Effects of Recent Prior Dengue Infection on Risk and Severity of Subsequent SARS-CoV-2 Infection: A Retrospective Cohort Study.

Background and Aims: Elucidating whether prior dengue potentially confers cross-protection against COVID-19 is of public health importance in tropical countries at risk of overlapping dengue and COVID-19 epidemics. However, studies to date have yielded conflicting results. We aimed to assess effects of recent prior dengue infection on risk and severity of subsequent SARS-CoV-2 infection among adult Singaporeans. Methods: A retrospective cohort study including all adult Singaporeans aged ≥18 years was conducted from 1 July 2021 through 31 October 2022, when a dengue outbreak driven by the DENV3 serotype preceded subsequent waves of SARS-CoV-2 Delta/Omicron transmission in Singapore. SARS-CoV-2 and dengue infection status were classified using national registries. Cox regression models adjusted for demographics, COVID-19 vaccination status, comorbidity, and socioeconomic-status were used to assess risks and severity (hospitalization, severe illness) of SARS-CoV-2 infection occurring after previous recorded dengue infection. Results: A total of 3 366 399 individuals were included, contributing 1 399 696 530 person-days of observation. A total of 13 434 dengue infections and 1 253 520 subsequent SARS-CoV-2 infections were recorded; with an average of 94.7 days (standard deviation = 83.8) between dengue infection and SARS-CoV-2 infection. Preceding dengue infection was associated with a modest increase in risk of subsequent SARS-CoV-2 infection (adjusted hazards ratio [aHR] = 1.13; 95% confidence interval [CI], 1.08-1.17), and significantly elevated risk of subsequent COVID-19 hospitalization (aHR = 3.25; 95% CI, 2.78-3.82) and severe COVID-19 (aHR = 3.39; 95% CI, 2.29-5.03). Conclusions: Increased risk of SARS-CoV-2 infection and adverse COVID-19 outcomes were observed following preceding dengue infection in a national population-based cohort of adult Singaporeans. This observation is of significance in tropical countries with overlapping dengue and COVID-19 outbreaks.

Immunity against conserved epitopes dominates after two consecutive exposures to SARS-CoV-2 Omicron BA.1.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure histories become increasingly complex through original and variant-adapted vaccines and infections with viral variants. Upon exposure to the highly altered Omicron spike glycoprotein, pre-immunized individuals predominantly mount recall responses of Wuhan-Hu-1 (wild-type)-imprinted memory B (BMEM) cells mostly targeting conserved non-neutralizing epitopes, leading to diminished Omicron neutralization. We investigated the impact of imprinting in individuals double/triple vaccinated with a wild-type-strain-based mRNA vaccine who, thereafter, had two consecutive exposures to Omicron BA.1 spike (breakthrough infection followed by BA.1-adapted vaccine). We found that depletion of conserved epitope-recognizing antibodies using a wild-type spike bait results in strongly diminished BA.1 neutralization. Furthermore, spike-specific BMEM cells recognizing conserved epitopes are much more prevalent than BA.1-specific BMEM cells. Our observations suggest that imprinted BMEM cell recall responses limit the induction of strain-specific responses even after two consecutive BA.1 spike exposures. Vaccine adaptation strategies need to consider that prior SARS-CoV-2 infections and vaccinations may cause persistent immune imprinting.

Adult outpatients with long COVID infected with SARS-CoV-2 Omicron variant. Part 1: Oral microbiota alterations.

BACKGROUND: Many individuals experience long COVID after SARS-CoV-2 infection. As microbiota can influence health, it may change with COVID-19. This study investigated differences in oral microbiota between COVID-19 patients with and without long COVID. METHODS: Based on a prospective follow-up investigation, this nested case-control study evaluated the differences in oral microbiota in individuals with and without long COVID (Symptomatic and Asymptomatic groups), which were assessed by 16S rRNA sequencing on tongue coating samples. A predictive model was established using machine learning based on specific differential microbial communities. RESULTS: One-hundred-and-eight patients were included (n=54 Symptomatic group). The Symptomatic group had higher Alpha diversity indices (observed_otus, Chao1, Shannon, and Simpson indices), differences in microbial composition (Beta diversity), and microbial dysbiosis with increased diversity and relative abundance of pathogenic bacteria. Marker bacteria (c__Campylobacterota, o__Coriobacteriales, o__Pseudomonadales, and o__Campylobacterales) were associated with long COVID by linear discriminant analysis effect size and receiver operating characteristic curves (AUC 0.821). CONCLUSION: There were distinct variations in oral microbiota between COVID-19 patients with and without long COVID. Changes in oral microbiota may indicate long COVID.

