Clinical Features and Outcome of Low and High Corticosteroids in Admitted COVID-19 Patients

Salma AlBahrani; Jaffar A. Al-Tawfiq; Arulanantham Zachariah Jebakumar; Mohammed Alghamdi; Nawaf Zakary; Mariam Seria; Abdulrahman Alrowis

doi:10.2991/jegh.k.210521.001

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Volume 11, Issue 3, September 2021, Pages 316 - 319

Clinical Features and Outcome of Low and High Corticosteroids in Admitted COVID-19 Patients

Authors

Salma AlBahrani¹^{, 2}, Jaffar A. Al-Tawfiq³^{, 4}^{, 5}^{, *}^,, Arulanantham Zachariah Jebakumar⁶^,, Mohammed Alghamdi¹, Nawaf Zakary¹, Mariam Seria¹, Abdulrahman Alrowis¹

¹Department of Medicine, King Fahad Military Medical Complex, Dhahran, Saudi Arabia

²Infectious Disease Unit, King Fahad Military Medical Complex, Dhahran, Saudi Arabia

³Infectious Disease Unit, Specialty Internal Medicine, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia

⁴Infectious Disease Division, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

⁵Infectious Disease Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

⁶Postgraduate Studies and Research, Prince Sultan Military College of Health Sciences, Dhahran, Saudi Arabia

^*Corresponding author. Email: jaffar.tawfiq@jhah.com; jaltawfi@yahoo.com

Corresponding Author

Jaffar A. Al-Tawfiq

Received 7 March 2021, Accepted 21 May 2021, Available Online 2 June 2021.

DOI: 10.2991/jegh.k.210521.001 How to use a DOI?
Keywords: SARS-CoV-2; COVID-19; steroid; high-dose steroid
Abstract: Introduction: There is no specific anti-viral therapies for 2019 Coronavirus Diseases (COVID-19) infection. Here, we compared patients receiving steroids at different dosages versus no steroids in severe and critical COVID-19 patients.

Methods: We retrospectively studied COVID-19 patients who received low-dose or high-dose corticosteroid therapy compared to no steroid.

Results: The study period, June–August 2020, included 169 patients with COVID-19 were included and there were 39.1% female and 60.9% male with an average age of 53.1 years. The distribution of cases was as follows: high-dose 39 (23.1%), low-dose 54 (32.0%), and no steroid 76 (45.5%). Of all the patients, Intensive Care Unit (ICU) admission was for 31 (18.3%), nine (5.3%) required intubation, and 52 (30.8%) had no comorbidities. There is no difference in the mean age between the different groups. However, those being treated with steroid were more likely to have a high sequential organ failure assessment (SOFA) score (0.37 ± 0.68, 0.36 ± 0.67 and 0.04 ± 0.34, for low-dose, high-dose steroid and no steroid groups, respectively (p = 0.001). Cox regression was not possible as the mortality rate was very low (3/169; 1.78%) and none of the multivariate methods would be possible. However, there was a significant difference in the hospital Length of stay (LOS) and the ICU LOS.

Conclusion: Cox regression was not possible as the mortality rate was very low (1.78%) and none of the multivariate methods would be possible as the model will not converge. However, in t-test only, intubation was associated risk of mortality.
Copyright: © 2021 The Authors. Published by Atlantis Press International B.V.
Open Access: This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

1. INTRODUCTION

The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) had resulted in a clinical spectrum of SARS-CoV-2 infection. Patients may present with symptoms ranging from mild to severe infection requiring intensive care unit admission. In addition, asymptomatic infections were also described [1–6]. The need for Intensive Care Unit (ICU) admission is estimated to be 5% with increased mortality compared to those who do not require ICU admission [7,8]. The physiologic description of the 2019 Coronavirus Diseases (COVID-19) consists of an initial viral replication phase and then the immune system reactions would lead to the development of inflammatory responses with a wide range of clinical findings [9,10]. The second phase of immune response may lead to a disproportionate and unregulated cytokine releasing storm resulting and subsequent emergence of acute respiratory distress syndrome, and death [11–13]. Based on the clinical presentation and the pathophysiology of COVID-19, the case fatality rates varies from 61.5% in those requiring intensive care admission in earlier studies [14] and may be lower as cited in more recent studies of a fatality rate of 25.8% [15].

