Antibody testing for COVID-19: A report from the National COVID Scientific Advisory Panel

Abstract

Background:The SARS-CoV-2 pandemic caused >1 million infections during January-March 2020. There is an urgent need for robust antibody detection approaches to support diagnostics, vaccine development, safe individual release from quarantine and population lock-down exit strategies. The early promise of lateral flow immunoassay (LFIA) devices has been questioned following concerns about sensitivity and specificity. Methods:We used a panel of plasma samples designated SARS-CoV-2 positive (from SARS-CoV-2 RT-PCR-positive individuals; n=40) and negative (samples banked in the UK prior to December-2019 (n=142)). We tested plasma for SARS-Cov-2 IgM and IgG antibodies by ELISA and using nine different commercially available LFIA devices. Results: ELISA detected SARS-CoV-2 IgM or IgG in 34/40 individuals with an RT-PCR-confirmed diagnosis of SARS-CoV-2 infection (sensitivity 85%, 95%CI 70-94%), vs 0/50 pre-pandemic controls (specificity 100% [95%CI 93-100%]). IgG levels were detected in 31/31 RT-PCRpositive individuals tested ≥10 days after symptom onset (sensitivity 100%, 95%CI 89-100%).IgG titres rose during the 3 weeks post symptom onset and began to fall by 8 weeks, but remained above the detection threshold. Point estimates for the sensitivity of LFIA devices ranged from 55-70% versus RT-PCR and 65-85% versus ELISA, with specificity 95-100% and 93-100% respectively. Within the limits of the study size, the performance of most LFIA devices was similar. Conclusions:The performance of current LFIA devices is inadequate for most individual patient applications. ELISA can be calibrated to be specific for detecting and quantifying SARS-CoV-2 IgM and IgG and is highly sensitive for IgG from 10 days following symptoms onset.

Modeling serological testing to inform relaxation of social distancing for COVID-19 control

“…If detectable antibodies serve as a correlate of immunity, serological testing may be used to identify protected individuals (11). While our understanding of the immunological response to SARS-CoV-2 infection remains incomplete, the vast majority of individuals experience seroconversion after 20 infection (12) and convalescent plasma from recovered COVID-19 cases appears to improve outcomes in critically ill patients (13)(14)(15). Together, these data suggest that recovered individuals have some protection against subsequent reinfection.…”

“…There are currently twelve serological assays for detection of SARS-CoV-2 antibodies that have been approved for 30 emergency use by Food and Drug Administration (17) with many others currently in development and approved in other countries (18). The performance of these tests vary considerably (17,19,20). For the purpose of informing social distancing policies, specificity rather than sensitivity is of primary concern.…”

“…To reflect the placement of test-positive individuals in high-contact roles, we assume that contacts at work and other (non-home, non-school) locations are preferentially with test-positive persons. When shielding is 5:1, this implies that the probability of interacting with a test-positive 20 individual is 5 times what would be expected given the frequency of test-positives in the population ( =4), following the model of 'fixed shielding' (described in (16)).…”

“…Moderate relaxation of social distancing and shielding alongside monthly testing results in a flattened curve that provides time to improve treatments and expand healthcare capacity, which could further reduce mortality rates (26). Thus, serological testing would allow a substantial fraction of the population to return to 20 work and other activities with relative safety, compared to a universal rollback of social distancing policies ( Figure S2, Table S2).…”

“…Using a transmission model, we examined how serology can be implemented to allow seropositive individuals to resume more normal levels of social interaction while offsetting the risks. We simulated the use of widespread serological testing with realistic assay characteristics, in which seropositive individuals partially restore their social contacts and 20 act as immunological 'shields'. If social distancing is relaxed by 50% at the same time that quarterly serological screening is initiated, approximately 120,000 deaths could be averted and a quarter of the US population could be released from social distancing in the first year of the epidemic, compared to a scenario without serological testing.…”