Prevalence of infection and reinfection among healthcare workers in a hospital of Northern China between BA.5/BF. 7 and XBB.1.5 wave.

BACKGROUND: Healthcare workers (HCWs) play a crucial role as frontline responders during the COVID-19 pandemic. This study aimed to analyze the epidemiological characteristics of the first SARS-CoV-2 infection and reinfection associated with the emergence of Omicron variant in HCWs. METHODS: We enrolled 760 HCWs who received 2-4 vaccination doses of COVID-19 and followed by BA.5/BF.7 and/or XBB.1.5 breakthrough infections between December 2022 and July 2023. Serum sample from each individual were collected approximately 1,3 and 6 months after last exposure. IgM, IgG and Total antibodies against SARS-CoV-2 were measured by chemiluminescent immunoassay. Meanwhile, we created an Enterprise WeChat link for HCWs to self-report SARS-CoV-2 infections, symptoms and post COVID-19 conditions. RESULTS: Our study revealed that the reinfection rate among HCWs reached 26.1%. The main symptoms were fever (91.2% vs. 60.1%), cough (78.8% vs. 58.0%), and sore throat (75.4% vs. 59.6%) during infection and reinfection in Omicron BA.5/BF.7 and XBB.1.5 wave, and the interval for reinfection ranged from 91 to 210 days (median 152 days). Fatigue (23.6%), memory loss (18.8%) and coughing (18.6%) were the most prevalent long COVID symptoms in HCWs, with a higher prevalence among female HCWs. CONCLUSIONS: HCWs reinfection with SARS-CoV-2 causes milder symptoms, but high reinfection rate and short intervals. Enhancing prevention strategies, protection and training is crucial to mitigating HCW infection risk and improving health services.

Analysis of B-cell receptor repertoire to evaluate immunogenicity of monovalent Omicron XBB.1.5 mRNA vaccines.

Monovalent Omicron XBB.1.5 mRNA vaccines were newly developed and approved by the FDA in Autumn 2023 for preventing COVID-19. However, clinical efficacy for these vaccines is currently lacking. We previously established the quantification of antigen-specific antibody sequence (QASAS) method to assess the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination at the mRNA level using B-cell receptor (BCR) repertoire assay and the coronavirus antibody database (CoV-AbDab). Here, we used this method to evaluate the immunogenicity of monovalent XBB.1.5 vaccines. We analyzed repeated blood samples of healthy volunteers before and after monovalent XBB.1.5 vaccination (BNT162b2 XBB.1.5 or mRNA-1273.815) for the BCR repertoire to assess BCR/antibody sequences that matched SARS-CoV-2-specific sequences in the database. The number of matched unique sequences and their total reads quickly increased 1 week after vaccination. Matched sequences included those bound to the Omicron strain and Omicron XBB sublineage. The antibody sequences that can bind to the Omicron strain and XBB sublineage revealed that the monovalent XBB.1.5 vaccines showed a stronger response than previous vaccines or SARS-CoV-2 infection before the emergence of XBB sublineage. The QASAS method was able to demonstrate the immunogenic effect of monovalent XBB.1.5 vaccines for the 2023-2024 COVID-19 vaccination campaign.

Acute and long COVID-19 symptoms and associated factors in the omicron-dominant period: a nationwide survey via the online platform Wenjuanxing in China.

