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Background: Natural infection or vaccination have provided robust immune defense against SARS-CoV-2 invasion, nevertheless, Omicron variants still successfully cause breakthrough infection, and the underlying mechanisms are poorly understood. Methods: Sequential blood samples were continuously collected at different time points from 252 volunteers who were received the CanSino Ad5-nCoV (n = 183) vaccine or the Sinovac CoronaVac inactivated vaccine (n= 69). The anti- SARS-CoV-2 prototype and Omicron BA.5.2 as well as XBB.1.16 variant neutralizing antibodies (Nab) in sera were detected by ELISA. Sera were also used to measure pseudo and live virus neutralization assay. The associations between the anti-prototype Nab levels and different HLA-ABC alleles were analyzed using artificial intelligence (AI)-deep learning techniques. The frequency of B cells in PBMCs was investigated by flow cytometry assay (FACs). Results: Individuals carrying the HLA-B*15 allele manifested the highest concentrations of anti-SARS-CoV-2 prototype Nab after vax administration. Unfortunately, these volunteers are more susceptible to Omicron BA.5.2 breakthrough infection due to their sera have poorer anti-BA.5.2 Nab and lower levels of viral neutralization efficacy. FACs confirmed that a significant decrease in CD19+CD27+RBD+ memory B cells in these HLA-B*15 population compared to other cohorts. Importantly, generating lower concentrations of cross-reactive anti-XBB.1.16 Nab post-BA.5.2 infection caused HLA-B*15 individuals to be further infected by XBB.1.16 variant. Conclusions: Individuals carrying the HLA-B*15 allele respond better to COVID-19 vax including the CanSino Ad5-nCoV and the Sinovac CoronaVac inactivated vaccines, but are more susceptible to Omicron variant infection, thus, a novel vaccine against this population is necessary for COVID-19 pandemic control in the future. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACTBackground 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.

Introduction: Following the surge of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in late 2019, there was an 11-month period of relative evolutionary stability. However, since late 2020, SARS-CoV-2 evolution has been characterised by the emergence of mutation sets impacting virus characteristics like transmissibility and antigenicity, termed “variants of concern.” This shift likely responds to changing immune profiles within the human population. There is mounting evidence suggesting that post-vaccination serum is less effective in neutralising certain SARS-CoV-2 genotypes. XBB is a recombinant variant comprising sublineages BA.2.10.1 and BA.2.75 of the Omicron variant. Aim: To investigate the genomic characterisation and epidemiology of the XBB recombinant variant of SARS-CoV-2 in Uttarakhand, India. Materials and Methods: A retrospective cross-sectional study was conducted at the Viral Research Diagnostic Laboratory (VRDL Lab), Government Doon Medical College (GDMC), Dehradun, Uttarakhand, India. A total of 1,162 nasopharyngeal swabs received between September 2022 and February 2023 from various healthcare facilities were included for Next Generation Sequencing (NGS) of coronavirus. NGS was performed and all results were forwarded to the Indian SARS-CoV-2 Genomics Consortium (INSACOG) and the Indian Biological Data Centre (IBDC) for variant determination. Data collection occurred from March to April 2023, with data analysis following from May to June 2023. Statistical analysis was conducted using Microsoft Excel and Omnicalculator. Results: Among the 1,162 processed samples, 41 (3.53%) were identified as the XBB variant of Omicron. Within the XBB variants, XBB.2 was predominant 22 (53.7%). Maximum XBB samples (38, 92.7%) originated from District Dehradun, Uttarakhand, India. Conclusion: SARS-CoV-2 has been evolving and advancing with each new variant coming across. As XBB is impacting both previously infected individuals and those vaccinated, there is an imperative to develop new and efficacious vaccines against circulating variants to reduce associated risks of morbidity and mortality.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARSCoV- 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. [ABSTRACT FROM AUTHOR]

Introduction: Following the surge of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in late 2019, there was an 11-month period of relative evolutionary stability. However, since late 2020, SARS-CoV-2 evolution has been characterised by the emergence of mutation sets impacting virus characteristics like transmissibility and antigenicity, termed "variants of concern." This shift likely responds to changing immune profiles within the human population. There is mounting evidence suggesting that post-vaccination serum is less effective in neutralising certain SARS-CoV-2 genotypes. XBB is a recombinant variant comprising sublineages BA.2.10.1 and BA.2.75 of the Omicron variant. Aim: To investigate the genomic characterisation and epidemiology of the XBB recombinant variant of SARS-CoV-2 in Uttarakhand, India. Materials and Methods: A retrospective cross-sectional study was conducted at the Viral Research Diagnostic Laboratory (VRDL Lab), Government Doon Medical College (GDMC), Dehradun, Uttarakhand, India. A total of 1,162 nasopharyngeal swabs received between September 2022 and February 2023 from various healthcare facilities were included for Next Generation Sequencing (NGS) of coronavirus. NGS was performed and all results were forwarded to the Indian SARS-CoV-2 Genomics Consortium (INSACOG) and the Indian Biological Data Centre (IBDC) for variant determination. Data collection occurred from March to April 2023, with data analysis following from May to June 2023. Statistical analysis was conducted using Microsoft Excel and Omnicalculator. Results: Among the 1,162 processed samples, 41 (3.53%) were identified as the XBB variant of Omicron. Within the XBB variants, XBB.2 was predominant 22 (53.7%). Maximum XBB samples (38, 92.7%) originated from District Dehradun, Uttarakhand, India. Conclusion: SARS-CoV-2 has been evolving and advancing with each new variant coming across. As XBB is impacting both previously infected individuals and those vaccinated, there is an imperative to develop new and efficacious vaccines against circulating variants to reduce associated risks of morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: This retrospective analysis aims to investigate the clinical characteristics of students infected with the SARS-CoV-2 Omicron variant in three Beijing schools. Additionally, we explore the dynamic trends of nucleic acid cycle threshold values (Ct values) and serum antibody titers throughout the disease course. Methods: Demographic, clinical, nucleic acid Ct values, and antibody titer data were collected from cases in a COVID-19 cluster in Beijing Ditan Hospital, Capital Medical University, spanning from September 6 to October 1, 2022. Results: A total of 107 students infected with Omicron (BA.5.2 and BA.2.76) were identified across three schools. Primary clinical manifestations included fever and upper respiratory symptoms (85/107, 79.4 %), with the majority being classified as mild cases (96/107, 89.7 %). Notably, middle school students in the second school exhibited a higher peak body temperature compared to college students in the first and third schools (39.5 °C vs. 38.4 °C, adjusted P = 0.005; 39.5 °C vs. 38.6 °C, adjusted P = 0.002). Analysis of dynamic changes in Ct values revealed the lowest median Ct value in nasopharyngeal swabs on the third day of illness, reaching 35 after 9–11 days. Oropharyngeal swab nucleic acid median Ct value reached 35 approximately 3–5 days post-onset. Serum antibody detection showed continuous negativity of IgM antibody titers from days 1–10, while IgG antibody titers were positive on the first day and increased rapidly after one week. Conclusions: The three COVID-19 cluster school outbreaks primarily resulted from Omicron infections, with no severe or fatal cases observed. Clinically, the selection of different types of SARS-CoV-2 nucleic acid swabs for virus detection can be tailored based on the infection's course.

