SARS-CoV-2 Molecular Evolution: A Focus on Omicron Variants in Umbria, Italy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 6 million deaths worldwide, and the spread of new variants over time increased the ability of this virus to cause infection. The Omicron variant was detected for the first time in Umbria, a region of central Italy, in November 2021 and it induced an unprecedented increase in the number of infection cases. Here, we analysed 3300 SARS-CoV-2 positive samples collected in Umbria between April 2022 and December 2023. We traced the molecular evolution of SARS-CoV-2 variants over time through the Next-Generation Sequencing (NGS) approach. We assessed correlation between SARS-CoV-2 infection and patients' health status. In total, 17.3% of our samples came from patients hospitalised as a consequence of COVID-19 infection even though 81.4% of them received at least three vaccine doses. We identified only Omicron variants, and the BA.5 lineage was detected in the majority of our samples (49.2%). Omicron variants outcompeted each other through the acquisition of mutations especially in Spike glycoprotein that are fingerprints of each variant. Viral antigenic evolution confers higher immunological escape and makes a continuous improvement of vaccine formulation necessary. The continuous update of international genomic databases with sequencing results obtained by emergent pathogens is essential to manage a possible future pandemic.

Impaired acute-phase humoral immunity is the major factor predicting unfavorable outcomes in multiple myeloma patients with SARS-CoV-2 Omicron variants outbreak infection.

At the end of 2022, a huge tide of SARS-CoV-2 infection mainly Omicron BA.4/5 developed in China. Multiple myeloma (MM) patients suffered cancer deterioration and mortality from COVID-19, yet profound analyses of Omicron variants-induced immunity function are scarce. We presented a longitudinal study in 218 MM patients and 73 healthy controls (HCs), reporting the prognostic factors and dynamic humoral and cellular immune responses. Neutralizing antibody and interferon γ ELISpot assay of SARS-CoV-2 was tested at three time points: 2-4, 8-10, and 14-16 weeks after infections. Our data showed older age, active MM, relapsed/refractory MM (R/RMM), immunotherapy, comorbidity, and non-vaccination were risk factors associated with hospitalization. Severe humoral immunity impairment within 2-4 weeks was especially seen in patients with unvaccinated, older age, immunotherapy, R/RMM and comorbidities, while T-cell response was relatively intact. Although antibodies of Omicron variants reached positive levels in MM patients at 8-10 weeks, half lost effective antibody protection at 14-16 weeks. However, most seronegative patients (76.2% at 2-4 weeks, 83.3% at 8-10 weeks) could develop effective T-cell response. Notably, the inactivated wild-type vaccinated patients exhibited weaker humoral and cellular immunity only at 2-4 weeks, escalating to similar levels as those in HCs later. Our findings indicate impairment of humoral immunity at acute-phase after infection is the major factor correlated with hospitalization. One-month suspension of immune therapy is suggested to prevent serious infection. These results confirm the value of inactivated vaccine, but indicate the need for additional booster at 14-16 weeks after infection for high-risk MM population.

Epitopes of an antibody that neutralizes a wide range of SARS-CoV-2 variants in a conserved subdomain 1 of the spike protein.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued, enabling the virus to escape from host immunity by changing its spike antigen, while biased toward the receptor-binding domain and N-terminal domain. Here, we isolated a novel pan-SARS-CoV-2 neutralizing antibody (which we named MO11) for even the recent dominators XBB.1.16 and EG.5.1, from a convalescent patient who had received three doses of an original mRNA COVID-19 vaccination. A cryo-electron microscopy analysis of the spike-MO11 complex at 2.3 Å atomic resolution revealed that it recognizes a conserved epitope hidden behind a glycan shield at N331 on subdomain 1 (SD1), holding both the N- and C-terminal segments comprising SD1. Our identification of MO11 unveiled the functional importance of SD1 for the spike's function, and we discuss the potential availability of a novel common epitope among the SARS-CoV-2 variants.IMPORTANCENovel severe acute respiratory syndrome coronavirus 2 variants with immune evasion ability are still repeatedly emerging, nonetheless, a part of immunity developed in responding to the antigen of earlier variants retains efficacy against recent variants irrespective of the numerous mutations. In exploration for the broadly effective antibodies, we identified a cross-neutralizing antibody, named MO11, from the B cells of the convalescent patient. MO11 targets a novel epitope in subdomain 1 (SD1) and was effective against all emerging variants including XBB.1.16 and EG.5.1. The neutralizing activity covering from D614G to EG.5.1 variants was explained by the conservation of the epitope, and it revealed the importance of the subdomain on regulating the function of the antigen for viral infection. Demonstrated identification of the neutralizing antibody that recognizes a conserved epitope implies basal contribution of such group of antibodies for prophylaxis against COVID-19.

