Variant-specific antibody profiling for tracking SARS-CoV-2 variant infections in children and adolescents.

Monitoring the seroprevalence of SARS-CoV-2 in children and adolescents can provide valuable information for effective SARS-CoV-2 surveillance, and thus guide vaccination strategies. In this study, we quantified antibodies against the spike S1 domains of several SARS-CoV-2 variants (wild-type, Alpha, Delta, and Omicron variants) as well as endemic human coronaviruses (HCoVs) in 1,309 children and adolescents screened between December 2020 and March 2023. Their antibody binding profiles were compared with those of 22 pre-pandemic samples from children and adolescents using an in-house Luminex®-based Corona Array (CA). The primary objectives of this study were to (i) monitor SARS-CoV-2-specific antibodies in children and adolescents, (ii) evaluate whether the S1-specific antibody response can identify the infecting variant of concern (VoC), (iii) estimate the prevalence of silent infections, and (iv) test whether vaccination or infection with SARS-CoV-2 induce HCoV cross-reactive antibodies. Both SARS-CoV-2 infection and vaccination induced a robust antibody response against the S1 domain of WT and VoCs in children and adolescents. Antibodies specific for the S1 domain were able to distinguish between SARS-CoV-2 VoCs in infected children. The serologically identified VoC was typically the predominant VoC at the time of infection. Furthermore, our highly sensitive CA identified more silent SARS-CoV-2 infections than a commercial ELISA (12.1% vs. 6.3%, respectively), and provided insights into the infecting VoC. Seroconversion to endemic HCoVs occurred in early childhood, and vaccination or infection with SARS-CoV-2 did not induce HCoV S1 cross-reactive antibodies. In conclusion, the antibody response to the S1 domain of the spike protein of SARS-CoV-2 is highly specific, providing information about the infecting VoC and revealing clinically silent infections.

Case reports of persistent SARS-CoV-2 infection outline within-host viral evolution in immunocompromised patients.

BACKGROUND: SARS-CoV-2 is responsible for the ongoing global pandemic, and the continuous emergence of novel variants threatens fragile populations, such as immunocompromised patients. This subgroup of patients seems to be seriously affected by intrahost viral changes, as the pathogens, which are keen to cause replication inefficiency, affect the impaired immune system, preventing efficient clearance of the virus. Therefore, these patients may represent an optimal reservoir for the development of new circulating SARS-CoV-2 variants. The following study aimed to investigate genomic changes in SARS-CoV-2-positive immunocompromised patients over time. METHODS: SARS-CoV-2-positive nasopharyngeal swabs were collected at different time points for each patient (patient A and patient B), extracted and then analyzed through next-generation sequencing (NGS). The resulting sequences were examined to determine mutation frequencies, describing viral evolution over time. CASE PRESENTATION: Patient A was a 53-year-old patient with onco-hematological disease with prolonged infection lasting for 51 days from May 28th to July 18th, 2022. Three confirmed SARS-CoV-2-positive samples were collected on May 28th, June 15th and July 4th. Patient B was 75 years old and had onco-hematological disease with prolonged infection lasting for 146 days. Two confirmed positive SARS-CoV-2 samples were collected at the following time points: May 21st and August 18th. CONCLUSION: Heat map construction provided evidence of gain and/or loss of mutations over time for both patients, suggesting within-host genomic evolution of the virus. In addition, mutation polymorphisms and changes in the SARS-CoV-2 lineage were observed in Patient B. Sequence analysis revealed high mutational pattern variability, reflecting the high complexity of viral replication dynamics in fragile patients.

