Delta Infection Research Articles

Apulian infectious diseases network: survey on the prevalence of delta infection among chronic HBV carriers in Apulia.

The current prevalence and clinical burden of Hepatitis Delta Virus (HDV) infection in Apulia are unknown. This study aimed to define the current epidemiological scenario of delta infection and to detect difficulties in the diagnosis and clinical management of HDV patients in Apulia. From May to September 2022, a fact-finding survey was conducted at eight Infectious Diseases Units of the Apulian region; each Unit was asked to complete a questionnaire on screening and diagnosis of HDV infection and demographic, virological, and clinical characteristics of HDV patients. A total of 1,461 HBsAg-positive subjects were followed up on an outpatient basis. Screening for HDV ranged from 30 to 90% of HBsAg + carriers in a single center. Overall, 952 HBsAg ± subjects (65%) were tested for HDV, and 80/952 (8.4%) were anti-HDV positive. Serum HDV RNA was detected only in 15/80 (19%) anti-HDV-positive subjects, and 12/15 patients (80%) were viremic. Sixty-five anti-HDV-positive subjects (81%) were from Italy; risk factors for HDV acquisition included the presence of HDV infection in the family (29/80 = 36%), drug addiction (12/80 = 15%), and co-infection with HCV or HIV (7/80 = 9%). Liver cirrhosis and hepatocellular carcinoma were diagnosed in 41 (51%) and 4 (5%) patients, respectively. Fifty-seven patients (71%) received nucleos(t)ide analog treatment. The results of this survey show that HDV screening is variable and insufficient, thus real prevalence data on delta infection are lacking in Apulia. Moreover, the HDV RNA test is not available in most laboratories and is not provided by the national health system. These results underline the need for an organizational model to optimize the management of HDV patients throughout the Apulian region.

Antibody correlates of protection against Delta infection after vaccination: A nested case-control within the UK-based SIREN study

To investigate serological correlates of protection against SARS-CoV-2 B.1.617.2 (Delta) infection after two vaccinations. We performed a case-control study, where cases were Delta infections after the second vaccine dose and controls were vaccinated, never infected participants, matched by age, gender and region. Sera were tested for anti-SARS-CoV-2 Spike antibody levels (anti-S) and neutralising antibody titres (nAbT), using live virus microneutralisation against Ancestral, Delta and Omicron (BA.1, B.1.1.529). We modelled the decay of anti-S and nAbT for both groups, inferring levels at matched calendar times since the second vaccination. We assessed differences in inferred antibody titres between groups and used conditional logistic regression to explore the relationship between titres and odds of infection. In total, 130 sequence-confirmed Delta cases and 318 controls were included. Anti-S and Ancestral nAbT decayed similarly between groups, but faster in cases for Delta nAbT (p=0.02) and Omicron nAbT (p=0.002). At seven days before infection, controls had higher anti-S levels (p<0.0001) and nAbT (p<0.0001; all variants) at matched calendar time. A two-fold increase in anti-S levels was associated with a 29% ([95% CI 14-42%]; p=0.001) reduction in odds of Delta infection. Delta nAbT>40 were associated with reduced odds of Delta infection (89%, [69-96%]; p<0.0001), with additional benefits for titres >100 (p=0.009) and >400 (p=0.007). We have identified correlates of protection against SARS-CoV-2 Delta, with potential implications for vaccine deployment, development, and public health response.

The emergence of SARS-CoV-2 lineages and associated saliva antibody responses among asymptomatic individuals in a large university community.

SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig)-as generated by the immune system following infection or vaccination-has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG), and ACE2 binding inhibition capacity in asymptomatic individuals between January 2021 and May 2022. These data were generated as part of a large university COVID monitoring program in Ohio, United States of America, and demonstrate that COVID incidence among asymptomatic individuals occurred in waves which mirrored those in surrounding regions, with saliva CoV2 viral loads becoming progressively higher in our community until vaccine mandates were established. Among the unvaccinated, infection with each CoV2 lineage (pre-Omicron) resulted in saliva Spike-specific IgM, IgA, and IgG responses, the latter increasing significantly post-infection and being more pronounced than N-specific IgG responses. Vaccination resulted in significantly higher Spike-specific IgG levels compared to unvaccinated infected individuals, and uninfected vaccinees' saliva was more capable of inhibiting Spike function. Vaccinees with breakthrough Delta infections had Spike-specific IgG levels comparable to those of uninfected vaccinees; however, their ability to inhibit Spike binding was diminished. These data are consistent with COVID vaccines having achieved hoped-for effects in our community, including the generation of mucosal antibodies that inhibit Spike and lower community viral loads, and suggest breakthrough Delta infections were not due to an absence of vaccine-elicited Ig, but instead limited Spike binding activity in the face of high community viral loads.