Real-world use of nirmatrelvir-ritonavir in COVID-19 outpatients during BQ.1, BQ.1.1., and XBB.1.5 predominant omicron variants in three U.S. health systems: a retrospective cohort study.

Background: Ritonavir-boosted Nirmatrelvir (NMV-r), a protease inhibitor with in vitro activity against SARS-CoV-2, can reduce risk of progression to severe COVID-19 among high-risk individuals infected with earlier variants, but less is known about its effectiveness against omicron variants BQ.1/BQ.1.1/XBB.1.5. We sought to evaluate effectiveness of NMV-r in BQ.1/BQ.1.1/XBB.1.5 omicron variants by comparing hospitalisation rates to NMV-r treated patients during a previous omicron phase and to contemporaneous untreated patients. Methods: We conducted a retrospective observational cohort study of non-hospitalised adult patients with SARS-CoV-2 infection using real-world data from three health systems in Colorado and Utah, and compared hospitalisation rates in NMV-r-treated patients in a BA.2/BA.2.12.1/BA.4/BA.5 variant-predominant (first) phase (April 3, 2022-November 12, 2022), with a BQ.1/BQ.1.1/XBB.1.5 variant-predominant (second) phase (November 13, 2022-March 7, 2023). In the primary analysis, we used Firth logistic regression with a two-segment (phase) linear time model, and pre-specified non-inferiority bounds for the mean change between segments. In a pre-specified secondary analysis, we inferred NMV-r effectiveness in a cohort of treated and untreated patients infected during the second phase. For both analyses, the primary outcome was 28-day all-cause hospitalisation. Subgroup analyses assessed treatment effect heterogeneity. Findings: In the primary analysis, 28-day all-cause hospitalisation rates in NMV-r treated patients in the second phase (n = 12,061) were non-inferior compared to the first phase (n = 25,075) (198 [1.6%] vs. 345 [1.4%], adjusted odds ratio (aOR): 0.76 [95% CI 0.54-1.06]), with consistent results among secondary endpoints and key subgroups. Secondary cohort analyses revealed additional evidence for NMV-r effectiveness, with reduced 28-day hospitalisation rates among treated patients compared to untreated patients during a BQ.1/BQ.1.1/XBB.1.5 predominant phase (198/12,061 [1.6%] vs. 376/10,031 [3.7%], aOR 0.34 [95% CI 0.30-0.38), findings robust to additional sensitivity analyses. Interpretation: Real-world evidence from major US healthcare systems suggests ongoing NMV-r effectiveness in preventing hospitalisation during a BQ.1/BQ.1.1/XBB.1.5-predominant phase in the U.S, supporting its continued use in similar patient populations. Funding: U.S. National Institutes of Health.

Immunogenicity and safety of boosting with a recombinant two-component SARS-CoV-2 vaccine: two randomized, parallel-controlled, phase 2 studies.

BACKGROUND: Recombinant protein vaccines are vital for broad protection against SARS-CoV-2 variants. This study assessed ReCOV as a booster in two Phase 2 trials. RESEARCH DESIGN AND METHODS: Study-1 involved subjects were randomized (1:1:1) to receive 20 µg ReCOV, 40 µg ReCOV, or an inactivated vaccine (COVILO®) in the United Arab Emirates. Study-2 participating individuals were randomized (1:1:1) to receive 20 µg ReCOV (pilot batch, ReCOV HA), 20 µg ReCOV (commercial batch, ReCOV TC), or 30 µg BNT162b2 (COMIRNATY®) in the Philippines. The primary immunogenicity objectives was to compare the geometric mean titer (GMT) and seroconversion rate (SCR) of neutralizing antibodies induced by one ReCOV booster dose with those of inactivated vaccine and BNT162b2, respectively, at 14 days post-booster. RESULTS: Heterologous ReCOV booster doses were safe and induced comparable immune responses to inactivated vaccines and BNT162b2 against Omicron variants and the prototype. They showed significant advantages in cross-neutralization against multiple SARS-CoV-2 variants, surpassing inactivated vaccines and BNT162b2, with good immune persistence. CONCLUSIONS: Heterologous ReCOV boosting was safe and effective, showing promise in combating COVID-19. The study highlights ReCOV's potential for enhanced protection, supported by strong cross-neutralization and immune persistence. CLINICAL TRIAL REGISTRATION: Study-1, www.clinicaltrials.gov, identifier is NCT05323435; Study-2, www.clinicaltrials.gov, identifier is NCT05084989.

