The Contribution of COVID-19 to Acute Respiratory Distress Syndrome-Related Mortality in the United States.

Acute respiratory distress syndrome (ARDS) is the most common severe pulmonary complication of the coronavirus disease 2019 (COVID-19). Although considered earlier in the pandemic to represent a different clinical entity than nonCOVID-19 ARDS [1], it is nevertheless estimated that ARDS is present in 75% of intensive care unit (ICU) patients with COVID-19 and in 90% of ICU non-survivors [2]. Importantly, autopsy data show that ARDS, as evidenced by findings of diffuse alveolar damage, is present either in all [3] or in the majority of decedents with COVID-19 [4]. The toll of pre-pandemic ARDS-related deaths in the United States was estimated at nearly 10,000/year [5]. With over 375,000 COVID-19-related deaths in the USA during the first year of the pandemic [6], the epidemiology of ARDS was likely transformed substantially [7]. Accurate accounting of the ARDS-related mortality burden during the COVID-19 pandemic can inform future preventive and interventional efforts, as well as health resource allocation. However, the impact of COVID-19 on ARDS-related mortality at a national level has not been quantified. We used the National Center for Health Statistics (NCHS) Multiple Cause of Death data set, which is available through the Centers for Disease Control Wide-ranging Online Data for Epidemiological Research (CDC WONDER) website [8] to obtain mortality and population data. The mortality data in NCHS are based on information from all death certificates filed in the 50 states and the District of Columbia, and provides up to 20 causes of death in addition to an underlying cause of death. We have identified decedents with a diagnosis of ARDS during 2015 2019, and with a diagnosis of COVID-19, ARDS, or both in 2020, listed among any of the 20 causes of death irrespective of the underlying cause of death, which could be ARDS, COVID-19, or other conditions (e.g., cardiovascular disease, etc.). ARDS and COVID-19 were identified by International Classification of Diseases, Tenth Revision, Clinical Modification codes J80 and J071, respectively. Negative binomial regression with log-link and robust standard errors was used on the 2015 2019 data to forecast the number of ARDS-related deaths in 2020. We then compared the number of observed vs. expected ARDS-related deaths in 2020. In addition, we examined the proportion of a diagnosis of COVID-19 among all decedents with a diagnosis of ARDS and reporting of a diagnosis of ARDS among all decedents with a diagnosis of COVID-19. We then repeated the later analysis within each of the Department of Health and Human Services (HHS) Regions. Data analysis was performed using R 4.0.5 (R Foundation for Statistical Computing, Vienna, Austria). The annual ARDS-related mortality and population data for 2015 2020 are detailed in Table 1. In 2020, there were 51,184 ARDS-related deaths, 384,536 COVID-19-related deaths, and 41,606 deaths with both in the USA. The predicted number of ARDS-related deaths for 2020 was 10,851 (95% confidence interval (CI) 9,714 12,120). The ratio of the observed vs. expected ARDS-related deaths was 4.71 (95% CI 4.62 4.82). A diagnosis of ARDS was reported in 10.8% of all COVID-19-related deaths, ranging from 8.2% (HHS regions 1 and 7) to 16.1% (HHS region 2). A diagnosis of COVID-19 was reported in 81.3% of ARDS-related deaths in 2020. The data on the proportion of a diagnosis of ARDS among decedents with COVID-19 within each HHS region are presented in Table 2. Our study shows that the COVID-19 pandemic was associated with nearly five-fold rise in ARDS-related deaths in the USA during 2020, and a diagnosis of COVID-19 was present in over 80% of all ARDS-related deaths that year. This magnitude of change is unprecedented in ARDS epidemiology. Nevertheless, this dramatic change is likely a substantial underestimate of the actual contribution of COVID-19 to ARDS-related mortality in 2020. Although ARDS was present, as noted earlier, in the majority of decedents with COVID-19 in autopsy studies [3, 4], a diagnosis of ARDS was reported only in about 1 in 10 of death certificates of all COVID-19-related deaths. The causes of the very low rate of death certificate-based ARDS diagnoses among COVID-19 decedents are unclear. However, this finding may reflect clinicians’ uncertainties Manuscript submitted March 27, 2023, accepted May 4, 2023 Published online May 31, 2023