aimed to identify risk factors for death in patients hospitalized with SARS-CoV-2 Omicron infection and to establish a scoring system for predicting mortality. METHODS: 1817 patients were enrolled at eight hospitals in China from December 2022 to May 2023, including 815 patients in the training group and 1002 patients in the validation group. Forty-six clinical and laboratory features were screened using LASSO regression and multivariable logistic regression. RESULTS: In the training set, 730 patients were discharged and 85 patients died. In the validation set, 918 patients were discharged and 84 patients died. LASSO regression identified age, levels of interleukin (IL) -6, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and D-dimer; neutrophil count, neutrophil-to-lymphocyte ratio (NLR) as associated with mortality. Multivariable logistic regression analysis showed that older age, IL-6, BUN, LDH and D-dimer were significant independent risk factors. Based on these variables, a scoring system was developed with a sensitivity of 83.6% and a specificity of 83.5% in the training group, and a sensitivity of 79.8% and a sensitivity of 83.0% in the validation group. CONCLUSIONS: A scoring system based on age, IL-6, BUN, LDH and D-dime can help clinicians identify patients with poor prognosis early.

Protection of Omicron Sub-Lineage Infection Against Reinfection with Another Omicron Sub-Lineage: Systematic Review, Meta-Analysis, and Meta-Regression - Worldwide, 2022-2023.

What is already known about this topic?: Both the decline in immunity over time and the evolution of the virus play a role in the level of protection offered by a prior infection. What is added by this report?: Point estimates indicated variations in protection levels based on the initial infecting variant and the reinfecting variant. There was a consistent correlation between real-world protection, antigenic distance, and humoral immunity levels. Specifically, shorter antigenic distances and higher humoral immunity levels corresponded to enhanced real-world protection. What are the implications for public health practice?: Our findings suggest that virological and immunological studies could help identify and assess the epidemic risk posed by new variants before they become dominant. Prompt incorporation of the latest variants into the antigen components of the coronavirus disease 2019 (COVID-19) vaccines can significantly contribute to effective epidemic prevention and control measures.

Characteristics and outcomes of patients with COVID-19 at high risk of disease progression receiving sotrovimab, oral antivirals, or no treatment: a retrospective cohort study.

BACKGROUND: The clinical benefit of coronavirus disease 2019 (COVID-19) treatments against new circulating variants remains unclear. We sought to describe characteristics and clinical outcomes of highest risk patients with COVID-19 receiving early COVID-19 treatments in Scotland. METHODS: Retrospective cohort study of non-hospitalized patients diagnosed with COVID-19 from December 1, 2021-October 25, 2022, using Scottish administrative health data. We included adult patients who met ≥ 1 of the National Health Service highest risk criteria for early COVID-19 treatment and received outpatient treatment with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or no early COVID-19 treatment. Index date was defined as the earliest of COVID-19 diagnosis or early COVID-19 treatment. Baseline characteristics and acute clinical outcomes in the 28 days following index were reported. Values of ≤ 5 were suppressed. RESULTS: In total, 2548 patients were included (492: sotrovimab, 276: nirmatrelvir/ritonavir, 71: molnupiravir, and 1709: eligible highest risk untreated). Patients aged ≥ 75 years accounted for 6.9% (n = 34/492), 21.0% (n = 58/276), 16.9% (n = 12/71) and 13.2% (n = 225/1709) of the cohorts, respectively. Advanced renal disease was reported in 6.7% (n = 33/492) of sotrovimab-treated and 4.7% (n = 81/1709) of untreated patients, and ≤ 5 nirmatrelvir/ritonavir-treated and molnupiravir-treated patients. All-cause hospitalizations were experienced by 5.3% (n = 25/476) of sotrovimab-treated patients, 6.9% (n = 12/175) of nirmatrelvir/ritonavir-treated patients, ≤ 5 (suppressed number) molnupiravir-treated patients and 13.3% (n = 216/1622) of untreated patients. There were no deaths in the treated cohorts; mortality was 4.3% (n = 70/1622) among untreated patients. CONCLUSIONS: Sotrovimab was often used by patients who were aged < 75 years. Among patients receiving early COVID-19 treatment, proportions of 28-day all-cause hospitalization and death were low.

