Pre-exposure to anti-TNFα decreases COVID-19 symptoms: a multicentre
retrospective cohort study
Abstract
AIM: Immune response hyperactivation is critical in the progression of
coronavirus disease (COVID-19). We studied the effect of the
pre-exposure to disease-modifying antirheumatic drugs (DMARDs) that
decrease immunological responses on the incidence of COVID-19 symptoms
to explore therapeutic approaches in its early stages. METHODS:
Multicentre retrospective cohort study including 2,494 patients with
inflammatory diseases recruited from 14 primary care centres in
Barcelona (Spain). The primary outcome was the presence of confirmed or
highly suspected COVID-19 (hsCOVID-19) symptoms reported during March
2020 at primary care or hospital emergency department. Multivariable
Poisson regression models were fitted to estimate hsCOVID-19 symptoms
relative risk (RR) adjusted by comorbidities. RESULTS: Biological
(RR=0.46, CI95%=0.31-0.67) and synthetic (RR=0.62, CI95%=0.43-0.91)
DMARDs used in immunomediated inflammatory diseases diminished the
incidence of symptomatic cases of hsCOVID-19. Striking sex differences
were revealed. Protective effects of anti-TNFα pre-exposure (RR=0.50,
CI95%=0.33-0.75) were higher in women (RR=0.33, CI95%=0.17-0.647),
whereas anti-IL6/12/17/23 compounds pre-exposure (RR=0.47,
CI95%=0.24-0.92) produced slightly higher protective effects in men
(RR=0.44, CI95%=0.15-1.68). Pre-exposure to low glucocorticoid doses
also revealed sex differences decreasing the incidence of hsCOVID-19
symptoms predominantly in women (RR=0.72, CI95%=0.42-1.22). A merely
protective effect of pre-exposure to chloroquine/hydroxychloroquine (RR
0.76, CI95%=0.36-1.62) was observed. CONCLUSION: We identified specific
DMARDs with different immune-depressor mechanisms that decrease
hsCOVID-19 symptoms with striking sex differences. These results
underline the potential interest of starting clinical trials with
anti-TNFα compounds in women to evaluate their efficacy in minimizing
disease progression in the early stages of COVID-19.