SMART-lipid nanoparticles enabled mRNA vaccine elicits cross-reactive humoral responses against the omicron sub-variants.

The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has necessitated the development of broad cross-reactive vaccines. Recent findings suggest that enhanced antigen presentation could lead to cross-reactive humoral responses against the emerging variants. Toward enhancing the antigen presentation to dendritic cells (DCs), we developed a novel shikimoylated mannose receptor targeting lipid nanoparticle (SMART-LNP) system that could effectively deliver mRNAs into DCs. To improve the translation of mRNA, we developed spike domain-based trimeric S1 (TS1) mRNA with optimized codon sequence, base modification, and engineered 5' and 3' UTRs. In a mouse model, SMART-LNP-TS1 vaccine could elicit robust broad cross-reactive IgGs against Omicron sub-variants, and induced interferon-γ-producing T cells against SARS-CoV-2 virus compared with non-targeted LNP-TS1 vaccine. Further, T cells analysis revealed that SMART-LNP-TS1 vaccine induced long-lived memory T cell subsets, T helper 1 (Th1)-dominant and cytotoxic T cells immune responses against the SARS-CoV-2 virus. Importantly, SMART-LNP-TS1 vaccine produced strong Th1-predominant humoral and cellular immune responses. Overall, SMART-LNPs can be explored for precise antigenic mRNA delivery and robust immune responses. This platform technology can be explored further as a next-generation delivery system for mRNA-based immune therapies.

Immunogenicity of an adenovirus-vectored bivalent vaccine against wild type SARS-CoV-2 and Omicron variants in a murine model.

BACKGROUND: The emergence and rapid spread of new mutant strains of SARS-CoV-2 necessitate the development of a new generation vaccine capable of neutralizing a broad range of variants. When the SARS-CoV-2 Omicron variant emerged, individuals in China had already received an inactivated (INA) or a type 5 adenovirus-vectored (Ad5) SARS-CoV-2 vaccine targeting the wild-type virus. We have recently developed a bivalent recombinant type 5 vaccine targeting both the wild-type strain and the Omicron variant (Ad5-nCoV/O). The objectives of this study were to assess the immunogenicity of the bivalent vaccine as a booster against both the wild type and the Omicron variant. METHODS: In the single immunization model, mice received one intramuscular immunization with monovalent or bivalent Ad5-vectored vaccines targeting both wild-type SARS-CoV-2 and Omicron variants. In the prime-boost model, mice were primed intramuscularly with an INA or Ad5-vectored vaccine targeting wild-type SARS-CoV-2, and then boosted intramuscularly or intranasally with heterologous or homologous INA or monovalent or bivalent Ad5-vectored vaccines targeting both wild-type SARS-CoV-2 and Omicron variants. The vaccine-induced antibody responses and cellular immune responses were measured using ELISA, pseudovirus-based neutralization assays, the intracellular cytokine staining (ICS) and ELISpot. RESULTS: Single-dose prime vaccination with the monovalent and bivalent vaccines elicited robust antibody responses and CD4 + and CD8 + cellular responses against the spike protein of WT and Omicron SARS-CoV-2. Both intramuscular and intranasal boost vaccination with the bivalent Ad5-nCoV/O following a prime with INA or Ad5-vectored vaccines induced strong serum neutralization antibody responses to both wild type and Omicron variants. A heterologous prime-boost vaccination elicited greater neutralization antibody responses than a homologous prime-boost vaccination when mice were boosted with Ad5-vectored vaccines following a prime with INA. Intranasal boost also resulted in significant mucosal IgA responses. CONCLUSION: The bivalent vaccine Ad5-nCoV/O exhibited robust immunogenicity, inducing broad-spectrum cross-neutralizing antibodies and cellular immune responses against both wild type and Omicron variants of SARS-CoV-2. The results demonstrated the potential of the bivalent vaccine in addressing the challenges posed by emerging SARS-CoV-2 Omicron variants.

