Objectives: To assess the efficacy of corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19).
Design, setting: Observational study in the two COVID-19-designated hospitals in Wuhu, Anhui province, China, 24 January – 24 February 2020.
Participants: Thirty-one patients infected with the severe acute respiratory coronavirus 2 (SARS-CoV-2) treated at the two designated hospitals.
Main outcome measures: Virus clearance time, length of hospital stay, and duration of symptoms, by treatment type (including or not including corticosteroid therapy).
Results: Eleven of 31 patients with COVID-19 received corticosteroid treatment. Cox proportional hazards regression analysis indicated no association between corticosteroid treatment and virus clearance time (hazard ratio [HR], 1.26; 95% CI, 0.58-2.74), hospital length of stay (HR, 0.77; 95% CI, 0.33-1.78), or duration of symptoms (HR, 0.86; 95% CI, 0.40-1.83). Univariate analysis indicated that virus clearance was slower in two patients with chronic hepatitis B infections (mean difference, 10.6 days; 95% CI, 6.2-15.1 days).
Conclusions: Corticosteroids are widely used when treating patients with COVID-19, but we found no association between therapy and outcomes in patients without acute respiratory distress syndrome. An existing HBV infection may delay SARS-CoV-2 clearance, and this association should be further investigated.
Objectives: An outbreak of novel coronavirus in 2019 threatens the health of people, and there is no proven pharmacological treatment. Although corticosteroids were widely used during outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, their efficacy remainedhighly controversial. We aimed to further evaluate the influence of corticosteroids on patients with coronavirus infection.
Methods: We conducted a comprehensive search of literature published in PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure (CNKI) from January 1, 2002 to March 15, 2020. All statistical analyses in this study were performed on stata14.0.
Results: A total of 5270 patients from 15 studies were included in this meta-analysis. The result indicated that critical patients were more likely to require corticosteroids therapy (risk ratio [RR] = 1.56, 95% confidence interval [CI] = 1.28-1.90, P<0.001). However, corticosteroid treatment was associated with higher mortality (RR = 2.11, 95%CI = 1.13-3.94, P = 0.019), longer length of stay (weighted mean difference [WMD] = 6.31, 95%CI = 5.26-7.37, P<0.001), a higher rate of bacterial infection (RR = 2.08, 95%CI = 1.54-2.81, P<0.001), and hypokalemia (RR = 2.21, 95%CI = 1.07-4.55, P = 0.032) but not hyperglycemia (RR = 1.37, 95%CI=0.68-2.76, P = 0.376) or hypocalcemia (RR = 1.35, 95%CI = 0.77-2.37, P = 0.302).
Conclusions: Patients with severe conditions are more likely to require corticosteroids. Corticosteroid use is associated with increased mortality in patients with coronavirus pneumonia.
Given the current SARS-CoV-2 (COVID-19) pandemic, the availability of reliable information for clinicians and patients is paramount. There have been a number of reports stating that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may exacerbate symptoms in COVID-19 patients. Therefore, this review aimed to collate information available in published articles to identify any evidence behind these claims with the aim of advising clinicians on how best to treat patients. This review found no published evidence for or against the use of NSAIDs in COVID-19 patients. Meanwhile, there appeared to be some evidence that corticosteroids may be beneficial if utilised in the early acute phase of infection, however, conflicting evidence from the World Health Organisation surrounding corticosteroid use in certain viral infections means this evidence is not conclusive. Given the current availability of literature, caution should be exercised until further evidence emerges surrounding the use of NSAIDs and corticosteroids in COVID-19 patients.
Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome virus (SARS-CoV-2) has become a global health care crisis. The Centers for Disease Control and Prevention (CDC) lists immunocompromised patients, including those requiring immunosuppression following renal transplantation, as high risk for severe disease from SARS-CoV-2. Treatment for other viral infections in renal transplant recipients often includes a reduction in immunosuppression; however, no current guidelines are available recommending the optimal approach to managing immunosuppression in the patients who are infected with SARS-CoV-2. It is currently advised to avoid corticosteroids in the treatment of SARS-CoV-2 outside of critically ill patients. Recently published cases describing inpatient care of COVID-19 in renal transplant recipients differ widely in disease severity, time from transplantation, baseline immunosuppressive therapy, and the modifications made to immunosuppression during COVID-19 treatment. This review summarizes and compares inpatient immunosuppressant management strategies of recently published reports in the renal transplant population infected with SARS-CoV-2 and discusses the limitations of corticosteroids in managing immunosuppression in this patient population.
