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. 2024 Aug 20;19(8):e0307265. doi: 10.1371/journal.pone.0307265

Outcomes of different steroid dosing regimens in critical Covid-19 pneumonia at a Kenyan hospital: A retrospective cohort study

John Otieno Odhiambo 1,*, Jasmit Shah 2, Nancy Kunyiha 1, Charles Makasa 1, Felix Riunga 1
Editor: Robert Jeenchen Chen3
PMCID: PMC11335146  PMID: 39163391

Abstract

Background

Among therapeutic options for severe and critical COVID- 19 infection, dexamethasone six milligrams once daily for ten days has demonstrated mortality benefit and is guideline recommended at this dose. In practice, variable doses of steroids have been used, especially in critical care settings. Our study aimed to determine the pattern of steroid dosing and outcomes in terms of critical care mortality, occurrence of dysglycaemias, and occurrence of superadded infections in patients with critical COVID-19.

Methods

A retrospective cohort study was carried out on all eligible patients admitted to the Aga Khan University Hospital, Nairobi, with critical COVID-19 between 1st March 2020 and 31st December 2021. The intervention of interest was corticosteroids quantified as the average daily dose in milligrams of dexamethasone. A steroid dose of six milligrams once a day was compared to high dose steroid dosing, which was defined as any dose greater than this. The primary outcome measure was ICU mortality and secondary outcomes included occurrence of dysglycaemias, superadded infections and duration of critical care admission.

Results

The study included 288 patients. The median age was 61.2 years (IQR: 49.7, 72.5), with 71.2% of patients being male. The most common comorbidities were diabetes mellitus (60.7%), hypertension (58%), and heart disease (12.2%). The average oxygen saturation and C-reactive protein at admission were 82% [IQR: 70.0–89.0]and 113.0 [IQR: 54.0–186.0], respectively. Fifty-eight percent of patients received a standard dose (6mg) of steroids. The mortality rate was higher in the high-dose group compared to the standard-dose group; however, the difference was not statistically significant (47.9% vs 43.7% p = 0.549). The two most common steroid associated adverse effects were uncomplicated hyperglycemia (62.2%) and superimposed bacterial pneumonia (20.1%). The high-dose group had a higher incidence of uncomplicated hyperglycemia compared to the standard-dose group (63.6% vs 61.1%). However, the incidence of diabetic ketoacidosis was lower in the high dose group (0.6% vs 6.6%). Oxygen saturation at admission was associated with survival where it was lower among non-survivor patients with critical COVID-19.

Conclusion

The study found that high-dose steroids in the treatment of critically ill patients with COVID-19 pneumonia did not confer any mortality benefit and were associated with an increased risk of dysglycemia and superimposed infections.

Definition of terms

COVID-19 pneumonia

Clinical and radiologic features consistent with pneumonia and a positive SARS CoV-2 PCR from a respiratory specimen.

Severe COVID-19

Those who are confirmed to have COVID-19 with oxygen saturations less than 94%, requiring oxygen supplementation.

Critical COVID-19

Those who are confirmed to have COVID-19 and have respiratory failure, septic shock, and/or multiple dysfunction. ≥ 0.6mmol/L.

High dose steroid

Dexamethasone dose higher than 6mg Once daily or its equivalence.

Low dose steroid/standard steroid dose

Dexamethasone 6mg once daily or its equivalence.

Dysglycemia

Hyperglycemia, diabetic ketoacidosis or hyperglycemic hyperosmolar state.

Diabetic ketoacidosis

Anyone confirmed to have Diabetes Mellitus with normal or high serum glucose level, blood pH less than 7.3/serum bicarbonate level <18.0mmol/L and serum ketone level.

Hyperglycemic hyperosmolar state

Plasma glucose level >33mmol/L and increased effective plasma osmolality >320mOsm/Kg in the absence of ketoacidosis.

Bloodstream infection

Isolation of a pathogenic microbe from at least one blood culture or isolation of an organism considered to be a skin commensal from at least two sets of blood cultures in the presence of a compatible syndrome as ascertained by an infectious diseases specialist in the study team.

Urinary tract infection

Defined as the growth of a bacterium or fungus in a cultured urine sample from a patient with clinical symptoms and/or the consideration of such urinary infection as clinically significant by an infectious disease specialist in the study team.

Bacterial/viral/mycobacterial/fungal pneumonia

Growth of a bacterial or fungal isolate from a respiratory sample (sputum/tracheal aspirate/ broncho alveolar lavage fluid) or a positive PCR from a respiratory sample with a compatible clinical syndrome as ascertained by an infectious disease specialist in the study team.

Heart disease

Ischemic heart disease, heart failure, or arrhythmias.

Introduction

Steroid use as a cornerstone of the management of severe to critical COVID-19 disease has been established by multiple randomized controlled trials and meta-analysis [1–3]. Dexamethasone was the first steroid to be studied and was found to lower 28-day mortality among patients requiring mechanical ventilation or oxygen supplementation when given at a dose of 6 milligrams once daily for 10 days or until discharge [1].

