Early initiation of corticosteroids in patients hospitalized with COVID-19 not requiring intensive respiratory support: cohort study

Abstract

ObjectivesTo determine whether early oral or parenteral corticosteroids compared to no corticosteroids are associated with decreased mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) who are not on intensive respiratory support (IRS) within 48 hours of admission.DesignObservational cohort studySettingNationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated US national healthcare systemParticipants9,058 patients admitted to a Veterans Affairs Medical Center between June 7, 2020-December 5, 2020 within 14-days after SARS-CoV-2 positive test; exclusion criteria include less than a 48 hour stay, receipt of prior systemic corticosteroids, and no indication of acute medical care for COVID-19.Main outcome measure90-day all-cause mortalityResultsOf 9,058 total patients (95% men, median age 71 years, 27% black), 6,825 (75%) were not on IRS within 48 hours. Among the 3,025 patients on no oxygen, 598 (20%) received corticosteroids and 283 (9%) died; of 3,800 patients on low-flow nasal cannula oxygen (NC), 2,808 (74%) received corticosteroids and 514 (13%) died. In stratified, inverse probability weighted Cox proportional hazards models comparing those who did and did not receive corticosteroids, patients on no oxygen experienced an 89% increased risk for 90-day mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.33 to 2.68); there was weak evidence of increased mortality among patients on NC (HR 1.21, 95% CI 0.94 to 1.57). Results were robust in subgroup analyses including restricting corticosteroids to dexamethasone, and in sensitivity analyses employing different modeling approaches.ConclusionsIn patients hospitalized with COVID-19, we found no evidence of a mortality benefit associated with early initiation of corticosteroids among those on no oxygen or NC in the first 48 hours, though there was evidence of potential harm. These real-world findings support that clinicians should consider withholding corticosteroids in these populations and further clinical trials may be warranted.

Dexamethasone attenuates interferon-related cytokine hyperresponsiveness in COVID-19 patients

“…Despite the proven efficacy of dexamethasone in lowering mortality predominantly in severe or critical COVID-19 patients, a large observational cohort study has demonstrated that dexamethasone treatment had no mortality benefit on those receiving supplemental oxygen via low-flow nasal cannula in the first 48 hours, while it increased mortality in patients not receiving oxygen (13). Moreover, dexamethasone has treatment-related adverse events, including hyperglycemia, cardiovascular events, and bacterial superinfections (83,84).…”

“…The greatest benefit was shown for patients receiving invasive mechanical ventilation compared to those on non-invasive oxygen support. A metaanalysis of the RECOVERY trial and subsequent studies support the beneficial effect on survival and ventilator-free days in patients with severe disease (12), but suggest that dexamethasone treatment in patients without oxygen support may be harmful (13).…”

Crosslink between SARS-CoV-2 replication and cystic fibrosis hallmarks

“…The results of several randomized trials support the protective effect of systemic corticosteroid therapy in hospitalized patients with COVID-19 that require supplemental oxygen (Sterne et al, 2020;Li et al, 2021). In contrast, corticosteroids have shown no benefits and may harm hospitalized patients with milder COVID-19 who do not require supplemental oxygen (Horby et al, 2021;Crothers et al, 2022). Therefore, WHO guidelines recommend the use of corticosteroids for hospitalized patients with severe COVID-19 disease who are in need of oxygen supplementation (Corticosteroids for COVID-19 [internet], 2020).…”

The aqueous root extract of Withania somnifera ameliorates LPS-induced inflammatory changes in the in vitro cell-based and mice models of inflammation

“…Corticosteroids, as mentioned above, are the choice of medication by a standard medical practitioner to combat inflammation occurring in the lungs and other vital organs of patients infected with Coronavirus due to their potent anti-inflammatory properties (Li et al, 2021). Dexamethasone, a corticosteroid that has been previously shown to inhibit LPS-induced inflammation in both in vitro and in vivo models have been recommended for use in Corona patients also (RECOVERY Collaborative Group, 2021;Crothers et al, 2021). The unguided use of corticosteroids in patients, however, can be harmful in patients with metabolic diseases such as diabetes, hypertension, and other inflammatory diseases due to their side effects (Sterne and Murthy, 2020).…”