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      Major Update 2: Antibody Response and Risk for Reinfection After SARS-CoV-2 Infection—Final Update of a Living, Rapid Review

      other
      , PhD, MPH, , MD, MPP, , MS, , MD, MS
      Annals of Internal Medicine
      American College of Physicians

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          Abstract

          In this final update of the living, rapid review on the role of antibodies after SARS-CoV-2 infection, the authors summarize the evidence on the durability of the antibody response and the level and duration of protection from previous infection on more current variants, including the Delta and Omicron variants.

          Abstract

          Background:

          The durability of the antibody response after SARS-CoV-2 infection and the role of antibodies in protection against reinfection are unclear.

          Purpose:

          To synthesize evidence on the SARS-CoV-2 antibody response and reinfection risk with a focus on gaps identified in our prior reports.

          Data Sources:

          MEDLINE (Ovid), EMBASE, CINAHL, World Health Organization Research Database, and reference lists from 16 December 2021 through 8 July 2022, with surveillance through 22 August 2022.

          Study Selection:

          English-language, cohort studies evaluating IgG antibody duration at least 12 months after SARS-CoV-2 infection, the antibody response among immunocompromised adults, predictors of nonseroconversion, and reinfection risk.

          Data Extraction:

          Two investigators sequentially extracted study data and rated quality.

          Data Synthesis:

          Most adults had IgG antibodies after SARS-CoV-2 infection at time points greater than 12 months (low strength of evidence [SoE]). Although most immunocompromised adults develop antibodies, the overall proportion with antibodies is lower compared with immunocompetent adults (moderate SoE for organ transplant patients and low SoE for patients with cancer or HIV). Prior infection provided substantial, sustained protection against symptomatic reinfection with the Delta variant (high SoE) and reduced the risk for severe disease due to Omicron variants (moderate SoE). Prior infection was less protective against reinfection with Omicron overall (moderate SoE), but protection from earlier variants waned rapidly (low SoE).

          Limitation:

          Single review for abstract screening and sequential review for study selection, data abstraction, and quality assessment.

          Conclusion:

          Evidence for a sustained antibody response to SARS-CoV-2 infection is considerable for both Delta and Omicron variants. Prior infection protected against reinfection with both variants, but, for Omicron, protection was weaker and waned rapidly. This information may have limited clinical applicability as new variants emerge.

          Primary Funding Source:

          Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098)

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          Most cited references41

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          Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study

          Background The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort. Methods Individual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta (ie, the relative risk in unvaccinated cases). Findings The adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with omicron compared with delta was 0·56 (95% CI 0·54–0·58); for hospital admission and death, HR estimates were 0·41 (0·39–0·43) and 0·31 (0·26–0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 (0·85–1·42) in those younger than 10 years, decreasing to 0·25 (0·21–0·30) in 60–69-year-olds, and then increasing to 0·47 (0·40–0·56) in those aged at least 80 years. For both variants, past infection gave some protection against death both in vaccinated (HR 0·47 [0·32–0·68]) and unvaccinated (0·18 [0·06–0·57]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination (HR 0·96 [0·88–1·04]); however, for unvaccinated cases, past infection gave moderate protection (HR 0·55 [0·48–0·63]). Omicron versus delta HR estimates were lower for hospital admission (0·30 [0·28–0·32]) in unvaccinated cases than the corresponding HR estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in omicron cases (HR for hospital admission 8–11 weeks post-booster vs unvaccinated: 0·22 [0·20–0·24]), with the protection afforded after a booster not being affected by the vaccine used for doses 1 and 2. Interpretation The risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity (in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Booster vaccination with mRNA vaccines maintains over 70% protection against hospitalisation and death in breakthrough confirmed omicron infections. Funding Medical Research Council, UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research, Community Jameel, and Engineering and Physical Sciences Research Council.
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            Humoral Immune Response to SARS-CoV-2 in Iceland

            Abstract Background Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed. Results Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR. Conclusions Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.
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              Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa

              Here, we provide two methods for monitoring reinfection trends in routine surveillance data to identify signatures of changes in reinfection risk and apply these approaches to data from South Africa’s SARS-CoV-2 epidemic to date. While we found no evidence of increased reinfection risk associated with circulation of Beta (B.1.351) or Delta (B.1.617.2) variants, we find clear, population-level evidence to suggest immune evasion by the Omicron (B.1.1.529) variant in previously infected individuals in South Africa. Reinfections occurring between 01 November 2021 and 31 January 2022 were detected in individuals infected in all three previous waves, and there has been an increase in the risk of having a third infection since mid-November 2021.
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                Author and article information

                Journal
                Ann Intern Med
                Ann Intern Med
                aim
                Annals of Internal Medicine
                American College of Physicians
                0003-4819
                1539-3704
                29 November 2022
                29 November 2022
                : M22-1745
                Affiliations
                [01]Scientific Resource Center for the Agency for Healthcare Research and Quality, Portland, Oregon (H.K.H., C.V.F.)
                [02]VA Portland Health Care System, Portland, Oregon (K.M.)
                [03]VA Portland Health Care System and Scientific Resource Center for the Agency for Healthcare Research and Quality, Portland, Oregon (M.H.)
                Author notes
                Disclaimer: The findings and conclusions in this document are those of the authors, who are responsible for its contents, and do not necessarily represent the views of the AHRQ. Therefore, no statement in this report should be construed as an official position of the AHRQ or the U.S. Department of Health and Human Services.
                Financial Support: By the AHRQ through the following contract: Scientific Resource Center (290-2017-00003-C).
                Reproducible Research Statement:  Study protocol: Registered at PROSPERO (CRD42020207098) and posted to the AHRQ Effective Health Care website (4). Statistical code: Not applicable. Data set: Available at http://SRDRPLUS.AHRQ.gov.
                Corresponding Author: Haley K. Holmer, PhD, MPH, Portland VA Research Foundation, Scientific Resource Center, AHRQ EPC Pro, 3710 SW US Veterans Hospital Road, Portland, OR 97239; e-mail, haley.holmer@ 123456va.gov .
                Author Contributions: Conception and design: C.V. Fiordalisi, M. Helfand, H.K. Holmer, K. Mackey.
                Analysis and interpretation of the data: M. Helfand, H.K. Holmer, K. Mackey.
                Drafting of the article: C.V. Fiordalisi, M. Helfand, H.K. Holmer, K. Mackey.
                Critical revision of the article for important intellectual content: C.V. Fiordalisi, M. Helfand, H.K. Holmer, K. Mackey.
                Final approval of the article: C.V. Fiordalisi, M. Helfand, H.K. Holmer, K. Mackey.
                Obtaining of funding: M. Helfand.
                Administrative, technical, or logistic support: C.V. Fiordalisi, M. Helfand.
                Collection and assembly of data: C.V. Fiordalisi, M. Helfand, H.K. Holmer, K. Mackey.
                Author information
                https://orcid.org/0000-0003-4198-8708
                https://orcid.org/0000-0003-4749-5664
                https://orcid.org/0000-0001-5610-1925
                https://orcid.org/0000-0003-4846-9900
                Article
                aim-olf-M221745
                10.7326/M22-1745
                9707440
                36442059
                9d584fdc-9017-4054-9eb3-6f8fd2e25147
                Copyright @ 2022

                This article is made available via the PMC Open Access Subset for unrestricted re-use for research, analyses, and text and data mining through PubMed Central. Acknowledgement of the original source shall include a notice similar to the following: "© 2020 American College of Physicians. Some rights reserved. This work permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited." These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                Categories
                Reviews
                8643, Antibodies
                10444, Antibody production
                3122457, COVID-19
                3124935, Omicron variant
                3124903, Reinfection
                2892, Systematic reviews
                early, Currently Online First
                coronavirus, Coronavirus Disease 2019 (COVID-19)
                poc-eligible, POC Eligible

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