Real-world evidence of novel treatments for COVID-19 on mortality: a nationwide comparative cohort study of hospitalized patients in the 1st, 2nd, 3rd and 4th wave in the Netherlands


Open Forum Infectious Diseases


Large clinical trials on drugs for hospitalized COVID-19 patients have shown significant effects on mortality. There may be a discrepancy with the observed real-world effect. We describe the clinical characteristics and outcomes of hospitalized COVID-19 patients in the Netherlands during four pandemic waves, and analyze the association of the newly introduced treatments with mortality, ICU-admission, and discharge alive.


We conducted a nationwide retrospective analysis of hospitalized COVID-19 patients between 27 February 2020 and 31 December 2021. Patients were categorized into waves and into treatment groups (hydroxychloroquine, remdesivir, neutralizing SARS-CoV-2 mAb, corticosteroids, and IL-6 antagonists). Four types of Cox-regression analyses were used: unadjusted, adjusted, propensity matched, and propensity weighted.


Among 5643 patients from 11 hospitals we observed a changing epidemiology during four pandemic waves, with a decrease in median age (67 to 64 years, p < 0.001), in in-hospital mortality on the ward (21% to 15%, p < 0.001), and a trend on the ICU (24% to 16%, p = 0.148). In ward patients, hydroxychloroquine was associated with increased mortality (1.54 (95% CI 1.22-1.96)); remdesivir with a higher rate of discharge alive within 29 days (1.16 (95% CI 1.03-1.31)). Corticosteroids were associated with a decrease in mortality (0.82 (95% CI 0.69-0.96); the results of IL-6 antagonists were inconclusive. In patients directly admitted to the ICU, hydroxychloroquine, corticosteroids, and IL-6 antagonists were not associated with decreased mortality.


Both remdesivir and corticosteroids were associated with better outcomes in ward patients with COVID-19. Continuous evaluation of real-world treatment effects is needed.

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