Longitudinal protection following natural SARS-CoV-2 infection and early vaccine responses: insights from a cohort of community based dental health care professionals

BackgroundThe threshold of protection for anti-SARS-CoV-2 spike glycoprotein antibodies and their longevity are not known. Interpretation of serological results in with respect to international reference material can inform this essential question. Methods1,507 West Midlands dental care professionals were recruited into this study in June 2020. Baseline seroprevalence of antibodies directed against the SARS-CoV-2 spike glycoprotein was determined and the cohort was followed longitudinally for 6 months until January/February 2021 through the second wave of the COVID-19 pandemic in the United Kingdom, and commencement of vaccination. ResultsBaseline seroprevalence was 16.3% in this cohort, compared to estimates in the general population of between 6-7%. Seropositivity was retained in over 70% of participants at 3 and 6-month follow up and conferred a 74% reduced risk of infection. During follow-up, no PCR-proven infections occurred in individuals with a baseline anti-SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. Post-vaccination, antibody responses were more rapid and of higher magnitude in individuals with who were seropositive at baseline. ConclusionNatural infection leads to a serological response that remains detectable in over 70% of individuals 6 months after initial sampling and 9 months from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech vaccine is associated with an antibody response indicative of immunological memory. FundingThe Association of Clinical Biochemistry and Laboratory Medicine and The Institute for Global Innovation (IGI) of the University of Birmingham.

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

ObjectiveTo determine clinical and ethnodemographic correlates of serological responses against the SARS-CoV-2 spike glycoprotein following mild-to-moderate COVID-19. DesignA retrospective cohort study of healthcare workers who had self-isolated due to COVID-19. SettingUniversity Hospitals Birmingham NHS Foundation Trust, UK (UHBFT). Participants956 health care workers were recruited by open invitation via UHBFT trust email and social media. InterventionParticipants 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. ResultsUsing 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. Conclusions and relevanceAssays 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. The combination of cough, and/or fever and/or anosmia identifies the majority of individuals who should self-isolate for COVID-19.

SARS-CoV-2 seroconversion in health care workers

BackgroundThe correlates of protection against SARS-CoV-2 and their longevity remain unclear. Studies in severely ill individuals have identified robust cellular and humoral immune responses against the virus. Asymptomatic infection with SARS-CoV-2 has also been described, but it is unknown whether this is sufficient to produce antibody responses. MethodsWe performed a cross-sectional study recruiting 554 health care workers from University Hospitals Birmingham NHS Foundation Trust who were at work and asymptomatic. Participants were tested for current infection with SARS-CoV-2 by nasopharyngeal swab for real-time polymerase chain reaction and for seroconversion by the measurement of anti-SARS-CoV-2 spike glycoprotein antibodies by enzyme linked immunosorbent assay. Results were interpreted in the context of previous, self-reported symptoms of illness consistent with COVID-19. ResultsThe point prevalence of infection with SARS-CoV-2, determined by the detection of SARS-CoV-2 RNA on nasopharnygeal swab was 2.39% (n=13/544). Serum was available on 516 participants. The overall rate of seroconversion in the cohort was 24.4% (n=126/516). Individuals who had previously experienced a symptomatic illness consistent with COVID-19 had significantly greater seroconversion rates than those who had remained asymptomatic (37.5% vs 17.1%, {chi}2 =21.1034, p<0.0001). In the week preceding peak COVID-19-related mortality at UHBFT, seroconversion rates amongst those who were suffering from symptomatic illnesses peaked at 77.8%. Prior symptomatic illness generated quantitatively higher antibody responses than asymptomatic seroconversion. Seroconversion rates were highest amongst those working in housekeeping (34.5%), acute medicine (33.3%) and general internal medicine (30.3%) with lower rates observed in participants working in intensive care (14.8%) and emergency medicine (13.3%). ConclusionsIn a large cross-sectional seroprevalence study of health-care workers, we demonstrate that asymptomatic seroconversion occurs, however prior symptomatic illness is associated with quantitatively higher antibody responses. The identification that the potential for seroconversion in health-care workers can associate differentially with certain hospital departments may inform future infection control and occupational health practices. Research in contextO_ST_ABSEvidence before the studyC_ST_ABSTo date, no study has examined the cross-sectional seroprevalence of anti-SARS-CoV-2 antibodies in health care workers during the COVID-19 pandemic. Existing evidence suggests that the levels of SARS-CoV-2 antibodies developing following infection may vary with disease severity in keeping with previous coronavirus pandemics. Added value of this studyWe demonstrate that seroconversion can occur in health care workers who have suffered no previous symptoms of SARS-Cov-2 infection. However, prior symptomatic infection tends to drive quantitatively superior antibody responses against the virus. We observed differential seroconversion rates in individuals working within different hospital departments. Using intensive care as a reference, the relative risk for seroconversion was greatest for those working in housekeeping, acute and general internal medicine. Implications of all the available evidenceInsight into the current seroprevalence of SARS-CoV-2 antibodies within a high-risk cohort of health-care workers is of direct relevance as a reference point for future community serological surveys. We provide further evidence of asymptomatic infection and seroconversion, strengthening the argument for regular, routine screening of health-care workers. Finally, we provide evidence that individuals working in particular roles within the NHS are at greater risk of seroconversion with significant implications for their occupational health.