Inhaled Corticosteroids and COVID-19: A Systematic Review and Clinical Perspective
Background: Coronavirus disease 2019 (COVID-19) is caused by SARS-coronavirus 2 (SARS-CoV-2). Angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among asthma patients may identify subgroups at risk for COVID19 morbidity.
Methods: We analyzed gene expression for ACE2 and TMPRSS2, and for intercellular adhesion molecule 1 (ICAM-1)(rhinovirus receptor as a comparator), in sputum cells from 330 participants in the Severe Asthma Research Program-3 and 79 healthy controls.
Results: Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes was similar in asthma and health. Among asthma patients, male gender, African Americans race, and history of diabetes mellitus, was associated with higher expression of ACE2 and TMPRSS2. Use of inhaled corticosteroids (ICS) was associated with lower expression of ACE2 and TMPRSS2, but treatment with triamcinolone acetonide (TA) did not decrease expression of either gene. These findings differed from those for ICAM-1, where gene expression was increased in asthma and less consistent differences were observed related to gender, race, and use of ICS.
Conclusion: Higher expression of ACE2 and TMPRSS2 in males, African Americans, and patients with diabetes mellitus provides rationale for monitoring these asthma subgroups for poor COVID19 outcomes. The lower expression of ACE2 and TMPRSS2 with ICS use warrants prospective study of ICS use as a predictor of decreased susceptibility to SARS-CoV-2 infection and decreased COVID19 morbidity.
We performed a meta-analysis to determine safety and efficacy of corticosteroids in SARS-CoV-2, SARS-CoV, and MERS-CoV infections. We searched PubMed, Web of Science, Medline, WanFang Chinese database, and ZhiWang Chinese database using Boolean operators and search terms covering SARS-CoV-2, SARS-CoV, OR MERS-CoV AND corticosteroids to find appropriate studies. Review Manager 5.3 was used to analyze results of meta-analysis. Observational studies were analyzed for quality using the modified Newcastle-Ottawa scale and randomized clinical trials, using the Jadad scale. Subjects were divided into those with severe-only and other (severe and not severe) cohorts based on published criteria. Efficacy endpoints studied included mortality, hospitalization duration, rates of intensive care unit (ICU) admission, use of mechanical ventilation, and a composite endpoint (death, ICU admission, or mechanical ventilation). We included 11 reports including 10 cohort studies and 1 randomized clinical trial involving 5249 subjects (2003-2020). Two discussed the association of corticosteroids and virus clearing and 10 explored how corticosteroids impacted mortality, hospitalization duration, use of mechanical ventilation, and a composite endpoint. Corticosteroid use was associated with delayed virus clearing with a mean difference (MD) = 3.78 days (95% confidence Interval [CI] = 1.16, 6.41 days; I2 = 0%). There was no significant reduction in deaths with relative Risk Ratio (RR) = 1.07 (90% CI = 0.81; 1.42; I2 = 80%). Hospitalization duration was prolonged and use of mechanical ventilation increased. In conclusion, corticosteroid use in subjects with SARS-CoV-2, SARS-CoV, and MERS-CoV infections delayed virus clearing and did not convincingly improve survival, reduce hospitalization duration or ICU admission rate and/or use of mechanical ventilation. There were several adverse effects. Because of a preponderance of observational studies in the dataset and selection and publication biases our conclusions, especially regarding SARS-CoV-2, need confirmation in a randomized clinical trial. In the interim we suggest caution using corticosteroids in persons with COVID-19.
Coronavirus disease 2019 (COVID-19) pneumonia, firstly reported in Wuhan, Hubei province, China, has rapidly spread around the world with high mortality rate among critically ill patients. The use of corticosteroids in COVID-19 remains a major controversy. Available evidences are inconclusive. According to WHO guidance, corticosteroids are not recommended to be used unless for another reason. Chinese Thoracic Society (CTS) proposes an expert consensus statement that suggests taking a prudent attitude of corticosteroid usage. In our clinical practice, we do not use corticosteroids routinely; only low-to-moderate doses of corticosteroids were given to several severely ill patients prudently. In this paper, we will present two confirmed severe COVID-19 cases admitted to isolation wards in Optical Valley Campus of Tongji hospital, Tongji Medical College, Huazhong University of Science and Technology. We will discuss questions related to corticosteroids usages.