Initial data on what the optimal dose of steroids should be was scant, and as a result, higher dose steroids were used in several centres [4–7]. More recently, large, randomized controlled trials have suggested that high dose steroids are no more effective than standard dose steroids and may even be associated with mortality and adverse effects [8, 9]. Uncertainty remains on whether high dose steroids would benefit those requiring high oxygen demands, including critically ill patients [10]. Of note is that very little data is available from Africa on treatment of severe and critical COVID-19 with different steroid regimens and outcomes [11]. In the ACCCOS study which investigated outcomes of patients admitted with COVID-19 in intensive or high care units across 10 African countries, steroid therapy was associated with lower risk of mortality [12]. However, no data was given on the dose, duration or complications associated with steroids. In the RECOVERY trial investigating 12 mg vs 6 mg of dexamethasone, only 15 patients out of 1272 randomised patients were from an African country [9]. Although steroids have improved clinical outcomes, their use, particularly at higher doses, has raised concerns for adverse events including superimposed infections and dysglycaemias [9, 13].

We therefore conducted a retrospective cohort study among patients admitted with critical COVID-19 at a referral hospital to investigate the pattern of steroid use in the management of these patients, and the effect on mortality, dysglycaemias and superadded infections.

Materials and methods

Study design

This was a retrospective cohort study conducted between 1st March 2020 and 31st December 2021.

Setting

The study was conducted at the Aga Khan University Hospital, Nairobi (AKUH, N).

Population

We included patients admitted with critical COVID-19 pneumonia between 1st March 2020 and 31st December 2021. Critical COVID-19 pneumonia with defined as those with COVID-19 pneumonia with respiratory failure, septic shock, or multiple organ dysfunction. Those who were pregnant and those who were transferred from other facilities to the critical care units were excluded from our study. Those with missing data that would make the objectives of the study un-assessable were also excluded.

Data collection

Patients were identified from a database maintained by the critical care team that included all patients admitted to the hospital between 1st March 2020, and 31st December 2021. Each file was identified by a unique number allocated to every patient on admission to the facility, and the file was retrieved physically from the hospital’s medical records department. The data collected were entered into REDCap [14]. The data collection was done from October 2022 to January 2023 and all data was de-identified for analysis. The variables of interest included demographic information, date of COVID-19 diagnosis, comorbid conditions, the average daily dose of steroid given in dexamethasone equivalents expressed in milligrams, duration of mechanical ventilation and critical care stay, outcome (discharged alive or dead), and adverse effects associated with corticosteroid use. The intervention of interest was the use of corticosteroids, and the primary outcome was the effect of different steroid doses (standard dose of six milligrams once a day of dexamethasone versus high dose steroids, which was defined as any dose greater than this) on ICU mortality. The secondary outcomes included adverse effects linked to steroid use, (specifically dysglycemia and infections), duration of critical care admission and duration of ventilatory support. Since this was a retrospective study, no consent was required and a waiver was sought and obtained from the Aga Khan University Institutional Scientific and Ethics Review Committee (2022/ISERC-32(v1)) and National Commission for Science, Technology and Innovation (NACOSTI) (Ref 494615).

Data analysis

The data collected was entered into REDCap database and then exported to IBM Statistical Package for the Social Sciences version 22.00(SPSS) for analysis. Categorical data such as comorbid conditions, dysglycemia and infections were presented as frequencies and percentages whereas continuous data for instance age of the patients, durations of ventilatory support and duration of critical care stay were presented as means and standard deviations. Univariate analysis was performed using Chi-squared or Fishers Exact test for categorical data whereas students t-test or Kruskal Wallis Test for continuous data when comparing more than 2 groups. Group comparisons were done based on standard dose (Dexamethasone 10mg OD/equivalence for 10 days) versus high dose (more than dexamethasone 10mg OD/equivalence for 10 days).

Results

Characteristics of the study population

Four hundred and sixty-eight patients were admitted to the critical care units between 1st March 2020 and 31st December 2021. Out of this, 293 were on ventilator support. Five patients were excluded because of incomplete records. Therefore, 288 patients were included in the study. The median age of the patients was 61.2 years (IQR: 49.7–72.5), with 71.2% being male. The most common comorbidities were diabetes mellitus, hypertension, and heart disease reported in 60.7%, 58%, and 12.2% of the patients, respectively. The median oxygen saturation and C-reactive protein at admission were 82.0% (IQR: 70.0–89.0) and 113.0 (IQR:54.0–186.0), respectively. The median duration to discharge from critical care unit was 11 days (IQR: 6–18) and the mortality rate was 45.5%. The median age of non survivors was higher than that of survivors (70.0 years (IQR:54.8–77.7) versus 57.7 years (IQR:47.9–66.7); p<0.001)). Table 1 details the study population characteristics.

Table 1. Demographic and clinical characteristics of 288 patients.

