key: cord-1049921-qu0lk1sh
authors: Petráš, Marek
title: Highly effective naturally acquired protection against COVID-19 persists for at least one year: A meta-analysis
date: 2021-09-16
journal: J Am Med Dir Assoc
DOI: 10.1016/j.jamda.2021.08.042
sha: 37eb5a1c9637a4d5458d9abd8ae544d971cfcc4e
doc_id: 1049921
cord_uid: qu0lk1sh

nan

To the Editor: 1

The current massive COVID-19 immunization campaign has initiated a change in the course 2 of the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 3

The duration of post-vaccination protection can be estimated from longer-term monitoring of 4 the persistence of naturally acquired protection (since November 2019). Therefore, this rapid 5 meta-analysis was conducted to evaluate the reinfection rates in post-COVID-19 patients as 6 the primary endpoint to predict protection not only in the general population but also in 7 vulnerable long-term care (LTC) recipients. individuals, measures of association including the 95% confidence intervals (95% CI), viral 16 variant of concern, follow-up period of ≥180 days, etc.) were extracted. 17

This was a rapid and pragmatic meta-analysis to estimate reduction in the risk of reinfection 18 in post-COVID-19 patients, expressed by the efficacy of naturally acquired protection, i.e. (1 19 measure of association) * 100%. Given the non-homogeneity of the studies identified, the 20 outcome was assessed using the random-effects model (DerSimonian-Laird method). 21

Analysis were performed using Stata version 17 (StataCorp, College Station, TX) at a 22 significance level of = 0.05 with a two-tailed 95% CI. The protocol of this study was not 23 registered. 24

A total of 15 eligible publications were identified to assess the risk of reinfection in post-27 COVID-19 patients. These publications reported the results of cohort studies conducted in the 28 general population (8 studies), in the population of healthcare workers (6) or in the military 29

(1) including either only adults or individuals regardless of age (i.e., also children and 30 adolescents). The mean or median age of the study populations ranged from 19 to 59 years. This meta-analysis confirmed a high, 87% level of protection acquired after COVID-19. 46

When assessing the efficacy in symptomatic patients only, their 92% level of protection was 47 close to that seen post-vaccination. Although all the studies were designed and conducted as cohort ones, the risk of bias was not 57

the same across the studies as documented by the different pooled efficacies from adjusted 58 and unadjusted measures of association. The published outcomes ranged between 69% and 59 98% and the lower limit of the 95% CI was above 47%. One may assume that the efficacy 60 results obtained from studies with a moderate/high risk of bias did not critically impact the 61 final pooled efficacy in this meta-analysis. It should not be forgotten that the level of 62 protection afforded by naturally acquired immunity depends on disease severity. 16 Highly effective naturally acquired protection against COVID-19 persisting for at least one year. A meta-analysis Table S1 : MOOSE Checklist Table S2 : Search strategy Figure S1 : Flowchart Table S3 : Descriptive information about included studies 

Qualifications of literature searchers (e.g., librarians and investigators)

The credential of the only literature researcher (Martina Franklová)

The search strategy is detailed in Appendix, Table S2 .

References of all retrieved articles and recent reviews were reviewed.

Medical Literature Analysis and Retrieval System Online (MEDLINE), EMBASE, Web of Science (WoS), MedRxiv and BioRxiv Search software used, name and version, including special features used (e.g., explosion)

No special search software was used.

Use of hand searching (e.g., reference lists of eligible articles)

References of all retrieved articles and recent reviews were reviewed.

Details of the literature search process are outlined in the flow chart ( Figure S1 ).

No language restrictions.

The search process was not restricted to peer-reviewed studies. Description of any contact with authors Not done.

Types of study designs considered Cohort studies only Relevance or appropriateness of studies gathered for assessing the hypothesis to be tested

(1) controlled studies; (2) exposure to SARS-CoV-2; (3) unexposed control group; and (4) outcome of interest determined by the measures of association, including the 95% confidence interval. Rationale for the selection and coding of data (eg, sound clinical principles or convenience) Study characteristics were extracted by one investigator (Marek Petráš -MP). Measures of associations (incl. 95% CI) for reinfection and primary infection were assessed separately whenever possible. The most adjusted measure of association was included when a study reported more than one measure. Documentation of how data were classified and coded (e.g., multiple raters, blinding, and interrater reliability) Data were independently extracted and analyzed by investigator (MP) with the final decision reached by consensus.

Assessment of confounding (e.g., comparability of cases and controls in studies where appropriate)

Analysis of sensitivity was conducted.

Assessment of study quality, including blinding of quality assessors: stratification or regression on possible predictors of study results

The quality of each study was assessed by investigator (MP).

The Q-statistic and I-squared statistic were used to assess the heterogeneity among studies. Statistical methods (e.g., complete description of fixed or random effects models, justification of whether the chosen models account for predictors of study results, doseresponse models, or cumulative meta-analysis) in sufficient detail to be replicated Description of the methods of meta-analyses, subgroup analyses, and assessment of publication bias are detailed in the "Results" section.

A graph summarizing individual study estimates and the overall estimate A forest plot of results is incorporated in the main body of text (Figure 1) .

A table giving descriptive information for each study included Supplement (Table S3) J o u r n a l P r e -p r o o f Criteria Brief description Results of sensitivity testing (e.g., subgroup analysis) See "Results" section Indication of statistical uncertainty of findings 95% confidence intervals are provided with all summary effect estimates.

The strength of evidencecohort studies; additional analyzes of effect of small and unpublished studies; the weakness -insufficient number of studies, limited follow-up time. Potential biases in the review process (e.g., publication bias) See "Methods", "Results" and "Discussion" section.

Justification for exclusion (e.g., exclusion of non-Englishlanguage citations) See "Methods" section Assessment of quality of included studies Analysis of sensitivity.

The pooled outcome of the analysis must be interpreted for rapid assessed one-year persistence of protection. Generalization of the conclusions (i.e., appropriate for the data presented and within the domain of the literature review)

The summary outcome can be generally accepted because all efficacies were higher than 50% including lower limit of 95% confidence interval.

Guidelines for future research Natural immunity acquired by COVID-19 illness is sufficient to prevent SARS-CoV-2 reinfection. Disclosure of funding source This research was not funded. J o u r n a l P r e -p r o o f SARS-CoV-2 AND reinfect* AND (convalescent OR natural OR naive OR naive)" and abstract or title "SARS-CoV-2 reinfect" (match all words) and posted between "01 Nov, 2020 and 07 Jun, 2021 ((corona* OR COVID-19 OR SARS-CoV) AND (reinfect* OR convalescent) AND (seronegative OR seropositive))" and title "corona* COVID-19 SARS-CoV" (match any words) and abstract or title "antibodies cohort" (match any words) and posted between "01 Nov, 2020 and 07 Jun, 2021" 

The risk of symptomatic reinfection during the 108 second COVID-19 wave in individuals previously exposed to SARS-CoV-2

Prior SARS-CoV-2 infection is associated with 111 protection against symptomatic reinfection

SARS-CoV-2 Infection Severity Is Linked to 113

Superior Humoral Immunity against the Spike. mBio

Emerging Evidence on Effectiveness of 115 COVID-19 Vaccines Among Residents of Long-Term Care Facilities