COVID‐19 and Immunological Dysregulation: Can Autoantibodies be Useful?

Abstract

Coronavirus disease 2019 (COVID-19) is often associated with interstitial pneumonia. However, there is insufficient knowledge on the presence of autoimmune serological markers in patients with COVID-19. We analyzed the presence and role of autoantibodies in patients with COVID-19-associated pneumonia. We prospectively studied 33 consecutive patients with COVID-19, 31 (94%) of whom had interstitial pneumonia, and 25 age-and sex-matched patients with fever and/or pneumonia with etiologies other than COVID-19 as the pathological control group. All patients were tested for the presence of antinuclear antibodies (ANAs), antiantiphospholipid antibodies (APLs), and anti-cytoplasmic neutrophil antibodies (ANCAs). Clinical, biochemical, and radiological parameters were also collected. Fifteen of 33 (45%) patients tested positive for at least one autoantibody, including 11 who tested positive for ANAs (33%), 8 who tested positive for anti-cardiolipin antibodies (IgG and/or IgM) (24%), and 3 who tested positive for anti-β2-glycoprotein antibodies (IgG and/or IgM) (9%). ANCA reactivity was not detected in any patient. Patients that tested positive for autoantibodies had a significantly more severe prognosis than other patients did: 6 of 15 (40%) patients with autoantibodies died due to COVID-19 complications during hospitalization, whereas only 1 of 18 (5.5%) patients who did not have autoantibodies died (p = 0.03). Patients with poor prognosis (death due to COVID-19 complications) had a significantly higher respiratory rate at admission (23 breaths per minute vs. 17 breaths per minute; p = 0.03) and a higher frequency of autoantibodies (86% vs. 27%; p = 0.008). In conclusion, autoantibodies are frequently detected in patients with COVID-19 possibly reflecting a pathogenetic role of immune dysregulation. However, given the small number of patients, the association of autoantibodies with an unfavorable prognosis requires further multicenter studies.

Latent rheumatic, thyroid and phospholipid autoimmunity in hospitalized patients with COVID-19

“…Several reports have shown diverse prevalence of autoantibodies. The most reported comprise the antiphospholipid antibodies, and ANAs [ [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] ]. Herein, we found that hospitalized patients with COVID-19 exhibited higher frequency of latent phospholipid, rheumatic and thyroid autoimmunity when compared with pre-pandemic controls.…”

“…One of the most intriguing phenomena of COVID-19 is the presence of autoimmunity. Indeed, a) autoimmune diseases (ADs) have been associated with the disease, in particular Guillain-Barré syndrome, autoimmune cytopenia, and antiphospholipid syndrome [ 1 ]; b) the presence of several autoantibodies has been confirmed [ [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] ], and c) autoantibodies against cytokines [ 15 ], and even against angiotensin-converting enzyme 2 (ACE-2) [ 16 ], the receptor for SARS-CoV-2, have been observed and associated with severity of disease.…”

Autoantibodies in COVID-19: frequency and function

“…And moreover, the outcome of ANAs positive patients (3 patients in ICU and 2 patients death) were worse than that of the autoantibody negative patients (all alive) [ 5 ]. Third, Pascolini S and colleagues found that 11 patients were positive (33.3%) for ANAs in 33 consecutive patients with COVID-19 [ 6 ]. And moreover, the outcome of ANAs positive patients were worse than ANA negative patients: the death rate of ANAs positive patients were 36.4% (4 death among 11 ANAs positive patients), while the death rate of ANAs negative patients were 13.6% (3 death among 22 ANAs negative patients).…”

“…The aPL are including anticardiolipin (aCL), anti-beta-2 glycoprotein I (aβ2GPI), anti-phosphatidylserine/prothrombin (aPS/PT) and lupus anticoagulant (LA). Nine studies that have tested the aPL in COVID-19 were reviewed ( Table 2 ) [ [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] ]. These studies showed that: aPL is frequent in COVID-19 patients.…”

Antinuclear antibodies (ANA) in COVID-19 infection

“…A report from Greece demonstrated that the positive rate of ANA was 34.5% in hospitalized patients 10 . In Italy, 34 COVID-19 cases were analyzed, and the detection rate of ANA was 35.3% 8,9 . Apart from those studies, a report from Japan, one of two (50%) severe covid-19 cases were found ANA positive 7 .…”