Age (years)    61.2 [49.7, 72.5] 
Gender  Male  205  71.2% 
Female  83  28.8% 
Comorbidities  Hypertension  167  58.0% 
Diabetes  175  60.8% 
CKD  30  10.4% 
Heart Disease  35  12.2% 
Malignancy  4  1.4% 
Chronic Lung Disease  26  9.0% 
Other  120  41.7% 
Outcome  Discharge from critical care 157  54.5% 
Dead  131  45.5% 
Dysglycemia  Uncomplicated Hyperglycemia  179  62.2% 
Diabetic Ketoacidosis  12  4.2% 
Hyperglycemic Hyperosmolar state  2  0.7% 
None  95  33.0% 
Infections  Urinary Tract Infections  27  9.4% 
Superimposed Pneumonia  58  20.1% 
Bloodstream Infection  48  16.7% 
None  194  67.4% 
Steroid Dose Category  Standard (6mg)  167  58.0% 
High (>6mg)  121  42.0% 
Duration of steroid use (Days)  10.0 [9.0, 15.0] 
Duration of critical care admission–all patients (Days)  11.0 [6.0, 18.0] 
Duration of critical care admission- non-survivors (Days)  10.0 [5.0, 17.0] 
SP02 at presentation 82.0 [70.0, 89.0]
CRP at admission 113.0 [54.0, 186.0]
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*Continuous variables presented as median [IQR]

Patterns of steroid use

Fifty eight percent of patients received a standard dose of steroids, while 42% received high dose steroids. The median dose of the high dose group 14.0 mg (IQR:9.5–18.3). The average daily dose of steroid in the high dose group was 15mg. The median duration of steroid use was 10 days (IQR:9–15). When comparing characteristics between those that received standard-dose steroids versus those that received high-dose steroids, CKD, dysglycemia, duration of steroid use and duration of critical care admission were statistically significant. Duration of steroid use was longer in the high dose group compared to the standard dose group (14 days (IQR: 10–19) versus 10 days (IQR: 7–12), p<0.001). Uncomplicated hyperglycemia was higher in the high-dose group compared to the standard-dose group (63.6% vs 61.1%, p = 0.025). Duration of critical care admission in non-survivors was longer in the high-dose group compared to the standard-dose group (11.5 days (IQR: 6–17) vs 8 days (IQR: 4–14), p = 0.036). CRP was found to be statistically significant among the dose groups where the CRP levels were low in the high dose group as compared to the standard dose group; 91.0 (IQR: 45.0–161.0) versus 125.0 (IQR: 62.5–199.5); p = 0.020. Details of the comparison between steroid dose groups are presented in Table 2.

Table 2. Comparison between standard and high dose steroid groups (n = 288).

  Standard Dose  High Dose  P Value 
(n = 167)  (n = 121) 
Age (years)    60.2 [49.5, 71.4]  64.2 [50.2, 73.4]  0.362 
Gender  Male  120  71.9%  85  70.2%  0.793 
Female  47  28.1%  36  29.8% 
Comorbidities  Hypertension  99  59.3%  68  56.2%  0.630 
Diabetes  105  62.9%  70  57.9%  0.395 
CKD  23  13.8%  7  5.8%  0.032 
Heart Disease  17  10.2%  18  14.9%  0.274 
Malignancy  3  1.8%  1  0.8%  0.642 
Chronic Lung Disease  17  10.2%  9  7.4%  0.533 
Other  66  39.5%  54  44.6%  0.399 
Dysglycemia  Uncomplicated Hyperglycemia  102  61.1%  77  63.6%  0.025 
Diabetic Ketoacidosis  11  6.6%  1  0.8% 
Hyperglycemic Hyperosmolar 0  0.0%  2  1.7% 
None  54  32.3%  41  33.9% 
Infections  Urinary Tract Infections  12  7.2%  15  12.4%  0.154 
Superimposed Pneumonia  27  16.2%  31  25.6%  0.054 
Bloodstream Infection  25  15.0%  23  19.0%  0.424 
Duration of steroid use (Days)  10.0 [7.0, 12.0]  14.0 [10.0, 19.0]  <0.001 
Outcome  Discharge from critical care  94  56.3%  63  52.1%  0.549 
Dead  73  43.7%  58  47.9% 
Duration of critical care admission- all patients (Days)  11.0 [6.0, 16.0]  11.0 [8.0, 23.0]  0.132 
Duration of critical care admission-non survivors (Days)  8.0 [4.0, 14.0]  11.5 [6.0, 17.0]  0.036 
SPO2 at presentation 82.0 [70.0, 89.0] 82.0 [70.0, 89.0] 0.560
CRP at admission 125.0 [62.5, 199.5] 91.0 [45.0, 161.0] 0.020
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*Continuous variable presented as median [IQR]

Outcomes

The overall ICU mortality was 45.5%. The median duration of critical care admission in non-survivors was 10 days (IQR: 5–17). When comparing the characteristics between survivors and non-survivors, age, heart disease, infections, and duration of steroid use were statistically significant. Survivors were younger than non-survivors (57.7 years vs 70.0 years, p<0.001). The median oxygen saturation at admission was lower in the non-survivors’ group as compared to the survivors group, 75.0 (IQR: 68.087.5) versus 85.0 (IQR: 75.0–89.5) and the difference was statistically significant (p<0.001). There were more superimposed bacterial pneumonias among non-survivors compared to the survivors (28.2% vs 13.4%, p = 0.002). Details of the comparison between outcomes are presented in Table 3.

Table 3. Comparison between outcomes of 288 patients (survivors vs non survivors).