Determinants of protection against SARS-CoV-2 Omicron BA.1 and Delta infections in fully vaccinated outpatients.

We aimed to evaluate the association between the humoral and cellular immune responses and symptomatic SARS-CoV-2 infection with Delta or Omicron BA.1 variants in fully vaccinated outpatients. Anti-receptor binding domain (RBD) IgG levels and interferon-gamma (IFN-γ) release were evaluated at PCR-diagnosis of SARS-CoV-2 in 636 samples from negative and positive patients during Delta and Omicron BA.1 periods. Median levels of anti-RBD IgG in positive patients were significantly lower than in negative patients for both variants (p < 0.05). The frequency of Omicron BA.1 infection in patients with anti-RBD IgG concentrations ≥1000 binding antibody units (BAU)/mL was 51.0% and decreased to 34.4% in patients with concentrations ≥3000 BAU/mL. For Delta infection, the frequency of infection was significantly lower when applying the same anti-RBD IgG thresholds (13.3% and 5.3% respectively, p < 0.05). In addition, individuals in the hybrid immunity group had a 4.5 times lower risk of Delta infection compared to the homologous vaccination group (aOR = 0.22, 95% CI: [0.05-0.64]. No significant decrease in the risk of Omicron BA.1 infection was observed in the hybrid group compared to the homologous group, but the risk decreased within the hybrid group as anti-RBD IgG titers increased (aOR = 0.08, 95% CI: [0.01-0.41], p = 0.008). IFN-γ release post-SARS-CoV-2 peptide stimulation was not different between samples from patients infected (either with Delta or Omicron BA.1 variant) or not (p > 0.05). Our results show that high circulating levels of anti-RBD IgG and hybrid immunity were independently associated with a lower risk of symptomatic SARS-CoV-2 infection in outpatients with differences according to the infecting variant (www.clinicaltrials.gov; ID NCT05060939).

Effects of previous infection, vaccination, and hybrid immunity against symptomatic Alpha, Beta, and Delta SARS-CoV-2 infections: an observational study

Protection against SARS-CoV-2 symptomatic infection and severe COVID-19 of previous infection, mRNA two-dose vaccination, mRNA three-dose vaccination, and hybrid immunity of previous infection and vaccination were investigated in Qatar for the Alpha, Beta, and Delta variants. Six national, matched, test-negative, case-control studies were conducted between January 18 and December 18, 2021 on a sample of 239,120 PCR-positive tests and 6,103,365 PCR-negative tests. Effectiveness of previous infection against Alpha, Beta, and Delta reinfection was 89.5% (95% CI: 85.5-92.3%), 87.9% (95% CI: 85.4-89.9%), and 90.0% (95% CI: 86.7-92.5%), respectively. Effectiveness of two-dose BNT162b2 vaccination against Alpha, Beta, and Delta infection was 90.5% (95% CI, 83.9-94.4%), 80.5% (95% CI: 79.0-82.0%), and 58.1% (95% CI: 54.6-61.3%), respectively. Effectiveness of three-dose BNT162b2 vaccination against Delta infection was 91.7% (95% CI: 87.1-94.7%). Effectiveness of hybrid immunity of previous infection and two-dose BNT162b2 vaccination was 97.4% (95% CI: 95.4-98.5%) against Beta infection and 94.5% (95% CI: 92.8-95.8%) against Delta infection. Effectiveness of previous infection and three-dose BNT162b2 vaccination was 98.1% (95% CI: 85.7-99.7%) against Delta infection. All five forms of immunity had >90% protection against severe, critical, or fatal COVID-19 regardless of variant. Similar effectiveness estimates were observed for mRNA-1273. A mathematical model accurately predicted hybrid immunity protection by assuming that the individual effects of previous infection and vaccination acted independently. Hybrid immunity, offering the strongest protection, was mathematically predicted by assuming that the immunities obtained from previous infection and vaccination act independently, without synergy or redundancy. The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114.