Multiple studies across the world had included multiple interventions to cure SARS-CoV-2 infections. However, the main stay of therapy of such patients relies on supportive care [16]. It is also important to use immunomodulatory agents to treat cytokine releasing storm and this is being studies as well [16] as the use of corticosteroid therapy [10,16,17]. The landmark of steroid therapy in COVID-19 patients is the RECOVERY trial which utilized dexamethasone at a dose of 6 mg intravenous or oral once a day [18]. In the Kingdom of Saudi Arabia, studies had been conducted to describe the epidemiology and clinical features including those who required ICU admission and those who were cared for in quarantine facilities [4–6,8,19]. Here, we sought to further evaluate the utilization and effect of high- and low-dose of corticosteroids in comparison to no-steroid therapy in patients with severe and critical conditions of COVID-19.

2. MATERIALS AND METHODS

This is a retrospective study of COVID-19 patients who received systemic corticosteroids and those were compared to no steroid therapy. Initial patients did not receive steroid and subsequent patients were given corticosteroid based on the results from the RECOVERY trial (6 mg p.o./i.v. once per day) in June 2020. Then in mid-July 2020, high-dose corticosteroid was used based on the hospital COVID-19 team consensus of slow clinical response in relation with low dexamethasone dosage.

High-dose weight-based dexamethasone dose was 0.1–0.2 mg/kg/day for moderate to severe illness and 0.2–0.4 mg/kg/day for critically ill. Methylprednisolone dose was 0.5–1 mg/kg/day for moderate to severe illness and 1–2 mg/kg/day for critically ill. Prednisone dose was 0.6–1.2 mg/kg/day for moderate to severe illness and 1.2–2.5 mg/kg/day. These doses were adjusted per use in connective tissue disease/autoimmune diseases. The indication for the use of steroid was per Infectious Diseases Society of America (IDSA) therapy recommendation in hospitalized with severe illness (O₂ saturation ≤94% on room air, the requirement of supplemental oxygen, mechanical ventilation or extracorporeal membrane oxygenation).

We collected the demographic of the patients, reviewed medical history, laboratory findings, chest radiology, medication use and clinical outcomes during the administering of glucocorticoids. The study was approved by the Institutional Review Board (IRB) of the King Fahad Military Medical Complex (AFHER-IRB-2020-032).

2.1. Statistical Analysis

Descriptive analysis was used for qualitative and quantitative variables. Then further statistical analysis was performed using correlation between variables and patient outcomes. Cox regression model was used to calculate Hazard Ratio (HRs) and 95% Confidence Intervals (CIs).

The demographic characters were compared between three groups (low steroid, high steroid and no steroid) using statistical tests such as ANOVA (F-test) and Chi-square test, as appropriate. All statistical tests will be two-sided. A p-value of ≤0.05 was considered statistically significant.

3. RESULTS

During the study period from June to August 2020, 169 patients with COVID-19 were included and there were 39.1% female and 60.9% male (Table 1). The average age was 53.1 with standard deviation 16.7. The distribution of the patients was as follows: High-dose 39 (23.1%), low-dose 54 (32.0%), and no steroid 76 (45.5%). Of all the patients, 103 (60.9%) were male, ICU admission for 31 (18.3%), nine (5.3%) required intubation, and 52 (30.8%) had no comorbidities. The other patients (68.2%) had comorbidities as shown in Table 1.

Demographic characters	Frequency	Percentage
Male	103	60.9
Female	66	39.1
High-dose steroid	39	23.1
Low-dose steroid	54	32
No steroid	76	45
ICU admission	31	18.3
Intubated	9	5.3
Without intubation	160	94.7
With oxygen	92	54.4
Without oxygen	77	45.6
Bronchial asthma	6	3.6
Diabetes mellitus	21	12.4
Hypertension	73	43.2
Obesity	9	5.3
SCD	5	3
SLE	3	1.8
No comorbidities	52	30.8

SCD, Sickle cell disease; SLE, Systemic lupus erythematosus.

Table 1

Socio-demographic characteristics of the cohort of the COVID-19 positive cases (n = 169)

The differences in the characteristics of the patients in the different groups are shown in Table 2. Those who received steroid were more likely to be in the ICU, require mechanical ventilation and have underlying comorbidities. There is no difference in the mean age between the different groups. However, those being treated with steroid were more likely to have a high Sequential Organ Failure Assessment (SOFA) score (0.37 ± 0.68, 0.36 ± 0.67 and 0.04 ± 0.34, for low-dose, high-dose steroid and no steroid groups, respectively (p = 0.001).

