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In a recent study posted to the medRxiv* preprint server, researchers assessed the longer- and short-term all-cause mortalities among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients.
Coronavirus disease 2019 (COVID-19) fatalities may occur due to virus, host, vaccine, and therapy variables. For instance, COVID-19 mortality may result from the infection’s ability to lead to adverse effects that result in the death of otherwise healthy individuals. COVID-19 mortality is also possible since SARS-CoV-2 infection worsens the health of individuals susceptible to short-term mortality regardless of the virus. COVID-19 mortality may potentially result from the long-term effects of acute SARS-CoV-2 infection. Understanding the relative impact of these pathways is essential for informing public health efforts regarding the optimal deployment of non-pharmacologic and pharmacologic interventions that can positively influence COVID-19 mortality.
In the present study, researchers evaluated the proportion of all-cause mortalities, including COVID-19-related mortalities, after an initial SARS-CoV-2 infection among SARS-CoV-2 infected individuals.
The team assessed the national mortality database along with the national datasets for COVID-19 laboratory testing, immunization, and mortality, which were retrieved via the national platform for digital-health information. A retrospective matched cohort research was performed to explore the incidence of all-cause death noted between a nationwide cohort of individuals with verified primary SARS-CoV-2 infection and a national reference control group including SARS-CoV-2-naive individuals.
The study groups were matched one-to-one according to gender, 10-year age cohorts, nationality, number of comorbidities, vaccination status, and type of vaccine. Matching allowed the balancing of confounders observed between exposure cohorts that may be associated with death or infection risks. Matching was also performed based on the week of the test detecting the primary COVID-19 infection among the primary-infection group and by the week of a COVID-19-negative test for the infection-naive cohort.
Iterative matching was performed to ensure that individuals in the infection-naive control group were alive and did not have any prior SARS-CoV-2 positive test, were not vaccinated with multiple vaccines, or were not vaccinated with a new dose between the time of the COVID-19-negative test and the beginning of the follow-up.
Each matched cohort comprised 6,85,871 individuals. In the analysis of acute COVID-19 mortality, the median follow-up duration was 91 days. In the primary-infection group, 342 deaths were observed during follow-up, while 288 deaths were noted in the infection-naive group. Among the 342 mortalities, 223 deaths were caused by COVID-19.
After 91 days of follow-up, the cumulative mortality incidence in the primary-infection group was 0.085%, and in the infection-naive group was 0.072%. During the acute scenario, the adjusted hazard ratio (aHR) was 1.19 for comparing the incidence of mortality within the unvaccinated primary-infection group and the unvaccinated infection-naive group. Subgroup studies found that the aHR was 1.34 in individuals with a higher clinical susceptibility to severe COVID-19 compared to 0.94 in those with a lower clinical susceptibility.
In the analysis of post-acute SARS-CoV-2 infection deaths, the median duration of follow-up for each group was 296 days. During follow-up, a total of 72 fatalities were documented in the cohort with primary infection, while 142 deaths were noted in the infection-naive group. Five of the 72 mortalities reported in the primary-infection group were due to COVID-19, which was linked to the primary infection. After 450 days of follow-up, the cumulative mortality incidence was 0.036% within the primary-infection group and 0.060% in the infection-naive group.
During the post-acute period, the aHR comparing mortality incidence in the unvaccinated primary-infection group to the unvaccinated infection-naive group was 0.50. Between the third and seventh month following the main infection, the aHR was 0.41, which rose to 0.76 in the following months. Those who were more clinically susceptible to severe COVID-19 had an aHR of 0.37 during the post-acute phase, while those who were less clinically susceptible to severe COVID-19 had an aHR of 0.77.
In the analysis of acute COVID-19 mortality, the team noted that the aHR that compared mortality incidences among the vaccinated primary infection and the vaccinated infection-naive groups was 0.74. Subgroup analysis indicated that the aHR was 0.64 in individuals with a greater clinical susceptibility to severe COVID-19 as compared to 1.08 in individuals having lesser clinical susceptibility. In the analysis of post-acute SARS-CoV-2 infection deaths, the aHR that compared the mortality incidence in the vaccinated primary-infection group to the infection-naive vaccinated group was 1.10. Subgroup studies indicated that the aHR was 0.96 in individuals with a higher clinical susceptibility to severe COVID-19 and 2.0 in those with a lower clinical susceptibility.
The study findings showed that the present data was consistent with the notion that COVID-19 mortality in Qatar is predominantly driven by the forward migration of persons having a comparatively short life expectancy. Furthermore, the pull-forward effect was evident in the entire population but was significantly more pronounced among individuals who were clinically more susceptible to severe COVID-19. In contrast, no such effect was detected among patients with lower clinical susceptibility. Even if there was no discernible influence for these deaths in Qatar’s population, the findings do not lessen the significance of COVID-19 mortalities among otherwise healthy individuals or deaths caused by long COVID.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.