Immune responses in COVID-19 patients during breakthrough infection with SARS-CoV-2 variants Delta, Omicron-BA.1 and Omicron-BA.5.

Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are increasingly observed in vaccinated individuals. Immune responses towards SARS-CoV-2 variants, particularly Omicron-BA.5, are poorly understood. We investigated the humoral and cellular immune responses of hospitalized COVID-19 patients during Delta and Omicron infection waves. The corresponding SARS-CoV-2 variant of the respective patients were identified by whole genome sequencing. Humoral immune responses were analyzed by ELISA and a cell culture-based neutralization assay against SARS-CoV-2 D614G isolate (wildtype), Alpha, Delta (AY.43) and Omicron (BA.1 and BA.5). Cellular immunity was evaluated with an IFN-γ ELISpot assay. On a cellular level, patients showed a minor IFN-γ response after stimulating PBMCs with mutated regions of SARS-CoV-2 variants. Neutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced. Double-vaccinated patients with Delta breakthrough infection showed a significantly increased neutralizing antibody response against Delta compared to double-vaccinated uninfected controls (median complete neutralization titer (NT100) 640 versus 80, p<0.05). Omicron-BA.1 infection increased neutralization titers against BA.1 in double-vaccinated patients (median NT100 of 160 in patients versus 20 in controls, p=0.07) and patients that received booster vaccination (median NT100 of 50 in patients versus 20 in controls, p=0.68). For boosted patients with BA.5 breakthrough infection, we found no enhancing effect on humoral immunity against SARS-CoV-2 variants. Neutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced in SARS-CoV-2 breakthrough infections. Delta and Omicron-BA.1 but not Omicron-BA.5 infections boosted the humoral immunity in double-vaccinated patients and patients with booster vaccination. Despite BA.5 breakthrough infection, those patients may still be vulnerable for reinfections with BA.5 or other newly emerging variants of concern.

Engineered Intranasal Virus Trap Provides Effective Protection Against SARS‐CoV‐2 Infection in Hamsters

AbstractAs face masks are no longer required in many public areas, SARS‐CoV‐2 continues to spread and pose health risks to vulnerable populations such as children, the elderly, and immunocompromised individuals. This study presents the development of an Fn‐LCB1‐based engineered intranasal virus trap (EIVT) designed to capture and neutralize multiple SARS‐CoV‐2 variants, limiting viral infection and transmission. Fn‐LCB1, a fusion protein consisting of an Fn domain that binds to fibronectin and an LCB1 domain with high affinity for the Spike protein receptor‐binding domain (RBD) of SARS‐CoV‐2 viruses, can be produced on a large scale and purified in soluble form with high thermal stability. In vitro experiments demonstrated the efficient neutralization of SARS‐CoV‐2 wildtype and several variants, including Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529) by Fn‐LCB1. Additionally, Fn‐LCB1 effectively protected against SARS‐CoV‐2 Delta infection in a noncontact viral transmission Syrian hamster model. This study establishes Fn‐LCB1 as a potent prophylactic agent against SARS‐CoV‐2 in vitro and in vivo, and serves as a proof‐of‐concept for the application of intranasal proteins to capture respiratory viruses and reduce live cell infections by competing with viral receptors.

Post COVID-19 condition after delta infection and omicron reinfection in children and adolescents.

The burden of COVID-19 in children and adolescents has increased during the delta and omicron waves, necessitating studies of long-term symptoms such as fatigue, dyspnoea and cognitive problems. Furthermore, immune responses in relation to persisting symptoms in younger people have not been well characterised. In this cohort study, we investigated the role of antibodies, vaccination and omicron reinfection upon persisting and long-term symptoms up to 8 months post-delta infection. SARS-CoV-2 RT-PCR positive participants (n=276, aged 10-20 years) were prospectively recruited in August 2021. We recorded the major symptoms of post COVID-19 condition and collected serum samples 3- and 8-months post delta infection. Binding antibodies were measured by spike IgG ELISA, and surrogate neutralising antibodies against Wuhan and delta variants by the hemagglutination test (HAT). After delta infection, persisting symptoms at 3 months were significantly associated with higher delta antibody titres (OR 2.97, 95% CI 1.57-6.04, p=0.001). Asymptomatic acute infection compared to symptomatic infection lowered the risk of persisting (OR 0.13, 95% CI 0.02-0.55, p=0.013) and long-term (OR 0.28 95% CI 0.11-0.66, p=0.005) symptoms at 3 and 8 months, respectively. Adolescents (16-20 years) were more likely to have long-term symptoms compared to children (10-15 years) (OR 2.44, 95% CI 1.37-4.41, p=0.003). This clinical and serological study compares long-term symptoms after delta infection between children and adolescents. The association between high antibody titres and persisting symptoms suggest the involvement of an immune mechanism. Similarly to adults, the dominant long-term symptoms in children are fatigue, dyspnoea and cognitive problems. This work was funded by the Ministry of Health and Care Services, Norway, the University of Bergen, Norway and Helse Vest, Norway (F-12621).