Studying the impacts of variant evolution for a generalized age-group transmission model.

The differences of SARS-CoV-2 variants brought the changes of transmission characteristics and clinical manifestations during the prevalence of COVID-19. In order to explore the evolution mechanisms of SARS-CoV-2 variants and the impacts of variant evolution, the classic SIR (Susceptible-Infected-Recovered) compartment model was modified to a generalized SVEIR (Susceptible-Vaccinated-Exposed-Infected-Recovered) compartment model with age-group and varying variants in this study. By using of the SVEIR model and least squares method, the optimal fittings against the surveillance data from Fujian Provincial Center for Disease Control and Prevention were performed for the five epidemics of Fujian Province. The main epidemiological characteristics such as basic reproduction number, effective reproduction number, sensitivity analysis, and cross-variant scenario investigations were extensively investigated during dynamic zero-COVID policy. The study results showed that the infectivities of the variants became fast from wild strain to the Delta variant, further to the Omicron variant. Meanwhile, the cross-variant investigations showed that the average incubation periods were shortened, and that the infection scales quickly enhanced. Further, the risk estimations with the new variants were performed without implements of the non-pharmaceutical interventions, based on the dominant variants XBB.1.9.1 and EG.5. The results of the risk estimations suggested that non-pharmaceutical interventions were necessary on the Chinese mainland for controlling severe infections and deaths, and also that the regular variant monitors were still workable against the aggressive variant evolution and the emergency of new transmission risks in the future.

Genotypic characterization of novel S-DEL variants of porcine epidemic diarrhea virus identified in South Korea.

The highly pathogenic genotype 2b (HP-G2b) of porcine epidemic diarrhea virus (PEDV), which caused a pandemic in 2013-2014, evolved in South Korea and became endemic, affecting the domestic pig industry. This study describes the genotypic traits of novel HP-G2b PEDV strains identified on affected farms experiencing low disease severity with < 10% neonatal mortality. Nucleotide sequencing revealed common deletion patterns, termed S-DEL2, resulting in a two-amino-acid deletion at positions 60 and 61, 61 and 62, or 63 and 64 in the N-terminal domain of the spike (S) protein of all isolates. The S barcode profiles of S-DEL2 variants differed from each other and shared 96.0-99.4% and 98.5-99.6% nt sequence identity with other South Korean HP-G2b PEDV strains in the S gene and in the complete genome sequence, respectively. Genetic and phylogenetic analysis showed that the S-DEL2 strains belonged to diverse domestic clades: CK, CK.1, CK.2, or NC. The emergence of novel S-DEL2 strains suggests that continuous evolution of PEDV occurs under endemic circumstances, resulting in genetic diversity and distinct clinical presentations. This study advances our knowledge regarding the genetic and pathogenic heterogeneity of PEDV and emphasizes the importance of active monitoring and surveillance to identify novel variants and determine their genotypic and phenotypic characteristics.

Combining genomic data and infection estimates to characterize the complex dynamics of SARS-CoV-2 Omicron variants in the US.

Omicron surged as a variant of concern in late 2021. Several distinct Omicron variants appeared and overtook each other. We combined variant frequencies and infection estimates from a nowcasting model for each US state to estimate variant-specific infections, attack rates, and effective reproduction numbers (Rt). BA.1 rapidly emerged, and we estimate that it infected 47.7% of the US population before it was replaced by BA.2. We estimate that BA.5 infected 35.7% of the US population, persisting in circulation for nearly 6 months. Other variants-BA.2, BA.4, and XBB-together infected 30.7% of the US population. We found a positive correlation between the state-level BA.1 attack rate and social vulnerability and a negative correlation between the BA.1 and BA.2 attack rates. Our findings illustrate the complex interplay between viral evolution, population susceptibility, and social factors during the Omicron emergence in the US.