  Survivors  Non-survivors P Value 
(n = 157)  (n = 131) 
Age (years)    57.7 [47.9, 66.7]  70.0 [54.8, 77.7]  <0.001 
Gender  Male  109  69.4%  96  73.3%  0.515 
Female  48  30.6%  35  26.7% 
Comorbidities  Hypertension  85  54.1%  82  62.6%  0.153 
Diabetes  88  56.1%  87  66.4%  0.090 
CKD  12  7.6%  18  13.7%  0.121 
Heart Disease  13  8.3%  11  16.8%  0.031 
Malignancy  2  1.3%  2  1.5%  1.000 
Chronic Lung Disease  11  7.0%  15  11.5%  0.218 
Other  58  36.9%  62  47.3%  0.093 
Dysglycemia Uncomplicated Hyperglycemia  93  59.2%  86  65.6%  0.106 
Diabetic Ketoacidosis  4  2.5%  8  6.1% 
Hyperglycemic Hyperosmolar  2  1.3%  0  0.0% 
None  58  36.9%  37  28.2% 
Infections  Urinary Tract Infections  14  8.9%  13  9.9%  0.840 
Superimposed Pneumonia  21  13.4%  37  28.2%  0.002 
Bloodstream Infection  18  11.5%  30  22.9%  0.011 
Steroid Dose Category  Standard (6mg)  94  59.9%  73  55.7%  0.549 
High (>6mg)  63  40.1%  58  44.3% 
Duration of steroid use (Days)  11.0 [10.0, 16.0]  10.0 [6.0, 14.0]  0.005 
SPO2 at presentation 85.0 [75.0, 89.5] 75.0 [68.0, 87.5] <0.001
CRP at admission 122.5 [56.0, 199.0] 107.0 [52.0, 179.0] 0.260
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*Continuous variable presented as median [IQR]

Discussion

In this single centre study, use of higher doses of corticosteroids in the management of critical COVID-19 pneumonia did not confer any mortality benefit and was associated with significantly more dysglycaemia as well as more than a two-fold increase in the occurrence of superimposed pneumonia. In the RECOVERY steroid dose study by Abbas [9], there was an increase in mortality, as well as an excess of superadded pneumonias and dysglycaemias, although the study population comprised of patients requiring simple oxygen supplementation and did not include critical COVID-19 pneumonia. In the COVID STEROID 2 trial by Munch et al, patients requiring high levels of oxygen supplementation, including invasive and non-invasive mechanical ventilation were included [8]. There was no significant mortality benefit for high dose compared to low dose steroids in this trial. There was no difference in superadded infections noted [8]. A meta-analysis by Pitre and colleagues suggested that higher doses of steroids probably reduced mortality with an uncertain effect on nosocomial infections [10]. Notably, the meta-analysis did not include data from the RECOVERY steroid dose study. In summary, our study is in line with most data, suggesting no added benefits and possible harm of high dose steroids in patients with critical COVID 19 pneumonia.

Our patient population was slightly older (61.2 years versus 56 years), with more males (71.2% versus 60.6%) and with diabetes more prevalent (60.8% versus 38%) than that seen in the ACCCOS cohort, which characterized patients with COVID-19 pneumonia admitted to critical care units in Africa [12]. The overall mortality rate was 45.5% which was similar to that seen in the ACCCOS cohort (48.2%) [12]. Non survivors were more likely to be older and have an underlying comorbid condition compared to survivors. The high prevalence of diabetes mellitus and the increase in dysglycaemias seen in the high steroid dose group present more evidence to use standard dose steroids, even in patients critically ill with COVID-19. Though not studied in our population, diabetes, and steroid use, with environmental factors, seemed to be the main risk factor for the mucormycosis outbreak seen in patients with COVID-19 pneumonia in India [13, 15].

In COVID-19, organ damage is caused by inflammation, as evidenced by elevated inflammatory markers in critical COVID-19 patients. In our study, the median C-reactive protein (CRP) level at admission was 113, and it was lower in the high-dose group than in the standard-dose group. The decision to administer steroids may have been at the discretion of the treating doctor and influenced by other factors rather than the level of inflammation. Furthermore, the difference in CRP levels between survivors and non-survivors was not statistically significant. However, the non-survivors had significantly lower oxygen saturation at presentation than the survivors. This was confirmed by a retrospective cohort study in Peru, which found that an oxygen saturation below 90% upon admission was a strong predictor of in-hospital mortality for adult COVID-19 patients [16].

Our study had several limitations. Due to its retrospective nature, missing data and uncontrolled biases may have influenced the results. However, only five patients were excluded from the study because of incomplete records. The effect of various COVID waves and variants was not assessed. Additionally, we did not include data on the different adjunct treatments for COVID-19 such as remdesivir, and anticoagulation which may have been major confounders on the outcomes. The study in a single centre may also limit generalizability of the findings. Our study is however, to the best of our knowledge, the first to attempt to investigate outcomes of high versus low dose steroids in critical COVID-19 pneumonia in an African population. Though it is a single centre study, a relatively large number of patients were included.

Conclusion

In this study, high dose steroids for the management of critical COVID-19 pneumonia did not improve mortality outcomes and were associated with more adverse events, specifically dysglycaemias and superadded infections.

Supporting information

S1 Checklist. STROBE statement—checklist of items that should be included in reports of observational studies.

