Inflammasome-Related Genetic Polymorphisms as Severity Biomarkers of COVID-19.

The most critical forms of coronavirus disease 2019 (COVID-19) are associated with excessive activation of the inflammasome. Despite the COVID-19 impact on public health, we still do not fully understand the mechanisms by which the inflammatory response influences disease prognosis. Accordingly, we aimed to elucidate the role of polymorphisms in the key genes of the formation and signaling of the inflammasome as biomarkers of COVID-19 severity. For this purpose, a large and well-defined cohort of 377 COVID-19 patients with mild (n = 72), moderate (n = 84), severe (n = 100), and critical (n = 121) infections were included. A total of 24 polymorphisms located in inflammasome-related genes (NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, IL18, NFKB1, ATG16L1, and MIF) were genotyped in all of the patients and in the 192 healthy controls (HCs) (who were without COVID-19 at the time of and before the study) by RT-qPCR. Our results showed that patients with mild, moderate, severe, and critical COVID-19 presented similar allelic and genotypic distribution in all the variants studied. No statistically significant differences in the haplotypic distribution of NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, and ATG16L1 were observed between COVID-19 patients, who were stratified by disease severity. Each stratified group of patients presented a similar genetic distribution to the HCs. In conclusion, our results suggest that the inflammasome polymorphisms studied are not associated with the worsening of COVID-19.

Clinical features and outcomes of interstitial lung disease in anti-Jo-1 positive antisynthetase syndrome.

BACKGROUND: Interstitial lung disease (ILD) is a common extra-muscular manifestation of antisynthetase (AS) syndrome. ILD prevalence is higher with anti-Jo-1 antibody positivity. Data on long-term outcomes in these patients are lacking. METHODS: Over 15 years, we identified subjects with anti-Jo-1 positive AS syndrome and ILD. Demographics, pulmonary function testing (PFT), high-resolution computed tomography (HRCT), histopathology, and long-term survival were analyzed. RESULTS: We identified 103 subjects (mean age 49.2 years, female predominance [70%]). The predominant myopathy was polymyositis (64%) followed by dermatomyositis (24%). In approximately half of studied subjects, AS syndrome and ILD were diagnosed within 6 months of each other. The majority had restriction on PFTs (98%). Non-specific interstitial pneumonia (NSIP) was the most common HRCT pattern (52%), followed by NSIP overlapping with organizing pneumonia (OP) (22%). Thirty-nine subjects had biopsy data. Ten-year survival was 68%. Multivariable analysis adjusted for age at ILD diagnosis, gender, FVC and DLCO, revealed that male gender (HR = 2.60, p = 0.04) and DLCO at presentation (HR = 0.94, p = 0.05) significantly predicted mortality. CONCLUSIONS: We present a large cohort of anti-Jo-1 positive AS syndrome with ILD and note good overall survival.