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The Omicron, or Pango lineage B.1.1.529, variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection against severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple BioNTech BNT162b2 messenger RNA-vaccinated health care workers (HCWs) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple-vaccinated individuals, but the magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCWs who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.

The impact of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOCs) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection plus two vaccine doses), S1 antibody, memory B cells, and heterologous neutralization of B.1.351, P.1, and B.1.617.2 plateaued, whereas B.1.1.7 neutralization and spike T cell responses increased. Serology using the Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over the 5 months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.

Introduction: During the COVID-19 pandemic, widespread introduction of SARS-CoV-2 antibody testing was introduced without a full understanding of the assays performance or the antibody kinetics following infection with SARS-CoV-2., Methods: We performed an evaluation of 2 anti-SARS-CoV-2 antibody assays with a more detailed look into the effect of immune status on antibody sensitivity., Results: Both assays demonstrated 100% specificity. The overall sensitivity of the Roche was 92.1% at ≥14 days and 94.8% at ≥21 days, and the overall sensitivity of the Abbott was 94.4% at ≥14 days and 98.2% at ≥21 days. 7/41 (17%) of patients included in this cohort were immunocompromised. Seroconversion was seen less commonly in the immunocompromised (4/7 [57.1%] seroconverted) and after excluding these patients 100% sensitivity was seen in both assays at ≥21 days., Discussion: Performance of both assays in the immunocompetent appeared excellent after 21 days postsymptom onset. Both assays are highly specific., Competing Interests: Declaration of competing interests The authors report no conflicts of interest relevant to this article., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: SARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity., Methods: Healthcare workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks. Serological analysis (n =12,990) was performed using semi-quantitative Euroimmun IgG to viral spike S1 domain and Roche total antibody to viral nucleocapsid protein (NP) assays. Comparisons were made to pseudovirus neutralizing antibody measurements., Findings: A total of 157/729 (21.5%) participants developed positive SARS-CoV-2 serology by one or other assay, of whom 31.0% were asymptomatic and there were no deaths. Peak Euroimmun anti-S1 and Roche anti-NP measurements correlated (r = 0.57, p<0.0001) but only anti-S1 measurements correlated with near-contemporary pseudovirus neutralising antibody titres (measured at 16-18 weeks, r = 0.57, p<0.0001). By 21 weeks' follow-up, 31/143 (21.7%) anti-S1 and 6/150 (4.0%) anti-NP measurements reverted to negative. Mathematical modelling revealed faster clearance of anti-S1 compared to anti-NP (median half-life of 2.5 weeks versus 4.0 weeks), earlier transition to lower levels of antibody production (median of 8 versus 13 weeks), and greater reductions in relative antibody production rate after the transition (median of 35% versus 50%)., Interpretation: Mild SARS-CoV-2 infection is associated with heterogeneous serological responses in Euroimmun anti-S1 and Roche anti-NP assays. Anti-S1 responses showed faster rates of clearance, more rapid transition from high to low level production rate and greater reduction in production rate after this transition. In mild infection, anti-S1 serology alone may underestimate incident infections. The mechanisms that underpin faster clearance and lower rates of sustained anti-S1 production may impact on the longevity of humoral immunity., Funding: Charitable donations via Barts Charity, Wellcome Trust, NIHR., Competing Interests: Declaration of Competing Interests DA and RB report consultancy fees from Oxford Immunotec, RKG reports grants from NIHR, during the conduct of the study; CM reports grants from Barts Charity during the conduct of the study; MN reports grants from Wellcome Trust, during the conduct of the study; DW reports personal fees from Barts Health NHS Trust during the conduct of the study. The authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is of public health concern in case of vaccine escape. Described are 3 patients with advanced human immunodeficiency virus (HIV)-1 and chronic SARS-CoV-2 infection in whom there is evidence of selection and persistence of novel mutations that are associated with increased transmissibility and immune escape. [ABSTRACT FROM AUTHOR]

Background Haemodialysis (HD) patients are extremely vulnerable to coronavirus disease 2019 (COVID-19). Their immune response after infection is unclear. We have found high seroconversion rates in this population, with 95% developing antibodies. It is unclear if and how long these antibodies persist. Here we investigate this with serial antibody (Ab) testing. Methods We identified HD patients who had confirmedsevere acute respiratory syndrome coronavirus 2 between March and May 2020 and measured monthly antibodies (immunoglobulin G/immunoglobulin M) in those who survived. We used a semiquantitative cut-off index to create a qualitative result and plotted optical density (OD) over time. We used linear regression to examine the slope, as well as noting peak OD and time to peak OD. We correlated these against baseline demographics, markers of illness severity and comorbidities. Results A total of 122 patients were analysed. All remained Ab positive during follow-up for a minimum of 148 days. Seventy-one percent had a positive gradient indicating increasing Ab positivity over time. We found that age (P = 0.01), duration of polymerase chain reaction positivity (P = 0.06) and the presence of symptoms (P = 0.05) were associated with a longer time to peak OD. Immunosuppression did not alter peak OD but did lead to a non-significant increase in time to peak OD, and more patients had a subsequent decrease in Ab levels (P = 0.02). Diabetic patients were more likely to have a positive slope (odds ratio 2.26). Conclusions These results indicate that HD patients have a robust and sustained Ab response after confirmed COVID-19 infection with no suggestion that immunosuppression weakens this response. Although it is unclear what protection these antibodies confer, this is encouraging that HD patients should respond to vaccination. [ABSTRACT FROM AUTHOR]

A case study of 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, is presented. Topics include Genomes were assembled with reference based assembly and a bioinformatics pipeline; and region of the genome and 50% cut-off for defining single nucleotide polymorphisms (SNPs).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine rollout has coincided with the spread of variants of concern. We investigated whether single-dose vaccination, with or without prior infection, confers cross-protective immunity to variants. We analyzed T and B cell responses after first-dose vaccination with the Pfizer/BioNTech messenger RNA vaccine BNT162b2 in health care workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody-secreting memory B cell response to the spike protein, and neutralizing antibodies effective against variants B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated, or unchanged T cell responses, depending on human leukocyte antigen (HLA) polymorphisms. Single-dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants. [ABSTRACT FROM AUTHOR]