(DOCX)

pone.0307265.s001.docx (33.4KB, docx)
S1 Data

(XLSX)

pone.0307265.s002.xlsx (36.7KB, xlsx)

Acknowledgments

We would like to acknowledge the following people:

1. Mr. Sabbath Kivuva, from the library department, for his contribution towards document formatting.

2. Staff at the Records department, led by Mr. Kaburia, for their help in retrieving the patients’ records.

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Horby P., et al., Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med, 2021. 384(8): p. 693–704. doi: 10.1056/NEJMoa2021436 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Tomazini B.M., et al., Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. Jama, 2020. 324(13): p. 1307–1316. doi: 10.1001/jama.2020.17021 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Sterne J.A.C., et al., Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. Jama, 2020. 324(13): p. 1330–1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Pinzón M.A., et al., Dexamethasone vs methylprednisolone high dose for Covid-19 pneumonia. PLoS One, 2021. 16(5): p. e0252057. doi: 10.1371/journal.pone.0252057 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Ranjbar K., et al., Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial. BMC Infect Dis, 2021. 21(1): p. 337. doi: 10.1186/s12879-021-06045-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Monreal E., et al., High versus standard doses of corticosteroids in severe COVID-19: a retrospective cohort study. Eur J Clin Microbiol Infect Dis, 2021. 40(4): p. 761–769. doi: 10.1007/s10096-020-04078-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Edalatifard M., et al., Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. Eur Respir J, 2020. 56(6). doi: 10.1183/13993003.02808-2020 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Munch M.W., et al., Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial. Jama, 2021. 326(18): p. 1807–1817. doi: 10.1001/jama.2021.18295 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet, 2023. 401(10387): p. 1499–1507. doi: 10.1016/S0140-6736(23)00510-X [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Pitre T., et al., Higher- versus Lower-Dose Corticosteroids for Severe to Critical COVID-19: A Systematic Review and Dose-Response Meta-analysis. Ann Am Thorac Soc, 2023. 20(4): p. 596–604. doi: 10.1513/AnnalsATS.202208-720OC [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Brotherton H., et al., Dexamethasone for COVID-19: data needed from randomised clinical trials in Africa. Lancet Glob Health, 2020. 8(9): p. e1125–e1126. doi: 10.1016/S2214-109X(20)30318-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Patient care and clinical outcomes for patients with COVID-19 infection admitted to African high-care or intensive care units (ACCCOS): a multicentre, prospective, observational cohort study. Lancet, 2021. 397(10288): p. 1885–1894. doi: 10.1016/S0140-6736(21)00441-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Hoenigl M., et al., The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries. Lancet Microbe, 2022. 3(7): p. e543–e552. doi: 10.1016/S2666-5247(21)00237-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Harris P.A., et al., The REDCap consortium: Building an international community of software platform partners. J Biomed Inform, 2019. 95: p. 103208. doi: 10.1016/j.jbi.2019.103208 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Joshi S., et al., Outbreak of Mucormycosis in Coronavirus Disease Patients, Pune, India. Emerg Infect Dis, 2022. 28(1): p. 1–8. doi: 10.3201/eid2801.211636 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Mejía F., et al., Oxygen saturation as a predictor of mortality in hospitalized adult patients with COVID-19 in a public hospital in Lima, Peru. PLoS One, 2020. 15(12): p. e0244171. doi: 10.1371/journal.pone.0244171 [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Robert Jeenchen Chen

21 Dec 2023

PONE-D-23-24666OUTCOMES OF DIFFERENT STEROID DOSING REGIMENS IN CRITICAL COVID-19 PNEUMONIA: A RETROSPECTIVE COHORT STUDYPLOS ONE

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Whilst you may use any professional scientific editing service of your choice, PLOS has partnered with both American Journal Experts (AJE) and Editage to provide discounted services to PLOS authors. Both organizations have experience helping authors meet PLOS guidelines and can provide language editing, translation, manuscript formatting, and figure formatting to ensure your manuscript meets our submission guidelines. To take advantage of our partnership with AJE, visit the AJE website (http://learn.aje.com/plos/) for a 15% discount off AJE services. To take advantage of our partnership with Editage, visit the Editage website (www.editage.com) and enter referral code PLOSEDIT for a 15% discount off Editage services.  If the PLOS editorial team finds any language issues in text that either AJE or Editage has edited, the service provider will re-edit the text for free.

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Data requests to a non-author institutional point of contact, such as a data access or ethics committee, helps guarantee long term stability and availability of data. Providing interested researchers with a durable point of contact ensures data will be accessible even if an author changes email addresses, institutions, or becomes unavailable to answer requests.

Before we proceed with your manuscript, please also provide non-author contact information (phone/email/hyperlink) for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If no institutional body is available to respond to requests for your minimal data, please consider if there any institutional representatives who did not collaborate in the study, and are not listed as authors on the manuscript, who would be able to hold the data and respond to external requests for data access? If so, please provide their contact information (i.e., email address). Please also provide details on how you will ensure persistent or long-term data storage and availability.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Odhiambo J.O. and collaborators performed a single center retrospective observational

study to investigate the effect of different posology of corticosteroids (i.e.,

dexamethasone 6 mg vs. higher equivalent dosages) in patients suffering from critical

COVID-19 pneumonia admitted to ICU of the Aga Khan Hospital in Nairobi, Kenya. I

personally worked in a European COVID ICU during the pandemic, and it was very

complicated and stressful. I imagine working in a low and middle-income country ICU in

such a situation could be exhausting; thus, I would like to thank you for conducting this

research effort, and I hope this review may help you.