Comparative spatial transcriptomic profiling of severe acute respiratory syndrome coronavirus 2 Delta and Omicron variants infections in the lungs of cynomolgus macaques.

Recently emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants are generally less pathogenic than previous strains. However, elucidating the molecular basis for pulmonary immune response alterations is challenging owing to the virus's heterogeneous distribution within complex tissue structure. Here, we revealed the spatial transcriptomic profiles of pulmonary microstructures at the SARS-CoV-2 infection site in the nine cynomolgus macaques upon inoculation with the Delta and Omicron variants. Delta- and Omicron-infected lungs had upregulation of genes involved in inflammation, cytokine response, complement, cell damage, proliferation, and differentiation pathways. Depending on the tissue microstructures (alveoli, bronchioles, and blood vessels), there were differences in the types of significantly upregulated genes in each pathway. Notably, a limited number of genes involved in cytokine and cell damage response were differentially expressed between bronchioles of the Delta- and Omicron-infection groups. These results indicated that despite a significant antigenic shift in SARS-CoV-2, the host immune response mechanisms induced by the variants were relatively consistent, with limited transcriptional alterations observed only in large airways. This study may aid in understanding the pathogenesis of SARS-CoV-2 and developing a clinical strategy for addressing immune dysregulation by identifying potential transcriptional biomarkers within pulmonary microstructures during infection with emerging variants.

WED-190 - The prognosis of hepatitis delta infections in Belgium is poor and determined by the hepatitis delta viremia

WED-190 - The prognosis of hepatitis delta infections in Belgium is poor and determined by the hepatitis delta viremia

Evolution of SARS-CoV-2 variants of concern over a period of Delta and Omicron cocirculation, among patients hospitalized for COVID-19 in an Italian reference hospital: Impact on clinical outcomes.

Despite the higher transmissibility of Omicron Variant of Concern (VOC), several reports have suggested lower risk for hospitalization and severe outcomes compared to previous variants of SARS-CoV-2. This study, enrolling all COVID-19 adults admitted to a reference hospital who underwent both the S-gene-target-failure test and VOC identification by Sanger sequencing, aimed to describe the evolving prevalence of Delta and Omicron variants and to compare the main in-hospital outcomes of severity, during a trimester (December 2021 to March 2022) of VOCs' cocirculation. Factors associated with clinical progression to noninvasive ventilation (NIV)/mechanical ventilation (MV)/death within 10 days and to MV/admission to intensive care unit (ICU)/death within 28 days, were investigated through multivariable logistic regressions. Overall, VOCs were: Delta n = 130/428, Omicron n = 298/428 (sublineages BA.1 n = 275 and BA.2 n = 23). Until mid-February, Delta predominance shifted to BA.1, which was gradually displaced by BA.2 until mid-March. Participants with Omicron VOC were more likely to be older, fully vaccinated, with multiple comorbidities and to have a shorter time from symptoms' onset, and less likely to have systemic symptoms and respiratory complications. Although the need of NIV within 10 days and MV within 28 days from hospitalization and the admission to ICU were less frequent for patients with Omicron compared to those with Delta infections, mortality was similar between the two VOCs. In the adjusted analysis, multiple comorbidities and a longer time from symptoms' onset predicted 10-day clinical progression, while complete vaccination halved the risk. Multimorbidity was the only risk factor associated with 28-day clinical progression. In our population, in the first trimester of 2022, Omicron rapidly displaced Delta in COVID-19 hospitalized adults. Clinical profile and presentation differed between the two VOCs and, although Omicron infections showed a less severe clinical picture, no substantial differences for clinical progression were found. This finding suggests that any hospitalization, especially in more vulnerable individuals, may be at risk for severe progression, which is more related to the underlying frailty of patients than to the intrinsic severity of the viral variant.

