Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response

Abstract

Objective: To determine clinical and ethnodemographic correlates of serological responses against the SARS-CoV-2 spike glycoprotein following mild-to-moderate COVID-19.

Design: A retrospective cohort study of healthcare workers who had self-isolated due to COVID-19.

Setting: University Hospitals Birmingham NHS Foundation Trust, UK (UHBFT).

Participants: 956 healthcare workers were recruited by open invitation via UHBFT trust email and social media between 27 April 2020 and the 8 June 2020.

Intervention: Participants volunteered a venous blood sample that was tested for the presence of anti-SARS-CoV-2 spike glycoprotein antibodies. Results were interpreted in the context of the symptoms of their original illness and ethnodemographic variables.

Results: Using an assay that simultaneously measures the combined IgG, IgA and IgM response against the spike glycoprotein (IgGAM), the overall seroprevalence within this cohort was 46.2% (n=442/956). The seroprevalence of immunoglobulin isotypes was 36.3%, 18.7% and 8.1% for IgG, IgA and IgM, respectively. IgGAM identified serological responses in 40.6% (n=52/128) of symptomatic individuals who reported a negative SARS-CoV-2 PCR test. Increasing age, non-white ethnicity and obesity were independently associated with greater IgG antibody response against the spike glycoprotein. Self-reported fever and fatigue were associated with greater IgG and IgA responses against the spike glycoprotein. The combination of fever and/or cough and/or anosmia had a positive predictive value of 92.3% for seropositivity in self-isolating individuals a time when Wuhan strain SARS-CoV-2 was predominant.

Conclusions and relevance: Assays employing combined antibody detection demonstrate enhanced seroepidemiological sensitivity and can detect prior viral exposure even when PCR swabs have been negative. We demonstrate an association between known ethnodemographic risk factors associated with mortality from COVID-19 and the magnitude of serological responses in mild-to-moderate disease.

Keywords: COVID-19; clinical epidemiology; respiratory infection.

Figure 1

Serological response against the SARS-CoV-2 spike glycoprotein in healthcare workers. (A) IgG, IgA and IgM responses in individuals demonstrating seropositivity in the combined IgGAM ELISA. Error bars represent binomial confidence intervals. (B) Venn diagram illustrating the relationship between IgG, IgA and IgM seropositivity in this cohort. (C) Optical densities (ODs) of the total serum antibody response determined by the combined IgGAM assay, in individuals with different patterns of IgG, IgA and IgM isotype seropositivity. Horizontal bars represent the median of all results above the assay cut-off. *Represents p<0.0001 (Kruskal-Wallis, Dunn’s post-test comparison) of each group compared with the group only detectable using the IgGAM assay. (D) Seroprevalence of IgG, IgA and IgM isotypes in relation to time from symptom onset. (E) Optical densities (ODs) of the total serum antibody response determined by the combined IgGAM assay in symptomatic individuals who had previously undergone PCR testing for the SARS-CoV-2. Horizontal bars represent the median of all results above the assay cut-off.

Figure 2

Self-reported symptoms in relation to seropositivity in healthcare workers: (A) self- reported symptoms in relation to seropositivity in healthcare workers. Number bars represent the percentage of participants experiencing symptom. Error bars represent the binomial confidence intervals. (B) Number of self-reported symptoms in relation to seropositivity in healthcare workers; data were compared using χ² (χ²=114.8, df=8, p<0.0001). (C) Number of self-reported symptoms in relation to optical density (OD) of the total serum antibody response determined by the combined IgGAM assay.

Figure 3

Relationship between age (A) and body mass index (BMI) (B) and the magnitude of the IgG response against the SARS-CoV-2 spike glycoprotein. Dotted red line represents assay cut-off.

Figure 4

COVID-19 risk in healthcare workers: (A) timing of isolation events in study participants, seroconversion rates (yellow bars) and UHBFT COVID-19 positive inpatients (grey bars) from February to May 2020. (B) Hospital departments and job roles (C) of participants who self-isolated because they directly experienced symptoms following the arrival for the first COVID-19 inpatient at UHBFT; yellow bars represent groups with higher thanaverage seroprevalence, and blue bars represent groups with lower than average seroprevalence. (D) Number of potential days lost due to isolation events in individuals who did not have a PCR test and were found to be seronegative at study enrolment. UHBFT, University Hospitals Birmingham NHS Foundation Trust.