The global dissemination of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) Omicron variants has been characterized by a distinct 9-base pair (bp) deletion within the nucleocapsid (N) gene, a genomic feature absent in previously circulating variants. In response to this unique characteristic, we have developed an innovative amplicon-competition strategy to differentiate Omicron lineages from other SARS-CoV-2 variants using a real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay. This novel methodology demonstrates high specificity and sensitivity, effectively detecting viral loads ranging from 1500 to 1.5x106 copies per milliliter in nasopharyngeal swab specimens. The potential applications of this approach extend beyond current needs, providing a robust framework for the genomic characterization of future variants exhibiting unique genetic signatures.

Abstract 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.

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 SARSCoV-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 SARSCoV-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 plantproduced S1 antigen could be a promising vaccine candidate against SARS-CoV2 variants including Omicron. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

[Display omitted] The recently prevalent variants of concerns (VOCs) of SARS-CoV-2 belong to Omicron variants which display increased transmissibility and evade from immune protection generated by vaccines and/or natural infections. Better immunization strategies should be explored to induce broader immune responses against evolving SARS-CoV-2 variants. Here, we used inactivated vaccines derived from ancestral (Wu), Delta (Del) and Omicron (Omi) strains to immunize mice with homologous booster (3 × Wu, 3 × Del and 3 × Omi) or heterologous sequential booster (Wu/Del/Omi and Omi/Wu/Del) to evaluate their responses against two pre-Omicron (Wu and Del) and four Omicron variants. Even though neutralization responses against Wu and Del variants were similar in heterologous and homologous immunization groups, heterologous immunization groups induced significantly stronger neutralizing antibody against BA.1 (4.1–11 folds higher) and BA.2 (4.7–14.2 folds higher) than those of homologous immunization groups. While homologous immunization only induced strong neutralizing responses to either pre-Omicron variants (Wu and Del) in 3 × Wu and 3 × Del groups or to Omicron variants (BA.1 and BA.2) in 3 × Omi group, heterologous immunization groups induced strong and broader neutralizing responses to both pre-Omicron (Wu, Del) and Omicron variants (BA.1 and BA.2). Homologous and heterologous immunization groups elicited similar antigen-specific T cell (IFN-γ+) and B cell responses. Compared with homologous immunization, heterologous immunization could induce stronger plasma cell responses, which have the potential to generate broader and stronger neutralizing antibodies. However, neither heterologous nor homologous immunization groups induced strong neutralizing antibody against variants with bigger genetic deviation, such as BA.4/5 or BF.7, only weak neutralizing responses were induced. Surveillance on SARS-CoV2 variants evolution and immunization strategy are needed to explore better vaccines with broader and stronger neutralizing antibodies against post pandemic COVID-19. [ABSTRACT FROM AUTHOR]

Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global health crisis, with genetic mutations and evolution further creating uncertainty about epidemic risk. It is imperative to rapidly determine the nucleic acid sequence of SARS-CoV-2 and its variants to combat the coronavirus pandemic. Our goal was to develop a rapid, room-temperature, point-ofcare (POC) detection system to determine the nucleic acid sequences of SARS-CoV-2 isolates, especially omicron variants. Methods: Based on the conserved nucleotide sequence of SARS-CoV-2, bioinformatics software was used to analyze, design, and screen optimal enzymatic isothermal amplification primers and efficient CRISPR RNAs (crRNAs) of CRISPR/Cas13a to the target sequences. Reverse transcription-recombinase polymerase amplification (RT-RPA) was used to amplify the virus, and CRISPR/Cas13a-crRNA was used to cleave the SARS-CoV-2 target sequence. The sensitivity of nucleic acid detection was assessed by serial dilution of plasmid templates. All reactions were performed at room temperature. Results: RT-RPA, combined with CRISPR/Cas13a, can detect the SARS-CoV-2 with a minimum content of 10² copies/μL, and can effectively distinguish between the original strain and the Omicron variant with a minimum limit of detection (LOD) of 10³ copies/μL. Conclusion: The method developed in this study has potential application in clinical detection of SARSCoV-2 and its omicron variants. [ABSTRACT FROM AUTHOR]

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 (Re) 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. [ABSTRACT FROM AUTHOR]

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.