The primary outcome of the study was mortality. Secondary outcomes were the

occurrence of superinfections, dysglycemia, and duration of ICU length of stay.

Two-hundred-eighty-eight patients entered the analysis. 48% received dexamethasone 6

mg; 52% higher dosages. Overall, 45.5% of patients died. No difference in mortality was

observed in the two groups (43.7% vs. 47.9%, p=0.549). Higher corticosteroid dosages

seemed to be associated with a higher incidence of dysglycemia and superinfection

events.

The authors have provided a description of an extensively studied topic but considered a

population rarely enrolled in trials and studies. Indeed, the major strength of this work is

the completely African population included. This aspect, in my opinion should be underlined,

both in the title, as well as in the abstract.

Nevertheless, the manuscript, in its current form, requires some improvements and

presents a lot of methodological issues and limitations that should be thoroughly

addressed:

� Follow STROBE guidelines to report observational study results, as required by

the Journal publication criteria.

� Please specify better the primary outcome: did you assess ICU mortality,

hospital mortality, or 28-day mortality? Moreover, I would suggest adding the

primary outcome result to the main text as well as in the table.

� Please, it could be interesting and could improve the quality of the manuscript to

report 1) at least a score or parameters of illness severity (i.e., P/F ratio,

Respiratory Rate, SOFA or SAPS score…); 2) the number of patients who

needed mechanical ventilation; 3) the kind of steroid administered; 4) the timing

of corticosteroid therapy starting compared to ICU admission.

� Univariate statistic tests used are completely described, but I would suggest

adjusting for possible confounders (i.e., age, sex, comorbidities, the severity of

illness) for a better evaluation of steroid dosage impact on outcome. Moreover,

if data permits, try to perform a survival analysis (and try to construct a Kaplan-

Meier curve figure).

� I would suggest reporting outcome measures in the outcome results section, not

in the population characteristic section.

� In the limitation section of the discussion, you stated that missing data may have

influenced the results. Please report the number of missing data for each

variable.

� I would suggest reporting Table 1, joined with Table 2, and reporting percentage

of subjects in Table 2 columns.

Reviewer #2: The study is good but, being a retrospective study it has its own limitations as has been pointed by the authors.A few questions for the authors-

1) They have mentioned high dose of steroids as any dose more than 6 mg dexamethasone, were patients on any other steroids like prednisone, methylprednisolone?When were the steroids started in these patients, as in within how many days of onset of symptoms?

2) Was there any comparison between the survivors and non survivors in terms of oxygen requirements, ventilators-NIV or invasive?

3) Was there any correlation between the d Dimer levels amongst the survivors and non survivor groups?

4) How many patients were on Remdesevir considering that these were the more severe cases and was there any correlation on this?

5)How many of these patients also received LMWH or oral anticoagulants and did this affect the outcome of the study?

6) How many patients underwent a bronchoscopy and BAL for the diagnosis of pneumonia?

Thank you.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Vittorio Scaravilli, MD

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2024 Aug 20;19(8):e0307265. doi: 10.1371/journal.pone.0307265.r002

Author response to Decision Letter 0

5 Feb 2024

Response to Reviewer’s Comments

PLOS ONE

OUTCOMES OF DIFFERENT STEROID DOSING REGIMENS IN CRITICAL COVID-19 PNEUMONIA: A RETROSPECTIVE COHORT STUDY

Thank you for the comments. Please find below the responses to both reviewers’ comments.

Reviewer 1

Reviewer #1: Odhiambo J.O. and collaborators performed a single center retrospective observational study to investigate the effect of different posology of corticosteroids (i.e., dexamethasone 6 mg vs. higher equivalent dosages) in patients suffering from critical COVID-19 pneumonia admitted to ICU of the Aga Khan Hospital in Nairobi, Kenya. I personally worked in a European COVID ICU during the pandemic, and it was very complicated and stressful. I imagine working in a low and middle-income country ICU in such a situation could be exhausting; thus, I would like to thank you for conducting this research effort, and I hope this review may help you.

The primary outcome of the study was mortality. Secondary outcomes were the occurrence of superinfections, dysglycemia, and duration of ICU length of stay.

Two-hundred-eighty-eight patients entered the analysis. 48% received dexamethasone 6 mg; 52% higher dosages. Overall, 45.5% of patients died. No difference in mortality was observed in the two groups (43.7% vs. 47.9%, p=0.549). Higher corticosteroid dosages seemed to be associated with a higher incidence of dysglycemia and superinfection events.

The authors have provided a description of an extensively studied topic but considered a population rarely enrolled in trials and studies. Indeed, the major strength of this work is the completely African population included. This aspect, in my opinion should be underlined, both in the title, as well as in the abstract.

Response: We have revised and added “At a Kenyan Hospital” in the title.

