In a recent study published in Open Forum Infectious Diseases, researchers described the clinical characteristics and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) in the Netherlands.
Study: 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. Image Credit: Nhemz/Shutterstock
Background
The first COVID-19 case in the Netherlands was identified on February 27, 2020. The Netherlands witnessed four COVID-19 waves by January 2022. COVID-19 characteristics and outcomes have been heterogeneous across the pandemic waves. When hospitalizations increased rapidly, multiple novel drugs were tested and implemented in clinical practice if preliminary evidence was encouraging.
Numerous randomized controlled trials evaluated antivirals, neutralizing antibodies, and immunosuppressive medications among hospitalized patients. Some trials have been instrumental in identifying therapies impacting COVID-19 mortality. Nevertheless, there is a discrepancy between the benefit of the implementation of therapeutics on mortality and the real-world effect.
About the study
In the present study, researchers described COVID-19 characteristics and outcomes in hospitalized patients and analyzed the association between new COVID-19 therapies and some clinical outcomes in the Netherlands. Data from the CovidPredict database and the Dutch National Intensive Care Evaluation (NICE) registry were used.
Eligible participants were adults (18 years or older) hospitalized with COVID-19 between February 27, 2020, and December 31, 2021. Readmissions within this period were also considered. The primary outcome of the study was in-hospital death. Secondary outcomes included 12-week mortality, admission to the intensive care unit (ICU), and discharge within 29 days.
Subjects were stratified into the following groups – remdesivir, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing monoclonal antibodies (mAbs), hydroxychloroquine, interleukin (IL)-6 antagonists, and corticosteroids.
Baseline patient characteristics and outcomes were compared using one-way analysis of variance (ANOVA), Kruskal-Wallis, and Chi-squared tests for parametric, non-parametric, and categorical data, respectively. Ward and ICU patients were separately analyzed. The primary and secondary outcomes were examined using Cox regression.
Findings
NICE registry data revealed 89,110 COVID-19 patients admitted to hospital wards and 16,590 patients admitted to the ICUs. Among these, 10,317 ward patients and 4511 ICU patients succumbed to COVID-19. Approximately 70% (5643) of patients from the CovidPredict database were eligible for inclusion.
Of these, 5187 were ward-admitted patients, and 456 were ICU patients. Six novel therapeutic modalities were implemented as standard or optional care during the study period. The therapeutics were hydroxychloroquine, lopinavir/ritonavir, casirivimab/imdevimab, remdesivir, dexamethasone, and tocilizumab/sarilumab.
The proportion of males admitted to hospital wards and the median age of ward patients decreased over COVID-19 waves. Likewise, crude in-hospital mortality for patients admitted to wards decreased from 21% in the first wave to 15% in the fourth wave. Hydroxychloroquine and lopinavir/ritonavir were almost exclusively used during the first wave, and remdesivir was used in the second wave.
Corticosteroids were the standard treatment in the second wave for patients requiring oxygen. IL6 antagonists were administered in the third wave, and mAbs in the fourth wave. ICU patients’ median age declined across COVID-19 waves, and mortality decreased from 30% in the first wave to 16% in the fourth.
Antiviral and immunosuppressive medications were started within two days of hospitalization in over 80% of cases. Hydroxychloroquine administered in the first two days of hospital admission increased the mortality risk and reduced the rate of discharge among ward patients. Remdesivir treatment was associated with lower in-hospital mortality and higher discharge rates.
MAb treatment showed no significant association with discharge or mortality outcomes. Corticosteroids are significantly associated with lower in-hospital and 12-week mortality rates and higher discharge rates in ward patients. IL6 antagonist treatment significantly increased ICU admissions and 12-week mortality and reduced discharge rate.
For patients directly admitted to ICU at admission, there were no associations of corticosteroids, hydroxychloroquine, and IL6 antagonists with mortality and discharge outcomes. In a sub-analysis of patients admitted to the ICU directly excluding first-wave patients, corticosteroid treatment was associated with a significant reduction in mortality outcomes in the adjusted Cox regression analysis.
Conclusions
In summary, the researchers observed the changing epidemiology of hospitalized COVID-19 patients across four pandemic waves. In-hospital mortality was reduced over COVID-19 waves in ward patients, while it did not change for ICU patients. Only remdesivir and corticosteroids exhibited positive associations with mortality and discharge outcomes among ward patients. Given the continued evolution of SARS-CoV-2, continuously evaluating the real-world efficacy of new anti-COVID-19 drugs is imperative.
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