key: cord-0988930-qpu3phm3
authors: Freeman, E. E.; McMahon, D. E.; Fox, L. P.; Fassett, M. S.
title: Timing of PCR and Antibody Testing in Patients with COVID-19 associated dermatologic manifestations
date: 2020-07-04
journal: nan
DOI: 10.1101/2020.07.03.20146134
sha: f8494f836441c2a05bb999b32adf5a6e156cbb14
doc_id: 988930
cord_uid: qpu3phm3

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.

Task Force.

The registry was reviewed by the Partners Healthcare (MGH) Institutional Review Board (IRB) and was determined to not meet the definition of Human Subjects Research.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 4, 2020. . https://doi.org/10.1101/2020.07.03.20146134 doi: medRxiv preprint

A recent study from France 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/perniolike 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 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.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 4, 2020. . https://doi.org/10.1101/2020.07.03.20146134 doi: medRxiv preprint 3 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.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 4, 2020. . https://doi.org/10.1101/2020.07.03.20146134 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted July 4, 2020. . https://doi.org/10.1101/2020.07.03.20146134 doi: medRxiv preprint

Negative SARS-CoV-2 PCR in patients with chilblain-like lesions

Registry: Crowdsourcing Dermatology in the Age of COVID-19

The spectrum of COVID-19-associated dermatologic manifestations: an international registry of 716 patients from 31 countries

Interpreting Diagnostic Tests for SARS-CoV-2

Convergent antibody responses to SARS-CoV-2 in convalescent individuals

International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity

The copyright holder for this preprint this version posted July 4, 2020. . https://doi.org/10.1101/2020.07.03.20146134 doi: medRxiv preprint