BACKGROUNDS: To our knowledge, there is no available nationwide data on omicron symptom patterns in China mainland. We aim to determine the acute and long COVID-19 symptoms in the omicron-dominant period and to evaluate its association with risk factors. METHODS: We designed a cross-sectional nationwide study and data about self-reported symptoms were collected by an online platform named Wenjuanxing. Eligible participants were aged 25-65 years and were symptomatic. In this study, the ratios of the number of people of different ages and genders were weighted by the data from the Seventh National Census (2020 years), and validated by a published nationwide representative study through comparing smoking rates. Descriptive indicators were calculated for demographic characteristics, diagnosis ways, and duration time, acute symptoms, hospitalization, severity and long COVID-19 symptoms. And, the associations between risk factors and acute and long COVID-19 symptoms were analyzed by multivariable logistic regression models. RESULTS: A total of 32,528 individuals diagnosed as COVID-19 infection from October 1, 2022 to February 21, 2023 were included. The first three acute symptoms of COVID-19 infection were fever (69.90%), headache (62.63%), and sore throat (54.29%), respectively. The hospitalization rate within 7 days was 3.07% and symptoms disappearance rate within 21 days was 68.84%, respectively. Among 3983 COVID-19 patients with 3 months or more time difference between first infection and participation into the study, the long COVID-19 rate was 19.68% and the primary symptoms were muscle weakness (19.39%), headache (17.98%) and smell/taste disorder (15.18%). Age groups, smoking, marriage status and vaccination were risk factors for numbers of acute phase symptoms and long COVID-19 symptoms. Lastly, female and current smokers also showed more numbers of symptoms during acute infection period. CONCLUSIONS: In Chinese mainland, our respondent indicated that current smokers and women were associated with acute COVID-19 symptoms, which should be treated with caution due to the lack of representative.

Real-world evaluation of early remdesivir in high-risk COVID-19 outpatients during Omicron including BQ.1/BQ.1.1/XBB.1.5.

BACKGROUND: A trial performed among unvaccinated, high-risk outpatients with COVID-19 during the delta period showed remdesivir reduced hospitalization. We used our real-world data platform to determine the effectiveness of remdesivir on reducing 28-day hospitalization among outpatients with mild-moderate COVID-19 during an Omicron period including BQ.1/BQ.1.1/XBB.1.5. METHODS: We did a propensity-matched, retrospective cohort study of non-hospitalized adults with SARS-CoV-2 infection between April 7, 2022, and February 7, 2023. Electronic healthcare record data from a large health system in Colorado were linked to statewide vaccination and mortality data. We included patients with a positive SARS-CoV-2 test or outpatient remdesivir administration. Exclusion criteria were other SARS-CoV-2 treatments or positive SARS-CoV-2 test more than seven days before remdesivir. The primary outcome was all-cause hospitalization up to day 28. Secondary outcomes included 28-day COVID-related hospitalization and 28-day all-cause mortality. RESULTS: Among 29,270 patients with SARS-CoV-2 infection, 1,252 remdesivir-treated patients were matched to 2,499 untreated patients. Remdesivir was associated with lower 28-day all-cause hospitalization (1.3% vs. 3.3%, adjusted hazard ratio (aHR) 0.39 [95% CI 0.23-0.67], p < 0.001) than no treatment. All-cause mortality at 28 days was numerically lower among remdesivir-treated patients (0.1% vs. 0.4%; aOR 0.32 [95% CI 0.03-1.40]). Similar benefit of RDV treatment on 28-day all-cause hospitalization was observed across Omicron periods, aOR (95% CI): BA.2/BA2.12.1 (0.77[0.19-2.41]), BA.4/5 (0.50[95% CI 0.50-1.01]), BQ.1/BQ.1.1/XBB.1.5 (0.21[95% CI 0.08-0.57]. CONCLUSION: Among outpatients with SARS-CoV-2 during recent Omicron surges, remdesivir was associated with lower hospitalization than no treatment, supporting current National Institutes of Health Guidelines.

People living with HIV with the Omicron variant infection have milder COVID-19 symptoms: results from a cross-sectional study.

