Association Between Prolonged Corticosteroids Use in COVID-19 and Increased Mortality in Hospitalized Patients

A Retrospective Study With Inverse Probability of Treatment Weighting Analysis

Marina Verçoza Viana; José Augusto Santos Pellegrini; Amanda Vilaverde Perez; Patrícia Schwarz; Daiandy da Silva; Cassiano Teixeira; Marcelo Basso Gazzana; Tatiana Helena Rech

Disclosures

Crit Care. 2023;27(143)

Abstract and Introduction

Abstract

Background: Previous studies have demonstrated a beneficial effect of early use of corticosteroids in patients with COVID-19. This study aimed to compare hospitalized patients with COVID-19 who received short-course corticosteroid treatment with those who received prolonged-course corticosteroid treatment to determine whether prolonged use of corticosteroids improves clinical outcomes, including mortality.

Methods: This is a retrospective cohort study including adult patients with positive testing for Sars-CoV-2 hospitalized for more than 10 days. Data were obtained from electronic medical records. Patients were divided into two groups, according to the duration of treatment with corticosteroids: a short-course (10 days) and a prolonged-course (longer than 10 days) group. Inverse probability treatment weighting (IPTW) analysis was used to evaluate whether prolonged use of corticosteroids improved outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were hospital infection and the association of different doses of corticosteroids with hospital mortality. Restricted cubic splines were used to assess the nonlinear association between mortality and dose and duration of corticosteroids use.

Results: We enrolled 1,539 patients with COVID-19. Among them, 1127 received corticosteroids for more than 10 days (prolonged-course group). The in-hospital mortality was higher in patients that received prolonged course corticosteroids (39.5% vs. 26%, p < 0.001). The IPTW revealed that prolonged use of corticosteroids significantly increased mortality [relative risk (RR) = 1.52, 95% confidence interval (95% CI): 1.24–1.89]. In comparison to short course treatment, the cubic spline analysis showed an inverted U-shaped curve for mortality, with the highest risk associated with the prolonged use at 30 days (RR = 1.50, 95% CI 1.21–1.78).

Conclusions: Prolonged course of treatment with corticosteroids in hospitalized patients with COVID-19 was associated with higher mortality.

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Crit Care. 2023;27(143) © 2023 BioMed Central, Ltd.
Copyright to this article is held by the author(s), licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original citation.

Abstract and Introduction
Background
Methods
Results
Discussion
Conclusions
References

Table 1. Baseline characteristics of patients
Characteristic	Overall (n = 1,539)	Short corticosteroids (n = 412)	Prolonged corticosteroids (n = 1,127)	p
All hospitalized patients (n = 1539)
Demographics
Age (years)	59 ± 15	61 ± 15	59 ± 14	0.008
Men (n, %)	837 (54.4)	221 (53.6)	616 (54.7)	0.766
Need for ICU at any time (n, %)	1,364 (88.6)	338 (82)	1,026 (91)	< 0.001
Use of corticosteroids
Maximum MED (mg)	46 (32–80)	32 (32–36)	56 (36–96)	< 0.001
Total length of corticosteroids use (days)	15 (10–24)	9 (7–10)	19 (14–28)	< 0.001
Biochemical measurements
CRP (mg/dL)	121 (62–199)	114 (56–188)	125 (67–206)	0.014
LDH (U/L)	481 (337–642)	455 (311–599)	491 (339–663)	0.024
D-dimer (mg/L)	1.9 (0.9–5.5)	1.9 (0.9–5.3)	1.9 (0.9–5.6)	0.869
	Overall (n = 622)	Short corticosteroids (n = 163)	Prolonged corticosteroids (n = 459)	p
Critically ill patients (n = 622)
Demographic
Age (years old)	57 ± 14	57 ± 15	57 ± 14	0.748
Men (n, %)	347 (55.8)	90 (55.2)	257 (56)	0.936
Use of corticosteroids
Maximum MED (mg)	53 (2.5–90)	32 (32–40)	64 (40–100)	< 0.001
Total duration of corticosteroid use (days)	15 (10–26)	9 (7–10)	20 (14–30)	< 0.001
Time from hospital admission to initiation of corticosteroids (days)	0 (0–0)	0 (0–1)	0 (0–0)	< 0.001
Biochemical measurements
CRP (mg/dL)	139 (83–219)	127 (75–197)	145 (84–229)	0.066
LDH (U/L)	553 (415–729)	527 (450–647)	562 (412–757)	0.315
D-dimer (mg/L)	2.3 (1.1–8.7)	2.3 (1.2–10.4)	2.3 (1.1–7.6)	0.376