Yuan-Yuan Wei,1,2,* Rui-Rui Wang,3,* Da-Wei Zhang,1,2,* Su-Hong Chen,2,4 Yuan-Yuan Tan,2,5 Wen-Ting Zhang,1,2 Ming-Feng Han,3 Guang-He Fei1,2 1Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 2Key Laboratory of Respiratory Diseases Research and Medical Transformation of Anhui Province, Hefei, Anhui, 230022, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, the Second People’s Hospital of Fuyang City, Fuyang, Anhui, 236015, People’s Republic of China; 4Department of Integrated Traditional Chinese and Western Medicine, Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 5Department of Emergency Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang-He Fei, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Tel +8655162922013, Fax +8655163635578, Email gh.fei@ahmu.edu.cn Ming-Feng Han, Department of Respiratory and Critical Care Medicine, the Second People’s Hospital of Fuyang City, Fuyang, Anhui, 236015, People’s Republic of China, Email fyhmf@163.comBackground: As multiple mutations of SARS-Cov-2 exist, there are now many viral variants with regional differences in distribution. The clinical characteristics of patients hospitalized with the virus also vary significantly, with those of the Omicron variants being strikingly different from those of the earliest wild-type variant. However, comprehensive data on this subject is lacking. It is therefore crucial to explore these differences to develop better clinical strategies for the management of COVID-19.Methods: A total of 554 confirmed COVID-19 cases in China were clinically classified as mild, moderate, severe, and critical according to their diagnoses and treatment plans. We compared the demographics and clinical characteristics of patients infected with the Omicron vs wild-type strains, between severe and non-severe cases. Bacterial co-infections with SARS-CoV-2 and correlation between inflammatory factors and T cells were analyzed.Results: Compared to the wild-type cases, the severe Omicron cases were older (median age 48.36 vs 73.24), and had more upper-respiratory symptoms and comorbidities. Decreased leukocyte counts were less pronounced, although more instances of significantly decreased CD4+ and CD8+ T-cell counts, elevated infection-related biomarkers (eg procalcitonin and C-reactive protein), and abnormal coagulation factors (including increased D-dimer and fibrinogen levels) were detected in the severe Omicron cases. The mean length of hospital stay was significantly shorter in the severe Omicron cases. CD4+ and CD8+ T cell numbers were negatively correlated with neutrophil-to-lymphocyte ratios, as well as serum interleukin-6, procalcitonin, and C-reactive protein levels.Conclusion: There were significant clinical differences between patients hospitalized with severe cases of Omicron- variant COVID-19 vs wild-type. The Omicron cases tended to be older and had more upper respiratory tract symptoms, comorbidities and bacterial co-infections. Elevated levels of inflammatory cytokines with T-cell depletion correlated with poor disease progression and prognosis. We hope these data provide a theoretical basis for future integrated prevention and control plans for COVID-19.Keywords: COVID-19, Omicron variants, wild-typeSARS-CoV-2, clinical characteristics, T cell depletion

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.

Abstract Background Home-quarantine is one of the most common measures implemented to prevent or minimize the transmission of COVID-19 among communities. This study assessed stress levels of the home-quarantined residents in Shanghai during a massive wave of COVID-19 epidemic this year, explored the stress sources perceived by the respondents, and analyzed the association between each of the sociodemographic factors and the stress level. Methods This online survey was launched during April 23 - 30, 2022, the early stage of a massive wave of COVID-19 in Shanghai, China. Participants were quarantined-residents negative for COVID-19. They were asked to list some situations that were their major concerns and perceived stressful, in addition to sociodemographic and COVID-19 related information. Moreover, they were asked to complete the Perceived Stress Scale-14 (PSS-14) for the assessment of stress level. Results A total of 488 valid questionnaires were collected from 192 male and 296 female respondents. Overall, 207 persons (42.42%) presented high stress level (PSS-14 score ≥43). The top three concerns perceived stressful by respondents are “not allowed to go outdoors”, “uncertain duration of the epidemic”, and “lack of food supply”. Fewer than 50% of the respondents perceived the other situations stressful. Higher proportions of young adults (≤ 29 years old), males, unemployed, singles, and those with low income (≤ 1999 yuan/month) perceived high stress compared to their counterparts, none of COVID-19 related factors is associated with the stress level, including location of residence, result of nucleic acid test, knowledge about COVID-19, whether vaccinated, and quarantine duration. Conclusion Home-quarantine applied to people negative for COVID-19 led to a lot of major concerns that may be perceived stressful, whereas the virus-related factors did not show significant impact on mental health of the respondents.

ABSTRACTWith the ongoing COVID-19 pandemic and the emergence of various SARS-CoV-2 variants, a comprehensive evaluation of long-term efficacy of antibody response in convalescent individuals is urgently needed. Several longitudinal studies had reported the antibody dynamics after SARS-CoV-2 acute infection, but the follow-up was mostly limited to 1 year or 18 months at the maximum. In this study, we investigated the durability, potency, and susceptibility to immune evasion of SARS-CoV-2-specific antibody in COVID-19 convalescents for 2 years after discharge. These results showed the persistent antibody-dependent immunity could protect against the WT and Delta variant to some extent. However, the Omicron variants (BA.1, BA.2, and BA.4/5) largely escaped this preexisting immunity in recovered individuals. Furthermore, we revealed that inactivated vaccines (BBIBP-CorV, CoronaVac, or KCONVAC) could improve the plasma neutralization and help to maintain the broadly neutralizing antibodies at a certain level. Notably, with the time-dependent decline of antibody, 1-dose or 2-dose vaccination strategy seemed not to be enough to provide immune protection against the emerging variants. Overall, these results facilitated our understanding of SARS-CoV-2-induced antibody memory, contributing to the development of immunization strategy against SARS-CoV-2 variants for such a large number of COVID-19 survivors.

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.

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, 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.

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. [ABSTRACT FROM AUTHOR]

Background Although a substantial fraction of the US population was infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during December 2021–February 2022, the subsequent evolution of population immunity reflects the competing influences of waning protection over time and acquisition or restoration of immunity through additional infections and vaccinations. Methods Using a Bayesian evidence synthesis model of reported coronavirus disease 2019 (COVID-19) data (diagnoses, hospitalizations), vaccinations, and waning patterns for vaccine- and infection-acquired immunity, we estimate population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States, by location (national, state, county) and week. Results By 9 November 2022, 97% (95%–99%) of the US population were estimated to have prior immunological exposure to SARS-CoV-2. Between 1 December 2021 and 9 November 2022, protection against a new Omicron infection rose from 22% (21%–23%) to 63% (51%–75%) nationally, and protection against an Omicron infection leading to severe disease increased from 61% (59%–64%) to 89% (83%–92%). Increasing first booster uptake to 55% in all states (current US coverage: 34%) and second booster uptake to 22% (current US coverage: 11%) would increase protection against infection by 4.5 percentage points (2.4–7.2) and protection against severe disease by 1.1 percentage points (1.0–1.5). Conclusions Effective protection against SARS-CoV-2 infection and severe disease in November 2022 was substantially higher than in December 2021. Despite this high level of protection, a more transmissible or immune evading (sub)variant, changes in behavior, or ongoing waning of immunity could lead to a new SARS-CoV-2 wave. [ABSTRACT FROM AUTHOR]