BACKGROUND: China braces for coronavirus disease 2019 (COVID-19) surge after adjusting the "zero COVID" strategy. We aimed to evaluate and compare the prevalence of clinical symptoms of the Omicron variant infection among people living with HIV (PLWH) and HIV-free people. METHODS: A cross-sectional study was conducted in Wuchang District, Wuhan, Hubei Province, in December 2022 by a self-administered online survey during the Omicron wave. Participants aged ≥ 18 years with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis were recruited. PLWH managed by the local healthcare system were recruited, while HIV-free people were recruited by sending out online surveys through WeChat. We compared the prevalence of clinical symptoms of COVID-19 between PLWH and HIV-free people, and factors associated with symptom occurrence among PLWH were accessed. RESULTS: Total, 687 PLWH and 1222 HIV-free people were enrolled. After adjusting sex, age, body mass index, comorbidities and COVID-19 vaccination status, the prevalences of all symptoms, including higher degree and long duration of fever (aOR 0.51, 95%CI 0·42 - 0·61; aOR 0.52, 95%CI 0·43 - 0·63), were significantly lower among PLWH than among HIV-free people. Among PLWH, CD4+ T lymphocyte count (CD4 count) between 350 ~ 499 cells/µL and detectable HIV viral load (HIV-VL) were associated with significantly decreased risks of fever (aOR 0·63, 95%CI 0·40 - 0·97; aOR 0·56, 95%CI 0·33 - 0·94), headache (aOR 0·61, 95%CI 0·41 - 0·91; aOR 0·55, 95%CI 0·34 - 0·92) and muscle soreness (aOR 0·57, 95%CI 0·39 - 0·84; aOR 0·57, 95%CI 0·39 - 0·84). No apparent association between the symptoms prevalence and three/four doses of inactivated COVID-19 vaccination among PLWH was observed; both males and older age were associated with significantly decreased risks of nasal congestion/runny nose (aOR 0·52, 95%CI 0·32 - 0·82; aOR 0·97, 95%CI 0·96 - 0·99) and headache (aOR 0·58, 95%CI 0·36 - 0·92; aOR 0·96, 95%CI 0·95 - 0·98); older age was associated with significantly decreased risks of higher degree of fever (aOR 0·97, 95%CI 0·95 - 0·98). CONCLUSIONS: PLWH have significantly milder symptoms of the Omicron variant infection than HIV-free people. PLWH who are male, older, have low CD4 count, and detectable HIV-VL have reduced occurrence of COVID-19 symptoms. However, continuous monitoring should be conducted among PLWH during the COVID-19 pandemic.

The clinical characteristics analysis of serum markers for the cardiovascular system in early-stage COVID-19 patients.

Background: This study aimed to investigate alterations in serum markers [creatine kinase-MB (CKMB), cardiac troponin T (cTnT), myoglobin (Myo), B-type natriuretic peptide (BNP), D-dimer (DD), procalcitonin (PCT) and interleukin-6 (IL6)] in early Omicron variant infection and analyzed their correlation with clinical parameters. Methods: Retrospective analysis of 1,138 mild/asymptomatic cases at Tianjin First Central Hospital, including age, gender, serum markers and nucleic acid test results. Statistical analysis used SPSS software, version 24.0. Results: Elevated cTnT, BNP (125-400), and DD (0.55-1.10) levels were prevalent at 12.92%, 15.64%, and 14.50%, respectively. Females had significantly higher proportions with slightly elevated BNP (19.34%) and DD (19.69%) levels. Patients over 35 had a higher proportion of slight elevation in BNP (20.00%). Abnormal levels of serum markers were significantly associated with older age, increased PCT and IL6 levels, as well as delayed nucleic acid clearance. Additionally, levels of immunoglobulin G (IgG) were notably reduced in these cases. Patients with prolonged nucleic acid clearance (>14 days) had higher BNP and DD levels upon admission. Logistic regression identified PCT (OR = 237.95) as the most significant risk factor for abnormal serum markers for cardiovascular system injury. Conclusion: Early Omicron infection might do subclinical damage to the cardiovascular system. Elevated cTnT, BNP and DD levels were correlated with age, gender, inflammatory factors, and IgG. Notably, high PCT level emerged as the most robust predictor of abnormal serum biomarkers.

Clinical characteristics and outcomes of children with COVID-19 in pediatric intensive care units during the Omicron wave in Taiwan.

