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Background: More than 12 billion doses of COVID-19 vaccine administrations and over 630 million natural infections should have developed adequate levels of herd immunity over the last three years. However, there have been many new waves of coronavirus infections. The development of safe and effective vaccines to control breakthrough SARS-CoV-2 infections remain an urgent priority. We have developed a recombinant VSV vector-based vaccine to fulfill this worldwide need. Method(s): We have used a recombinant vesicular stomatitis virus (rVSV)-based prime-boost immunization strategy to develop an effective COVID-19 recall vaccine candidate. We have constructed an attenuated recombinant VSV genome carrying the full-length Spike protein gene of SARS-CoV-2. Adding the honeybee melittin signal peptide (msp) at the N-terminus enhanced the protein expression and adding the VSV G protein transmembrane domain and the cytoplasmic tail (Gtc) at the C-terminus of the Spike protein allowed efficient incorporation of the Spike protein into pseudotype VSV. Result(s): In immunized mice, rVSV with chimeric rVSV-msp-S-Gtc induced high levels of potent neutralizing antibodies (nAbs) and CD8+ T cell responses, while the full-length Spike with Gtc proved to be the superior immunogen. More importantly, rVSV-msp-S-Gtc-vaccinated animals were completely protected from subsequent SARS-CoV-2 challenges. Furthermore, rVSV-Wuhan and rVSV-Delta vaccines, and an rVSV-Trivalent (mixed rVSV-Wuhan, -Beta and -Delta) vaccine elicited potent nAbs against live SARS-CoV-2 Wuhan (USAWA1), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) viruses. Heterologous boosting of rVSV-Wuhan with rVSV-Delta induced strong nAb responses against Delta and Omicron viruses, with the rVSV-Trivalent vaccine consistently inducing effective nAbs against all the SARS-CoV-2 variants tested. All rVSV-msp-S-Gtc vaccines also elicited an immunodominant Spike-specific CD8+ T cell response. Conclusion(s): rVSV vaccines targeting SARS-CoV-2 variants of concern can be considered as an effective booster vaccine in the global fight against COVID-19.
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Background: The unprecedented scale of the COVID-19 pandemic and rapid evolution of SARS-CoV-2 variants underscores the need for broadly active inhibitors with a high barrier to resistance. The coronavirus main protease (Mpro) is an essential viral enzyme required for viral polyprotein processing and is highly conserved across human coronaviruses. Pomotrelvir (PBI-0451) is a novel Mpro inhibitor currently completing phase 2 clinical trial. Here we describe the mechanism of action, broad activity against SARS-CoV-2 clinical isolates, combination studies with other SARS-CoV-2 inhibitors and favorable resistance profile of pomotrelvir. Method(s): The kinetic parameters of pomotrelvir Mpro inhibition and its interaction with nirmaltrevir were determined in a kinetic protease assay. The IC50s of pomotrelvir on mutant Mpro proteins were measured in an endpoint Mpro assay. Combination studies of pomotrelvir with remdesivir and molnupiravir were carried out in A549-hACE2 cells infected with SARS-CoV-2 NLuc virus. Activity against SARS-CoV-2 clinical variants was assessed by infection of A549-ACE2-TMPRSS2 cells followed by immunostaining of the viral nucleocapsid protein. Result(s): Pomotrelvir is a potent competitive inhibitor of SARS-CoV-2 Mpro (Ki =2.7 nM). Binding of pomotrelvir and the Mpro inhibitor nirmatrelvir to the active site is mutually exclusive. In the SARS-CoV-2 NLuc assay, pomotrelvir is additive when combined with remdesivir or molnupiravir, two nucleoside analogs targeting viral RNA synthesis. When the effect of Mpro substitutions previously selected in a resistance study of pomotrelvir were analyzed in an enzyme assay, only Mpro-N133H showed a significant increase in IC50 (45-fold). The catalytic efficiency of Mpro-N133H is reduced by 10-fold and the recombinant virus SARSCoV-2 (WA1) -N133H is not viable, suggesting that N133H has lower replicative fitness. Lastly, pomotrelvir exhibits broad activity against all SARS-CoV-2 clinical isolates tested to date, including five omicron variants. Conclusion(s): PBI-0451 is a potent competitive inhibitor of SARS-CoV-2 Mpro and is broadly active against SARS-CoV-2 clinical isolates including omicron variants. Results from inhibitor interaction studies support the potential combination of pomotrelvir with remdesivir and molnupiravir but not nirmatrelvir. Enzymatic characterization of in vitro selected pomotrelvir resistant variants indicates they either confer no resistance or have reduced fitness.