Lombardy, the largest and most densely populated Italian region, was severely hit in February 2020 by the first pandemic wave of SARS-CoV-2 and associated COVID-19. Since then, additional infection waves spread in the region. The aim of this study was to compare the first with the subsequent waves using the administrative database of the Lombardy Welfare directorate. In the time frames of the four 2020–2022 waves, the absolute number of infected cases, sites of management and crude mortality rate associated with SARS-CoV-2 positivity were extracted from the database. Infected cases progressively increased in the region by approximately 5-fold in the second versus the first wave, 4-fold in the third and 20-fold during the most recent wave mainly associated with the omicron variant. The crude death decreased from 18.7% in the first to 2% in the second and third wave to reach a 0.3% nadir at the time of the fourth wave. This study confirms that in Lombardy outcomes of public health and health-care relevance such as deaths and number of hospitalizations declined dramatically across the four virus waves and reached very low values in 2022 when, at variance with the first three SARS-CoV-2 waves, the majority of infected cases had been previously vaccinated. [ABSTRACT FROM AUTHOR]

Abstract 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 (Re) 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.

This study aims to analyze the neutralization ability against Omicron parental variants in five clusters of individuals with different Coronavirus disease (COVID-19) immunity backgrounds, including individuals receiving a homologous or heterologous vaccine without prior infection, recovered patients with homologous or heterologous vaccination, and recovery patients without vaccination. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surrogate virus neutralization assay was performed on serum samples. Spearman correlation analysis showed that the percent inhibition against Omicron B.1.1.529 and BA.2 was significantly related to the period of serum collection (r = 0.730 and 0.787, p < 0.001, respectively). Very strong correlation between percent inhibition of neutralizing antibody against Omicron B.1.1.529 and BA.2 variants (rs = 0.973, p < 0.001) was also observed. The neutralizing activity of the sera from recovery patients receiving homologous and heterologous vaccine against the wild-type, B.1.1.529, and BA.2 Omicron variants was significantly higher (p < 0.001) than that of recovery patients without vaccination. This study robustly showed that the breakthrough SARS-CoV-2 Omicron variant in individuals who received homologous and heterologous vaccines had a high level of neutralizing activity against B.1.1.529 and BA.2 parental lineage of XBB subvariants. Therefore, the next-generation COVID-19 vaccine against emerging variants is needed to improve resilience against ongoing variants, particularly for persons who have never been infected. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary and extrapulmonary manifestations have been described after infection with SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The virus is known to persist in multiple organs due to its tropism for several tissues. However, previous reports were unable to provide definitive information about whether the virus is viable and transmissible. It has been hypothesized that the persisting reservoirs of SARS-CoV-2 in tissues could be one of the multiple potentially overlapping causes of long COVID. Methods: In the present study, we investigated autopsy materials obtained from 21 cadaveric donors with documented first infection or reinfection at the time of death. The cases studied included recipients of different formulations of COVID-19 vaccines. The aim was to find the presence of SARS-CoV-2 in the lungs, heart, liver, kidneys, and intestines. We used two technical approaches: the detection and quantification of viral genomic RNA using RT-qPCR, and virus infectivity using permissive in vitro Vero E6 culture. Results: All tissues analyzed showed the presence of SARS-CoV-2 genomic RNA but at dissimilar levels ranging from 1.01 × 102 copies/mL to 1.14 × 108 copies/mL, even among those cases who had been COVID-19 vaccinated. Importantly, different amounts of replication-competent virus were detected in the culture media from the studied tissues. The highest viral load were measured in the lung (-1.4 × 106 copies/mL) and heart (-1.9 × 106 copies/mL) samples. Additionally, based on partial Spike gene sequences, SARS-CoV-2 characterization revealed the presence of multiple Omicron sub-variants exhibiting a high level of nucleotide and amino acid identity among them. Discussion: These findings highlight that SARS-CoV-2 can spread to multiple tissue locations such as the lungs, heart, liver, kidneys, and intestines, both after primary infection and after reinfections with the Omicron variant, contributing to extending knowledge about the pathogenesis of acute infection and understanding the sequelae of clinical manifestations that are observed during post-acute COVID-19. [ABSTRACT FROM AUTHOR]

Since early 2022, various Omicron variants have dominated the SARS-CoV-2 pandemic in most countries. All Omicron variants are B-cell immune escape variants, and antibodies induced by first-generation COVID-19 vaccines or by infection with earlier SARS-CoV-2 variants largely fail to protect individuals from Omicron infection. In the present study, we investigated the effect of Omicron infections in triple-vaccinated and in antigen-naive individuals. We show that Omicron breakthrough infections occurring 2-3.5 months after the third vaccination restore B-cell and T-cell immune responses to levels similar to or higher than those measured 14 days after the third vaccination, including the induction of Omicron-neutralizing antibodies. Antibody responses in breakthrough infection derived mostly from cross-reacting B cells, initially induced by vaccination, whereas Omicron infections in antigen-naive individuals primarily generated B cells binding to the Omicron but not the Wuhan spike protein. Although antigen-naive individuals mounted considerable T-cell responses after infection, B-cell responses were low, and neutralizing antibodies were frequently below the limit of detection. In summary, the detection of Omicron-associated B-cell responses in primed and in antigennaive individuals supports the application of Omicron-adapted COVID-19 vaccines, but calls into question their suitability if they also contain/encode antigens of the original Wuhan virus. [ABSTRACT FROM AUTHOR]

