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 new treatments for COVID-19 on mortality: a comparative nationwide cohort study of wave 1, 2, 3 and 4 hospitalized patients in the Netherlands. Image credit: Nhemz/Shutterstock
background
The first case of COVID-19 in the Netherlands was identified on 27 February 2020. The Netherlands witnessed four waves of COVID-19 in January 2022. The characteristics and outcomes of COVID-19 have been heterogeneous in pandemic waves. When hospitalizations increased rapidly, multiple new drugs were tested and implemented in clinical practice if preliminary evidence was encouraging.
Numerous randomized controlled trials have evaluated antivirals, neutralizing antibodies, and immunosuppressive medications among hospitalized patients. Some trials have been instrumental in identifying therapies that affect mortality from COVID-19. However, there is a discrepancy between the benefit of therapeutic implementation on mortality and the real-world effect.
About the study
In the present study, researchers described the characteristics and outcomes of COVID-19 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 Register of Intensive Care Evaluation (NICE) were used.
Eligible participants were adults (aged 18 years or older) hospitalized with COVID-19 between February 27, 2020 and December 31, 2021. Readmissions during this period were also considered. The primary outcome of the study was in-hospital death. Secondary outcomes included mortality at 12 weeks, intensive care unit (ICU) admission, and discharge within 29 days.
Subjects were stratified into the following groups: remdesivir, anti-SARS-CoV-2 acute respiratory syndrome 2 (mAbs) 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-square tests for parametric, nonparametric, and categorical data, respectively. Ward and ICU patients were analyzed separately. Primary and secondary outcomes were examined using Cox regression.
discoveries
Data from the NICE register revealed 89,110 patients with COVID-19 admitted to hospital wards and 16,590 patients admitted to ICUs. Among these, 10,317 ward patients and 4,511 ICU patients succumbed to COVID-19. Approximately 70% (5643) of patients in the CovidPredict database were eligible for inclusion.
Of these, 5187 were patients admitted to the ward and 456 were patients in the ICU. Six new 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 men admitted to hospital wards and the average age of ward patients declined with the waves of COVID-19. Likewise, the gross in-hospital mortality of patients admitted to wards decreased from 21% in the first wave to 15% in the fourth wave. Hydroxychloroquine and lopinavir/ritonavir were used almost exclusively in the first wave, and remdesivir was used in the second.
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. The average age of ICU patients decreased in the waves of COVID-19, and mortality decreased from 30% in the first wave to 16% in the fourth.
Antiviral and immunosuppressive medications were started two days after hospitalization in more than 80% of cases. Hydroxychloroquine given within the first two days of hospital admission increased the risk of mortality and reduced the discharge rate among ward patients. Treatment with remdesivir was associated with lower in-hospital mortality and higher discharge rates.
MAb treatment showed no significant association with discharge outcomes or mortality. Corticosteroids are significantly associated with lower in-hospital and 12-week mortality rates and higher discharge rates in ward patients. Treatment with IL6 antagonists significantly increased ICU admissions and mortality at 12 weeks and reduced the discharge rate.
For patients admitted directly to the ICU at the time of admission, there were no associations of corticosteroids, hydroxychloroquine, and IL6 antagonists with mortality and discharge outcomes. In a subanalysis of patients admitted to the ICU directly excluding patients from the first wave, corticosteroid treatment was associated with a significant reduction in mortality outcomes in adjusted Cox regression analysis.
Conclusions
In summary, the researchers observed the changing epidemiology of hospitalized patients with COVID-19 across four pandemic waves. In-hospital mortality decreased with waves of COVID-19 in ward patients, while it did not change for ICU patients. Only remdesivir and corticosteroids showed positive associations with mortality and discharge outcomes among ward patients. Given the continuous evolution of SARS-CoV-2, it is imperative to continuously evaluate the actual effectiveness of new anti-COVID-19 drugs.