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Background Delta and Omicron are two main variants that have been prevalent since 2021. However, the Omicron variant of severe acute respiratory syndrome coronavirus 2 shows a less severe clinical presentation and high transmissibility. Therefore, we carried out this retrospective study to evaluate Omicron severity compared with the Delta variant and further comprehend the differences in clinical characteristics in patients with the Omicron variant. Methods We extracted clinical data and compared clinical severity, symptoms, vaccination status, laboratory parameters, viral shedding time, and computed tomography (CT) imaging between the two groups of patients, which included 109 COVID-19 cases with the Delta variant and 183 cases with the Omicron variant, from January 19 to April 1, 2022, in Beijing Ditan Hospital. In addition, the Beijing Center for Disease Prevention and Control conducted whole-genome sequencing. Results We obtained 94 strains of variants of concern/Delta and 110 strains of variants of concern/Omicron. For the 110 Omicron strains, three were assigned as BA.1.1, 53 as BA.2, and 54 as BA.2.2. Among patients with the Delta variant, 54% (59/109) were moderate, which was significantly higher than that of patients with the Omicron variant (7% (12/183), P < 0.001). The number of patients with mild symptoms in the Omicron group was significantly higher than in the Delta group (80% vs. 35%, P < 0.001). Compared with the Omicron group, patients with underlying diseases or obesity, 60 years or older, or unvaccinated in the Delta group had more severe disease, and there was a significant difference between the two groups. The viral shedding time in the Omicron group was shorter than in the Delta group ((11.9 ± 5.9) vs. (14.0 ± 5.8) days, P = 0.003). Among the 183 patients in the Omicron group, 104 (57%) had dry or sore throat symptoms, more than those in the Delta group (34% (37/109);P < 0.001). In the Delta group, patients in the moderate group had more fever and cough symptoms than those in the mild group. The remission time of CT imaging in the Omicron group was shorter than in the Delta group ((9.0 ± 5.2) vs. (13.2 ± 4.2) days, P = 0.018). Conclusions Patients with Delta variants are more likely to have pneumonia, mainly with fever and cough symptoms, while patients with the Omicron variant are mostly mild, with more prominent dry or sore throat symptoms. In addition, patients with the Omicron variant have a short viral shedding time and rapid absorption of pneumonia. © Wolters Kluwer Health, Inc. All rights reserved.
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Background: Implementation of vaccination programmes has had a transformational impact on control of the SARS-CoV-2 pandemic, but the need for effective antiviral drugs remains. Molnupiravir (MPV) targets viral RNA polymerase inhibiting replication via lethal mutagenesis and nirmatrelvir (NTV) is a protease inhibitor boosted with ritonavir when given clinically. This study aimed to assess the virological efficacy of NTV and MPV individually and in combination against the SARS-CoV-2 BA.1 Omicron variant in a K18-hACE2 mouse model. Method(s): K18-hACE2 mice were inoculated intranasally with 103 PFU of SARSCoV-2 BA.1 Omicron (B.1.1.529). After 24 hours, mice were orally dosed q12H, as outlined in Figure 1. At 2, 3, and 4-days post infection mice were sacrificed, and lung samples harvested. Animals were weighed and monitored daily throughout. Subsequently, viral replication in the lung was quantified using qRT-PCR to measure total (N-gene) and sub-genomic (E-gene) viral RNA. Data were normalized to 18S for quantitation. Viral exposures expressed as Areas Under viral load Curves (AUCs) were calculated by the trapezoidal method using mean values at each timepoint. Separate studies in Syrian golden hamsters using individual drugs were also conducted, and total serum IgG was measured by ELISA at 4-days post infection. Result(s): Mice gained weight in all groups post-treatment, with no significant difference between groups. A reduction in lung viral exposure was evident in all treatment groups compared to the vehicle control dosed mice (Figure 1). Coadministration of NTV with MPV displayed a trend towards lower lung viral exposure compared to the vehicle control with ~40-and ~45-fold reduction in AUC for N-and SgE-gene assays, respectively. Dosed individually, NTV and MPV reduced viral exposure 5.7-and 7.7-fold for the N-gene assay, respectively. Differences in total serum IgG concentrations were evident between vehicle and NTV-(34-fold reduction, P=0.018), and MPV-(4.2-fold reduction, P=0.053) treated hamsters. Conclusion(s): These data show virological efficacy of NTV and MPV against the SARS-CoV-2 BA.1 Omicron variant. The combination of NTV and MPV demonstrated a lower viral RNA exposure in the lung than either drug alone, albeit not statistically significant. Initial data indicate potential immune alterations in NTV and MPV dosed hamsters. Studies to clarify the utility of NTV/ MPV combinations and further characterize the impact of antiviral therapy on IgG are warranted.