Values are mean ± SD or median and interquartile range
ICU intensive care unit, MV mechanical ventilation, MED methylprednisolone equivalent dose, CRP C-reactive protein, LDH lactate dehydrogenase

Table 2. Outcomes of hospitalized patients with COVID-19 pneumonia
Outcomes	Overall (n = 1539)	Short corticosteroids (n = 412)	Prolonged corticosteroids (n = 1127)	p
All hospitalized patients (n = 1539)
In-hospital mortality (n, %)	552 (35.9)	107 (26)	445 (39.5)	< 0.001
ICU mortality (n, %)	473 (30.7)	75 (18.2)	398 (35.3)	< 0.001
Hospital LOS (days)	23 (16–33)	17 (13–24)	25 (17–36)	< 0.001
Transfer to another facility (n, %)	138 (9)	35 (8.5)	103 (9.1)	0.771
ICU LOS (days)	16 (8–27)	11 (5–17)	19 (10–30)	< 0.001
Time spent on MV (days)	16 (10–27)	11 (6–15)	18 (11–29)	< 0.001
Number of antibiotics used	4 (2–6)	2 (1–4)	4 (2–6)	< 0.001
Days on antibiotics	16 (8–31)	11 (6–20)	20 (10–34)	< 0.001
Number of positive hemoculture	0.00 [0.00, 2.00]	0.00 [0.00, 1.00]	1.00 [0.00, 2.00]	< 0.001
	Overall (n = 622)	Short corticosteroids (n = 163)	Prolonged corticosteroids (n = 459)	p
Critically ill patients (n = 622)
In-hospital mortality (n, %)	267 (42.9)	44 (27)	223 (48.6)	< 0.001
ICU mortality (n, %)	258 (41.5)	41 (25.2)	217 (47.3)	< 0.001
Hospital LOS (days)	25 (17–35)	18 (14–28)	27 (19–38)	< 0.001
ICU LOS (days)	21 (14–31)	14 (11–21)	23 (16–34)	< 0.001
Time spent on MV (days)	18 (12–29)	13 (7–19)	21 (14–32)	< 0.001
Number of antibiotics used	5 (3–7)	4 (2–5)	5 (4–7)	< 0.001
Days on antibiotics	23 (12–38)	13 (7–24)	26 (14–42)	< 0.001
Number of positive hemoculture	1.00 [0.00, 2.00]	1.00 [0.00, 2.00]	1.00 [0.00, 2.00]	< 0.001

Values are mean ± SD or median and interquartile range
ICU intensive care unit, LOS length of stay, MV mechanical ventilation

Table 3. Association of prolonged use of corticosteroids and outcomes using the inverse probability of treatment weighting analysis
Outcome	Relative risk	95% CI	p value
All hospitalized patients (n = 1539)
In-hospital mortality	1.76	1.41–2.22	< 0.001
Number of antibiotics used	1.12	1.06–1.19	< 0.001
Number of positive hemocultures	1.25	1.12–1.40	< 0.001
Critically ill patients (n = 622)
In-hospital mortality	2.37	1.67–3.47	< 0.001
Number of antibiotics used	1.19	1.09–1.29	< 0.001
Number of positive hemocultures	1.11	0.96–1.28	0.155