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. 2021 Feb 23;10(5):e019506. doi: 10.1161/JAHA.120.019506

Table 1.

Recent Clinical Studies That Evaluated Anti‐SARS‐COV‐2 Antibodies in COVID‐19

Author Publication Date Study Design (n) Test Patient Population Longitudinal Follow‐Up Main Results Limitation
Premkumar et al 19 June 11, 2020 Prospective cohort (n=63) IgG/IgM binding to spoke RBD antigen and SARS‐CoV‐2 neutralization assay Symptomatic PCR confirmed subjects with SARS‐CoV‐2 39 d Strong correlation between levels of RBD‐binding antibodies and SARS‐CoV‐2 neutralizing antibodies

Single center

Small sample

Short surveillance period

Steensels et al 11 June 15, 2020 Cross‐sectional (n=4125) IgG/IgM Lateral flow assay against nucleocapsid protein* Asymptomatic workers at Hospital East‐Limburg 8 d 6.4% had IgG antibodies to SARS‐CoV‐2

Single center

No long‐term follow‐up

Short‐surveillance period

Only 74% of total sample enrolled

Long et al 2 June 18, 2020 Matched case‐control (n=178) IgG and IgM ELISA against spike protein Asymptomatic cases, defined as individuals with a positive nucleic acid test result with without clinical symptoms 8 wk

20.8% had asymptomatic infection (37/178)

Median percentage decrease in IgG level was 71.1% (range, 32.8%–88%)

Neutralizing antibodies decreased by 81.1%

Inaccurate estimate of asymptomatic infection in general population

Variability in sensitivity/specificity

Confounding because of prior SARS infections

Wang et al 12 July 7, 2020 (n=23) IgG and IgM ELISA to spike, S1, S2, RBD, and nucleocapsid proteins Symptomatic cases (12 severely ill and 11 mildly ill) from 3 hospitals 6 wk after symptom onset (baseline was measured during symptom onset)

Lower level of IgM was observed in mildly ill patients, but similar IgG responses in mildly and severely ill patients

Anti‐SARS‐CoV‐2 spike and nucleocapsid IgG levels correlated with neutralization titers

Small sample

Short follow‐up period

Wajnberg et al 13 July 17, 2020 Prospective cohort (n=51 829) IgG ELISA against spike protein Confirmed SARS‐CoV‐2 infection by PCR or suspected disease 82 d (range of interval after symptom onset 52–104 d)

38% had ELISA antibody test IgG spike protein at baseline

Follow‐up beyond 3‐mo not available
Wu et al 20 July 24, 2020 Prospective cohort (n=349) IgM and IgG ELISA RBD of the spike protein Symptomatic patients with COVID‐19 26 wk

IgG against spike and nucleocapsid was maintained at high positive rates and titers at 6 mo

IgG positively correlated with neutralizing activity

Missing samples at 9 and 11 wk

Not all samples were assessed in virus neutralizing tests

Rodda et al 14 August 15, 2020 Prospective case‐control (n=15) IgM, IgA, and IgG ELISA against RBD spike protein Mildly symptomatic PCR‐confirmed COVID‐19 3 mo following symptoms onset (median=86 d) Sustained immunity (including neutralizing antibodies) against SARS‐CoV‐2 Small samples
Gudbjartsson et al 15 September 1, 2020 Prospective cohort (n=1797) Pan‐immunoglobulin assays, antibodies against nucleocapsid, RBD, S1 Symptomatic participants recovered from COVID‐19 3 mo after recovery

Over 90% of qPCR‐positive patients tested positive with both pan‐Ig antibody and remained positive at 120 d after diagnosis

Some diminution of antibody titer was observed

Low prevalence of infection in Iceland
Patel et al 16 September 4, 2020 Prospective cohort (n=249) IgG ELISA against spike protein Convenience sample of healthcare personnel at Vanderbilt University Medical Center 60 d

7.6% had anti‐SARS‐CoV‐2 antibodies at baseline

42% had antibodies that persisted at 60 d

All participants who were positive at baseline had antibody titers decrease at 60 d

Single center

Small sample

Convenience sampling

Lacking information on timing of infection

Ibarrondo et al 17 September 10, 2020 Prospective cohort (n=34) IgG ELISA against spike protein Participants recovered from mild COVID‐19 infection Mean 86 d (range, 44–119 d) The estimated mean change in IgG level was an estimated half‐life of 36 d

Short follow‐up of ≈3 mo

Small sample size

Bolke et al 18 September 23, 2020 Prospective cohort (n=151) IgA and IgG antibodies Symptomatic participants 120 d after the onset of symptoms IgA and IgG levels remained unchanged

Small sample

Limited reported data

Terpos et al 18 September 23, 2020 Phase 2 prospective cohort (n=259) IgG and IgA antibodies against spike protein S1 Symptomatic participants or +PCR 100 d Rapid reduction in anti‐SARS‐CoV‐2 antibody in patients recovered from COVID‐19 Limited data
Katsuna et al 18 September 23, 2020 Prospective cohort (n=81) ELISA antibodies against spike protein Symptomatic participants (mild, moderate, and severe disease) 60 d

Titers were higher in those with severe disease

All patients showed decreased antibody titers after 60 d of symptom onset

Limited data
Ripperger et al 21 October 5, 2020 Prospective cohort (serum samples 75) ELISA antibodies against RBD and S2 Symptomatic and asymptomatic PCR confirmed patients with COVID‐19 3 mo post disease onset

Spike RBD and S2 and neutralizing antibodies remained detectable 5–7 mo post‐onset

α‐nucleocapsid capsid titers diminished

Seroconversion from (+) to (−) before testing

No data beyond 226 d

Wajnberg et al 22 October 28, 2020 Prospective cohort (n=30 082) IgG ELISA against spike protein Mild‐to‐moderate confirmed SARS‐CoV‐2 infection by PCR or suspected disease or exposure to SARS‐COV‐2 5 mo Anti‐spike binding titers significantly correlate with neutralization of authentic SARS‐CoV‐2 No follow‐up date beyond 5 mo
Ladhani et al 23 November 6, 2020 Prospective cohort (n=518) IgG ELISA against spike protein and nucleocapsid and neutralization assay Asymptomatic and Symptomatic Median=36 d Most participants had neutralizing antibodies during follow‐up regardless of age and symptoms

Survival bias

Lack of serial testing to infected individuals

Dan et al 24 November 16, 2020

Cross‐sectional (n=185)

Prospective follow‐up (n=41)

IgG ELISA against spike protein Asymptomatic‐Mild‐moderate‐severe COVID‐19 cases 6 mo Spike IgG was relatively stable >6+ mo

Many of original sample were lost to follow‐up

Serial measurements with 3 time points are lacking

Dan et al 25 January 6, 2020 Prospective cohort (n=188)

IgG ELISA against spike protein

RBD IgG

SARS‐CoV‐2 neutralizing antibodies

Asymptomatic‐Mild‐moderate‐severe COVID‐19 cases 6 mo Spike IgG was relatively stable >6+ mo

Serial measurements with 3 time points are lacking

COVID‐19 indicates coronavirus disease 2019; IgA, immunoglobulin A; IgG, immunoglobulin G; IgM,immunoglobulin M; PCR, polymerase chain reaction; RBD, receptor binding domain; and SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2.

*

Immunoglobulin M results were excluded.

Six‐hundred healthcare personnel were eligible.