Background: There is no proven antiviral or immunomodulatory therapy for COVID-19. The disease progression associated with the pro-inflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19.
Methods: We conducted a single pre-test, single post-test quasi-experiment in a multi-center health system in Michigan from March 12 to March 27, 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on March 20, 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of standard of care (SOC) and early corticosteroid groups were evaluated, with a primary composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality. All patients had at least 14 days of follow-up.
Results: We analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in SOC and early corticosteroid groups, respectively.The composite endpoint occurred at a significantly lower rate in the early corticosteroid group (34.9% vs. 54.3%, p=0.005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was also observed in the early corticosteroid group (8 vs. 5 days, p < 0.001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (aOR: 0.41; 95% CI [0.22 – 0.77]).
Conclusion: An early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes.
Background: At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.
Methods: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks.
Discussion: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019.
Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is a new rapidly spreading infectious disease. Current guidance from the World Health Organisation (WHO) highlights asthmatics as a high-risk group for severe illness from COVID-19. Viruses are common triggers of asthma exacerbations and the current SARS-CoV-2 pandemic raises several questions regarding the optimum management strategies. Here, we discuss the contentious issue of whether the mainstay therapies systemic corticosteroids should be used in the routine management of COVID-19-associated asthma exacerbations. Recent guidance from the WHO has advised against the use of corticosteroids if COVID-19 is suspected due to concerns that these agents may impair protective innate anti-viral immune responses. This may not be appropriate in the unique case of asthma exacerbation, a syndrome associated with augmented type 2 inflammation, a disease feature that is known to directly inhibit anti-viral immunity. Corticosteroids, through their suppressive effects on type 2 inflammation, are thus likely to restore impaired anti-viral immunity in asthma and, in contrast to non-asthmatic subjects, have beneficial clinical effects in the context of SARS-CoV-2 infection.
No specific and effective anti-viral treatment has been approved for COVID-19 so far. Systemic corticosteroid has been sometimes administered to severe infectious diseases combined with the specific treatment. However, as lack of the specific anti-SARS-CoV-2 drug, systemic steroid treatment has not been recommended for COVID-19. We report here three cases of the COVID-19 pneumonia successfully treated with ciclesonide inhalation. Rationale of the treatment is to mitigate the local inflammation with inhaled steroid that stays in the lung and to inhibit proliferation of the virus by antiviral activity. Larger and further studies are warranted to confirm the result of these cases.
The aim was to investigate the effectiveness of glucocorticoid therapy in patients with COVID-19. A systematic search of the literature across nine databases was conducted from inception until 15th March 2020, following the PRISMA guidelines. Patients with a validated diagnosis of COVID-19 and using corticosteroids were included, considering all health outcomes. Four studies with 542 Chinese participants were included. Two studies reported negative findings regarding the use of corticosteroids in patients with COVID-19, i.e., corticosteroids had a detrimental impact on clinical outcomes. One study reported no significant association between the use of corticosteroids and clinical outcomes. However, one study, on 201 participants with different stages of pneumonia due to COVID-19, found that in more severe forms, the administration of methylprednisolone significantly reduced the risk of death by 62%. The literature to date does not fully support the routine use of corticosteroids in COVID-19, but some findings suggest that methylprednisolone could lower mortality rate in more severe forms of the condition.
Background and aims: The impact of Coronavirus disease 2019 (COVID-19) on patients with inflammatory bowel disease (IBD) is unknown. We sought to characterize the clinical course of COVID-19 among IBD patients and evaluate the association between demographics, clinical characteristics, and immunosuppressant treatments on COVID-19 outcomes.
Methods: Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is a large, international registry created to monitor outcomes of IBD patients with confirmed COVID-19. We calculated age-standardized mortality ratios (SMRs) and utilized multivariable logistic regression to identify factors associated with severe COVID-19, defined as intensive care unit admission, ventilator use, and/or death.