Boosting with variant-matched adenovirus-based vaccines promotes neutralizing antibody responses against SARS-CoV-2 Omicron sublineages in mice.

Global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron subvariants, such as BA.4, BA.5 and XBB.1.5, has been leading the recent wave of coronavirus disease 2019 (COVID-19). Unique mutations in the spike proteins of these emerging Omicron subvariants caused immune evasion from the pre-existing protective immunity induced by vaccination or natural infection. Previously, we developed AdCLD-CoV19-1, a non-replicating recombinant adenoviral vector that encodes the receptor binding domain of the spike protein of the ancestral SARS-CoV-2 strain. Based on the same recombinant adenoviral vector platform, updated vaccines that cover unique mutations found in each Omicron subvariant, including BA.1, BA.2, BA.4.1 and BA.5, were constructed. Preclinical studies revealed that each updated vaccine as a booster shot following primary vaccination targeting the ancestral strain improved neutralizing antibody responses against the pseudovirus of its respective strain most effectively. Of note, boosting with a vaccine targeting the BA.1 or BA.2 Omicron subvariant was most effective in neutralization against the pseudovirus of the BA.2.75 strain, whereas BA.4.1/5-adapted booster shots were most effective in neutralization against the BQ.1, BQ1.1 and BF.7 strains. Therefore, it is imperative to develop a vaccination strategy that can cover the unique spike mutations of currently circulating Omicron subvariants in order to prevent the next wave of COVID-19.

Phylogenetic, Sequencing, and Mutation Analysis of SARS-CoV-2 Omicron (BA.1) and Its Subvariants (BA.1.1, BA.2) During the Fifth Wave of the COVID-19 Pandemic in the Iraqi Kurdistan Region.

Introduction In December 2019, a global outbreak of SARS-CoV-2 occurred in Wuhan, China, resulting in the COVID-19 pandemic. Since then, the virus has spread to all countries, necessitating a worldwide initiative to create effective treatments and vaccines. Methods The RNA of samples QIAamp Viral RNA Mini Kit (Qiagen, MD). SARS-CoV-2 RNA was reverse transcribed with SuperScript IV VILO (ThermoFisher Scientific, Waltham, MA). The virus cDNA was amplified in two multiplexed PCR reactions using Q5 DNA High-fidelity Polymerase (New England Biolabs, Ipswich, MA). The genome was entirely sequenced from 40 samples at the Scripps Research Institute (TSRI) in California, USA. The samples were sequenced using a NovaSeq 6000 SP Reagent Kit v1.5 (Illumina, USA). The TSRI then entered these sequences into the GISAID database. The virus sequence was matched to the SARS-COV-2 virus identified in Wuhan, China (accession number: NC 045512.2) using Illumina sequencing technology (Illumina, CA), finding 95 different changes. The NextClade (clades.nextstrain.org) and Mega 11 (https://www.megasoftware.net) software tools were used to analyze SARS-CoV-2 genome sequence alignment and mutation studies. Results Following a sequencing analysis, it was determined that the spike glycoprotein (S) included a total of 38 mutations. Thirty of these mutations were found in the ORF1a gene. Additionally, 11 mutations were found in the ORF1b gene, with the remaining mutations found in the nucleocapsid (N), membrane protein (M), open reading frames 6 (ORF6), open reading frames 9 (ORF9), and envelope (E) genes. The phylogenetic analysis and transmission studies indicated that the isolates discovered in Iraq had separate infection origins and were closely linked to those discovered in other nations and states. Conclusion According to the findings of this study, a new vaccine can be developed based on identifying new Omicron variant mutations and subvariants such as BA.2, which were identified for the first time in Iraq.

Analysis of the protective efficacy of approved COVID-19 vaccines against Omicron variants and the prospects for universal vaccines.