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The COVID-19 outbreak began in December 2019 and was declared a global health emergency by the World Health Organization. The four most dominating variants are Beta, Gamma, Delta, and Omicron. After the administration of vaccine doses, an eminent decline in new cases has been observed. The COVID-19 vaccine induces neutralizing antibodies and T-cells in our bodies. However, strong variants like Delta and Omicron tend to escape these neutralizing antibodies elicited by COVID-19 vaccination. Therefore, it is indispensable to study, analyze and most importantly, predict the response of SARS-CoV-2-derived t-cell epitopes against Covid variants in vaccinated and unvaccinated persons. In this regard, machine learning can be effectively utilized for predicting the response of COVID-derived t-cell epitopes. In this study, prediction of T-cells Epitopes' response was conducted for vaccinated and unvaccinated people for Beta, Gamma, Delta, and Omicron variants. The dataset was divided into two classes, i.e., vaccinated and unvaccinated, and the predicted response of T-cell Epitopes was divided into three categories, i.e., Strong, Impaired, and Over-activated. For the aforementioned prediction purposes, a self-proposed Bayesian neural network has been designed by combining variational inference and flow normalization optimizers. Furthermore, the Hidden Markov Model has also been trained on the same dataset to compare the results of the self-proposed Bayesian neural network with this state-of-the-art statistical approach. Extensive experimentation and results demonstrate the efficacy of the proposed network in terms of accurate prediction and reduced error. © 2023 Tech Science Press. All rights reserved.
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Background: The SARS-CoV-2 Omicron variant is highly immune evasive but is attenuated in cell and animal models of infection, which many reports attribute to spike mutations. However, the phenotype and contribution to viral fitness of Omicron non-spike mutations remain unknown. Method(s): To study mutations across the entire genome independent of spike, we developed a novel cloning and replicon system capable of generating mutants within 6 hours and obtaining phenotypic results within 3-4 days. Result(s): Using a series of Omicron replicons, we found that ORF1ab harbors critical mutations, especially in the nonstructural protein 6 (NSP6), which lower viral fitness and are currently evolving in Omicron subvariants. In addition, Omicron mutations in several NSPs epistatically interact and are critical for viral replication and polyprotein processing. Conclusion(s): Collectively, we describe a robust replicon technology to study mutations across the genome and our data highlight the need to vigilantly study and monitor non-spike mutations in emerging Omicron subvariants.
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Background Effectiveness of COVID-19 mRNA vaccines is influenced by SARS-CoV-2 variant and history of prior infection. Data regarding protection against SARS-CoV-2 infection among adolescents, accounting for prior infection and time since vaccination, are limited. Methods SARS-CoV-2 testing and immunization data from the Kentucky Electronic Disease Surveillance System and the Kentucky Immunization Registry, August–September 2021 (Delta predominance) and January 2022 (Omicron Predominance) among adolescents aged 12–17 years, were used to assess association of SARS-CoV-2 infection with mRNA vaccination and prior SARS-CoV-2 infection. Estimated protection was derived from prevalence ratios ([1-PR] x 100%). Results During Delta predominance, 89,736 tested adolescents were evaluated. Completion of primary series (2nd dose of mRNA vaccine ≥14 days prior to testing) and history of prior infection (>90 days prior to testing) were both protective against SARS-CoV-2 infection (primary series: 81%, 95% CI 79.7–82.3;prior infection: 66%, 95% CI 62.0–69.6). Prior infection plus primary series provided the greatest protection (92.3%, 95% CI 88.0–95.1). During Omicron predominance, 67,331 tested adolescents were evaluated. Primary series alone provided no benefit against SARS-CoV-2 infection after 90 days;prior infection was protective for up to one year (24.2%, 95% CI 17.2–30.7). Prior infection plus booster vaccination provided the greatest protection against infection (82.4%, 95% CI 62.1–91.8). Discussion Strength and duration of protection against infection provided by COVID-19 vaccination and prior SARS-CoV-2 infection differed by variant. Vaccination provided additional benefit to the protection offered by prior infection alone. Remaining up to date with vaccination is recommended for all adolescents regardless of infection history.