Demographic characters	Low-dose steroid	High-dose steroid	No steroid group	p
Male	37 (68.5%)	28 (71.8%)	38 (50%)	0.03
Female	17 (31.5%)	11 (28.2%)	38 (50%)	0.03
ICU admission	18 (33.3)	12 (30.8)	1 (1.3)	<0.0001
Intubation	7 (13)	2 (5.1)	0	0.005
Initial O₂ requirement	45 (83.3)	38 (97.4)	9 (11.8)	<0.0001
Comorbidity
Bronchial asthma	1 (1.9)	3 (7.7)	2 (2.6)	<0.0001
Diabetes mellitus	9 (16.7)	2 (5.1)	10 (13.2)
Hypertension	27 (50)	18 (46.2)	28 (36.8)
Obesity	2 (3.7)	6 (15.4)	1 (1.3)
Sickle cell disease	0	1 (2.6)	4 (5.2)
Systemic lupus erythematosus	0	1 (2.6)	2 (2.6)
No comorbidities	15 (27.8)	8 (20.5)	29 (38.2)
Age mean (SD)	55.65 (16.95)	54.18 (15.67)	50.71 (16.97)	F-value 1.49 (p = 0.23)
SOFA score mean (SD)	0.37 (0.68)	0.36 (0.67)	0.04 (0.34)	0.001
Hospital LOS mean (SD)	10.30 (17.56)	5.95 (6.26)	2.97 (2.18)	0.001 (F-test)
ICU LOS mean (SD)	18 (58.1)	12 (38.7)	1 (3.2)	<0.0001
Initial oxygen requirement	45 (83.3)	38 (97.4)	9 (9.8)	<0.0001
Hydroxychloroquine	19 (35.2)	10 (25.6)	20 (26.3)	0.48
Azithromycin	49 (90.7)	36 (92.3)	57 (75)	0.02
Favipiravir	2 (3.7)	8 (20.5)	1 (1.3)	0.000
Triple therapy (PEGylated interferon, ribavirin, lopinavir/ritonavir)	16 (29.6)	1 (2.6)	0	<0.0001
Death	0	1 (33.3%)	2 (66.7%)	0.49

Table 2

A comparison between the different groups (low-dose steroid, high-dose steroid and no steroid group)

There was a significant difference in the hospital Length of stay (LOS) and the ICU LOS (Table 2). In addition, there is a significant difference in the use of azithromycin, favipiravir, and triple anti-viral therapy (PEGylated interferon, ribavirin, lopinavir/ritonavir). The low-dose steroid group was more likely to be on triple therapy than the high-dose steroid group (29.6% vs. 2.6%; p < 0.0001) and less likely to be on favipiravir (3.7% vs. 20.5%; p < 0.0001).

We tried to do multivariate analysis. However, Cox regression was not possible as the mortality rate was very low (3/169; 1.78%) and none of the multivariate methods would be possible as the model will not converge. However, a crosstabs and t-tests to show the differences are shown in Table 3. Only, intubation was associated risk of mortality.

Parameters associated with status	Status		Chi-square (p-value)

	Alive	Dead
Comorbidities
Bronchial asthma	6 (100)	0	4.02 (0.67)
Diabetes mellitus	21 (100)	0
Hypertension	70 (95.9)	3 (4.1)
Obesity	9 (100)	0
Sickle cell disease	5 (100)	0
Systemic lupus erythematosus	3 (100)	0
Age group
≤52	87 (100)	0	3.24 (0.07)
>52	79 (96.3)	3 (3.7)
O₂ requirement
Yes	89 (96.7)	3 (3.3)	2.56 (0.11)
No	77 (100)	0
Intubated
Yes	8 (88.9)	1 (11.1)	4.75 (0.03)^*
No	158 (98.8)	2 (1.3)
ICU stay
Yes	30 (96.8)	1 (3.2)	0.46 (0.50)
No	136 (98.6)	2 (1.4)
Group
Steroid	92 (98.9)	1 (1.1)	0.58 (0.45)
Non steroid	74 (97.4)	2 (2.6)
High/Low
High dose	38 (97.4)	1 (2.6)	1.44 (0.49)
Low dose	54 (100)	0
No Steroid	74 (97.4)	2 (2.6)
Favipiravir
Yes	10 (90.9)	1 (9.1)	3.61 (0.06)
No	156 (98.7)	2 (1.3)
Triple therapy
Yes	17 (100)	0	0.34 (0.56)
No	49 (98)	3 (2)
Hydroxychloroquine
Yes	49 (100)	0	1.25 (0.26)
No	117 (97.5)	3 (2.5)
Tocilizumab
Yes	24 (100)	0	0.51 (0.48)
No	142 (97.9)	3 (2.1)
Gender
Male	102 (99)	1 (1)	0.98 (0.32)
Female	64 (97)	2 (3)

*

indicates significant p value.