By the end of 2022, different variants of Omicron had rapidly spread worldwide, causing a significant impact on the Coronavirus disease 2019 (COVID-19) pandemic situation. Compared with previous variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), these new variants of Omicron exhibited a noticeable degree of mutation. The currently developed platforms to design COVID-19 vaccines include inactivated vaccines, mRNA vaccines, DNA vaccines, recombinant protein vaccines, virus-like particle vaccines, and viral vector vaccines. Many of these platforms have obtained approval from the US Food and Drug Administration (FDA) or the WHO. However, the Omicron variants have spread in countries where vaccination has taken place; therefore, the number of cases has rapidly increased, causing concerns about the effectiveness of these vaccines. This article first discusses the epidemiological trends of the Omicron variant and reviews the latest research progress on available vaccines. Additionally, we discuss progress in the development progress and practical significance of universal vaccines. Next, we analyze the neutralizing antibody effectiveness of approved vaccines against different variants of Omicron, heterologous vaccination, and the effectiveness of multivalent vaccines in preclinical trials. We hope that this review will provide a theoretical basis for the design, development, production, and vaccination strategies of novel coronavirus vaccines, thus helping to end the SARS-CoV-2 pandemic.

High number of seizures and unconsciousness in patients with SARS-CoV-2 omicron variants: a retrospective study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variants are now a pandemic. There are differences in clinical features in SARS-CoV-2 variants and we conducted this study to assess the clinical features of coronavirus disease (COVID-19) in children with SARS-CoV-2 omicron variants. The study included children with COVID-19 arrivedto Tokyo Metropolitan Toshima Hospital between January 2020 and October 2022. The clinical features of 214 children with SARS-CoV-2 non-omicron variants and 557 children with omicron variants were compared. In the SARS-CoV-2 omicron variant group, more patients had fever, sore throat, nausea and/or vomiting, and seizures and/or disorders of consciousness. In SARS-CoV-2 non-omicron variants, there was only one patient with seizure and/or unconsciousness whereas there were 92 children in omicron variants. Among these 92 patients, 46 (49%) were diagnosed with simple febrile seizures; 23 (25%), with complex febrile seizures; 10 (11%) with status epilepticus; and two (2%) with encephalopathy. Their mean age was 4.0 ± 3.0 years-a wider age distribution than that in other febrile seizures but similar to that in febrile seizures in patients with influenza. SARS-CoV-2 omicron variants are likely to cause seizures and unconsciousness in children and their age distribution was wider than other febrile seizures patients but similar to those in influenza patients. In clinical practice in patients with COVID-19 and influenza, clinicians should be aware of these features.

SARS-CoV-2 spike protein S1 subunit induces potent neutralizing responses in mice and is effective against Delta and Omicron variants.

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, belongs to the betacoronavirus genus. This virus has a high mutation rate, which rapidly evolves into new variants with different properties, such as increased transmissibility or immune evasion. Currently, the most prevalent global SARS-CoV-2 variant is Omicron, which is more transmissible than previous variants. Current available vaccines may be less effective against some currently existing SARS-CoV-2 variants, including the Omicron variant. The S1 subunit of the spike protein of SARS-CoV-2 has been a major target for COVID-19 vaccine development. It plays a crucial role in the virus's entry into host cells and is the primary target for neutralizing antibodies. In this study, the S1 subunit of the spike protein of SARS-CoV-2 was engineered and produced at a high level in Nicotiana benthamiana plant. The expression level of the recombinant S1 protein was greater than the 0.5-g/kg fresh weight, and the purification yield was at least ~0.3 g of pure protein/kg of plant biomass, which would make a plant-produced S1 antigen an ideal vaccine candidate for commercialization. Purified, the plant-produced SARS-CoV-2 S1 protein exhibited significantly higher binding to the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2). Moreover, we also show that recombinant S1 protein/antigen-elicited antibodies can neutralize the Delta or Omicron variants. Collectively, our results demonstrate that a plant-produced S1 antigen could be a promising vaccine candidate against SARS-CoV-2 variants including Omicron.