Emergence of SARS-CoV-2 Variants Are Induced by Coinfections With Dengue.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019 has accumulated a series of point mutations and evolved into several variants of concern (VOCs), some of which are more transmissible and potentially more severe than the original strain. The most notable VOCs are Alpha, Beta, Gamma, Delta, and Omicron, which have spread to various parts of the world. This study conducted surveillance in Jashore, Bangladesh to identify the prevalence of SARS-CoV-2 coinfected with dengue virus and their genomic effect on the emergence of VOCs. A hospital-based COVID-19 surveillance from June to August, 2021 identified 9 453 positive patients in the surveillance area. The study enrolled 572 randomly selected COVID-19-positive patients, of which 11 (2%) had dengue viral coinfection. Whole genome sequences of SARS-CoV-2 were analyzed and compared between coinfection positive and negative group. In addition, we extracted 185 genome sequences from GISAID to investigate the cross-correlation function between SARS-CoV-2 mutations and VOC; multiple ARIMAX(p,d,q) models were developed to estimate the average number of amino acid (aa) substitution among different SARS-CoV-2 VOCs. The results of the study showed that the coinfection group had an average of 30.6 (±1.7) aa substitutions in SARS-CoV-2, whereas the dengue-negative COVID-19 group had that average of 25.6 (±1.8; P < .01). The coinfection group showed a significant difference of aa substitutions in open reading frame (ORF) and N-protein when compared to dengue-negative group (P = .03). Our ARIMAX models estimated that the emergence of SARS-CoV-2 variants Delta required additional 9 to 12 aa substitutions than Alpha, Beta, or Gamma variant. The emergence of Omicron accumulated additional 19 (95% confidence interval [CI]: 15.74, 21.95) aa substitution than Delta. Increased number of point mutations in SARS-CoV-2 genome identified from coinfected cases could be due to the compromised immune function of host and induced adaptability of pathogens during coinfections. As a result, new variants might be emerged when series of coinfection events occur during concurrent two epidemics.

MVA-based vaccine candidates expressing SARS-CoV-2 prefusion-stabilized spike proteins of the Wuhan, Beta or Omicron BA.1 variants protect transgenic K18-hACE2 mice against Omicron infection and elicit robust and broad specific humoral and cellular immune responses.

Despite the decrease in mortality and morbidity due to SARS-CoV-2 infection, the incidence of infections due to Omicron subvariants of SARS-CoV-2 remains high. The mutations acquired by these subvariants, mainly concentrated in the receptor-binding domain (RBD), have caused a shift in infectivity and transmissibility, leading to a loss of effectiveness of the first authorized COVID-19 vaccines, among other reasons, by neutralizing antibody evasion. Hence, the generation of new vaccine candidates adapted to Omicron subvariants is of special interest in an effort to overcome this immune evasion. Here, an optimized COVID-19 vaccine candidate, termed MVA-S(3P_BA.1), was developed using a modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein from the Omicron BA.1 variant. The immunogenicity and efficacy induced by MVA-S(3P_BA.1) were evaluated in mice in a head-to-head comparison with the previously generated vaccine candidates MVA-S(3P) and MVA-S(3Pbeta), which express prefusion-stabilized S proteins from Wuhan strain and Beta variant, respectively, and with a bivalent vaccine candidate composed of a combination of MVA-S(3P) and MVA-S(3P_BA.1). The results showed that all four vaccine candidates elicited, after a single intramuscular dose, protection of transgenic K18-hACE2 mice challenged with SARS-CoV-2 Omicron BA.1, reducing viral loads, histopathological lesions, and levels of proinflammatory cytokines in the lungs. They also elicited anti-S IgG and neutralizing antibodies against various Omicron subvariants, with MVA-S(3P_BA.1) and the bivalent vaccine candidate inducing higher titers. Additionally, an intranasal immunization in C57BL/6 mice with all four vaccine candidates induced systemic and mucosal S-specific CD4+ and CD8+ T-cell and humoral immune responses, and the bivalent vaccine candidate induced broader immune responses, eliciting antibodies against the ancestral Wuhan strain and different Omicron subvariants. These results highlight the use of MVA as a potent and adaptable vaccine vector against new emerging SARS-CoV-2 variants, as well as the promising feature of combining multivalent MVA vaccine candidates.

The Clinical Severity of COVID-19 Variants of Concern: Retrospective Population-Based Analysis.