Investigation of Clinical Manifestations and Laboratory Findings of COVID-19 During National Peaks of Alpha, Beta, Delta, and Omicron in the Pediatric Emergency Department of Mofid Children's Hospital, Tehran, Iran

Background: The global spread of the coronavirus since 2019 has caused significant concern. Objectives: In this study, we aimed to investigate the clinical manifestations and laboratory findings of children infected with the alpha, beta, delta, and omicron strains. Methods: We included all patients who were referred to Mofid Children's Hospital during the peak of the alpha strain in November 2020, the beta strain in April 2021, the delta strain in August 2021, and the omicron strain in February 2022, corresponding to the national peaks of four SARS-CoV-2 variants of concern (VOC). All patients had a positive nasopharyngeal PCR test and were admitted to the emergency ward. We analyzed the collected data using SPSS software. Results: A total of 649 patients were included in this survey, of whom 58.1% were male. The most and least frequent clinical manifestations were fever and skin presentation, respectively. The mean white blood cell count (WBC) was 8423.9 ± 5427.3. The mean values for C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were 30.14 ± 20.07 and 38 ± 22.6, respectively. There was no significant association between coronavirus type, age, and gender. Gastroenteritis, urinary tract infection, and croup showed a statistically significant positive correlation with delta, beta, and omicron (P-values of &lt; 0.003, 0.000, and 0.000, respectively). Cough was more frequent in patients infected with alpha and beta subtypes, while lymphocyte counts were elevated in patients suffering from delta, omicron, and alpha. C-reactive protein and ESR levels were significantly increased in patients with delta infection, and in patients with omicron infection, CRP levels were significantly elevated. Conclusions: Our study revealed that the different strains of COVID-19, corresponding to the World Health Organization (WHO) peak of VOCs, can cause variable clinical symptoms in children. These findings could be helpful in the diagnosis of COVID-19.

HDV RNA Levels and Progression of Hepatitis Delta Infection: A 14 Year Follow Up Experience in Italy

Background: Identification of outcome predictors is one of the unmet needs in chronic HDV infection. Until recently, no reliable quantitative assays for HDV RNA were available. Aims: To evaluate the impact of baseline viremia on natural history of HDV infection in a cohort of patients whose serum samples were stored at their first visit 15 years ago. Methods: Quantitative HBsAg, HBeAg, HBeAb, HBV DNA, HDV RNA, genotypes, and liver disease severity were assessed at baseline. Patients who were no longer on active follow-up were recalled and re-evaluated in August 2022. Results: The majority of patients were male (64.9%); the median age was 50.1 years; and all patients were Italian, with only three born in Romania. All were HBeAg negative with HBV genotype D infection. Patients were subdivided three groups: 23 were in active follow-up (Group 1), 21 were recalled due to no longer being in follow-up (Group 2), and 11 died (Group 3). Liver cirrhosis was diagnosed in 28 subjects at the first visit; 39.3% of diagnosed patients were in Group 3, 32.1% were in Group 1 and 28.6% were in Group 2 (p = 0.001). Baseline HBV DNA IU/mL Log10 were 1.6 (1.0–5.9) in Group 1, 1.3 (1.0–4.5) in Group 2, and 4.1 (1.5–4.5) in Group 3; median baseline HDV RNA Log10 levels were 4.1 (0.7–6.7) in Group 1, 3.2 (0.7–6.2) in Group 2, and 5.2 (0.7–6.7) in Group 3, resulting significantly higher rates among patients in Group 3 compared to the other groups (p = 0.038). Eighteen patients in Group 2, as compared to 7 in Group 1, had undetectable HDV RNA at the follow-up evaluation (p = 0.001). Conclusions: HDV chronic infection is a heterogeneous disease. It may not only progress but also improve over time in patients, who eventually become HDV RNA-undetectable. HDV RNA levels may help identify the subgroup of patients with less progressive liver disease.