BACKGROUND: Since April 2022, the SARS-CoV-2 Omicron variant has caused a notable increase in pediatric COVID-19 cases in Taiwan. During the acute phase of infection, some children required admissions to pediatric intensive care units (PICU). This study aimed to analyze their clinical presentations and outcomes while exploring associated factors. METHODS: Medical records were retrospectively collected from patients with COVID-19 (aged <18 years) admitted to our PICU from April 2022-March 2023. Early stage is defined as the period without adequate vaccination and treatment guidelines for children from April-June 2022, and the remaining months are referred to as late stage. Clinical characteristics and outcomes were compared between patients in early and late stages. RESULTS: We enrolled 78 children with COVID-19, with a median length of stay (LOS) in PICU of 3 days and a 5% mortality rate. Patients admitted during the early stage had lower vaccination rates (7% vs. 50%), higher pediatric logistic organ dysfunction scores (2 vs. 0.1), and longer LOS in the PICU (6 vs. 2 days) than those admitted during the late stage. Multivariate analysis identified admission during the early stage as a risk factor for prolonged LOS (>7 days) in the PICU (odds ratio: 3.65, p = 0.047). CONCLUSION: Without available vaccinations and suitable treatment guidelines, children with COVID-19 tended to have more severe illness and prolonged LOS in the PICU. These observations highlight the importance of vaccinations and familiarity of medical providers with adequate management of this newly-emerging infectious disease.

Impact of corticosteroid doses on prognosis of severe and critical COVID-19 patients with Omicron variant infection: a propensity score matching study.

BACKGROUND: There is lack of research on corticosteroid use for severe and critical COVID-19 patients with Omicron variant infection. METHODS: This multi-center retrospective cohort study involved 1167 patients from 59 ICUs across the mainland of China diagnosed with severe or critical SARS-CoV-2 Omicron variant infection between November 1, 2022, and February 11, 2023. Patients were segregated into two groups based on their corticosteroid treatment-usual dose (equivalent prednisone dose 30-50 mg/day) and higher dose (equivalent prednisone dose > 50 mg/day). The primary outcome was 28-day ICU mortality. Propensity score matching was used to compare outcomes between cohorts. RESULTS: After propensity score matching, 520 patients in the usual dose corticosteroid group and 260 patients in the higher dose corticosteroid group were included in the analysis, respectively. The mortality was significantly higher in the higher dose corticosteroid group (67.3%, 175/260) compared to the usual dose group (56.0%, 291/520). Logistic regression showed that higher doses of corticosteroids were significantly associated with increased mortality at 28-day (OR = 1.62,95% CI 1.19-2.21, p = 0.002) and mortality in ICU stay (OR = 1.66,95% CI 1.21-2.28, p = 0.002). Different types of corticosteroids did not affect the effect. CONCLUSIONS: The study suggests that higher-dose corticosteroids may lead to a poorer prognosis for severe and critical COVID-19 patients with Omicron variant infection in the ICU. Further research is needed to determine the appropriate corticosteroid dosage for these patients.

Association of coinfections with differences in outcomes across COVID-19 variants.

Background: In previous studies, there was an increase in mortality with secondary coinfections in all COVID-19 variants. However, no prior study has explored the association of coinfection with outcomes of hospitalized patients among the COVID-19 variants (Alpha, Delta, and Omicron). Methods: This observational cohort study involved 21,186 patients hospitalized with COVID-19 in 25 hospitals in Texas. Patients were divided into groups by surges of COVID-19: Alpha (November 1, 2020-February 10, 2021), Delta (July 10, 2021-October 14, 2021), and Omicron (December 21, 2021-March 3, 2022). Data were collected from electronic health records using methodology from the Viral Respiratory Illness Universal Study COVID-19 registry (NCT04323787) of COVID-19 hospitalizations. Multivariable Cox-proportional hazard regression model assessed the adjusted effect of different surge periods on mortality. Results: Bacterial coinfections varied among hospitalization surges associated with Alpha (8.5%), Delta (11.7%), and Omicron (11.9%) variants. Adjusted analyses showed a higher 30-day and 90-day mortality in all variants when coinfections were present compared with isolated COVID-19 infection. In particular, 30-day and 90-day mortality were significantly worse with Delta compared to Alpha and Omicron. Conclusions: All variants were associated with a higher mortality when bacterial coinfections were present. Delta was associated with a higher risk-adjusted mortality at 30 days and thereafter.

Hospitalized children with COVID-19 infection during large outbreak of SARS-CoV-2 Omicron strain: a retrospective study in Chaozhou, Guangdong, China.