BACKGROUND: SARS-CoV-2 variants of concern (VOCs) emerged and rapidly replaced the original strain worldwide. The increased transmissibility of these new variants led to increases in infections, hospitalizations, and mortality. However, there is a scarcity of retrospective investigations examining the severity of all the main VOCs in presence of key public health measures and within various social determinants of health (SDOHs). OBJECTIVE: This study aims to provide a retrospective assessment of the clinical severity of COVID-19 VOCs in the context of heterogenous SDOHs and vaccination rollout. METHODS: We used a population-based retrospective cohort design with data from the British Columbia COVID-19 Cohort, a linked provincial surveillance platform. To assess the relative severity (hospitalizations, intensive care unit [ICU] admissions, and deaths) of Gamma, Delta, and Omicron infections during 2021 relative to Alpha, we used inverse probability treatment weighted Cox proportional hazard modeling. We also conducted a subanalysis among unvaccinated individuals, as assessed severity differed across VOCs and SDOHs. RESULTS: We included 91,964 individuals infected with a SARS-CoV-2 VOC (Alpha: n=20,487, 22.28%; Gamma: n=15,223, 16.55%; Delta: n=49,161, 53.46%; and Omicron: n=7093, 7.71%). Delta was associated with the most severe disease in terms of hospitalization, ICU admissions, and deaths (hospitalization: adjusted hazard ratio [aHR] 2.00, 95% CI 1.92-2.08; ICU: aHR 2.05, 95% CI 1.91-2.20; death: aHR 3.70, 95% CI 3.23-4.25 relative to Alpha), followed generally by Gamma and then Omicron and Alpha. The relative severity by VOC remained similar in the unvaccinated individual subanalysis, although the proportion of individuals infected with Delta and Omicron who were hospitalized was 2 times higher in those unvaccinated than in those fully vaccinated. Regarding SDOHs, the proportion of hospitalized individuals was higher in areas with lower income across all VOCs, whereas among Alpha and Gamma infections, 2 VOCs that cocirculated, differential distributions of hospitalizations were found among racially minoritized groups. CONCLUSIONS: Our study provides robust severity estimates for all VOCs during the COVID-19 pandemic in British Columbia, Canada. Relative to Alpha, we found Delta to be the most severe, followed by Gamma and Omicron. This study highlights the importance of targeted testing and sequencing to ensure timely detection and accurate estimation of severity in emerging variants. It further sheds light on the importance of vaccination coverage and SDOHs in the context of pandemic preparedness to support the prioritization of allocation for resource-constrained or minoritized groups.

High-Throughput and Integrated CRISPR/Cas12a-Based Molecular Diagnosis Using a Deep Learning Enabled Microfluidic System.

CRISPR/Cas-based molecular diagnosis demonstrates potent potential for sensitive and rapid pathogen detection, notably in SARS-CoV-2 diagnosis and mutation tracking. Yet, a major hurdle hindering widespread practical use is its restricted throughput, limited integration, and complex reagent preparation. Here, a system, microfluidic multiplate-based ultrahigh throughput analysis of SARS-CoV-2 variants of concern using CRISPR/Cas12a and nonextraction RT-LAMP (mutaSCAN), is proposed for rapid detection of SARS-CoV-2 and its variants with limited resource requirements. With the aid of the self-developed reagents and deep-learning enabled prototype device, our mutaSCAN system can detect SARS-CoV-2 in mock swab samples below 30 min as low as 250 copies/mL with the throughput up to 96 per round. Clinical specimens were tested with this system, the accuracy for routine and mutation testing (22 wildtype samples, 26 mutational samples) was 98% and 100%, respectively. No false-positive results were found for negative (n = 24) samples.

Novel SARS-CoV-2 inhibition properties of the anti-cancer Kang Guan Recipe herbal formula.

The ongoing COVID-19 pandemic is a persistent challenge, with continued breakthrough infections despite vaccination efforts. This has spurred interest in alternative preventive measures, including dietary and herbal interventions. Previous research has demonstrated that herbal medicines can not only inhibit cancer progression but also combat viral infections, including COVID-19 by targeting SARS-CoV-2, indicating a multifaceted potential to address both viruses and cancer. Here, we found that the Kang Guan Recipe (KGR), a novel herbal medicine formula, associates with potent inhibition activity against the SARS-CoV-2 viral infection. We demonstrate that KGR exhibits inhibitory activity against several SARS-CoV-2 variants of concern (VOCs). Mechanistically, we found that KGR can block the interaction of the viral spike and human angiotensin-converting enzyme 2 (ACE2). Furthermore, we assessed the inhibitory effect of KGR on SARS-CoV-2 viral entry in vivo, observing that serum samples from healthy human subjects having taken KGR exhibited suppressive activity against SARS-CoV-2 variants. Our investigation provides valuable insights into the potential of KGR as a novel herbal-based preventive and therapeutic strategy against COVID-19.

