Evaluation of SARS-CoV-2 antibodies in 24 patients presenting with chilblains-like lesions during the COVID-19 pandemic.

To the Editor: Chilblains-like lesions have been reported in primarily young, healthy patients with suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection , and are characterized histopathologically by chilblains-like changes, without necrosis. Although SARS-CoV-2 viral particles have been identified within endothelial cells of patients with chilblains-like lesions, negative results or absent SARS-CoV-2 laboratory testing in other patients has created uncertainty about the relationship between coronavirus disease 2019 (COVID-19) and chilblains-like lesions. We evaluated this relationship by performing multiple tests for SARS-CoV-2 antibodies on patients with chilblains-like lesions during a surge of SARS-CoV-2 infections.

Our dermatology service offered antibody testing to 26 consecutive patients with chilblains-like lesions evaluated during a surge of SARS-CoV-2-infections. Two patients declined participation. Testing was performed on the following platforms: Abbott Architect (IgA, immunoglobulin [Ig] M, IgG, repeat IgG; Abbott, Abbott Park, IL); DiaSorin Liaison (Saluggia, Italy) SARS-CoV-2 S1/S2 (IgG); and Euroimmun SARS CoV-2 enzyme-linked immunosorbent assay (IgG) (Euroimmun US, Mountain Lakes, NJ). Clinical information was obtained via medical record review.

All 24 patients (100%) tested negatively for SARS-CoV-2 IgG on 2 separate tests on the Abbott Architect platform, 21 (87.5%) tested negatively on the Euroimmun IgG platform, and 23 (95.8%) tested negatively on the Liaison Sars-Cov-2 platform (Table I ).

Table I

Clinical description and SARS-CoV-2 polymerase chain reaction (PCR) and antibody test results of patients with chilblain-like lesions evaluated between April 13 and May 24, 2020

Patient	Sex/age, y	Lesion location	Symptoms	Dur., d∗	Systemic symptoms	SARS-CoV-2 laboratory testing
						PCR	Antibody test platforms†
							Abbott (initial)	Abbott (repeat)	Euroimmun	Liaison
1	F/27	B/l dorsal and palmar fingers, toes	Pruritus	60	None	(−)	IgG (−), IgM (e), IgA (−)	IgG (−)	IgG (+)	IgG (−)
2	F/30	B/l dorsal toes	Tenderness	26	Fatigue, sinus congestion	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
3	F/27	B/l dorsal and plantar toes	Tenderness	31	Fatigue, sore throat (EBV viral capsid IgM+)	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
4	M/64	B/l dorsal toes	Discomfort	10	None	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
5	M/26	B/l dorsal toes	Pain, swelling	22	Globus sensation in throat	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
6	M/33	R dorsal toes	Tenderness	20	None	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (+)	IgG (−)
7	F/11	R 1st distal toe	NA	25	None	NP	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
8	M/12	B/l dorsal toes	Stinging, swelling	32	Lethargy, poor appetite	NP	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (+)	IgG (−)
9	M/41	B/l dorsal toes	Stinging, tenderness, pruritus	33	Fatigue, sore throat	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
10	F/55	B/l plantar toes	Burning, tenderness	23	None	NP	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
11	F/24	B/l dorsal toes	Pain, pins and needles	30	Fever, chills, fatigue, sore throat, cough	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
12	M/31	B/l dorsal and palmar fingers	Soreness, tenderness	28	None	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
13	M/25	B/l dorsal and lateral toes	Tenderness, pruritus	22	Fatigue, sore throat, dry cough, sinus congestion	(+)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
14	M/37	B/l dorsal toes	Pruritus	12	Sore throat, myalgias	(−)	IgG (−), IgM (+), IgA (−)	IgG (−)	IgG (−)	IgG (−)
15	M/31	R dorsal and plantar toes	Tenderness	24	Fatigue, headaches	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
16	F/19	B/l dorsal toes	Pain	14	None	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
17	F/28	R dorsal toes	NA	21	Sore throat, rhinorrhea	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
18	M/59	B/l dorsal and plantar toes	None	NA	None	(−)	IgG (−), IgM (−), IgA (−)	NP	NP	NP
19	M/28	B/l dorsal toes	Pruritus	21	Chills	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
20	F/33	R dorsal toes	Pain, tenderness, pruritus, swelling	31	Papular rash on chest and axillary fold	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
21	F/31	R dorsal toes	Pruritus	21	Sore throat, diarrhea	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
22	F/32	R 2nd palmar finger	Tenderness, pruritus	22	Sinus congestion	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (lp)
23	M/25	L dorsal toes	Pain, pruritus	8	Cough, shortness of breath, rhinorrhea; sore throat	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)
24	F/41	R plantar toes	Pain	8	None	(−)	IgG (−), IgM (−), IgA (−)	IgG (−)	IgG (−)	IgG (−)

B/l, Bilateral; Dur., duration; EBV, Epstein-Barr virus; F, female; IgG (lp), IgG low positive; IgM (e), IgM equivocal result; L, left; M, male; NA, data not available; NP, test not performed; R, right; −, negative test result; +, positive test result.

Duration from reported onset of pernio symptoms to time of SARS-CoV-2 serology laboratory draw.

Abbott Architect, Abbott, Abbott Park, Illinois; DiaSorin Liaison, Saluggia, Italy; Euroimmun US, Mountain Lakes, New Jersey.

All 24 patients (100%) tested negatively for IgA antibodies, 22 (91.7%) tested negatively for IgM, and 21 (91.67%) completed nasopharyngeal polymerase chain reaction testing for SARS-CoV2. Of these, 20 (95.2%) tested negatively. No patients reported a prior history of chilblains.

We observed minimal evidence of SARS-CoV-2 antibodies in patients identified with chilblains-like lesions because only 4 of 24 patients (16.7%) tested had any positive results and none had multiple positive results.

Despite our findings, an association between chilblains-like lesions and SARS-CoV-2 infections may exist. Our patients may have had SARS-Cov-2 infection but failed to mount a detectable antibody response. Chilblains-like lesions may be associated with mild infections in patients and who test negative on polymerase chain reaction, and patients with mild clinical courses may mount weak antibody responses. Problems with the timing or accuracy of antibody tests could produce negative results. Our patients were tested an average of 23.65 days from symptom onset, a timing thought to correlate with detectable IgG levels; however, 4 patients reported fewer than 14 days of cutaneous symptoms before testing, which may not have allowed sufficient time to produce antibodies. By testing patients on multiple platforms, we sought to reduce the likelihood of false-negative results. The observed discordance in IgG results in 4 patients suggests individual results may be unreliable.

Inappropriate patient selection through diagnostic error, anchoring bias, or selection bias could have occurred, although we attempted to minimize this by having multiple board-certified dermatologists review each patient's photographs. An epiphenomenon, whereby the COVID-19 pandemic leads to changes in behavior that may predispose patients to chilblains-like lesions without a causal link, is also possible.

In conclusion, we found a low frequency of SARS-CoV-2 antibodies in 24 patients presenting with chilblains-like lesions during a SARS-CoV-2 outbreak and discordance across different testing platforms. Patients presenting with chilblains-like lesions should not be presumed to have serologic immunity to SARS-CoV-2 as a result of recovery from prior infection, without confirmatory testing.