OBJECTIVE: We aimed to investigate the clinical findings of hospitalized paediatric COVID-19 patients by the end of 2022. METHOD: All confirmed children with COVID-19 infection admitted into Chaozhou Central Hospital during the COVID-19 outbreak from 19 December 2022 to 1 February 2023 were included. Detailed clinical data of those children were evaluated retrospectively. RESULTS: A total of 286 children, ranging in age from 1 month to 13 years old, were diagnosed with SARS-CoV-2 infection. Among these cases, 138 (48.3%) were categorized as mild, 126 (44.0%) as moderate and 22 (7.7%) as severe/critical. Symptoms varied among the children and included fever, upper respiratory tract symptoms, convulsions, sore throat, poor appetite, dyspnoea and gastrointestinal symptoms. Notably, febrile convulsions were observed in 96 (33.6%) patients, while acute laryngitis was documented in 50 (17.5%) cases. Among the severe/critical patients, eight developed multisystem inflammatory syndrome in children (MIS-C), and tragically, one patient's condition worsened and resulted in death. Furthermore, MRI scans revealed abnormal brain signals in six severe/critical patients. The severe/critical group also exhibited more pronounced laboratory abnormalities, including decreased haemoglobin and elevated ALT, AST, LDH and CK levels. CONCLUSIONS: Febrile convulsions and acute laryngitis are frequently observed in children diagnosed with SARS-CoV-2 Omicron infection. Moreover, MIS-C and abnormal neuroimaging appear to be relatively common phenomena in severe/critical cases.

Social Vulnerability and Compliance With World Health Organization Advice on Protective Behaviors Against COVID-19 in African and Asia Pacific Countries: Factor Analysis to Develop a Social Vulnerability Index.

BACKGROUND: COVID-19 protective behaviors are key interventions advised by the World Health Organization (WHO) to prevent COVID-19 transmission. However, achieving compliance with this advice is often challenging, particularly among socially vulnerable groups. OBJECTIVE: We developed a social vulnerability index (SVI) to predict individuals' propensity to adhere to the WHO advice on protective behaviors against COVID-19 and identify changes in social vulnerability as Omicron evolved in African countries between January 2022 and August 2022 and Asia Pacific countries between August 2021 and June 2022. METHODS: In African countries, baseline data were collected from 14 countries (n=15,375) during the first Omicron wave, and follow-up data were collected from 7 countries (n=7179) after the wave. In Asia Pacific countries, baseline data were collected from 14 countries (n=12,866) before the first Omicron wave, and follow-up data were collected from 9 countries (n=8737) after the wave. Countries' socioeconomic and health profiles were retrieved from relevant databases. To construct the SVI for each of the 4 data sets, variables associated with COVID-19 protective behaviors were included in a factor analysis using polychoric correlation with varimax rotation. Influential factors were adjusted for cardinality, summed, and min-max normalized from 0 to 1 (most to least vulnerable). Scores for compliance with the WHO advice were calculated using individuals' self-reported protective behaviors against COVID-19. Multiple linear regression analyses were used to assess the associations between the SVI and scores for compliance to WHO advice to validate the index. RESULTS: In Africa, factors contributing to social vulnerability included literacy and media use, trust in health care workers and government, and country income and infrastructure. In Asia Pacific, social vulnerability was determined by literacy, country income and infrastructure, and population density. The index was associated with compliance with the WHO advice in both time points in African countries but only during the follow-up period in Asia Pacific countries. At baseline, the index values in African countries ranged from 0.00 to 0.31 in 13 countries, with 1 country having an index value of 1.00. The index values in Asia Pacific countries ranged from 0.00 to 0.23 in 12 countries, with 2 countries having index values of 0.79 and 1.00. During the follow-up phase, the index values decreased in 6 of 7 African countries and the 2 most vulnerable Asia Pacific countries. The index values of the least vulnerable countries remained unchanged in both regions. CONCLUSIONS: In both regions, significant inequalities in social vulnerability to compliance with WHO advice were observed at baseline, and the gaps became larger after the first Omicron wave. Understanding the dimensions that influence social vulnerability to protective behaviors against COVID-19 may underpin targeted interventions to enhance compliance with WHO recommendations and mitigate the impact of future pandemics among vulnerable groups.

First SARS-CoV-2 Omicron infection as an effective immune booster among mRNA vaccinated individuals: final results from the first phase of the PRIBIVAC randomised clinical trial.