The mediating role of SARS-CoV-2 variants between income and hospitalisation due to COVID-19: A period-based mediation analysis.

The mechanisms facilitating the relationship between low income and COVID-19 severity have not been partitioned in the presence of SARS-CoV-2 variants of concern (VOC). To address this, we used causal mediation analysis to quantify the possible mediating role infection with VOC has on the relationship between neighbourhood income (exposure) and hospitalisation due to COVID-19 among cases (outcome). A population-based cohort of 65,629 individuals residing in British Columbia, Canada, was divided into three periods of VOC co-circulation in the 2021 calendar year whereby each period included co-circulation of an emerging and an established VOC. Each cohort was subjected to g-formula mediation techniques to decompose the relationship between exposure and outcome into total, direct and indirect effects. In the mediation analysis, the total effects indicated that low income was associated with increased odds of hospitalisation across all periods. Further decomposition of the effects revealed that income is directly and indirectly associated with hospitalisation. The resulting indirect effect through VOC accounted for approximately between 6 and 13% of the total effect of income on hospitalisation. This study underscores, conditional on the analysis, the importance of addressing underlying inequities to mitigate the disproportionate impact on historically marginalised communities by adopting an equity lens as central to pandemic preparedness and response from the onset.

Trends in SARS-CoV-2 Cycle Threshold Values in Bosnia and Herzegovina-A Retrospective Study.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which led to the COVID-19 pandemic, has significantly impacted global public health. The proper diagnosis of SARS-CoV-2 infection is essential for the effective control and management of the disease. This study investigated the SARS-CoV-2 infection using RT-qPCR tests from laboratories in Bosnia and Herzegovina. We performed a retrospective study of demographic data and Ct values from 170,828 RT-qPCR tests from April 2020 to April 2023, representing 9.3% of total national testing. Samples were collected from 83,413 individuals across different age groups. Of all tests, 33.4% were positive for SARS-CoV-2, with Ct values and positivity rates varying across demographics and epidemic waves. The distribution was skewed towards older age groups, although lower positivity rates were observed in younger age groups. Ct values, indicative of viral load, ranged from 12.5 to 38. Lower Ct values correlated with higher positive case numbers, while higher Ct values signaled outbreak resolution. Additionally, Ct values decreased during epidemic waves but increased with the dominance of certain variants. Ct value-distribution has changed over time, particularly after the introduction of SARS-CoV-2 variants of interest/concern. Established Ct value trends might, therefore, be used as an early indicator and additional tool for informed decisions by public health authorities in SARS-CoV-2 and future prospective pandemics. Moreover, they should not be overlooked in future epidemiological events.

Bioinformatic elucidation of conserved epitopes to design a potential vaccine candidate against existing and emerging SARS-CoV-2 variants of concern.

The COVID-19 pandemic caused by SARS-CoV-2 poses a significant adverse effects on health and economy globally. Due to mutations in genome, COVID-19 vaccine efficacy decreases. We used immuno-informatics to design a Multi epitope vaccine (MEV) candidate for SARS-CoV-2 variants of concern (VOCs). Hence, we predicted binders/epitopes MHC-I, CD8+, MHC-II, CD4+, and CTLs from spike, membrane and envelope proteins of VOCs. In addition, we assessed the conservation of these binders and epitopes across different VOCs. Subsequently, we designed MEV by combining the predicted CTL and CD4+ epitopes from spike protein, peptide linkers, and an adjuvant. Further, we evaluated the binding of MEV candidate against immune receptors namely HLA class I histocompatibility antigen, HLA class II histocompatibility antigen, and TLR4, achieving binding scores of -1265.3, -1330.7, and -1337.9. Molecular dynamics and normal mode analysis revealed stable docking complexes. Moreover, immune simulation suggested MEV candidate elicits both innate and adaptive immune response. We anticipate that this conserved MEV candidate will provide protection from VOCs and emerging strains.