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The third SARS-CoV-2 pandemic wave causing Omicron variant has comparatively higher replication rate and transmissibility than the second wave-causing Delta variant. The exact mechanism behind the differential properties of Delta and Omicron in respect to infectivity and virulence is not properly understood yet. This study reports the analysis of different mutations within the receptor binding domain (RBD) of spike glycoprotein and non-structural protein (nsp) of Delta and Omicron strains. We have used computational studies to evaluate the properties of Delta and Omicron variants in this work. Q498R, Q493R and S375F mutations of RBD showed better docking scores for Omicron compared to Delta variant of SARS-CoV-2, whereas nsp3_L1266I with PARP15 (7OUX), nsp3_L1266I with PARP15 (7OUX), and nsp6_G107 with ISG15 (1Z2M) showed significantly higher docking score. The findings of the present study might be helpful to reveal the probable cause of relatively milder form of COVID-19 disease manifested by Omicron in comparison to Delta variant of SARS-CoV-2 virus.Copyright © 2023, The Author(s), under exclusive licence to Indian Virological Society.
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Background: The Cystic Fibrosis Foundation (CFF) advises that all persons with cystic fibrosis (PwCF) visit a cystic fibrosis (CF) care center every 3 months for evaluation, treatment, surveillance, counseling, and education [1]. In March 2020, our clinic went into modified operations in response to the COVID-19 pandemic, necessitating a temporary change in our ability to conduct routine face-to-face visits. Within 1 month, we operationalized virtual visits in addition to face-to-face visits. During the pandemic, staff noticed a drop in clinic attendance, and we implemented a quality improvement (QI) plan to study and address this trend. Method(s): Our QI team is a multidisciplinary group that is part of the Cystic Fibrosis Learning Network (CFLN). We defined the clinic fill rate (CFR) as the number of people seen over the number of available clinic slots. Each week, we determined the number of PwCF scheduled the following week and compared that number with no-shows and cancellations that occurred during that 7-day period. We also determined the number of PwCF scheduled 1 month ahead to compare it with weekly data. We used a key driver diagram to help focus our interventions (change ideas). Using run charts, we analyzed data each week to identify trends and variances. We used plan-do-study-act cycles and implemented initial interventions centered on publicizing CFF follow-up guidelines in town hall meetings, emails, and newsletters. We later identified PwCF who had a no-show history, and before clinics, our social worker communicated with each family (telephone or text) to remind them of the upcoming visit and identify any barriers to attending. During our study, Oregon experienced a surge in COVID-19 cases from the omicron variant, andwe overlaid our data with a graph of cases. Result(s): CFR was measured in 598 encounters over 28 weeks. CFR 1 month in advancewas 79%. In theweek before clinic, CFRwas 84%. After theweek, overall CFR was 66% (68% for face-to-face visits, 58% for virtual visits). Fifteen percent of our cancellations were COVID-related (increasing to 21% during the surge), but CFR did not change during the surge. After our intervention, those contacted in advance came to clinic 93% of the time, and our CFR improved to 74.8%. Conclusion(s): An 84% CFR, measured 1 week ahead of clinic, was dropping to an average of 66% because of late cancellations and no-shows, and widespread education about clinic attendance guidelines did not increase the rate. Having our social worker communicate directly with PwCF increased the overall CFR closer to our advance numbers, and 93% came to clinic. These communications also served as an additional patient interaction during which other social work needs were identified. Overall reduced clinic attendance may be related to the indirect impact of the pandemic and benefits of modulator therapy.We need to gather more postimplementation data and to consider different approaches to partnering with PwCF to achieve ideal follow-up.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved
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Background: Omicron subvariants questioned the efficacy of the approved therapies for the early COVID-19. In vitro data show that remdesivir (RDV), molnupiravir (MLN), and nirmatrelvir/ritonavir (NMV/r) all retained activity against all sub-lineages, while poor neutralizing activity was observed for Sotrovimab (SOT) and Tixagevimab/cilgavimab (TIX/CIL). No data about the risk of clinical failure or even in vivo antiviral activity are available. Method(s): Single-center observational comparison study enrolling all consecutive patients (pts) seen for care with a confirmed SARS-CoV-2 Omicron diagnosis and who met the AIFA criteria for eligibility for treatment with RDV, MLN, NMV/r, TIX/CIL, or SOT. Treatment allocation was subject to drug availability, time from symptoms onset, and comorbidities. Nasopharyngeal swab (NPS) VL was measured on day 1 (D1) and D7 and was expressed by log2 cycle threshold (CT) scale. Comparisons between treatment groups were made by Chi-square, and Wilcoxon paired tests. Primary endpoint was D1-D7 VL variation. Potential decrease in VL and average treatment effect (ATE) were calculated from fitting marginal linear regression models weighted for calendar month of drug initiation, duration of symptoms, and immunodeficiency using NMV/r as the comparator trial arm. Result(s): A total of 971 pts received treatments (SOT 321, MLN 231, NMV/r 211, TIX/CIL 70, and RDV 138): female 457 (47%), median age 67 yrs (IQR 56-78), 93% vaccinated;12% with negative baseline serology. At D1, median time from symptoms onset was 3 days (IQR 2,4). 