Background: Home-quarantine is one of the most common measures implemented to prevent or minimize the transmission of COVID-19 among communities. This study assessed stress levels of the home-quarantined residents in Shanghai during a massive wave of COVID-19 epidemic this year, explored the stress sources perceived by the respondents, and analyzed the association between each of the sociodemographic factors and the stress level. Methods: This online survey was launched during April 23 - 30, 2022, the early stage of a massive wave of COVID-19 in Shanghai, China. Participants were quarantined-residents negative for COVID-19. They were asked to list some situations that were their major concerns and perceived stressful, in addition to sociodemographic and COVID-19 related information. Moreover, they were asked to complete the Perceived Stress Scale-14 (PSS-14) for the assessment of stress level. Results: A total of 488 valid questionnaires were collected from 192 male and 296 female respondents. Overall, 207 persons (42.42%) presented high stress level (PSS-14 score ≥43). The top three concerns perceived stressful by respondents are "not allowed to go outdoors", "uncertain duration of the epidemic", and "lack of food supply". Fewer than 50% of the respondents perceived the other situations stressful. Higher proportions of young adults (≤ 29 years old), males, unemployed, singles, and those with low income (≤ 1999 yuan/month) perceived high stress compared to their counterparts, none of COVID-19 related factors is associated with the stress level, including location of residence, result of nucleic acid test, knowledge about COVID-19, whether vaccinated, and quarantine duration. Conclusion: Home-quarantine applied to people negative for COVID-19 led to a lot of major concerns that may be perceived stressful, whereas the virus-related factors did not show significant impact on mental health of the respondents. [ABSTRACT FROM AUTHOR]

Introduction: Vaccination against SARS-CoV-2 and the prevalence of Omicron variants have reduced the risk of the severe clinical progress of COVID-19. However, the risk of breakthrough infections has increased, and early administration of an effective antiviral treatment is significant in order to prevent the severe progression of COVID-19 in vulnerable patients with comorbidities. Patients and methods: Adults with confirmed SARS-CoV-2 infection were included in a matched-pair retrospective study based on age, gender, comorbidities and vaccination status. They were divided into two groups: group A (n = 200) consisted of outpatients at increased risk of severe clinical progress who were treated with nirmatrelvir/ritonavir and group B (n = 200) consisted of non-hospitalized patients who did not receive antiviral treatment. Demographic data, clinical outcome (death, intubation), days of hospitalization, time for recovery, adverse events and treatment compliance were reported. Results: The median age (75.24 ± 13.12 years in the study group and 76.91 ± 14.02 years in the comparison group) and the proportion of males (59% vs. 60.5%, respectively) were similar between the two groups. A total of 6.5% of patients in group A and 10.5% in group B were unvaccinated against SARS-CoV-2. Three patients from group A (1.5%) and one hundred eleven (55.5%) from group B required hospitalization. The duration of hospitalization (3 days vs. 10 days in group B, p < 0.001) and the total time needed for recovery (5 days vs. 9 days, p < 0.001) was shorter in the study group. A rebound of SARS-CoV-2 infection within 8–12 days after diagnosis was documented in 6.5% of patients in group A and 8% of patients in group B. Conclusion: Oral treatment with nirmatrelvir/ritonavir in high-risk non-hospitalized patients was safe and effective in preventing the severe clinical progress of COVID-19 pneumonia. Early administration of antiviral agents in vulnerable outpatients combined with a full vaccination scheme is significant in order to avoid hospitalization and severe clinical outcomes. [ABSTRACT FROM AUTHOR]

Given the pandemic of severe acute respiratory syndrome coronavirus 2 Omicron variants, booster vaccination (BV) using inactivated virus vaccines (the third dose) has been implemented in China. However, the immune responses after BV, especially those against Omicron, in patients with chronic hepatitis B virus (HBV) infection (CHB) are unclear. In this prospective longitudinal study, 114 patients with CHB and 68 healthy controls (HCs) were recruited after receiving inactivated vaccination. The anti‐receptor‐binding domain (RBD) immunoglobulin G (IgG), neutralizing antibodies (NAbs), neutralization against Omicron (BA2.12.1, BA.4/5), and specific B/T cells were evaluated. In patients, anti‐RBD IgG was elevated significantly after BV; the titers were as high as those in HCs. Similar results were obtained for the NAbs. However, compared with that against wild type (WT), the neutralization against Omicron was compromised after BV. The frequency of RBD+ atypical memory B cells increased, but spike‐specific cluster of differentiation 4+/8+ T cells remained unchanged after BV. Moreover, no serious adverse events or HBV reactivation were observed after BV. These results suggest that BV significantly enhanced antibody responses against WT; however, it resulted in compromised antibody responses against Omicron in patients with CHB. Hence, new all‐in‐one vaccines and optimal vaccination strategies should be studied promptly. [ABSTRACT FROM AUTHOR]

We performed an annotation of 35 mutations in the spike protein of the SARS-CoV-2 Omicron variant. Our analysis of the mutations indicates that Omicron has gained prominent immune evasion and potential for enhanced transmissibility. Previous modeling study has revealed that continued evolution in both immune evasion and enhanced transmissibility by SARS-CoV-2 would compromise vaccines as tools for the pandemic control. To combat the future variants of SARS-CoV-2, the world needs novel antiviral drugs that are effective at curb viral spreading without introducing additional selective pressure towards resistant variants.

The global COVID-19 is still in a pandemic state, and Omicron is still the dominant variant in the world, accounting for about 99% of the global gene sequence. Many regions around the world are experiencing the seventh wave of the epidemic. This round of epidemics is mainly caused by Omicron subvariants BA.4 and BA.5, but the epidemiological characteristics of Omicron subvariants BA.4 and BA.5 are still unclear, bringing great challenges to the prevention and control of the epidemic in countries and regions. In this study, discovery and epidemic status, the incubation period, transmissibility, clinical symptoms, case fatality rate, and the protective effect of vaccines of Omicron subvariants BA.4 and BA.5 were reviewed, in order to provide reference for scientific prevention and control of Omicron subvariants BA.4 and BA.5.