Immunogenicity, reactogenicity, and safety of a second booster with BNT162b2 or full-dose mRNA-1273: A randomized VACCELERATE trial in adults aged ≥75 years (EU-COVAT-1-AGED Part B).

OBJECTIVES: To assess the safety and immunogenicity of a fourth vaccination (second booster) in individuals aged ≥75 years. METHODS: Participants were randomized to BNT162b2 (Comirnaty, 30 µg) or messenger RNA (mRNA)-1273 (Spikevax, 100 µg). The primary end point was the rate of two-fold antibody titer increase 14 days after vaccination, targeting the receptor binding domain (RBD) region of wild-type SARS-CoV-2. The secondary end points included changes in neutralizing activity against wild-type and 25 variants. Safety was assessed by monitoring solicited adverse events (AEs) for 7 days. RESULTS: A total of 269 participants (mean age 81 years, mRNA-1273 n = 135/BNT162b2 n = 134) were included. Two-fold anti-RBD immunoglobulin (Ig) G titer increase was achieved by 101 of 129 (78%) and 116 of 133 (87%) subjects in the BNT162b2 and the mRNA-1273 group, respectively (P = 0.054). A second booster of mRNA-1273 provided higher anti-RBD IgG geometric mean titer: 21.326 IU/mL (95% confidence interval: 18.235-24.940) vs BNT162b2: 15.181 IU/mL (95% confidence interval: 13.172-17.497). A higher neutralizing activity was noted for the mRNA-1273 group. The most frequent AE was pain at the injection site (51% in mRNA-1273 and 48% in BNT162b2). Participants in the mRNA-1273 group had less vaccine-related AEs (30% vs 39%). CONCLUSIONS: A second booster of either BNT162b2 or mRNA-1273 provided substantial IgG increase. Full-dose mRNA-1273 provided higher IgG levels and neutralizing capacity against SARS-CoV-2, with similar safety profile for subjects of advanced age.

Designing and expression of novel recombinant fusion protein for efficient antigen screening of SARS-CoV-2.

Corona virus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), claimed millions globally. After the report of the first incidence of the virus, variants emerged with each posing a unique threat than its predecessors. Though many advanced diagnostic assays like real-time PCR are available for screening of SARS-CoV-2, their applications are being hindered because of accessibility and cost. With the advent of rapid assays for antigenic screening of SARS-CoV-2 made diagnostics far easy as the assays are rapid, cost-effective and can be used at point-of-care settings. In the present study, a fusion construct was made utilising highly immunogenic B cell epitopes from the three important structural proteins of SARS-CoV-2. The protein was expressed; purified capture mAbs generated and rapid antigen assay was developed. Eight hundred and forty nasopharyngeal swab samples were screened for the evaluation of the developed assay which showed 37.14% positivity, 96.51% and 100% sensitivity and specificity respectively. The assay developed was supposed to identify SARS-CoV-2 wild-type as well as variants of concern and variants of importance in real-time conditions.

Multivalent mRNA Vaccine Elicits Broad Protection against SARS-CoV-2 Variants of Concern.

SARS-CoV-2 new waves are primarily caused by changes to the spike protein (S), which can substantially decrease the efficacy of vaccines. Therefore, we tested several multivalent mRNA-LNP vaccines, targeting the full-length S proteins of different variants, and identified an optimal combination for protection against VOCs in BALB/c mice. The tested formulations included trivalent (WT + BA.5 + XBB.1.5), pentavalent (WT + BA.5 + XBB.1.5 + BQ.1.1 + CH.1.1), and octavalent (WT + BA.5 + XBB.1.5 + BQ.1.1 + CH.1.1 + Alpha + Delta + BA.2) vaccines. Among these multivalent vaccines, the pentavalent vaccine showed superior protection for almost all tested variants. Despite this, each multivalent vaccine elicited greater broad-spectrum neutralizing antibodies than the previously evaluated bivalent vaccine (WT + BA.5). Subsequently, we redesigned the multivalent vaccine to efficiently generate neutralizing antibodies against recent VOCs, including EG.5.1. Immunization with the redesigned pentavalent vaccine (WT + EG.5.1 + XBB.1.16 + Delta + BA.5) showed moderate levels of protection against recent Omicron VOCs. Results suggest that the neutralization activity of multivalent vaccines is better than those of the tested bivalent vaccines against WT + BA.5 and WT + EG.5.1. Moreover, the pentavalent vaccine we developed may be highly useful for neutralizing new Omicron VOCs.