379 (39%) pts were infected with BA.1, 215 (22%) with BA.2, 372 with BA.4/5 (38%), and 5 with BQ.1 (0,5%). D1 mean viral load was 4.02 log2. Adjusted analysis (ATE) showed that NMV/r significantly reduced VL compared to all the other drugs in pts infected with all sublineages, (Fig.1A-B) while less evidence for a difference vs. TIX/CIL was seen in those infected with BA.2 (p=0.05) (Fig.1 C-D). Conclusion(s): In this analysis of in vivo early VL reductions, NMV/r appears to be the drug showing the greatest antiviral activity, regardless of the underlying subvariant, perhaps with the exception of TIX/CIL in people infected with BA.2 for which there was less evidence for a difference. In the Omicron era, due to the high prevalence of vaccinated people and in absence of clinical events, VL is one of the possible alternative endpoints which guarantees adequate statistical power. Fig 1 SARS-CoV-2 RNA levels at D1 and D7 in patients treated with Nirmatrelvir/ ritonavir, Sotrovimab, Molnupiravir, Remdesivir, and Tixagevimab/cilgavimab. Dot-plots showing the comparison of viral loads detected at D1 and D7 and the variation of RNA levels observed between the two time-points by intervention in (A) all patients treated with Nirmatrelvir/ritonavir (n=211), Sotrovimab (n=321), or Molnupiravir (n=231), or Remdesivir (n=138), or Tixagevimab/ cilgavimab (n=136);(C) patients with Omicron BA.2 infection treated with Nirmatrelvir/ritonavir (n=58), Sotrovimab (n=81), or Molnupiravir (n=21), or Remdesivir (n=37), or Tixagevimab/cilgavimab (n=18);(D) patients with Omicron BA.4/5 infection treated with Nirmatrelvir/ritonavir (n=102), Sotrovimab (n=92), or Molnupiravir (n=110), or Remdesivir (n=16), or Tixagevimab/cilgavimab (n=52). Viral RNA levels are expressed as log2 CT values. The horizontal dashed line represents the limit of detection (CT: 40.0), values >=40 are considered negative. Mean of log2 CT values, and SD are shown in the graph. Statistical analysis of the differences in viral loads by intervention as compared to Nirmatrelvir/ritonavir was performed by Mann-Whitney test. Potential decrease in VL and average treatment effect (ATE) were calculated from fitting marginal linear regression models weighted for calendar month of drug initiation, duration of symptoms, and immunodeficiency using NMV/r as the comparator trial arm. Results are shown (B) for patients infected with all Omicron sublineages and (D) for those infected with Omicron BA.2 sublineage.
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China has shown strong social cohesion and epidemic prevention and control actions in the face of the sudden new crown epidemic. This study uses questionnaire survey (N=208) data to investigate the important role of group factors and individual anxiety as mediating variables in the panic buying of the new crown epidemic through an empirical study. It was found that group factors significantly and positively influenced panic buying and individual anxiety significantly and positively influenced panic buying;government control significantly influenced panic buying through the mediating effect of group factors and individual anxiety. By exploring the mechanism of government control on panic buying and the role of group factors and individual anxiety as mediating variables, the study proposes thoughts on the way government control is guided in public crisis events. Government control is a policy risk, which affects individual anxiety through group factors and thus panic buying, and panic buying can lead to scarcity of goods and thus market risk. [ FROM AUTHOR] Copyright of Journal of Pharmaceutical Negative Results is the property of ResearchTrentz and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
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Multiple severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) variants continue to evolve carrying flexible amino acid substitutions in the spike protein's receptor binding domain (RBD). These substitutions modify the binding of the SARS-CoV-2 to human angiotensin-converting enzyme 2 (hACE2) receptor and have been implicated in altered host fitness, transmissibility and efficacy against antibody therapeutics and vaccines. Reliably predicting the binding strength of SARS-CoV-2 variants RBD to hACE2 receptor and neutralizing antibodies (NAbs) can help assessing their fitness, and rapid deployment of effective antibody therapeutics, respectively. Here, we introduced a two-step computational framework with threefold validation that first identified dissociation constant as a reliable predictor of binding affinity in hetero-dimeric and -trimeric protein complexes. The second step implements dissociation constant as descriptor of the binding strengths of SARS-CoV-2 variants RBD to hACE2 and NAbs. Then, we examined several variants of concern (VOCs) such as Alpha, Beta, Gamma, Delta, and Omicron and demonstrated that these VOCs RBD bind to the hACE2 with enhanced affinity. Furthermore, the binding affinity of Omicron variant's RBD was reduced with majority of the RBD-directed NAbs, which is highly consistent with the experimental neutralization data. By studying the atomic contacts between RBD and NAbs, we revealed the molecular footprints of four NAbs (GH-12, P2B-1A1, Asarnow-3D11, and C118)-that may likely neutralize the recently emerged omicron variant-facilitating enhanced binding affinity. Finally, our findings suggest a computational pathway that could aid researchers identify a range of current NAbs that may be effective against emerging SARS-CoV-2 variants.