Background: With the rapid development of the genomic sequence data for the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants Delta (B.1.617.2) and Omicron (B.1.1.529), it is vital to successfully identify mutations within the genome. Objective: The main objective of the study is to investigate the full-length genome mutation analysis of 157 SARS-CoV-2 and its variant Delta and Omicron isolates. This study also provides possible effects at the structural level to understand the role of mutations and new insights into the evolution of COVID-19 and evaluates the differential level analysis in viral genome sequence among different nations. We have also tried to offer a mutation snapshot for these differences that could help in vaccine formulation. This study utilizes a unique and efficient method of targeting the stable genes for the drug discovery approach. Methods: Complete genome sequence information of SARS-CoV-2, Delta, and Omicron from online resources were used to predict structure domain identification, data mining, and screening; employing different bioinformatics tools. BioEdit software was used to perform their genomic alignments across countries and a phylogenetic tree as per the confidence of 500 bootstrapping values was constructed. Heterozygosity ratios were determined in-silico. A minimum spanning network (MSN) of selected populations was determined by Bruvo's distance role-based framework. Results: Out of all 157 different strains of SARS-CoV-2 and its variants, and their complete genome sequences from different countries, Corona nucleoca and DUF5515 were observed to be the most conserved domains. All genomes obtained changes in comparison to the Wuhan-Hu-1 strain, mainly in the TRS region (CUAAAC or ACGAAC). We discovered 596 mutations in all genes, with the highest number (321) found in ORF1ab (QHD43415.1), or TRS site mutations found only in ORF7a (1) and ORF10 (2). The Omicron variant has 30 mutations in the Spike protein and has a higher alpha-helix shape (23.46%) than the Delta version (22.03%). T478 was also discovered to be a prevalent polymorphism in Delta and Omicron variations, as well as genomic gaps ranging from 45 to 65aa. All 157 sequences contained variations and conformed to Nei's Genetic distance. We discovered heterozygosity (Hs) 0.01, mean anticipated Hs 0.32, the genetic diversity index (GDI) 0.01943989, and GD within population 0.01266951. The Hedrick value was 0.52324978, the GD coefficient was 0.52324978, the average Hs was 0.01371452, and the GD coefficient was 0.52324978. Among other countries, Brazil has the highest standard error (SE) rate (1.398), whereas Japan has the highest ratio of Nei's gene diversity (0.01). Conclusions: The study's findings will assist in comprehending the shape and kind of complete genome, their streaming genomic sequences, and mutations in various additions of SARS-CoV-2, as well as its different variant strains like Omicron. These results will provide a scientific basis to design the vaccines and understand the genomic study of these viruses.

In January 2022, the SARS‐CoV‐2 Omicron variants initiated major outbreaks and dominated the transmissions in Hong Kong, displacing an earlier outbreak seeded by the Delta variants. To provide insight into the transmission potential of the emerging variants, we aimed to compare the epidemiological characteristics of the Omicron and Delta variants. We analyzed the line‐list clinical and contact tracing data of the SARS‐CoV‐2 confirmed cases in Hong Kong. Transmission pairs were constructed based on the individual contact history. We fitted bias‐controlled models to the data to estimate the serial interval, incubation period and infectiousness profile of the two variants. Viral load data were extracted and fitted to the random effect models to investigate the potential risk modifiers for the clinical viral shedding course. Totally 14 401 confirmed cases were reported between January 1 and February 15, 2022. The estimated mean serial interval (4.4 days vs. 5.8 days) and incubation period (3.4 days vs. 3.8 days) were shorter for the Omicron than the Delta variants. A larger proportion of presymptomatic transmission was observed for the Omicron (62%) compared to the Delta variants (48%). The Omicron cases had higher mean viral load over an infection course than the Delta cases, with the elder cases appearing more infectious than the younger cases for both variants. The epidemiological features of Omicron variants were likely an obstacle to contact tracing measures, imposed as a major intervention in settings like Hong Kong. Continuously monitoring the epidemiological feature for any emerging SARS‐CoV‐2 variants in the future is needed to assist officials in planning measures for COVID‐19 control. [ABSTRACT FROM AUTHOR]

This research aimed to determine the levels of COVID-19 booster dose vaccinations in Thai populations in areas with environmental risk exposure during the Omicron outbreak. Five of twenty provinces in Thailand were selected by assessing environmental risk exposure for study settings. A total of 1038 people were interviewed by a structured questionnaire. The predicting factors of COVID-19 booster dose vaccinations were analyzed by univariate and multivariate analysis. The results showed that 69.4% (95% CI 66.5–72.1) of the population was vaccinated with COVID-19 booster doses. Multiple logistics regression revealed that the female gender (AOR 1.49, 95% CI 1.11–2.00), all age groups from 38 to 60 years old, all education levels of at least secondary school, high income (AOR 1.16, 95% CI 1.15–2.24), populations having experience with COVID-19 infection (AOR 2.27, 95% CI 2.05–3.76), knowledge of vaccine (AOR 1.78, 95% CI 1.11–2.83), and trusting attitude (AOR 1.76, 95% CI 1.32–2.36) were factors among those more likely to take COVID-19 booster dose vaccinations in high-environmental-risk-exposure areas. Therefore, an effective booster dose campaign with education programs to increase attitudes toward booster vaccinations should be implemented for the resilience of COVID-19 prevention and control. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Direct comparative effectiveness of booster doses of BNT162b2 and mRNA-1273 after BNT162b2 primary vaccination is unknown. Methods We investigated comparative effectiveness of BNT162b2 and mRNA-1273 booster dose using data from registry systems for vaccination and coronavirus disease 2019 (COVID-19) infection in a local city in Japan. We followed participants aged ≥16 years who completed the BNT162b2 primary vaccination between 22 November 2021, and 15 April 2022. We collected information on age, sex, vaccination status, vaccine type, and infection status. Age was categorized as 16–44, 45–64, 65–84, and ≥85 years. Vaccine effectiveness for mRNA-1273 and no booster vaccination against BNT162b2 was estimated using age-stratified Cox regression adjusted for age, sex, and days since the second vaccination. The estimated hazard ratios for mRNA-1273 and no booster vaccinations were integrated separately using random effects meta-analyses. Results During the study period, we identified 62 586 (40.4%), 51 490 (33.2%), and 40 849 (26.4%) participants who received BNT162b2, mRNA-1273, and no booster dose, respectively. The median age was 69, 71, and 47 years for BNT162b2, mRNA-1273, and no booster dose, respectively. The integrated hazard ratio with reference to BNT162b2 was 1.72 for no booster vaccination and 0.62 for mRNA-1273. The comparative effectiveness of mRNA-1273 was similar across age categories. Conclusions Both homologous and heterologous vaccinations are effective against Omicron variants. In the head-to-head comparison, the effect was stronger in people who received heterologous vaccination than in those who received homologous vaccination. These findings may help improve logistics and decision making in future vaccination programs. [ABSTRACT FROM AUTHOR]