COVID-19 vaccine updates for people under different conditions.

SARS-CoV-2 has caused global waves of infection since December 2019 and continues to persist today. The emergence of SARS-CoV-2 variants with strong immune evasion capabilities has compromised the effectiveness of existing vaccines against breakthrough infections. Therefore, it is important to determine the best utilization strategies for different demographic groups given the variety of vaccine options available. In this review, we will discuss the protective efficacy of vaccines during different stages of the epidemic and emphasize the importance of timely updates to target prevalent variants, which can significantly improve immune protection. While it is recognized that vaccine effectiveness may be lower in certain populations such as the elderly, individuals with chronic comorbidities (e.g., diabetes with poor blood glucose control, those on maintenance dialysis), or those who are immunocompromised compared to the general population, administering multiple doses can result in a strong protective immune response that outweighs potential risks. However, caution should be exercised when considering vaccines that might trigger an intense immune response in populations prone to inflammatory flare or other complications. In conclusion, individuals with special conditions require enhanced and more effective immunization strategies to prevent infection or reinfection, as well as to avoid the potential development of long COVID.

Protective non-neutralizing SARS-CoV-2 monoclonal antibodies.

Recent studies show an important role for non-neutralizing anti-spike antibodies, including monoclonal antibodies (mAbs), in robustly protecting against SARS-CoV-2 infection. These mAbs use Fc-mediated functions such as complement activation, phagocytosis, and cellular cytotoxicity. There is an untapped potential for using non-neutralizing mAbs in durable antibody treatments; because of their available conserved epitopes, they may not be as sensitive to virus mutations as neutralizing mAbs. Here, we discuss evidence of non-neutralizing mAb-mediated protection against SARS-CoV-2 infection. We explore how non-neutralizing mAb Fc-mediated functions can be enhanced via novel antibody-engineering techniques. Important questions remain to be answered regarding the characteristics of protective non-neutralizing mAbs, including the models and assays used for study, the risks of ensuing detrimental inflammation, as well as the durability and mechanisms of protection.

COVID-19 in a common woolly monkey (Lagothrix lagothricha): First evidence of fatal outcome in a nonhuman primate after natural SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization in March 2020. Since then, viral spread from humans to animals has occurred worldwide. Nonhuman primates (NHPs) have been found to be susceptible to reverse-zoonosis transmission of SARS-CoV-2, but initial research suggested that platyrrhine primates are less susceptible than catarrhine primates. Here we report the natural SARS-CoV-2 infection of a common woolly monkey (Lagothrix lagothricha) from a wildlife rehabilitation center in Ecuador. The course of the disease, the eventual death of the specimen, and the pathological findings are described. Our results show the susceptibility of a new platyrrhine species to SARS-CoV-2 and provide evidence for the first time of a COVID-19-associated death in a naturally infected NHP. The putative route of transmission from humans, and implications for captive NHPs management, are also discussed. Given that common woolly monkeys are at risk of extinction in Ecuador, further understanding of the potential threat of SARS-CoV-2 to their health should be a conservation priority. A One Health approach is the best way to protect NHPs from a new virus in the same way that we would protect the human population.

SARS-CoV-2 humoral immunity in people living with HIV-1.

The effect of COVID-19 on the high number of immunocompromised people living with HIV-1 (PLWH), particularly in Africa, remains a critical concern. Here, we identify key areas that still require further investigation, by examining COVID-19 vaccine effectiveness, and understanding antibody responses in SARS-CoV-2 infection and vaccination in comparison with people without HIV-1 (PWOH). We also assess the potential impact of pre-existing immunity against endemic human coronaviruses on SARS-CoV-2 responses in these individuals. Lastly, we discuss the consequences of persistent infection in PLWH (or other immunocompromised individuals), including prolonged shedding, increased viral diversity within the host, and the implications on SARS-CoV-2 evolution in Africa.

