The Protection of Naturally Acquired Antibodies Against Subsequent SARS-CoV-2 Infection: A Systematic Review and Meta-Analysis

Figures & data

Figure 1. Flow diagram of the included studies. One study identified from the second citation search was included in the meta-analysis. [24].

Table 1. Description of included studies and reported outcomes.

NO.	Authors Years	Population and Location	Age (years)	Study Time	Length of Follow-up, mo^c	The Definition of reinfection	Serologic Assay	Effect Measure	Adjusted Variables	Quality assessment^e
1	John T. Wilkins MD et al, 2020 [44]	6510 HCWs in Chicago, USA	Mean (SD) 41(12)	2020.05.26-2021.01.08	7.5	A positive PCR result detected more than 90 days after baseline seropositive result, or the first positive PCR test plus 1 or more of the following characteristics: in-home exposure to someone infected with SARS-CoV-2, consistent symptoms, or a physician diagnosis of active infection.	CMIA; Anti-NP IgG tested by ARCHITECT Immunoassay System (Abbott)	Adjusted RR	Age, Gender, Race and Occupation	7 (HQ)
2	Sheila F Lumley et al, 2020 [45]	About 12600 HCWs in Oxford shire, UK	Median (IQR) 38 (29,49)	2020.04.23-2020.11.30	7.3	A positive PCR result detected more than 60 days after the previous PCR positive test.	1. ELISA; Anti-S IgG tested by an ELISA platform developed by the University of Oxford 2. CMIA; Anti-NP IgG tested by ARCHITECT Immunoassay System (Abbott)	Adjusted RR	Calendar time, Age, and Gender,	6 (MQ)
3	H. Abo-Leyah et al, 2021 [46]	2063 HCWs in Scotland, UK	Median 46	2020.05.28-2020.12.02	6.2	A positive PCR result detected more than 60 days after a baseline seropositive result.	CLIA; Anti-S total antibodies tested by the Siemens SARS-CoV-2 total antibody assay	Unadjusted HR	Age and Gender	6 (MQ)
4	Anna Jeffery-Smith et al, 2021 [47]	103 care homes residents and 106 staffs in London, UK	Median (IQR) A care home residents: 84 (76-89) L care home residents: 85 (78-89)	2020.05-2020.10	5.0	Reinfection was defined as an individual testing positive for the SARS-CoV-2 RT–PCR test while having evidence of previous seropositivity detected using any assay (more than 90 days ago).	1.ELISA; Anti-RBD IgG and anti-S IgG tested by an uncommercially kit 2.CMIA; Anti-NP IgG tested by a commercial assay (Abbott, Illinois, United States)	Unadjusted RR^b	-	5 (MQ)
5	Raymond A. Harvey et al, 2021^d[48]	3257478 general population in USA	Median (SD) 48 (20)	2020.01.08-2020.08.26	7.6	A positive PCR result detected more than 90 days after the baseline seropositive result.	–	Unadjusted RR	–	6 (MQ)
6	Adrian M. Shields et al, 2021^a [49]	1507 HCWs in the West Midlands region, UK	Median (IQR) 37 (29-47)	2020.05-2021.01	8.0	A positive PCR result detected after a baseline seropositive result.	ELISA; Anti-S total antibodies tested by a commercially total antibody assay (Product code: MK654, Birmingham)	Adjusted RR	Age, Gender, Ethnicity and Smoking	7 (HQ)
7	Antonio Leidi et al (1), 2021 [50]	8344 general population in Geneva, Switzerland	Mean (SD) Pos: 47 (17) Neg: 47 (16)	2020.04.03 -2021.01.25	9.8	Two independent adjudicators evaluated suspected cases based on the reason for testing, subject’s illness history (including date of symptom onset), and the value and temporal evolution in RT–PCR cycle threshold (Ct).	ELISA; Anti-S IgG tested by a commercially kit (Euroimmun, Lübeck, Germany #EI 2606–9601 G)	Unadjusted HR	–	7 (HQ)
8	Candice L. Clarke et al, 2021 [51]	356 hemodialysis patients in London, UK	Mean (IQR) Pos: 65 (55-73) Neg: 68 (55-77)	2020.02.24-2021.01.01	10.3	A positive PCR result detected more than 60 days after a baseline seropositive result.	1. ELISA; Anti-RBD IgG tested by an uncommercially kit (Imperial SARS-CoV-2 Hybrid DABA) 2.CMIA; Anti-NP IgG tested by ARCHITECT Immunoassay System (Abbott)	Unadjusted RR^b	–	6 (MQ)
9	Victoria Jane Hall et al, 2021 [52]	25661 HCWs in UK	Median (IQR) 46 (35-54)	2020.02.01-2021.01.11	14.3	A positive PCR result detected more than 90 days after a previous positive PCR test, or at least 4 weeks after a baseline seropositive result.	–	Unadjusted RR	Week group, Age group, Gender, Ethnicity, Staff role, Index of multiple deprivation, Region	8 (HQ)
10	Andrew G Letizia et al, 2021 [53]	3249 marine recruits in Parris Island, USA	Range 18–20	2020.05.11-2020.11.02	5.8	A positive PCR result detected more than 14 days after a baseline seropositive result.	ELISA; Anti-RBD IgG and anti-S IgG tested by an uncommercially kit	Adjusted HR	Age, Gender and Race	7 (HQ)
11	Mattia Manica et al, 2021 [27]	6074 general population in the Autonomous Province of Trento, Italy	Median (IQR) 50 (32-63)	2020.05.05-2021.01.31	8.9	A positive PCR result detected after a baseline seropositive result.	CMIA; Anti-NP IgG tested by ARCHITECT Immunoassay System (Abbott)	Adjusted RR	Age	8 (HQ)
12	L. J. Abu-Raddad et al, 2021^d [54]	43044 seropositive population in Qatar and 149934 seronegative population in 167 nationalities	Median (IQR) POS: Male 38 (31-47), Female is 35 (28-45) Neg: Male 39 (30-50), Female 35 (28-47)	2020.04.16-2020.12.31	8.5	A PCR-positive swab at least 14 days after the first positive antibody test and no PCR-positive swab within the 45 days preceding the reinfection swab.	ECLIA; Anti-NP IgG tested by Roche Elecsys® Anti-SARS-CoV-2 assay (Roche, Switzerland)	Unadjusted RR	–	6 (MQ)
13	Maria Krutikov et al, 2021 [24]	682 residents and 1429 staff members of long-term care facilities in UK	Median (IQR) Residents 86 (79–91) Staff members 47 (34–56)	2020.10.01-2021.02.01	4.0	A positive PCR result detected more than 28 days after the initial seropositive result.	CMIA; Anti-NP IgG tested by ARCHITECT Immunoassay System (Abbott)	Unadjusted RR^b	–	5 (MQ)
14	Antonio Leidi et al (2), 2021 [55]	10582 essential workers in Geneva, Switzerland	Mean (SD) Pos: 44 (11) Neg: 45 (11)	2020.05-2021.01	8.0	Positive RT–PCR or antigenic rapid diagnostic test in seropositive individuals were clinically investigated by two independent adjudicators.	ELISA; Anti-S IgG tested by a commercially kit (Euroimmun anti-SARS-CoV-2 IgG ELISA)	Adjusted HR	Age, Sex, Smoking status, Obesity and Formal educational level	7 (HQ)
15	Hannah E Maier et al, 2021 [25]	2338 general population in Managua, Nicaragua	Mean (SD) 24 (18)	2020.03.01-2021.03.31	13.0	A positive PCR result detected after a baseline seropositive result.	ELISA; Anti-RBD IgG tested by an uncommercially kit following the Krammer laboratory protocol	Unadjusted RR^b	–	8 (HQ)
16	Sebastian Havervall et al, 2021 [56]	300 HCWs in Stockholm, Sweden	Median (IQR) 46 (35-54)	2020.04.09-2021.02.26	10.6	A positive PCR result detected more than 7 months after a baseline seropositive result.	Luminex; Anti-S IgG tested by a bead-based high-throughput multiplex assay based on the FlexMap3D (Luminex Corp.) platform	Unadjusted RR^b	–	5 (MQ)
17	Charles F Schuler 4^th et al, 2021 [57]	653 subjects were either HCWs or patients with a high risk of exposure to COVID-19 in Michigan, USA	Median (IQR) 41 (31-51)	2020.05-2021.02	9.0	A positive PCR result detected after a baseline seropositive result.	1. ECLIA; Anti-NP total antibodies tested by Roche Elecsys® Anti-SARS-CoV-2 assay (Roche, Switzerland) 2.CLIA; Anti-S total antibodies tested by an ADVIA Centaur XPT analyzer (Siemens)	Unadjusted RR^b	–	5 (MQ)
18	Philipp Kohler et al, 2021 [58]	4812 HCWs in Northern and Eastern Switzerland	Median38.9	2020.06.22-2021.03.09	8.5	A positive PCR result detected more than 90 days after a baseline seropositive result.	ECLIA; Anti-NP total antibodies (Roche, Switzerland)	Unadjusted RR	–	5 (MQ)
19	Luke Muir et al, 2021 [59]	217 patients in blood and transplant waiting list for renal transplantation in UK	Mean (SD) Pos: 54.5 (11.9) Neg: 53.6 (12.7)	2020.06-2021.01	7.0	A positive PCR result detected more than 60 days after a baseline seropositive result.	ELISA; Anti-S IgG and anti-N IgG tested by uncommercially kits	Unadjusted RR^b	–	7 (HQ)

