Search

Purpose of Review: To explore the origins of new severe acute respiratory coronavirus 2 (SARS-CoV-2) variants in immunocompromised individuals and whether the emergence of novel mutations in these individuals is responsible for the development of variants of concern (VOC)., Recent Findings: Next generation sequencing of samples from chronically infected immunocompromised patients has enabled identification of VOC- defining mutations in individuals prior to the emergence of these variants worldwide. Whether these individuals are the source of variant generation is uncertain. Vaccine effectiveness in immunocompromised individuals and with respect to VOCs is also discussed., Summary: Current evidence on chronic SARS-CoV-2 infection in immunocompromised populations is reviewed including the relevance of this to the generation of novel variants. Continued viral replication in the absence of an effective immune response at an individual level or high levels of viral infection at the population level are likely to have contributed to the appearance of the main VOC., (Copyright © 2023 Wolters Kluwer Health, Inc. 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., Competing Interests: Potential conflicts of interest. M. M. reports an honorarium to self for a presentation for ViiV, February 2020, and for an HIV workshop for Janssen in November 2018 and support for attendance at the 17th EACS Conference, November 2019, from Gilead; registration for the EACS Conference, October 2021, from ViiV; and registration for the International AIDS Conference, July 2021, from ViiV. S. D. reports receiving support for attending the EACS Conference from ViiV (virtual conference) in October 2021. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We observed an increased frequency of massive perivillous fibrin deposition (MPFD) during the second coronavirus disease 2019 (COVID-19) pandemic wave dominated by the Alpha variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MPFD associated with 100% reverse transcription polymerase chain reaction (RT-PCR) positivity for SARS-CoV-2 and detection by immunohistochemistry. The Alpha variant was identified in all placentas with MPFD that could be sequenced., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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.

Objectives: Recently emerging SARS-CoV-2 variants have been associated with an increased rate of transmission within the community. We sought to determine whether this also resulted in increased transmission within hospitals., Methods: We collected viral sequences and epidemiological data of patients with community and healthcare associated SARS-CoV-2 infections, sampled from 16th November 2020 to 10th January 2021, from nine hospitals participating in the COG-UK HOCI study. Outbreaks were identified using ward information, lineage and pairwise genetic differences between viral sequences., Results: Mixed effects logistic regression analysis of 4184 sequences showed healthcare-acquired infections were no more likely to be identified as the Alpha variant than community acquired infections. Nosocomial outbreaks were investigated based on overlapping ward stay and SARS-CoV-2 genome sequence similarity. There was no significant difference in the number of patients involved in outbreaks caused by the Alpha variant compared to outbreaks caused by other lineages., Conclusions: We find no evidence to support it causing more nosocomial transmission than previous lineages. This suggests that the stringent infection prevention measures already in place in UK hospitals contained the spread of the Alpha variant as effectively as other less transmissible lineages, providing reassurance of their efficacy against emerging variants of concern., (Copyright © 2021. Published by Elsevier Ltd.)

Background: We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing., Methods: We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew's Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for "viral infection", "transcriptome", "biomarker", and "blood". We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive participants) during their first week of PCR positivity., Findings: We identified 20 candidate blood transcriptomic signatures of viral infection from 18 studies and evaluated their accuracy among 169 blood RNA samples from 96 participants over 24 weeks. Participants were recruited between March 23 and March 31, 2020. 114 samples were from 41 participants with SARS-CoV-2 infection, and 55 samples were from 55 test-negative controls. The median age of participants was 36 years (IQR 27-47) and 69 (72%) of 96 were women. Signatures had little overlap of component genes, but were mostly correlated as components of type I interferon responses. A single blood transcript for IFI27 provided the highest accuracy for discriminating between test-negative controls and test-positive individuals at the time of their first positive SARS-CoV-2 PCR result, with AUROC of 0·95 (95% CI 0·91-0·99), sensitivity 0·84 (0·70-0·93), and specificity 0·95 (0·85-0·98) at a predefined threshold (Z score >2). The transcript performed equally well in individuals with and without symptoms. Three other candidate signatures (including two to 48 transcripts) had statistically equivalent discrimination to IFI27 (AUROCs 0·91-0·95)., Interpretation: Our findings support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection for screening individuals at high risk of infection, such as contacts of index cases, to facilitate early case isolation and early use of antiviral treatments as they emerge., Funding: Barts Charity, Wellcome Trust, and National Institute of Health Research., Competing Interests: We declare no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

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.)

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection., (Copyright © 2020, American Association for the Advancement of Science.)

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]

The exponential growth in coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across the UK has been successfully reversed by social distancing and lockdown.[1] RNA testing for prevalent infection is a key part of the exit strategy, but the role of testing for asymptomatic infection remains unclear.[2] Understanding the determinants of asymptomatic or pauci-symptomatic infection will provide new opportunities for personalised risk stratification and reveal much-needed correlates of protective immunity, whether induced by vaccination or natural exposure. Taken together, these data suggest that the rate of asymptomatic infection among HCWs more likely reflects general community transmission than in-hospital exposure. Prospective patients should be reassured that as the overall epidemic wave recedes, asymptomatic infection among HCWs is low and unlikely to be a major source of transmission. [Extracted from the article]