BACKGROUND: Understanding how SARS-CoV-2 breakthrough infections impacts the breadth of immune responses against existing and pre-emergent SARS-CoV-2 strains is needed to develop an evidence-based long-term immunisation strategy. METHODS: We performed a randomised, controlled trial to assess the immunogenicity of homologous (BNT162b2) versus heterologous (mRNA-1273) booster vaccination in 100 BNT162b2-vaccinated infection-naïve individuals enrolled from October 2021. Post hoc analysis was performed to assess the impact of SARS-CoV-2 infection on humoral and cellular immune responses against wild-type SARS-CoV-2 and/or Omicron subvariants. FINDINGS: 93 participants completed the study at day 360. 71% (66/93) of participants reported first SARS-CoV-2 Omicron infection by the end of the study with similar proportions of infections between homologous and heterologous booster groups (72.3% [34/47] vs 69.6% [32/46]; p = 0.82). Mean wildtype SARS-CoV-2 anti-S-RBD antibody level was significantly higher in heterologous booster group compared with homologous group at day 180 (14,588 IU/mL; 95% CI, 10,186-20,893 vs 7447 IU/mL; 4646-11,912; p = 0.025). Participants who experienced breakthrough infections during the Omicron BA.1/2 wave had significantly higher anti-S-RBD antibody levels against wildtype SARS-CoV-2 and antibody neutralisation against BA.1 and pre-emergent BA.5 compared with infection-naïve participants. Regardless of hybrid immunity status, wildtype SARS-CoV-2 anti-S-RBD antibody level declined significantly after six months post-booster or post-SARS-CoV-2 infection. INTERPRETATION: Booster vaccination with mRNA-1273 was associated with significantly higher antibody levels compared with BNT162b2. Antibody responses are narrower and decline faster among uninfected, vaccinated individuals. Boosters may be more effective if administered shortly before infection outbreaks and at least six months after last infection or booster. FUNDING: Singapore NMRC, USFDA, MRC.

The Development of Epitope-Based Recombinant Protein Vaccines against SARS-CoV-2.

The COVID-19 pandemic continues to cause infections and deaths, which are attributable to the SARS-CoV-2 Omicron variant of concern (VOC). Moderna's response to the declining protective efficacies of current SARS-CoV-2 vaccines against Omicron was to develop a bivalent booster vaccine based on the Spike (S) protein from the Wuhan and Omicron BA.4/BA.5 strains. This approach, while commendable, is unfeasible in light of rapidly emerging mutated viral strains. PubMed and Google Scholar were systematically reviewed for peer-reviewed papers up to January 2024. Articles included focused on specific themes such as the clinical history of recombinant protein vaccine development against different diseases, including COVID-19, the production of recombinant protein vaccines using different host expression systems, aspects to consider in recombinant protein vaccine development, and overcoming problems associated with large-scale recombinant protein vaccine production. In silico approaches to identify conserved and immunogenic epitopes could provide broad protection against SARS-CoV-2 VOCs but require validation in animal models. The recombinant protein vaccine development platform has shown a successful history in clinical development. Recombinant protein vaccines incorporating conserved epitopes may utilize a number of expression systems, such as yeast (Saccharomyces cerevisiae), baculovirus-insect cells (Sf9 cells), and Escherichia coli (E. coli). Current multi-epitope subunit vaccines against SARS-CoV-2 utilizing synthetic peptides are unfeasible for large-scale immunizations. Recombinant protein vaccines based on conserved and immunogenic proteins produced using E. coli offer high production yields, convenient purification, and cost-effective production of large-scale vaccine quantities capable of protecting against the SARS-CoV-2 D614G strain and its VOCs.

Pre- and post-Ad26.COV2·S booster dose antibody levels predict COVID-19 disease risk.