Association of immune-related adverse events with COVID-19 pneumonia in lung cancer patients receiving immune checkpoint inhibitors: a cross-sectional study in China.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are commonly used to treat lung cancer patients, but their use can lead to immune-related adverse events (irAEs), which pose a challenge for treatment strategies. The impact of irAEs on the incidence of COVID-19 pneumonia in lung cancer patients during the ongoing COVID-19 pandemic is unclear. This study aims to investigate the association between irAEs and COVID-19 pneumonia in lung cancer patients receiving ICIs. METHODS: We conducted a cross-sectional study of lung cancer patients who received ICIs and were infected with COVID-19 due to the Omicron variant between December 2022 and February 2023 in China. We collected data on irAEs and COVID-19 outcomes. Logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between irAEs and the incidence of COVID-19 pneumonia. RESULTS: A total of 193 patients were enrolled, with 72 patients (37.30%) in the irAEs group and 121 patients (62.70%) in the non-irAEs group. Twenty-six patients (13.47%) developed COVID-19 pneumonia and 6 patients (3.11%) progressed to severe cases after COVID-19 infection. Multivariate logistic regression showed that the lung cancer patients who experienced irAEs was significantly associated with a higher incidence rate of COVID-19 pneumonia (OR = 9.56, 95%CI: 2.21-41.33; P = 0.0025). CONCLUSION: Our study suggests that lung cancer patients receiving ICIs and experiencing irAEs may have a higher risk of developing COVID-19 pneumonia due to the Omicron variant. Therefore, close monitoring of these patients during the COVID-19 pandemic is necessary to mitigate this risk.

Analyzing the emerging patterns of SARS-CoV-2 Omicron subvariants for the development of next-gen vaccine: An observational study.

Background and Aim: Understanding the prevalence and impact of SARS-CoV-2 variants has assumed paramount importance. This study statistically analyzed to effectively track the emergence and spread of the variants and highlights the importance of such investigations in developing potential next-gen vaccine to combat the continuously emerging Omicron subvariants. Methods: Transmission fitness advantage and effective reproductive number (R e) of epidemiologically relevant SARS-CoV-2 sublineages through time during the study period based on the GISAID data were estimated. Results: The analyses covered the period from January to June 2023 around an array of sequenced samples. The dominance of the XBB variant strain, accounting for approximately 57.63% of the cases, was identified during the timeframe. XBB.1.5 exhibited 37.95% prevalence rate from March to June 2023. Multiple variants showed considerable global influence throughout the study, as sporadically documented. Notably, the XBB variant demonstrated an estimated relative 28% weekly growth advantage compared with others. Numerous variants were resistant to the over-the-counter vaccines and breakthrough infections were reported. Similarly, the efficacy of mAB-based therapy appeared limited. However, it's important to underscore the perceived benefits of these preventive and therapeutic measures were restricted to specific variants. Conclusion: Given the observed trends, a comprehensive next-gen vaccine coupled with an advanced vaccination strategy could be a potential panacea in the fight against the pandemic. The findings suggest that targeted vaccine development could be an effective strategy to prevent infections. The study also highlights the need of global collaborations to rapidly develop and distribute the vaccines to ensure global human health.

Detection of SARS-CoV-2 omicron variants by immunochromatographic kit.

An immunochromatographic kit using antibodies against recombinant N protein of an omicron B.1.1.529 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was developed to detect SARS-CoV-2 omicron variants. The kit detected omicron variants (BA.1.18, BA.1.1, BA.2, BA.2.12.1, BA.2.75, BA.4.1, BA.4.6, BE.1, BA.5.2.1, XE, BF.7, BF.7.4.1, XBB.1, XBB.1.5 and BQ.1.1) as well as Wuhan strain and a delta variant.

Protection of COVID-19 Vaccination Against Hospitalization During the Era of Omicron BA.4 and BA.5 Predominance: A Nationwide Case-Control Study Based on the French National Health Data System.

Background: Knowing the duration of effectiveness of coronavirus disease 2019 (COVID-19) booster doses is essential to providing decision-makers with scientific arguments about the frequency of subsequent injections. We estimated the level of protection against COVID-19-related hospitalizations (Omicron BA.4-BA.5) over time after vaccination, accounting for breakthrough infections. Methods: In this nationwide case-control study, all cases of hospitalizations for COVID-19 identified in the comprehensive French National Health Data System between June 1, 2022, and October 15, 2022, were matched with up to 10 controls by year of birth, sex, department, and an individual COVID-19 hospitalization risk score. Conditional logistic regressions were used to estimate the level of protection against COVID-19-related hospitalizations conferred by primary and booster vaccination, accounting for history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Results: A total of 38 839 cases were matched to 377 653 controls; 19.2% and 9.9% were unvaccinated, respectively, while 68.2% and 77.7% had received ≥1 booster dose. Protection provided by primary vaccination reached 45% (95% CI, 42%-47%). The incremental effectiveness of booster doses ranged from 69% (95% CI, 67%-71%; ≤2 months) to 22% (95% CI, 19%-25%; ≥6 months). Specifically, the second booster provided an additional protection compared with the first ranging from 61% (95% CI, 59%-64%; ≤2 months) to 7% (95% CI, 2%-13%; ≥4 months). Previous SARS-CoV-2 infection conferred a strong, long-lasting protection (51% ≥20 months). There was no incremental effectiveness of a second booster among individuals infected since the first booster. Conclusions: In the era of Omicron BA.4 and BA.5 predominance, primary vaccination still conferred protection against COVID-19 hospitalization, while booster doses provided an additional time-limited protection. The second booster had no additional protection in case of infection since the first booster.