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This retrospective case-series analysis evaluated 403 fully vaccinated with Vero Cell or Sputnik V vaccines patients hospitalized in the 6th City Clinical Hospital of Minsk in the period between January 01 and February 28, 2022 with the main diagnosis of "coronavirus infection (COVID-19)". The diagnosis was confirmed by PCR or SARS-CoV-2 virus antigen tests, as well as chest computed tomography data. The study revealed higher prevalence of older patients (over 65 years) infected with the SARS-CoV-2 virus and hospitalized in early 2022, at the height of the wave of the pandemic due to the spread of the Omicron variant. Most patients (91.8 %) had moderate symptoms. More than half of them received oxygen support. A relatively small number of inpatient, only 8 persons (1.9 %), were hospitalized in the intensive care unit (ICU) and four of them needed mechanical ventilation. Comor-bid conditions and high incidence of mortality (63.5 %) were common in ICU patients. Hypertension and obesity prevailed in the structure of comorbid pathology of all inpatient persons (74.2 and 24.3 %, respectively). Patients of therapeutic departments had relatively short length of stay in the hospital, as well as low in-hospital mortality (0.5 %) and low incidence of complications (5.3 %).Copyright © 2023 The authors.
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Background: At the global level, the dynamics of the COVID-19 pandemic have been driven by several epidemiological waves, determined by the emergence of new SARS-CoV-2 variants from the original viral lineage from Wuhan, China. While the SARS-CoV-2 dynamic has been described globally, there is a lack of data from Sub-Saharan African. Method(s): A laboratory-based survey was conducted in Cameroon, from March 1, 2020 to March 30, 2022, through an assessment of the evolutionary patterns of SARS-CoV-2 lineages across the four COVID-19 waves in the country. Data on full-length sequencing from all four sequencing laboratories were consecutively entered into the GISAID platform. These data were downloaded, and the molecular phylogeny of the SARS-CoV-2 sequences was performed using Nexstrain. The Mann-Whitney U test was used to calculate the correlation between the duration of each outbreak and the number of confirmed cases and between hospitalised cases and CFR, with a p value < 0.05 considered statistically significant. Result(s): A total of 3,881 samples were successfully processed, of which 38.9% (n=1,509) using PCR mutation assay, 41.5% (n=1,612) using targeted sequencing, and 19.6% (n=760) using whole-genome sequencing. The mean age of the study population was 36 years (min-max: 2-86), and 45% were within the age range 26-45. Regarding gender distribution, 50.9% were male, and 49.1% were female. Phylogenetic analysis of the 760 whole-genome sequences generated from March 2020 to March 2022 revealed that the greater proportion of SARS-CoV-2 circulating in Cameroon belonged to the viral sub-lineages of the original strain from Wuhan (74%), 15% Delta variant, 6% Omicron variant, 3% Alpha variant and 2% Beta variant.The pandemic was driven by SARS-CoV-2 lineages of origin in Wave 1 (16 weeks, 2.3% CFR), the Alpha and Beta variants in Wave 2 (21 weeks, 1.6% CFR), Delta variants in Wave 3 (11 weeks, 2.0% CFR), and Omicron variants in Wave 4 (8 weeks, 0.73% CFR), with a declining trend over time (p=0.01208). Conclusion(s): In a nutshell, the SARS-CoV-2 epidemic in Cameroon appears to have been driven by the SARS-CoV-2 lineage of origin in Wave 1, the cointroduction of the Alpha and Beta variants in Wave 2, the Delta variant in Wave 3, and the Omicron variant in Wave 4, with an overall declining trend in the wave duration, confirmed cases and hospitalisations over time.The SARS-CoV-2 lineage of origin and the Delta variant appeared to be the drivers of COVID-19 severity in Cameroon.