Estimated vaccine effectiveness against SARS-CoV-2 Delta and Omicron infections among health care workers and the general adult population in Norway, August 2021 – January 2022

BackgroundHealth care workers (HCW) have a higher exposure to SARS-CoV-2 virus than other professionals and to protect both HCW and patients, HCW have been prioritized for vaccination against SARS-CoV-2 in many countries. Estimating the COVID-19 vaccine effectiveness among HCW is important to provide recommendations to protect risk groups. MethodsWe estimated vaccine effectiveness against SARS-CoV-2 infections using Cox proportional hazard models among HCW with comparisons in the general population, from 1 August 2021 to 28 January 2022. Vaccine status is specified as a time-varying covariate and all models incorporated explicit time and were adjusted for age, sex, comorbidities, county of residence, country of birth, and living conditions. Data from the adult Norwegian population (aged 18–67 years) and HCW workplace data (as registered 1 January 2021) were collated from the National Preparedness Register for COVID-19 (Beredt C19). ResultsVaccine effectiveness was higher for Delta than for the Omicron variant in HCW (71 % compared to 19 %) as well as in non-HCW (69 % compared to −32 %). For the Omicron variant a 3rd dose provides significantly better protection against infection than 2 doses in both HCW (33 %) and non-HCW (10 %). Further, HCW seem to have better vaccine effectiveness than non-HCW for the Omicron, but not for the Delta variant. ConclusionsVaccine effectiveness were comparable between HCW and non-HCW for the delta variant, but significantly higher in HCW than non-HCW for the omicron variant. Both HCW and non-HCW got increased protection from a third dose.

Evaluation of Waning of SARS-CoV-2 Vaccine–Induced Immunity

Estimates of the rate of waning of vaccine effectiveness (VE) against COVID-19 are key to assess population levels of protection and future needs for booster doses to face the resurgence of epidemic waves. To quantify the progressive waning of VE associated with the Delta and Omicron variants of SARS-CoV-2 by number of received doses. PubMed and Web of Science were searched from the databases' inception to October 19, 2022, as well as reference lists of eligible articles. Preprints were included. Selected studies for this systematic review and meta-analysis were original articles reporting estimates of VE over time against laboratory-confirmed SARS-CoV-2 infection and symptomatic disease. Estimates of VE at different time points from vaccination were retrieved from original studies. A secondary data analysis was performed to project VE at any time from last dose administration, improving the comparability across different studies and between the 2 considered variants. Pooled estimates were obtained from random-effects meta-analysis. Outcomes were VE against laboratory-confirmed Omicron or Delta infection and symptomatic disease and half-life and waning rate associated with vaccine-induced protection. A total of 799 original articles and 149 reviews published in peer-reviewed journals and 35 preprints were identified. Of these, 40 studies were included in the analysis. Pooled estimates of VE of a primary vaccination cycle against laboratory-confirmed Omicron infection and symptomatic disease were both lower than 20% at 6 months from last dose administration. Booster doses restored VE to levels comparable to those acquired soon after the administration of the primary cycle. However, 9 months after booster administration, VE against Omicron was lower than 30% against laboratory-confirmed infection and symptomatic disease. The half-life of VE against symptomatic infection was estimated to be 87 days (95% CI, 67-129 days) for Omicron compared with 316 days (95% CI, 240-470 days) for Delta. Similar waning rates of VE were found for different age segments of the population. These findings suggest that the effectiveness of COVID-19 vaccines against laboratory-confirmed Omicron or Delta infection and symptomatic disease rapidly wanes over time after the primary vaccination cycle and booster dose. These results can inform the design of appropriate targets and timing for future vaccination programs.

A new mouse model expressing human ACE2, TMPRSS2, and FCGRT for evaluating human antibody responses to SARS-CoV-2