Table 3

Risk of death in relation to multiple factors using Chi-square test

4. DISCUSSION

The use of corticosteroid for the therapy of patients admitted with COVID-19 had been approved by the Saudi ministry of health on June 17, 2020. The protocol called for the use of steroid in adults with a respiratory rate ≥30/min, blood oxygen saturation equal to or less than 93%, a ration of the PaO₂/FiO₂ of less than 300, the presence of lung infiltration of 50% within 24–48 h [20]. In a recent study from Saudi Arabia, 40 patients with severe COVID-19 were treated with a combination of corticosteroid and tocilizumab and the mortality rate was 15% [13]. The patients in the high-dose steroid had a higher rate of the use of favipiravir than those in the low-dose steroid. The use of favipiravir was 38% in a study from Tokyo, Japan [21]. In a recent randomized controlled trial, the use of favipiravir was associated with shorter duration of illness in those with mild-moderate COVID-19 [22]. The mean days of ICU and hospital stay was 6 and 22 days in a study from Tokyo [21]. However, the mean (±SD) of ICU and hospital stay were 10.30 (±17.56) and 18 (5 ± 8.1) for low-dose steroid and were 12 (38.7) and 5.95 (6.26) for high-dose steroid, respectively.

The use of high-dose corticosteroid is not well studied in relation to COVID-19 cases. In a study from Tokyo, Japan, 16 (66.7%) of 24 patients received high-dose methylprednisolone (500–1000 mg) [21]. In a report of two cases, there was a suggestion that high-dose steroid might be of benefit in low resource countries [23]. In a retrospective study comparing high-dose versus conventional doses of corticosteroid, it was noted that high-dose group were more likely to have comorbid conditions [24]. The study showed that the risk of mortality and the need for mechanical ventilation was higher in the high-dose corticosteroid even after adjusting for baseline characteristics [24].

In our study, the ICU admitted patients were prescribed high-dose steroid and this can be explained by their illness severity, although most of them had required oxygen but were less to be mechanically intubated and had a shorter LOS. Moreover, underlying comorbidities was almost similar between the high versus the low steroid group except for hypertensive patients were more in low steroid group. In addition, the use of antiviral agents was more with low steroid group. However, our study is a retrospective study and thus no firm conclusions could be drawn and the role of high-dose steroid remains to be established if any. Cox regression was not possible as the mortality rate was very low (1.78%) and none of the multivariate methods would be possible as the model will not converge. However, in t-test only, intubation was associated risk of mortality.

CONFLICTS OF INTEREST

The authors declare they have no conflicts of interest.

AUTHORS’ CONTRIBUTION

All authors contributed to the data gathering, analysis, or drafting the first draft. All authors approved the final draft.

FUNDING

No financial support was provided.

Footnotes

Data availability statement: Data available upon reasonable request.

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Journal: Journal of Epidemiology and Global Health
Volume-Issue: 11 - 3
Pages: 316 - 319
Publication Date: 2021/06/02
ISSN (Online): 2210-6014
ISSN (Print): 2210-6006
DOI: 10.2991/jegh.k.210521.001 How to use a DOI?
Open Access: This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

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ris enw bib

TY  - JOUR
AU  - Salma AlBahrani
AU  - Jaffar A. Al-Tawfiq
AU  - Arulanantham Zachariah Jebakumar
AU  - Mohammed Alghamdi
AU  - Nawaf Zakary
AU  - Mariam Seria
AU  - Abdulrahman Alrowis
PY  - 2021
DA  - 2021/06/02
TI  - Clinical Features and Outcome of Low and High Corticosteroids in Admitted COVID-19 Patients
JO  - Journal of Epidemiology and Global Health
SP  - 316
EP  - 319
VL  - 11
IS  - 3
SN  - 2210-6014
UR  - https://doi.org/10.2991/jegh.k.210521.001
DO  - 10.2991/jegh.k.210521.001
ID  - AlBahrani2021
ER  -

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