Vaccination status and disease severity of COVID-19 in different phases of the pandemic.

This study aimed to explore the clinical profile and the impact of vaccination status on various health outcomes among COVID-19 patients diagnosed in different phases of the pandemic, during which several variants of concern (VOCs) circulated in South Carolina (SC). The current study included 861,526 adult COVID-19 patients diagnosed between January 2021 and April 2022. We extracted their information about demographic characteristics, vaccination, and clinical outcomes from a statewide electronic health record database. Multiple logistic regression models were used to compare clinical outcomes by vaccination status in different pandemic phases, accounting for key covariates (e.g. historical comorbidities). A reduction in mortality was observed among COVID-19 patients during the whole study period, although there were fluctuations during the Delta and Omicron dominant periods. Compared to non-vaccinated patients, full-vaccinated COVID-19 patients had lower mortality in all dominant variants, including Pre-alpha (adjusted odds ratio [aOR]: 0.33; 95%CI: 0.15-0.72), Alpha (aOR: 0.58; 95%CI: 0.42-0.82), Delta (aOR: 0.28; 95%CI: 0.25-0.31), and Omicron (aOR: 0.29; 95%CI: 0.26-0.33) phases. Regarding hospitalization, full-vaccinated parties showed lower risk of hospitalization than non-vaccinated patients in Delta (aOR: 0.44; 95%CI: 0.41-0.47) and Omicron (aOR: 0.53; 95%CI: 0.50-0.57) dominant periods. The findings demonstrated the protection effect of the COVID-19 vaccines against all VOCs, although some of the full-vaccinated population still have symptoms to varying degrees from COVID-19 disease at different phases of the pandemic.

Characteristics and Functions of Infection-enhancing Antibodies to the N-terminal Domain of SARS-CoV-2.

Background: Fcγ-receptor (FcγR)-independent enhancement of SARS-CoV-2 infection mediated by N-terminal domain (NTD)-binding monoclonal antibodies (mAbs) has been observed in vitro, but the functional significance of these antibodies in vivo is less clear. Methods: We characterized 1,213 SARS-CoV-2 spike (S)-binding mAbs derived from COVID-19 convalescent patients for binding specificity to the SARS-CoV-2 S protein, VH germ-line usage, and affinity maturation. Infection enhancement in a vesicular stomatitis virus (VSV)-SARS-CoV-2 S pseudovirus (PV) assay was characterized in respiratory and intestinal epithelial cell lines, and against SARS-CoV-2 variants of concern (VOC). Proteomic deconvolution of the serum antibody repertoire was used to determine functional attributes of secreted NTD-binding mAbs. Results: We identified 72/1213 (5.9%) mAbs that enhanced SARS-CoV-2 infection in a PV assay. The majority (68%) of these mAbs recognized the NTD, were identified in patients with mild and severe disease, and persisted for at least 5 months post-infection. Infection enhancement by NTD-binding mAbs was not observed in intestinal and respiratory epithelial cell lines and was diminished or lost against SARS-CoV-2 VOC. Proteomic deconvolution of the serum antibody repertoire from 2 of the convalescent patients identified, for the first time, NTD-binding, infection-enhancing mAbs among the circulating immunoglobulins directly isolated from serum. Functional analysis of these mAbs demonstrated robust activation of FcγRIIIa associated with antibody binding to recombinant S proteins. Conclusions: Functionally active NTD-specific mAbs arise frequently during natural infection and can last as major serum clonotypes during convalescence. These antibodies display functional attributes that include FcγR activation, and may be selected against by mutations in NTD associated with SARS-CoV-2 VOC.

Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron-BA.1 variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the United States became increasingly significant. The number of detected introductions varied from 96 and 101 for Alpha and Delta to 39 for Omicron-BA.1. Most of these introductions left a low number of descendants (<10), suggesting a limited impact on the evolution of the pandemic in Galicia. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.