Timing of PCR and Antibody Testing in Patients with COVID-19 associated dermatologic manifestations

Freeman, E. E.; McMahon, D. E.; Fox, L. P.; Fassett, M. S.

A recent study from Spain noted 40 patients with chilblain-like lesions in suspected COVID-19.1 None tested PCR positive for SARS-CoV-2, but 30% had detectable antibodies. The rapid increase in chilblain/pernio-like cases during the COVID-19 pandemic is likely SARS-CoV-2-associated. The relationship between skin symptom onset and COVID-19 PCR/antibody test timing, however, remains uncharacterized. We established an international registry for cutaneous manifestations of COVID-19.2, 3 Providers reported time between dermatologic symptom onset and positive/negative COVID-19 laboratory results, when available. From 8 April-30 June, 2020, 906 laboratory-confirmed or suspected COVID-19 cases with dermatologic manifestations were reported, 534 of which were chilblains/pernio.3 Among PCR-tested patients, 57%(n=208) overall and 15%(n=23) of chilblains/pernio cases were PCR-positive. Antibody positivity was 37%(n=39) overall and 19%(n=15) for chilblains/pernio. We evaluated 163 patients with timing information on PCR and/or antibody testing (Table 1). For patients with suspected COVID-19 and any cutaneous manifestation, PCR-positive testing occurred median 6 (IQR 1-14) days after dermatologic symptoms started while PCR-negative testing occurred median 14 (IQR 7-24) days later. For patients with pernio/chilblains, PCR-positivity was noted 8 (IQR 5-14) days after symptoms and negativity median 14 (IQR 7-28) days later. Antibody testing (IgM or IgG) was positive median 30 (IQR 19-39) days after symptom onset for all dermatologic manifestations and 27 (IQR 24-33) days after chilblains/pernio onset. Like Hubiche et al, our data highlight the low frequency of SARS-CoV-2 PCR+ testing in COVID-19 patients with cutaneous manifestations. Positive predictive values for COVID-19 PCR are influenced by viral shedding kinetics, which are difficult to assess in non-respiratory presentations.4 Our data reveal that early PCR testing is more likely to be positive than later testing, even when date-of-onset is defined by cutaneous manifestations rather than systemic symptoms. Most COVID-19 antibody data are from systemically-ill patients; the kinetics of antibody production in mild-to-moderate COVID-19 infections remain unclear.5 Here, positive antibodies resulted median 30 days from disease onset, beyond the frequently used 14-21 day testing window. In outpatients with true infection, many factors influence the likelihood of a positive antibody result: antibody production, test availability, assay sensitivity, and timing of care-seeking in relation to symptom-onset. These variables influence our interpretation of individual test results and our understanding of the association between pernio and COVID-19. More population-level testing data is necessary to optimize diagnostic test timing. Positive identification of COVID-19 in minimally-symptomatic patients, including patients with skin findings, is critical to the public health effort.