Pre-exposure to anti-TNFα decreases COVID-19 symptoms: a multicentre
retrospective cohort study
BACKGROUND AND PURPOSE: 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.
EXPERIMENTAL APPROACH: 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. KEY
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.
CONCLUSIONS AND IMPLICATIONS: 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.