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Background: Given effectiveness of SARS-CoV-2 vaccines and outpatient antiviral and monoclonal antibody therapy for reducing progression to severe COVID-19, we sought to estimate the impact of these interventions on risk of hospitalization following SARS-CoV-2 infection in a large US healthcare system. Method(s): All patients >=18 of age in the UNC Health system, with first positive SARS-CoV-2 RT-PCR test or U07.1 ICD-10-CM (diagnosis date) during 07/01/2021- 05/31/2022, were included. The outcome was first hospitalization with U07.1 ICD-10-CM primary diagnosis <=14 days after SARS-CoV-2 diagnosis date. SARS-CoV-2 vaccinations were included if received >=14 days prior to diagnosis. Outpatient therapies were included if administered after diagnosis date and before hospital admission. Age, gender, race, ethnicity, and comorbidities associated with COVID-19 (using ICD-10-CM, if documented >=14 days prior to diagnosis date) were also evaluated. Risk ratios for hospitalization were estimated using generalized linear models, and predictors identified using extreme gradient boosting using feature influence with Shapley additive explanations algorithm. Result(s): The study population included 54,886 patients, 41% men and 27% >=60 years of age. One-third of SARS-CoV-2 diagnoses occurred July-December 2021 and 67% December-May 2022 (predominantly Delta and Omicron variants, respectively). Overall 7.0% of patients were hospitalized for COVID-19, with median hospitalization stay of 5 days (IQR: 3-9). 32% and 12% of patients received >=1 SARS-CoV-2 vaccine dose and outpatient therapy, respectively. Unadjusted and age-adjusted hospitalization risk decreased with vaccination and outpatient therapy (TABLE). Comparing patients who received 3 vaccine doses versus none we observed a 66% relative reduction in risk, with stronger association for more recent vaccination. For patients who received nirmatrelvir/ ritonavir versus no therapy we observed a 99% relative reduction in risk. In predictive models, older age was the most influential predictor of being hospitalized with COVID-19, while vaccination and outpatient therapy were the most influential factors predicting non-hospitalization. Conclusion(s): The impact of recent SARS-CoV-2 vaccination and outpatient antiviral and monoclonal antibody therapy on reducing COVID-19 hospitalization risk was striking in this large healthcare system covering Delta and Omicron variant timeframes. SARS-CoV-2 vaccinations and outpatient therapeutics are critical for preventing severe COVID-19. Unadjusted and age-adjusted risk ratios for hospitalization among patients with SARS-CoV-2.
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Background: Confirmed COVID-19 case counts underestimate SARS-CoV-2 infections, particularly in countries with limited testing capacity. Pregnant women attending antenatal care (ANC) clinics have served as healthy population surrogates to monitor diseases like HIV and malaria. We measured SARS-CoV-2 seroprevalence among women attending ANC clinics to assess infection trends over time in Zambia. Method(s): We conducted repeated cross-sectional surveys among pregnant women aged 15-49 years attending their first ANC visits in 3 districts of Zambia during September 2021-September 2022. Up to 200 women per district were enrolled each month, completing a standardized questionnaire. Dried blood spot samples were collected for serologic testing for prior infection using the Tetracore FlexImmArrayTM SARS-CoV-2 Human IgG Antibody Test and HIV testing according to national guidelines. We calculated odds ratios (ORs) for SARS-CoV-2 seroprevalence by demographic characteristics, adjusting for the district. Result(s): A total of 5,351 women were enrolled at 29 study sites between September 2021 and September 2022. Participants' median age was 25 years (interquartile range: 21-30), 530 (9.9%) tested positive for HIV, and 101 (1.9%) reported a prior positive COVID-19 test. Overall, SARS-CoV-2 seroprevalence was 67%, and rose from 49% in September 2021 to 85% in September 2022 (Figure 1). The greatest increase in seroprevalence occurred during the 4th wave caused by the Omicron variant (48% in December 2021 to 63% in January 2022). Seroprevalence was significantly higher among women living in urban districts (Chipata and Lusaka) compared to rural Chongwe District (Chipata OR: 1.2, 95% confidence interval [CI]: 1.1-1.4;Lusaka OR: 1.7, 95% CI: 1.5-2.0). The age group was not significantly associated with seroprevalence after adjusting for the district (aOR: 1.1, 95% CI: 1.0-1.2). Seroprevalence was significantly lower among women living with HIV than women living without HIV (aOR: 0.8, 95% CI: 0.6-0.9). Conclusion(s): Overall, two-thirds of women in the three surveyed districts in Zambia had evidence of SARS-CoV-2 exposure, rising to 85% after the Omicron variant spread throughout the country. ANC clinics have a potential role in ongoing SARS-CoV-2 serosurveillance and can continue to provide insights into SARS-CoV-2 infection dynamics. Furthermore, they provide a platform for focused SARS-CoV-2 prevention messaging and COVID-19 management in pregnant women at higher risk of severe disease. (Figure Presented).
