Lack of antinuclear antibodies in convalescent coronavirus disease 2019 patients with persistent symptoms

MJ Peluso, IJ Thomas, SE Munter… - Clinical Infectious …, 2022 - academic.oup.com
MJ Peluso, IJ Thomas, SE Munter, SG Deeks, TJ Henrich
Clinical Infectious Diseases, 2022academic.oup.com
To the Editor—We read with great interest the recent article by Seeßle et al [1] who reported
that 77.1% of 96 patients with coronavirus disease 2019 (COVID-19) had persistent
symptoms 12 months following acute infection. Of particular interest, antinuclear antibody
(ANA) titers were observed to be elevated in 43.6% of participants at this late timepoint.
Interestingly, the number of symptoms participants reported was higher in those with a
positive ANA, and significantly more females with concentration problems had ANA titers> 1 …
To the Editor—We read with great interest the recent article by Seeßle et al [1] who reported that 77.1% of 96 patients with coronavirus disease 2019 (COVID-19) had persistent symptoms 12 months following acute infection. Of particular interest, antinuclear antibody (ANA) titers were observed to be elevated in 43.6% of participants at this late timepoint. Interestingly, the number of symptoms participants reported was higher in those with a positive ANA, and significantly more females with concentration problems had ANA titers> 1: 160. These findings are intriguing given that autoimmunity has been proposed as a potential underlying etiology of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC)[2–4].
We established a convalescent severe acute respiratory syndrome coronavirus 2 infection cohort and have collected clinical and laboratory data in participants with and without PASC. We measured ANA titers in a convenience sample of participants approximately 4 and 8 months following initial infection (M4 and M8 timepoints, respectively) using an enzyme-linked immunosorbent assay with reflex to an indirect fluorescent assay using HEp-2 substrate in a commercial reference laboratory (ARUP Laboratories). The screen is designed to detect antibodies against doublestranded DNA, histones, SS-A (Ro), SS-B (La), Smith, Smith/RNP, Scl-70, Jo-1, centromeric proteins, and other HEp-2 cell nuclear antigens. We tested 46 samples at 4 months and 69 samples 8 months after acute infection from individuals with and without PASC as shown in Table 1. At M4, 57% had at least 1 PASC symptom; at M8, 78% had at least 1 PASC symptom (8 participants had data at both the M4 and M8 timepoints). No ANAs were detected in the M4 participants and only 3 of 69 participants at M8 had a positive ANA screen and reflex indirect fluorescent assay. The participants with detectable ANAs were female and none had been hospitalized or had a known preexisting autoimmune disorder. No participant with a history of autoimmune disease (9.5% in the M4 cohort and 4.3% in the M8 cohort) had detectable ANAs (Table 1). All participants with a positive ANA reported at least 1 symptom, although 2 with higher titers (1: 320) had 2 or fewer symptoms, whereas the participant with a low titer (1: 80) reported 19 symptoms. Like the prior study, a large proportion (up to 40%) of our PASC cohort reports neurocognitive symptoms 4 and 8 months following acute infection [5]. The reason for the discrepancies between our cohort and the study by Seeßle et al is not known but raises concerns about the generalizability of the prior observation that a very large proportion
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