ABSTRACT The increased transmissibility of SARS-CoV-2 variants of concern (VOCs) has raised questions regarding the environmental stability of these viruses. Although a prolonged survival time has been reported for SARS-CoV-2, how long new variants can persist on contaminated surfaces and how environmental factors affect the persistence time are not fully characterized. The present study provides a comprehensive assessment of the stability of Omicron variants BA.1 and BA.5, which are currently circulating strains, on the surfaces of widely used transport packaging materials. By monitoring viable virus detection over a 7-day period under different environmental conditions, it was found that the environmental stability of SARS-CoV-2 Omicron variants depended heavily on the surface type, temperature, and virus concentration. In addition, virus nucleic acid exhibited high stability on the material surface independent of whether viable virus was detected. These findings provide useful information for logistics practitioners and the general public to appropriately deal with transport items under different conditions to minimize the risk of epidemic transmission. IMPORTANCE This study shows the environmental stability of SARS-CoV-2 Variants Omicron BA.1 and BA.5 on surfaces of widely used transport packaging materials. The findings demonstrate that the environmental stability of the SARS-CoV-2 Omicron variants varies based on material type. The viability of SARS-CoV-2 on material surfaces depends heavily on temperature and viral titer. Low temperatures and high viral titers promote virus survival. Moreover, in contrast to virus viability, virus nucleic acid exhibits high stability on the surfaces of widely used materials, making the detection of virus nucleic acid unsuitable for evaluating the risk of epidemic transmission.

IntroductionPulmonary and extrapulmonary manifestations have been described after infection with SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The virus is known to persist in multiple organs due to its tropism for several tissues. However, previous reports were unable to provide definitive information about whether the virus is viable and transmissible. It has been hypothesized that the persisting reservoirs of SARS-CoV-2 in tissues could be one of the multiple potentially overlapping causes of long COVID.MethodsIn the present study, we investigated autopsy materials obtained from 21 cadaveric donors with documented first infection or reinfection at the time of death. The cases studied included recipients of different formulations of COVID-19 vaccines. The aim was to find the presence of SARS-CoV-2 in the lungs, heart, liver, kidneys, and intestines. We used two technical approaches: the detection and quantification of viral genomic RNA using RT-qPCR, and virus infectivity using permissive in vitro Vero E6 culture.ResultsAll tissues analyzed showed the presence of SARS-CoV-2 genomic RNA but at dissimilar levels ranging from 1.01 × 102 copies/mL to 1.14 × 108 copies/mL, even among those cases who had been COVID-19 vaccinated. Importantly, different amounts of replication-competent virus were detected in the culture media from the studied tissues. The highest viral load were measured in the lung (≈1.4 × 106 copies/mL) and heart (≈1.9 × 106 copies/mL) samples. Additionally, based on partial Spike gene sequences, SARS-CoV-2 characterization revealed the presence of multiple Omicron sub-variants exhibiting a high level of nucleotide and amino acid identity among them.DiscussionThese findings highlight that SARS-CoV-2 can spread to multiple tissue locations such as the lungs, heart, liver, kidneys, and intestines, both after primary infection and after reinfections with the Omicron variant, contributing to extending knowledge about the pathogenesis of acute infection and understanding the sequelae of clinical manifestations that are observed during post-acute COVID-19.

Since early 2022, various Omicron variants have dominated the SARS-CoV-2 pandemic in most countries. All Omicron variants are B-cell immune escape variants, and antibodies induced by first-generation COVID-19 vaccines or by infection with earlier SARS-CoV-2 variants largely fail to protect individuals from Omicron infection. In the present study, we investigated the effect of Omicron infections in triple-vaccinated and in antigen-naive individuals. We show that Omicron breakthrough infections occurring 2–3.5 months after the third vaccination restore B-cell and T-cell immune responses to levels similar to or higher than those measured 14 days after the third vaccination, including the induction of Omicron-neutralizing antibodies. Antibody responses in breakthrough infection derived mostly from cross-reacting B cells, initially induced by vaccination, whereas Omicron infections in antigen-naive individuals primarily generated B cells binding to the Omicron but not the Wuhan spike protein. Although antigen-naive individuals mounted considerable T-cell responses after infection, B-cell responses were low, and neutralizing antibodies were frequently below the limit of detection. In summary, the detection of Omicron-associated B-cell responses in primed and in antigen-naive individuals supports the application of Omicron-adapted COVID-19 vaccines, but calls into question their suitability if they also contain/encode antigens of the original Wuhan virus.

The Omicron (B.1.1.529) variant was first reported in South Africa and rapidly spread worldwide in early November 2021. This caused panic in various countries, so it is necessary to understand Omicron Variant. This paper summarizes omicron variant-related research achievements. Studies have shown that Omicron Variant contains many mutations that make it more infectious and transmissible. At the same time, immune escape is also caused, resulting in reduced efficacy of existing vaccines, increased risk of reinfection, treatment failure or reduction of monoclonal antibody therapies, and detection failure. However, current data indicate that Omicron Variant causes mild clinical symptoms and few severe cases and deaths. Omicron Variant is valid for a range of nonpharmaceutical interventions against SARS-CoV-2. Improving diagnostic accuracy and enabling timely isolation and treatment of diagnosed cases is also critical to interrupting the spread of omicron variants. COVID-19 vaccine boosters could undoubtedly help control Omicron spread and infection. However, developing a vaccine specific to Omicron Variant is also imminent.

