Intravenous methylprednisolone pulse therapy and the risk of in-hospital mortality among acute COVID-19 patients: Nationwide clinical cohort study

Table 4 Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of in-hospital mortality after pulse methylprednisolone therapy and an intermediate/higher dose of methylprednisolone among acute COVID-19 patients with or without invasive mechanical ventilation (iMV)

	iMV-free patients		iMV-receiving patients
Pulse methylprednisolone therapy (≥ 500 mg per day)^a	Not prescribed	Prescribed	Not prescribed	Prescribed
No. at risk	63,149	1814	1955	430
No. of deaths	1441	353	483	123
Crude mortality	2.3%	19.5%	24.7%	28.6%
Multivariable-adjusted^b HRs (95% CIs)	Reference	2.86 (2.53–3.22)	Reference	1.01 (0.88–1.16)
Marginal structural model^c HRs (95% CIs)	Reference	3.38 (3.02–3.79)	Reference	0.59 (0.52–0.68)

Intermediate/high dose of methylprednisolone (40–250 mg per day)	Not prescribed	Prescribed	Not prescribed	Prescribed
No. at risk	64,500	2253	1790	595
No. of deaths	2012	238	456	150
Crude in-hospital mortality	3.1%	10.6%	26.0%	25.2%
Multivariable-adjusted^b HRs (95% CIs)	Reference	1.76 (1.53–2.02)	Reference	0.85 (0.71–1.03)
Marginal structural model^c HRs (95% CIs)	Reference	2.38 (2.11–2.70)	Reference	0.80 (0.71–0.89)

COVID-19 coronavirus disease 2019
^aThe median (interquartile range) prescribed pulse methylprednisolone therapy was 1000 (500–1000) mg per day; the median (interquartile range) intermediate/higher dose of intravenous methylprednisolone was 80 (40–250) mg per day
^bMultivariable-adjusted models were adjusted to demographic information (age, sex, smoking status, and body mass index), status at hospital admission (coma, shock, cardio-respiratory failure, and transferred hospital), and history of comorbidities (cancer, chronic lung disease, ischemic heart disease, diabetes, cerebral vascular disease, chronic heart failure, arrhythmia, hypertension, chronic kidney disease, dementia, dyslipidaemia, iron deficiency anaemia, peripheral vascular disease, and liver cirrhosis)
^cMarginal structural model controlled further for the time to other clinical implications (time implicated to intensive care unit administration, renal replacement therapy administration, extracorporeal membrane oxygenation, vasopressin, blood transfusion, dexamethasone, tocilizumab, ivermectin, hydroxychloroquine, remdesivir, baricitinib, macrolides, carbapenems, required oxygen, non-invasive positive pressure ventilation, intermediate/higher doses or pulse methylprednisolone therapy, and anti-fungal interventions)

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