Identifying immune correlates of risk following COVID-19 vaccine boosters has become paramount as a result of the challenges in generating additional efficacy data. The trial data described here was collected in the United States, with a large part of the study conduct coinciding with the emergence of the SARS-CoV-2 Omicron BA.1 variant. The vaccine trial involved the administration of a booster dose of Ad26.COV2·S at least 6 months after primary vaccination with either a single dose of Ad26.COV2·S or a 2-dose BNT162b2 vaccine regimen. Immunogenicity was assessed through Wuhan Spike binding antibodies (bAb), neutralizing antibodies (nAb), and Omicron BA.1 cross-neutralizing antibodies (nAb BA.1) at Day 1 (pre-boost), Day 15-, and 6-months post-boost. Immune correlates analyses demonstrate that, higher titers of bAb, nAb, and nAb BA.1 at Day 15 were consistently associated with a lower risk of symptomatic COVID-19 following a booster dose of Ad26.COV2·S, irrespective of the primary vaccine regimen. Similar results were obtained using multivariable analyses. Furthermore, Day 1 nAb levels against the Wuhan reference strain exhibited a statistically significant inverse relationship with the risk of symptomatic COVID-19. These findings highlight the value of assessing immune correlates for vaccine boosters, especially in the context of emerging SARS-CoV-2 variants. Clinical trials registration:NCT04999111.

SARS-CoV-2 variants divergently infect and damage cardiomyocytes in vitro and in vivo.

BACKGROUND: COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear. METHODS: The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo. RESULTS: Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs. CONCLUSIONS: In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.

A potent, broadly neutralizing human monoclonal antibody that efficiently protects hACE2-transgenic mice from infection with the Wuhan, BA.5, and XBB.1.5 SARS-CoV-2 variants.

The COVID-19 pandemic has uncovered the high genetic variability of the SARS-CoV-2 virus and its ability to evade the immune responses that were induced by earlier viral variants. Only a few monoclonal antibodies that have been reported to date are capable of neutralizing a broad spectrum of SARS-CoV-2 variants. Here, we report the isolation of a new broadly neutralizing human monoclonal antibody, iC1. The antibody was identified through sorting the SARS-CoV-1 RBD-stained individual B cells that were isolated from the blood of a vaccinated donor following a breakthrough infection. In vitro, iC1 potently neutralizes pseudoviruses expressing a wide range of SARS-CoV-2 Spike variants, including those of the XBB sublineage. In an hACE2-transgenic mouse model, iC1 provided effective protection against the Wuhan strain of the virus as well as the BA.5 and XBB.1.5 variants. Therefore, iC1 can be considered as a potential component of the broadly neutralizing antibody cocktails resisting the SARS-CoV-2 mutation escape.

Immune and inflammation features of severe and critical Omicron infected patients during Omicron wave in China.

OBJECTIVE: The current study aimed to investigate the baseline immune and inflammatory features and in-hospital outcomes of patients infected with the Omicron variant (PIWO) who presented with different disease severities during the first wave of mass Omicron infections in the Chinese population has occurred. METHOD: A cross-sectional study was conducted on 140 hospitalized PIWO between December 11, 2022, and February 16, 2023. The clinical features, antibodies against SARS-CoV-2, immune cells, and inflammatory cytokines among mildly, severely, and critically ill PIWO at baseline and during follow-up period were compared. RESULT: Patients with severe (n = 49) and critical (n = 35) disease were primarily male, needed invasive mechanical ventilation treatment, and exhibited higher mortality than those with mild disease (n = 56). During acute infection, SARS-CoV-2-specific antibody levels fluctuated with disease severity, serum antibodies increased and the incidence of severe cases decreased in critically ill PIWO over time. Antibody titers in severe or critical PIWO with no antibody responses at baseline did not increase significantly over time. Meanwhile, CD4+T cell, CD8+T cell, and natural killer cell counts were negatively correlated with disease severity, whereas interleukin (IL)-6 and IL-10 levels were positively correlated. In addition, combined diabetes, immunosuppressive therapy before infection, serum amyloid A, IL-10 and neutrophil counts were independently associated with severe and critical illness in PIWO. Among the 11 nonsurvivors, 8, 2, 1 died of respiratory failure, sudden cardiac death, and renal failure, respectively. Compared with survivors, nonsurvivors exhibited lower seropositivity of SARS-CoV-2-specific antibody, reduced CD3+T and CD4+T cell counts, and higher IL-2R, IL-6, IL-8, and IL-10 levels. Of note, lactate dehydrogenase was a significant risk factor of death in severe or critically ill PIWO. CONCLUSION: This present study assessed the dynamic changes of SARS-CoV-2-specific antibodies, immune cells and inflammatory indexes between severely and critically ill PIWO. Critical and dead PIWO featured compromised humoral immune response and excessive inflammation, which broadened the understanding of the pathophysiology of Omicron infection and provides warning markers for severe disease and poor prognosis.