HCWs: Health-care Workers; SD: Standard Deviation; IQR: Interquartile Range; CMIA: Chemiluminescent Microparticle Immunoassay; CLIA: Chemiluminescence Immunoassay; ELISA: Enzyme-Linked Immunosorbent Assay; RR: Relative Risk; HR: Hazard Ratio; HQ: High Quality; MQ: Medium Quality; LQ: Low Quality;

^a This article is a preprint and has not been peer-reviewed.

^b A 2×2 contingency table was constructed to calculate it, as the effect size is not available in the article.

^c Length of Follow-up (months) = [(the date of study start – the date of study end)$÷$365$\times$12], or (the month of study start – the month of study end).

^d This is a database study.

^e Quality assessment of the included studies using the NOS

Figure 2. Forest plot of the pooled incidence rate ratio for SARS-CoV-2 infection comparing baseline seropositive and seronegative individuals.

Figure 3. Forest plot of the protection provided by naturally acquired antibodies against future symptomatic COVID-19 between baseline seropositive and seronegative individuals.

Figure 4. Forest plot of the protection provided by naturally acquired antibodies against future asymptomatic COVID-19 between baseline seropositive and seronegative individuals.

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Data availability statement

Data extracted from included studies can be obtained from https://github.com/chenqi160/Data.