Nevertheless, the manuscript, in its current form, requires some improvements and presents a lot of methodological issues and limitations that should be thoroughly addressed:

• Follow STROBE guidelines to report observational study results, as required by the Journal publication criteria.

Response: Thank you. We have attached the STROBE Checklist and submitted as per the criteria.

• Please specify better the primary outcome: did you assess ICU mortality, hospital mortality, or 28-day mortality? Moreover, I would suggest adding the primary outcome result to the main text as well as in the table.

Response: The primary outcome was ICU Mortality and we have edited the manuscript accordingly.

• Please, it could be interesting and could improve the quality of the manuscript to report 1) at least a score or parameters of illness severity (i.e., P/F ratio, Respiratory Rate, SOFA or SAPS score…); 2) the number of patients who needed mechanical ventilation; 3) the kind of steroid administered; 4) the timing of corticosteroid therapy starting compared to ICU admission.

Response: I agree, this could improve the quality of the study. However, we did not collect data on the different scoring systems. Additionally, we only included the steroid doses in dexamethasone equivalence but not the specific steroids used.

• Univariate statistic tests used are completely described, but I would suggest adjusting for possible confounders (i.e., age, sex, comorbidities, the severity of illness) for a better evaluation of steroid dosage impact on outcome. Moreover, if data permits, try to perform a survival analysis (and try to construct a Kaplan-Meier curve figure).

Response: Unfortunately, we did not collect survival data and thus it was beyond the scope of this study to do Kaplan Meier and survival analysis.

• I would suggest reporting outcome measures in the outcome results section, not in the population characteristic section.

Response: We have tried to edit the manuscript accordingly.

• In the limitation section of the discussion, you stated that missing data may have influenced the results. Please report the number of missing data for each variable.

Response: Thank you. We have included this in the limitation section. Only five patients were excluded from the study due to incomplete records.

• I would suggest reporting Table 1, joined with Table 2, and reporting the percentage of subjects in Table 2 columns.

Response: We have retained the tables as it is on the flow of the results.

Reviewer 2

Reviewer #2: The study is good but, being a retrospective study, it has its own limitations as has been pointed by the authors. A few questions for the authors-

1. They have mentioned high dose of steroids as any dose more than 6 mg dexamethasone, were patients on any other steroids like prednisone, methylprednisolone? When were the steroids started in these patients, as in within how many days of onset of symptoms?

Response: Yes, other types of steroids were used but in the data collection tool we only included steroid doses which were all converted to dexamethasone into dexamethasone equivalence.

2. Was there any comparison between the survivors and non survivors in terms of oxygen requirements, ventilators-NIV or invasive?

Response: Thank you for this. This may have been a good comparison to do. All the patients included in the study were on ventilatory support, but we did not include the specific type of support.

3. Was there any correlation between the d Dimer levels amongst the survivors and non survivor groups?

Response: No data was collected on D-dimer levels or any other coagulation parameters.

4. How many patients were on Remdesevir considering that these were the more severe cases and was there any correlation on this?

Response: This was beyond the scope of our study and has been included as part of the limitations.

5. How many of these patients also received LMWH or oral anticoagulants and did this affect the outcome of the study?

Response: We did not include data on the anticoagulation. However, as per the hospital policy and guidelines, all patients admitted to critical care unit are put on prophylactic anticoagulation or treatment doses in case of evidence of thrombosis unless there are contraindications.

6. How many patients underwent a bronchoscopy and BAL for the diagnosis of pneumonia?

Response: Thank you for this. Unfortunately, this was beyond the scope of our study.

Attachment

Submitted filename: PLOS ONE response letter - John.docx

pone.0307265.s003.docx (19.3KB, docx)

Decision Letter 1

Robert Jeenchen Chen

17 Mar 2024

PONE-D-23-24666R1OUTCOMES OF DIFFERENT STEROID DOSING REGIMENS IN CRITICAL COVID-19 PNEUMONIA: A RETROSPECTIVE COHORT STUDYPLOS ONE

Dear Dr. Odhiambo,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please revise.

Please submit your revised manuscript by May 01 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Unfortunately, the authors, despite the changes in the manuscript were not able to address any of the instance I raised.

Reviewer #2: All comments have been addressed to satisfaction and the article can be accepted if found to be suitable for publication by the editor.

Reviewer #3: It is difficult to conclude that high doses of steroids do not influence the prognosis.

Can you compare the data that can assess the severity of the 2 groups? Particularly saturation at admission and during progression.

or add this mention to the limitations of this study.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Abdelbassat Ketfi

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2024 Aug 20;19(8):e0307265. doi: 10.1371/journal.pone.0307265.r004

Author response to Decision Letter 1

8 Apr 2024

Response to Reviewer’s Comments

PLOS ONE

OUTCOMES OF DIFFERENT STEROID DOSING REGIMENS IN CRITICAL COVID-19 PNEUMONIA: A RETROSPECTIVE COHORT STUDY

Thank you for the comments. Please find below the responses to both reviewers’ comments.

Reviewer #1: Unfortunately, the authors, despite the changes in the manuscript were not able to address any of the instance I raised.