Abstract Protection against viruses is most often measured by levels of plasma binding and neutralizing antibodies (Abs) in vitro, which do not capture the full picture of Ab immunity, including Fc functions. The continuing evolution of SARS-CoV-2 underscores the need to understand protection mediated by Abs. We generated triple knock-in (TKI) mice expressing human ACE2, TMPRSS2, and FCGRT in place of murine genes. A human anti-SARS-CoV-2 IgG1 with a half-life extending mutation but not wild-type IgG1 exhibited long half-life and protected against BA.2 infection in lungs, thereby validating our TKI mice for evaluating human Ab clearance and function. We next evaluated protective efficacy of plasma samples from vaccinated San Diegans against Delta or BA.5 by performing passive transfer experiments. Treatment with pooled plasma from vaccination plus infection but not triple vaccination individuals cleared infectious Delta in lungs of TKI mice, although Delta-binding and -neutralizing Ab titers in vitro were similar between the two groups of people. In contrast, neither group’s plasma impacted lung viral burden upon BA.5 challenge. Thus, Abs elicited by vaccination plus infection but not triple vaccination reduce Delta infection in this mouse model, and Abs from both groups are ineffective against BA.5. These results are consistent with epidemiological data, and show that in vitro Ab titers do not predict in vivo protection. Our TKI mouse model represents an important tool to test efficacy of human monoclonal Abs against SARS-CoV-2/related CoVs, predict human polyclonal Ab-mediated protection against newly emerging variants/CoVs, and dissect mechanisms of Ab-mediated protection in vivo. Results will aid development of pan CoV vaccines.

Understanding of SARS-CoV-2 pathogenicity in COVID-19 cynomolgus macaque model and consideration of its reinfection

Abstract Although rapid vaccination has been progressing in the world as a countermeasure against COVID-19, the pandemic of SARS-CoV-2 is still raging worldwide due to the continuous emergence of several variants. We have established the COVID-19 cynomolgus macaque (CM) model using healthy young CMs and advanced-age CMs and the differences observed between the pathologies of young and elderly macaques were similar that those seen in humans. In the present study, we analyzed viral dynamics and pathology of SARS-CoV-2 variants of concern (VOCs) from Wuhan to Omicrons using the COVID-19 CM model. Delta infection displayed a greater virulence and Omicron infection showed a lesser virulence. Elucidation of how adaptive immunity in patients is induced by SARS-CoV-2 natural infection is critical for establishing a vaccine strategy, serologic therapies, public health control and prediction of infection. Therefore, we conducted the prolonged rechallenge analysis using the COVID-19 CM model reinoculated with either the same or a different strain of SARS-CoV-2 that was used for the initial infection. Re-infection was confirmed between different virus strains and PCR re-positivity was also observed between same VOC strain in some cases. Anti-RBD antibodies against Wuhan, Alpha, and Delta, were well induced by each VOC infection, but not against Omicrons. Antigen-specific cellular responses are also currently being analyzed. Overall, studies using COVID-19 CM models should contribute to the elucidation of the complicated pathophysiology of COVID-19. In addition, COVID-19 CM model should be useful for understand the virus evolution and to consider vaccine strategy to overcome the COVID-19 pandemic. AMED JP21fk0108414 AMED JP223fa727002 JSPS 21K19395

The emergence of SARS-CoV-2 lineages and associated antibody responses among asymptomatic individuals in a large university community

Abstract SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig)—as generated by the immune system following natural infection or vaccination—has helped limit CoV2 transmission from asymptomatic individuals to more susceptible populations. The emergence of new Omicron lineages with extensive Spike and Nucleocapsid (N) mutations threatens our reliance on natural and vaccine-initiated Ig responses to limit COVID transmission; therefore, it is important to understand the relationships between CoV2 lineage emergence, CoV2-specific Ig levels, and their cross-neutralization capacity in asymptomatic individuals. Here, we describe the relationships between COVID incidence and CoV2 viral load, lineage, and CoV2-specific Ig levels (IgM, IgA, and IgG) in the saliva of asymptomatic individuals between Jan 2021 and May 2022. These data were generated as part of a large university COVID monitoring program and demonstrate that COVID incidence among asymptomatic individuals occurred in waves which mirrored those in surrounding regions, with saliva CoV2 viral loads becoming progressively higher until vaccine requirements were established. Among the unvaccinated, infection with each CoV2 lineage (pre-Omicron) resulted in Spike-specific IgM, IgA, and IgG responses, with Spike-specific IgG increasing significantly post-infection and being more pronounced than N-specific IgG responses. Among the vaccinated, saliva from those with breakthrough Delta infections had Spike-specific IgG levels that were comparable to those who were uninfected; their capacity to inhibit Spike function, however, was diminished relative to those who were uninfected. The Ohio State University

Cohorting children in a childcare setting: a strategy to reduce SARS-CoV-2 Delta transmission, August-September 2021.

