key: cord-0713854-nybxpzle authors: Muratori, Paolo; Lenzi, Marco; Muratori, Luigi; Granito, Alessandro title: Antinuclear antibodies in COVID 19 date: 2021-05-01 journal: Clin Transl Sci DOI: 10.1111/cts.13026 sha: b0dbfbf8210cd1874208095f326c50329be22b7d doc_id: 713854 cord_uid: nybxpzle nan No funding was received for this work. We appreciated very much the interesting study by Chang et al. 1 on the presence of antinuclear antibodies (ANAs) in patients with moderate/critical coronavirus disease 2019 (COVID 19). Both we and Chang and collaborators described the presence and significance of ANAs in patients with COVID-19. The two experiences can be compared because Chang et al. studied a number of cases only slightly larger than us. In our opinion, the most important finding is represented by the presence of the nucleolar ANA reactivity, which, in the study by Chang et al., 1 as in ours, 2 is the most frequently detected among the different ANA patterns. In this regard, it is worth mentioning that the nucleolar ANA pattern is one of the several ANA pattern detectable by Indirect immunofluorescence (Figure 1 ), together with other patterns, such as speckled, homogenous, multiple nuclear dots, and rim like membranous; this pattern can be the serological marker of systemic sclerosis and its antigenic target is the topoisomerase I protein (or scl70). Interestingly, it is of major relevance to note that among the clinical manifestations of systemic sclerosis, it includes pulmonary involvement in the form of a restrictive syndrome secondary to interstitial pneumopathy resembling COVID-19 interstitial pneumonia. In our experience, 2 however, all cases of nucleolar pattern were subsequently tested for anti-Extractable Nuclear Antigens (anti-ENAs), as previously described, 3 and no one was positive for anti-topoisomerase I, whereas in Chang's study no anti-ENAs were tested for. The lack of positivity for the known anti-ENA reactivities clearly means that we are dealing with unknown target antigens that need to be identified in order to better understand the underlying pathophysiological mechanisms. It would be very interesting to verify and confirm the frequency of the nucleolar ANA pattern in this peculiar setting of patients by other multicenter studies with the aim then to characterize this reactivity and to identify the underlying molecular target COMMENTARY because it could prove useful in understanding its significance and possible pathophysiological mechanisms. Extending the evaluation of ANA in COVID-19 to other experiences, we can observe a similar prevalence to ours in a Greek study, 4 where the authors found an ANA positivity in 10 patients out of 29 (34%), and, interestingly, 7 of them exhibited a nucleolar ANA pattern. Moreover, two recent studies from Nanjing (China) and from Seattle (United States) reported a frequency of ANA of 50% and 25% respectively, even though the detection of these reactivities was not carried out by indirect immunofluorescence but by immunochemical method. 4, 5 Results of ANA detection and characterization in patients with COVID-19 from different reported cohorts are shown in Table 1 . We and others observed that ANA-positive patients had a worse prognosis compared with the negative ones with respect to COVID-19 disease, but there are a number of limitations that prevent conclusions from being drawn, ranging from the low number of patients studied, the different methods used for autoantibodies detection and the genetic heterogeneity of the patients included in the different studies. Autoantibodies in moderate and critical cases of COVID19 COVID-19 and immunological dysregulation: can autoantibodies be useful? Antibodies to SS-A/ Ro-52kD and centromere in autoimmune liver disease: a clue to diagnosis and prognosis of primary biliary cirrhosis Autoantibodies in COVID-19: frequency and function Prevalence of autoantibody responses in acute coronavirus disease 2019 (COVID-19) We thank all patients and their families involved in the study. We thank all healthcare workers involved in the diagnosis and treatment of patients.