Response: We appreciate the comments and suggestions from Reviewer 1. Some of the suggestions such as reporting at least a score or parameters of illness severity (i.e., P/F ratio, Respiratory Rate, SOFA or SAPS score…) or performing survival analysis was beyond the scope of the current project as the different data was not collected. Furthermore, we attached the STROBE guidelines to report the observational study as requested. We tried to address as much as possible and edited the manuscript accordingly.

Reviewer #2: All comments have been addressed to satisfaction and the article can be accepted if found to be suitable for publication by the editor.

Response: We appreciate the comments and suggestions from Reviewer 2.

Reviewer #3: It is difficult to conclude that high doses of steroids do not influence the prognosis. Can you compare the data that can assess the severity of the 2 groups? Particularly saturation at admission and during progression or add this mention to the limitations of this study.

Response: We appreciate the comments from Reviewer 3. We included all the patients with critical COVID-19 and on ventilator support as per the inclusion criteria. However, we did not collect any data on the measures of severity such as oxygen saturations. We have, therefore, added it to our limitations as you have advised.

Attachment

Submitted filename: PLOS ONE response letter - 8th April.docx

pone.0307265.s004.docx (16.4KB, docx)

Decision Letter 2

Robert Jeenchen Chen

1 May 2024

PONE-D-23-24666R2OUTCOMES OF DIFFERENT STEROID DOSING REGIMENS IN CRITICAL COVID-19 PNEUMONIA: A RETROSPECTIVE COHORT STUDYPLOS ONE

Dear Dr. Odhiambo,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please revise.

Please submit your revised manuscript by Jun 15 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The choice not to collect further descriptive data from the two cohorts, unfortunately, is not agreeable. The severity data of the pathology wouldn't have had solely a descriptive purpose but could have helped the authors to consider possible confounders in the statistical analysis: such as whether patients who had taken higher doses of steroids were the most severe and thus at higher risk of superinfection

Reviewer #2: All queries have been addressed to satisfaction and may be considered for publication if the article meets the other requirements.

Reviewer #3: (No Response)

Reviewer #4: the points mentioned by the authors in the limitation are very important for the study. because of these deficiencies, it is not suitable for publication. also the discussion section is inadequate

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Abdelbassat Ketfi

Reviewer #4: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2024 Aug 20;19(8):e0307265. doi: 10.1371/journal.pone.0307265.r006

Author response to Decision Letter 2

14 Jun 2024

If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

Response: Thank you for taking time out of your schedule to review our paper and we are happy to note that all your queries were addressed.

Reviewer #1: The choice not to collect further descriptive data from the two cohorts, unfortunately, is not agreeable. The severity data of the pathology wouldn't have had solely a descriptive purpose but could have helped the authors to consider possible confounders in the statistical analysis: such as whether patients who had taken higher doses of steroids were the most severe and thus at higher risk of superinfection

Response: Having realised that this would improve the quality of the manuscript as was highlighted by the reviewer, we went back and collected data on markers of severity of the disease for instance CRP and oxygen saturation at admission. Due to medical records being paper documents and also limited data available, we aimed at collecting CRP and oxygen saturation. From furtner analyses, it was evident that oxygen saturation at admission was significantly lower in the non-survivors’ group than the survivors’ group whereas as CRP was significantly lower in the high dose group as compared to the standard dose group.

Reviewer #2: All queries have been addressed to satisfaction and may be considered for publication if the article meets the other requirements.

Response: Thank you for taking time out of your schedule to review our paper and we are happy to note that all your queries were addressed.

Reviewer #4: The points mentioned by the authors in the limitation are very important for the study. The discussion section is inadequate

Response: Thank you so much for the point you have raised. We have delt with one of the major limitations which was lack of data on the markers of severity such as the level of the inflammatory markers and oxygen saturations at admission and put up an additional paragraph in the discussion section. We believe that this has improved the quality of the manuscript and hopefully accepted for publication.

Attachment

Submitted filename: PLOS ONE Comments- John 14th June 2024.docx

pone.0307265.s005.docx (16.9KB, docx)

Decision Letter 3

Robert Jeenchen Chen

3 Jul 2024

OUTCOMES OF DIFFERENT STEROID DOSING REGIMENS IN CRITICAL COVID-19 PNEUMONIA: A RETROSPECTIVE COHORT STUDY

PONE-D-23-24666R3

Dear Dr. Odhiambo,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

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Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

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Reviewer #3: Yes

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Reviewer #3: Yes

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Reviewer #2: Yes

Reviewer #3: Yes

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Acceptance letter

Robert Jeenchen Chen

8 Jul 2024

PONE-D-23-24666R3

PLOS ONE

Dear Dr. Odhiambo,

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Academic Editor

PLOS ONE

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    Supplementary Materials

    S1 Checklist. STROBE statement—checklist of items that should be included in reports of observational studies.

    (DOCX)

    pone.0307265.s001.docx (33.4KB, docx)
    S1 Data

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    Attachment

    Submitted filename: PLOS ONE response letter - John.docx

    pone.0307265.s003.docx (19.3KB, docx)
    Attachment

    Submitted filename: PLOS ONE response letter - 8th April.docx

    pone.0307265.s004.docx (16.4KB, docx)
    Attachment

    Submitted filename: PLOS ONE Comments- John 14th June 2024.docx

    pone.0307265.s005.docx (16.9KB, docx)

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