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Introduction: During the COVID-19 pandemic, various virus variants evolved worldwide. COVID-19 omicron (CO) was associated with a decrease in length of hospital stay, ICU admission and death [1] as compared to COVID-19 delta (CD). To estimate impact of CO on ICUs worldwide, we investigated characteristics, disease course and outcome of critically ill CO patients. Method(s): Of 8562 critically ill COVID-19 patients included in the prospective international multicenter RISC-19-ICU registry [2,3], characteristics and outcome were compared for 1890 CD and 272 CO patients admitted to ICU between 1-2021 and 9-2022. Mixed model analysis corrected for individual center effects and adjusted for age, sex, vaccination status, use of steroids and anticoagulants was used. Result(s): There was no difference in age, sex and BMI between groups. CO patients had more comorbidities [mean difference (MD) 0.7, 95% CI (0.5-1.0), p = 0.02], especially arterial hypertension, and higher SAPS II score [MD 0.0 (0-0.1), p < 0.001], SOFA score [MD 0.1 (0.1-0.3), p < 0.0001]. CO patients presented with higher cardiovascular system SOFA subscore, but better PF-ratio at ICU admission and smaller risk for intubation and mechanical ventilation throughout their ICU stay [OR 0.5 (0.3-0.8)]. There was no difference in ECMO treatments, ICU length of stay [MD 0.6 (0-11.4), p = 0.72] or ICU survival [HR 1 (0.7-1.5), p = 0.88] between the two groups. Conclusion(s): We show that critically ill CO patients present with more comorbidities, less severe respiratory disease but more severe hemodynamic instability at ICU admission as compared to CD patients, although the ICU length of stay and mortality was similar. These differences could be explained by differences in disease characteristics caused by CO, or by the increasing prevalence of CO as co-factor to preexisting disease. Continued monitoring of critically ill CO patients in ICUs worldwide is warranted.
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Background: Maternally derived antibodies are crucial for neonatal immunity. Understanding the binding and -cross neutralization capacity of maternal/ cord antibody responses to COVID-19 vaccination during pregnancy can inform neonatal immunity. Method(s): Here we characterized binding and neutralizing antibody profile at delivery in 24 pregnant individuals following two doses of Moderna mRNA-1273 or Pfizer BNT162b2 vaccination. We evaluated the transplacental antibody transfer by profiling maternal and umbilical cord blood. We analyzed for SARS-CoV-2 multivariant cross-neutralizing antibody levels for wildtype Wuhan, Delta, Omicron BA1, BA2, and BA4/BA5 variants by enzyme-linked immunosorbent assay Results: Our results reveal that current vaccination induced significantly higher (p=0.003) RBD-specific binding IgG titers in cord blood compared to maternal blood for both Wuhan and Omicron BA1 strain. Interestingly, binding IgG antibody levels for the Omicron BA1 strain were significantly lower (P< 0.0001) when compared to the Wuhan strain in both maternal and cord blood. In contrast to the binding, the Omicron BA1, BA2, BA4/5 specific neutralizing antibody levels were significantly lower (P< 0.0001) compared to the Wuhan and Delta variants. It is interesting to note that the BA4/5 neutralizing capacity was not at all detected in both maternal and cord blood. Conclusion(s): Our data suggest that the initial series of COVID-19 mRNA vaccines were immunogenic in pregnant women, and vaccine-elicited binding antibodies were detectable in cord blood at significantly higher levels for Wuhan and Delta variants but not for Omicron variants. Interestingly, the vaccination did not induce neutralizing antibodies for Omicron variants. These results provide novel insight into the impact of vaccination on maternal humoral immune response and transplacental antibody transfer for SARS-CoV-2 variants and support the need for boosters as new variants emerge.