Autoantibodies and Severity of COVID-19 in Lung Transplant Recipients

PURPOSE: COVID-19 in lung transplant recipients (LTR) results in case-fatality rate of 10-46%. Disease severity is variable and it is unclear why certain groups of patients develop severe disease. Recent report suggests that 10% of patients with life threatening COVID-19 have auto-antibodies (AAbs) against type 1 interferons (IFN-1) but very few describe their impact in LTR. We therefore sought to identify AAbs in LTR with COVID-19 by using a customized proteomic microarray (CPM) bearing 120 antigens. METHODS: We retrieved samples collected for routine care within 3 months prior to and after diagnosis of COVID-19 of 13 LTR. IgA and IgG AAbs were analyzed using CPM. Predefined antibody score (ab-score) was used for downstream analysis. COVID severity was defined as per center for disease control guidelines. Changes in ab-scores from pre- to post-COVID were assessed via Wilcoxon signed-rank tests; association between continuous variables and AAbs using Spearman's correlation. Linear mixed-effects models were used to analyze the association between changes in AAbs pre- to post-COVID and COVID severity. RESULTS: Among 13 LTR COVID severity was moderate (n=6), severe (n=4) and critical (n=3). Levels of 76 IgA antibodies and 9 IgG antibodies increased between pre and post covid samples (FDR adjusted p<0.05). In exploratory analysis, antibody response over time for one IgA antibody (IgA Nucleosome) and four IgG AAbs correlated with higher COVID severity (unadjusted p<0.05). IFN lambda is an antiviral cytokine and AAbs to it correlated with COVID severity (p=0.031). Such AAbs are shown to block the ability to block SARS-CoV-2 in vitro. No significant differences were observed in antibody response in the groups who were alive (n=9) versus deceased (n=4) and three inflammatory markers, ferritin, D dimer and absolute lymphocyte count. CONCLUSION: Change in antibody response of five AAbs correlated with COVID severity in a small group of LTR. The results of this study are considered exploratory and need further validation.