Humoral Responses Elicited after a Fifth Dose of SARS-CoV-2 mRNA Bivalent Vaccine.

While an important part of the world's population is vaccinated against SARS-CoV-2, new variants continue to emerge. We observe that even after a fifth dose of the mRNA bivalent vaccine, most vaccinated individuals have antibodies that poorly neutralize several Omicron subvariants, including BQ.1.1, XBB, XBB.1.5, FD.1.1, and CH.1.1. However, Fc-effector functions remain strong and stable over time against new variants, which may partially explain why vaccines continue to be effective. We also observe that donors who have been recently infected have stronger antibody functional activities, including neutralization and Fc-effector functions, supporting the observations that hybrid immunity leads to better humoral responses.

Risk Factors and Drug Efficacy for Severe Illness in Hemodialysis Patients Infected with the Omicron Variant of COVID-19.

INTRODUCTION: The Omicron variant of the novel coronavirus (COVID-19) has been spreading more rapidly and is more infectious, posing a higher risk of death and treatment difficulty for patients undergoing hemodialysis. This study aims to explore the severity rate and risk factors for hemodialysis patients infected with the Omicron variant and to conduct a preliminary analysis of the clinical efficacy of drugs. METHODS: Clinical and biochemical indicators of 219 hemodialysis patients infected with the Omicron variant were statistically analyzed. The patients were divided into two groups based on whether they were severely ill or not, and multiple regression analysis was conducted to determine the risk factors for severe illness. The severely ill patients were then grouped based on discharge or death, and the treatment drugs were included as influencing factors for multiple regression analysis to determine the risk factors and protective factors for death of severely ill patients, and drug efficacy analysis was conducted. RESULTS: Analysis showed that diabetes, low oxygen saturation, and high C-reactive protein (CRP) were independent risk factors for severe illness in hemodialysis patients infected with the Omicron variant. A history of diabetes and high C-reactive significantly increased the risk of severe illness in patients (aOR: 1.450; aOR: 1.011), while a high oxygen saturation level can reduce this risk (aOR: 0.871). In addition, respiratory distress was an independent risk factor for death in severely patients, significantly reducing the probability of discharge for patients (aOR: 0.152). The drugs thymalfasin and Tanreqing significantly increased the probability of discharge for patients (aOR: 1.472; aOR: 3.104), with the latter having a higher correlation, but with a relatively longer effective course. CONCLUSION: Hemodialysis patients infected with the Omicron variant of COVID-19 should pay special attention to their history of diabetes, CRP, and oxygen saturation levels, as well as respiratory distress symptoms, to reduce the risk of severe illness and death. In addition, thymalfasin and Tanreqing may be considered in treatment.

Systemic immune profiling of Omicron-infected subjects inoculated with different doses of inactivated virus vaccine.

SARS-CoV-2 primary strain-based vaccination exerts a protective effect against Omicron variants-initiated infection, symptom occurrence, and disease severity in a booster-dependent manner. Yet, the underlying mechanisms remain unclear. During the 2022 Omicron outbreak in Shanghai, we enrolled 122 infected adults and 50 uninfected controls who had been unvaccinated or vaccinated with two or three doses of COVID-19 inactive vaccines and performed integrative analysis of 41-plex CyTOF, RNA-seq, and Olink on their peripheral blood samples. The frequencies of HLA-DRhi classical monocytes, non-classical monocytes, and Th1-like Tem tended to increase, whereas the frequency of Treg was reduced by booster vaccine, and they influenced symptom occurrence in a vaccine dose-dependent manner. Intercorrelation and mechanistic analysis suggested that the booster vaccination induced monocytic training, which would prime monocytic activation and maturation rather than differentiating into myeloid-derived suppressive cells upon Omicron infections. Overall, our study provides insights into how booster vaccination elaborates protective immunity across SARS-CoV-2 variants.