High Anti-Interferon-Alpha Autoantibody Levels in Severe/Critical COVID-19 Patients from Peru

Innate immune responses through the production of type I interferon-α (anti-IFN-α) play an essential role in the defense against viruses. The autoantibodies (auto-Abs) anti-IFN-α are implicated in COVID-19 pathogenesis with higher levels among patients with worse prognoses. The study aimed to assess the levels of anti-IFN-α auto-Abs in Peruvian patients with severe/critical hospitalized COVID-19 compared to asymptomatic/mild COVID-19 outpatients and healthy controls. We analyzed 101 serum samples, including 56 (55.5%) severe/critical, 13 (12.3%) asymptomatic/mild COVID-19 patients, and 32 (32.2%) healthy controls, which we tested using a commercial ELISA anti-IFN-α-auto-Abs kit. We observed seropositivity of 48.2% (26/54) to anti-IFN-α auto-Abs among the severe/critical COVID-19 group, but 0% (0/13) and 3.1% (1/32) among the asymptomatic/mild COVID-19 and healthy groups (P = 0.021), respectively. Furthermore, we observed a significant association between the log₁₀ of anti-IFN-α auto-Abs and the COVID-19 status, with the log₁₀ of anti-IFN-α auto-Abs levels being significantly higher among the severe/critical COVID-19 group compared to the healthy controls (β = 1.20; confidence interval [95% CI]: 0.72-1.67; P < 0.001). Such association remains significant either when adjusted by age and gender (adjusted β = 1.16; 95% CI: 0.62-1.70; P < 0.001) and when adjusted by the subjects' age, gender, and obesity (adjusted β = 1.16; 95% CI: 0.62-1.70; P < 0.001). Despite not measuring neutralizing activity, this study highlights the high frequency of these auto-Abs in the Peruvian population with a worse prognosis of COVID-19.