Childcare centres can be high-risk settings for SARS-CoV-2 transmission due to age, vaccination status, and infection control challenges. We describe the epidemiology and clinical characteristics of a childcare SARS-CoV-2 Delta outbreak. When the outbreak occurred, little was known about the transmission dynamics of SARS-CoV-2 ancestral and Delta strains among children. Vaccinations for coronavirus disease 2019 (COVID-19) were not mandatory for childcare staff, and children (< 12 years) were ineligible. A retrospective cohort design of childcare attendees was used to investigate age-cohorts exposure and transmission of SARS-CoV-2. We defined a case as a person who tested positive to SARS-CoV-2; we defined a close contact as a person who attended the childcare during 16-20 August 2021. Childcare centre exposures were defined by three cohorts: younger children (0-< 2.5 years) with designated staff; older children (2.5-5 years) with designated staff; and a staff-only group that moved between both age cohorts. We calculated the number and proportion of SARS-CoV-2 Delta infections, symptom profile and severity in children and adults, secondary attack rates, and relative risks (RR) with 95% confidence intervals (CIs) to compare age-cohort exposures and SARS-CoV-2 infection. There were 38 outbreak cases that tested positive to SARS-CoV-2 Delta infection, comprising one primary case, 11 childcare attendees and 26 household members. Child attendees were in two non-interacting groups, 0-< 2.5 years and 2.5-5 years, with designated staff, separate rooms, and independent ventilation. The greatest risk of infection to childcare attendees was in the < 2.5 years age cohort which had a secondary attack rate of 41% and were five times more likely to be infected with SARS-CoV-2 (RR = 5.73; 95% CI: 1.37-23.86; p ≤ 0.01). No identified transmission (n = 0/21) occurred in the ≥ 2.5 years age cohort. Young children play an important role in SARS-CoV-2 Delta transmission to their peers and staff in childcare settings and to household members. Cohorting may be effective at limiting the propagation of SARS-CoV-2 in childcare settings. These findings highlight a need for multi-layered mitigation strategies and implementation support to manage respiratory infection control challenges at childcares. If prevention measures are not in place, this may facilitate ongoing transmission in these settings and into the broader community.

Intranasal infection by SARS-CoV-2 Omicron variants can induce inflammatory brain damage in newly weaned hamsters

ABSTRACT Children infected by SARS-CoV-2 Omicron variant may develop neurological complications. To study the pathogenesis in the growing brain, we intranasally challenged newly-weaned or mature hamsters with SARS-CoV-2 Omicron BA.2, BA.5, or Delta variant. Omicron BA.2 and Delta infection produced a significantly lower viral load in the lung tissues of newly-weaned than mature hamsters despite comparable histopathological damages. Newly-weaned hamsters had higher brain viral load, significantly increased cerebrospinal fluid concentration of TNF-α and CXCL10 and inflammatory damages including mild meningitis and parenchymal vascular congestion, despite sparse expression of nucleocapsid antigen in brain cells. Furthermore, 63.6% (28/44) of all SARS-CoV-2 infected newly-weaned hamsters showed microgliosis in olfactory bulb (OB), cerebral cortex, and hippocampus. In infected mature hamsters, microgliosis was observed mainly in OB and olfactory cortex of 35.3% (12/34) of their brains. Neuronal degeneration was found in 75% (33/44) of newly-weaned hamsters affecting multiple regions including OB, olfactory cortex, midbrain cortex, and hippocampus, while such changes were mainly observed in the hippocampus of mature hamsters. Importantly, similar brain histopathology was also observed in Omicron BA.5-infected newly-weaned hamsters. Our study suggested that SARS-CoV-2 may affect the brain at a young age. This kind of brain involvement and histological changes are not virus variant or subvariant specific. Incidentally, a moderate amount of eosinophilic infiltration was observed in the mucosa of nasal turbinate and trachea of newly-weaned hamsters infected by Omicron BA.2 and BA.5 but not Delta variant. This histological finding is consistent with the higher incidence of laryngotracheobronchitis in young children infected by the Omicron variant. Summary Intranasal infection of newly-weaned Syrian hamsters by SARS-CoV-2 Omicron variants can lead to brain inflammation and neuron degeneration with detectable low level of viral load and sparse expression of viral nucleoprotein.