Steroids may reduce risk for death after severe COVID-19 hospitalization
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Anti-inflammatory medications like steroids at hospital discharge may reduce post-acute infection mortality risk in patients who experienced hyperinflammation from severe COVID-19, according to data published in Frontiers in Medicine.
“Patients who have recovered from COVID-19 are at increased risk for hospitalization and death within 6-12 months after the initial episode,” Arch G. Mainous III, PhD, of the University of Florida, and colleagues wrote. “This morbidity and mortality is typically not listed or considered as a COVID-19 linked hospitalization or death in the medical records and thus are underreported as a post-acute COVID-19 sequelae. The reason for this phenomenon of severe outcomes as post-acute sequelae of COVID-19 is not well understood.
“Moreover, even 40-60 days post-acute COVID-19 infection there is evidence of a significant remaining inflammatory response in patients,” they added. “... Following from this hyperinflammation, the use of steroids as anti-inflammatory treatments among patients with high inflammation during the initial COVID-19 episode may do more than just help in the initial episode but may act as a buffer to the downstream morbidity and mortality from the initial COVID-19 episode.”
To examine the relationship between systemic inflammation in hospitalized adults with COVID-19 and post-recovery mortality, Mainous and colleagues analyzed a longitudinal cohort of patients within a large health care system. Patients included in the analysis were aged 18 years or older and tested for COVID-19 between Jan. 1, 2020, and Dec. 31, 2021, in the University of Florida Health System. Patients were only included if they were hospitalized for COVID-19.
Patients were considered to be hospitalized if they were admitted within 30 days of a positive COVID-19 test. Additionally, patients were only included in the final analysis if they retained at least 365 days of follow-up.
C-reactive protein (CRP) was the unit used to measure inflammation, and patients were only included if they underwent one CRP test “within their initial COVID-19 episode of care,” the researchers wrote. If multiple tests were performed, the highest value was used for the analysis. Mainous and colleagues also assessed intravenous dexamethasone administered during hospitalization, as well as prescriptions for oral dexamethasone that were prescribed at the hospital or post-discharge.
The primary outcome was 365-day all-cause mortality, derived from electronic health records and the Social Security Death Index. However, patients were censored at the date of their death and causes of death were not reliably reported, the researchers wrote.
According to the researchers, higher-than-normal CRP was associated with other markers of severe COVID-19, including the use of supplemental oxygen and intravenous dexamethasone.
In addition, increased CRP correlated with an increased mortality risk following recovery from acute COVID-19, with an unadjusted hazard ratio of 1.6 (95% CI, 1.18-2.17) and an adjusted hazard ratio of 1.61 (95% CI, 1.19-2.2). Meanwhile, oral steroid prescription at hospital discharge was associated with a lower risk for death (HR = 0.49; 95% CI, 0.73-0.94).
“Hyperinflammation present with severe COVID-19 is associated with an increased mortality risk after hospital discharge,” Mainous and colleagues wrote. “Although suggestive, treatment with anti-inflammatory medications like steroids upon hospital discharge is associated with a decreased post-acute COVID-19 mortality risk.
“This suggests that treating inflammation may also benefit other post-acute sequelae like long COVID,” they added. “A reconceptualization of COVID-19 as both an acute and chronic condition may be useful.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
The sequelae to COVID-19 infection are being studied extensively. Dr. Leonard Calabrese has been lecturing extensively on this topic and there has been an explosion of publications. This study looked at post-COVID-19 mortality. Previous studies have shown an increased mortality 12 months after hospitalization for COVID-19. This study confirmed that but narrowed the group to those with an elevated C-reactive protein.
The authors suggest that COVID-19 should be considered an acute and chronic disease, as their analysis revealed that an inflammation marker — CRP — could predict mortality post-discharge. They also found those being discharged on corticosteroids had a lower mortality. They note that this was an observation and not confirmed by a clinical trial. With the plethora of long-COVID publications, it is reasonable to conclude that this is a real phenomenon.
From my own practice, in addition to post-COVID-19 symptoms, such as brain fog and fatigue, we are seeing patients who were in a low disease assessment state with their rheumatic disease pre-COVID-19 who then flared and have been difficult to control since.
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