BackgroundA third mRNA vaccine booster is recommended to improve immunity against SARS-CoV-2 in kidney transplant recipients (KTRs). However, the immunity against SARS-CoV-2 Ancestral strain and Delta and Omicron variants elicited by the third dose of inactivated booster vaccine in KTRs remains unknown.MethodsThe blood parameters related to blood cells count, hepatic function, kidney function, heart injury and immunity were explored clinically from laboratory examinations. SARS-CoV-2 specific antibody IgG titer was detected using an enzyme-linked immunosorbent assay. Cellular immunity was analyzed using interferon-γ enzyme-linked immunospot assay.ResultsThe results showed that there were no severe adverse effects and apparent changes of clinical laboratory biomarkers in KTRs and healthy volunteers (HVs) after homologous inactivated vaccine booster. A third dose of inactivated vaccine booster significantly increased anti-Ancestral-spike-trimer-IgG and anti-Ancestral-receptor binding domain (RBD)-IgG titers in KTRs and HVs compared with the second vaccination. However, the anti-Delta-RBD-IgG and anti-Omicron-RBD-IgG titers were significantly lower than anti-Ancestral-RBD-IgG titer in KTRs and HVs after the third dose. Notably, only 25.6% (10/39) and 10.3% (4/39) of KTRs had seropositivity for anti-Delta-RBD-IgG and anti-Omicron-RBD-IgG after booster, which were significantly lower than HVs (anti-Delta-RBD-IgG: 100%, anti-Omicron-RBD-IgG: 77.8%). Ancestral strain nucleocapsid protein and spike specific T cell frequency after booster was not significantly increased in KTRs compared with the second dose, significantly lower than that in HVs. Moreover, 33.3% (12/36), 14.3% (3/21) and 14.3% (3/21) of KTRs were positive for the Ancestral strain and Delta and Omicron spike-specific T cells, which were significantly lower than HVs (Ancestral: 80.8%, Delta: 53.8%, and Omicron: 57.7%).ConclusionsA third dose of inactivated booster vaccine may significantly increase humoral immunity against the Ancestral strain in KTRs, while humoral and cellular immunity against the Delta and Omicron variants were still poor in KTRs.

Recent times witnessed an upsurge in the number of COVID19 cases which is primarily attributed to the emergence of several omicron variants, although there is substantial population vaccination coverage across the globe. Currently, many therapeutic antibodies have been approved for emergency usage. The present study critically evaluates the effect of mutations observed in several omicron variants on the binding affinities of different classes of RBD-specific antibodies using a combined approach of immunoinformatics and binding free energy calculations. Our binding affinity data clearly show that omicron variants achieve antibody escape abilities by incorporating mutations at the immunogenic hotspot residues for each specific class of antibody. K417N and Y505H point mutations are primarily accountable for the loss of class I antibody binding affinities. The K417N/Q493R/Q498R/Y505H combined mutant significantly reduces binding affinities for all the class I antibodies. E484A single mutation, on the other hand, drastically reduces binding affinities for most of the class II antibodies. E484A and E484A/Q493R double mutations cause a 33–38% reduction in binding affinity for an approved therapeutic monoclonal antibody. The Q498R RBD mutation observed across all the omicron variants can reduce ∼12% binding affinity for REGN10987, a class III therapeutic antibody, and the L452R/Q498R double mutation causes a ∼6% decrease in binding affinities for another class III therapeutic antibody, LY-CoV1404. Our data suggest that achieving the immune evasion abilities appears to be the selection pressure behind the emergence of omicron variants. [Display omitted] • Omicron variants achieve mutations at the RBD-antibody interaction hotspots residues. • Hotspot residue mutations observed in omicron variants reduce antibody binding affinities. • K417N and Y505H point mutations are primarily accountable for the loss of class I antibody binding affinities. • E484A RBD mutation causes significant loss in binding affinity with class II therapeutic mAbs. • Q498R RBD mutation reduces binding affinity for class III therapeutic mAbs. [ABSTRACT FROM AUTHOR]

Since the outbreak of COVID‑19, severe acute respiratory syndrome coronavirus 2 genome is still mutating, forming a variety of variants with strong transmission capacity, causing the spread of the epidemic worldwide, posing a serious threat to people's physical and mental health, and posing a major challenge to global public health. Omicron remains the main variant in several outbreaks worldwide, accounting for about 99% of the global genetic sequence. Recently, the World Health Organization announced that the subvariant of Omicron BA.5 has been found in more than 100 countries and regions around the world, causing the global epidemic rebound. However, there are few studies on the subvariant BA.5. This article reviews the latest research progress in epidemiology, infectivity, pathogenicity, vaccine and monoclonal antibody protection against Omicron subvariant BA.5, in order to provide reference for scientific prevention and control of Omicron subvariant BA.5. [ABSTRACT FROM AUTHOR]

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.

This study aims to analyze the neutralization ability against Omicron parental variants in five clusters of individuals with different Coronavirus disease (COVID-19) immunity backgrounds, including individuals receiving a homologous or heterologous vaccine without prior infection, recovered patients with homologous or heterologous vaccination, and recovery patients without vaccination. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surrogate virus neutralization assay was performed on serum samples. Spearman correlation analysis showed that the percent inhibition against Omicron B.1.1.529 and BA.2 was significantly related to the period of serum collection (r = 0.730 and 0.787, p < 0.001, respectively). Very strong correlation between percent inhibition of neutralizing antibody against Omicron B.1.1.529 and BA.2 variants (rs = 0.973, p < 0.001) was also observed. The neutralizing activity of the sera from recovery patients receiving homologous and heterologous vaccine against the wild-type, B.1.1.529, and BA.2 Omicron variants was significantly higher (p < 0.001) than that of recovery patients without vaccination. This study robustly showed that the breakthrough SARS-CoV-2 Omicron variant in individuals who received homologous and heterologous vaccines had a high level of neutralizing activity against B.1.1.529 and BA.2 parental lineage of XBB subvariants. Therefore, the next-generation COVID-19 vaccine against emerging variants is needed to improve resilience against ongoing variants, particularly for persons who have never been infected.