Antibody response to SARS-CoV-2 infection in humans: A systematic review

Abstract

Background Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. Methods Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14–22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. Conclusions Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.

Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents

“…Virus neutralizing activity at ID50 was detected in 17 of 22 (77%) serum samples collected from adult participants during acute infection, 16 of 19 (84%) samples collected at 2 months after acute infection, and 13 of 14 (93%) samples collected at 4 months after acute infection (Supplemental Figure 6). As observed among children and adolescents, acute infection samples for which there was no appreciable neutralizing activity were collected earlier after symptom onset than acute infection samples with detectable neutralizing antibodies [median (IQR) of 4 (3, 8) vs. 16 (12,20) , although these differences were not statistically significant at 4 months (Figure 4c).…”

“…[11][12][13][14][15][16][17] To date, studies of SARS-CoV-2 immune responses in pediatric populations have focused primarily on children hospitalized for severe COVID-19 or who developed multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening inflammatory condition that can occur after SARS-CoV-2 infection. [18][19][20][21][22] While these studies provide important insights into the immune responses of children and adolescents who develop these rare manifestations of SARS-CoV-2 infection, surprisingly little is known about the immune responses of the much larger population of children with asymptomatic or mild symptomatic SARS-CoV-2 infection.…”

Survey of symptoms following COVID-19 vaccination in India

“…Hence it is not possible to infer whether the muted post-vaccination symptoms among older people was a sign of immune senescence. Although symptoms are known to correlate with neutralising antibody levels during COVID-19 (5), the presence of symptoms following vaccination does not reliably predict antibody response (6).…”

Five Commercial Immunoassays for SARS-CoV-2 Antibody Determination and Their Comparison and Correlation with the Virus Neutralization Test

“…The last issue we wanted to address is the correlation of the production of neutralizing antibodies with age. Such information is still rare, and some authors point out the necessity of obtaining such data [27]. We tried to create a homogeneous group of patients with respect to the course of the disease, so that the levels of antibodies were comparable across the age spectrum.…”