Results: 525 cases from 33 countries were reported (Median age 43 years, 53% men). Thirty-seven patients (7%) had severe COVID-19, 161 (31%) were hospitalized, and 16 patients died (3% case fatality rate). SMRs for IBD patients were 1.8 (95% confidence interval [CI] 0.9-2.6), 1.5 (95% CI 0.7-2.2), and 1.7 (95% CI 0.9-2.5) relative to data from China, Italy, and the US, respectively. Risk factors for severe COVID-19 among IBD patients included increasing age (adjusted odds ratio [aOR] 1.04, 95% CI 1.01-1.02), ≥2 comorbidities (aOR 2.9, 95% CI 1.1-7.8), systemic corticosteroids (aOR 6.9, 95% CI 2.3-20.5), and sulfasalazine or 5-aminosalicylate use (aOR 3.1, 95% CI 1.3-7.7). TNF antagonist treatment was not associated with severe COVID-19 (aOR 0.9, 95% CI 0.4-2.2).
Conclusions: Increasing age, comorbidities, and corticosteroids are associated with severe COVID-19 among IBD patients, although a causal relationship cannot be definitively established. Notably, TNF antagonists do not appear to be associated with severe COVID-19.
We describe the case of a critically-ill patient with myocarditis and severe ARDS related to COVID-19 infection. This case highlights management strategies including the use of corticosteroids, an IL-6 inhibitor, and an aldose reductase inhibitor resulting in complete clinical recovery.
Objective: To investigate the effect of corticosteroids therapy on the inflammatory response in a critically ill coronavirus disease 2019 (COVID-19) patient.
Methods: A 55-year old female patient with critical ill COVID-19 was admitted in Taizhou Hospital on January 19, 2020. The patient was treated with methylprednisolone 80 mg on the 2nd day after admission. Thereafter, the dose was adjusted in a timely manner and the therapy lasted for 13 days. The peripheral lymphocyte subsets (CD3+T, CD4+ T, CD8+ T, NK cells, B cells), as well as serum levels of lymphocyte factors (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were dynamically monitored.
Results: On D1 of admission, the numbers of peripheral blood CD3+ T, CD4+ T, CD8+ T, and NK cells were significantly lower than the normal range. With the improvement of the disease, the numbers of CD3+ T, CD8+ T and CD4 + T cells gradually recovered and showed a linear growth trend (linear fitting equation: Y=18.59X+109.4, P<0.05). On D2 of admission, the patient’s IL-6 and IL-10 levels were significantly higher than normal values, IFN-γ was at a normal high value, and then rapidly decreased; IL-2, IL-4, and TNF-α were all in the normal range. On the D6 and D7, the IL-6 and IL-10 decreased to the normal range for the first time. On the D18, the sputum virus nucleic acid test was negative for the first time, and the fecal virus nucleic acid test was still positive; on the D20 the sputum and fecal virus nucleic acid test were both negative. On D34, the patient recovered and was discharged. At the discharge the muscle strength score of the patient was 44 and the daily life ability evaluation was 90.
Conclusions: In the absence of effective antiviral drugs, early use of appropriate doses of corticosteroids in critically ill patient with COVID-19 can quickly alleviate inflammatory response and improve clinical symptoms, however, it may reduce the number of T cells, and to adjust the dose in time is necessary.
Background: While antenatal corticosteroids are routinely used to decrease adverse neonatal outcomes following preterm delivery, corticosteroids are also associated with worse outcomes in patients with viral respiratory infections. Currently in the setting of the COVID-19 pandemic, it is unclear whether antenatal corticosteroids for infant benefit outweigh the potential harm to a pregnant woman with a COVID-19 infection.Objective: To determine at which gestational ages administering antenatal corticosteroids is the optimal management strategy for hospitalized women with preterm prelabor rupture of membranes (PPROM) who have a COVID-19 infection.
Methods: We designed a decision-analytic model to assess the maternal and infant outcomes associated with antenatal corticosteroid administration for risk of preterm delivery following rupture of membranes in the setting of a COVID-19 infection. We used a theoretical cohort of 10,000 women at each gestational age between 24 and 32 weeks who were hospitalized with PPROM and found to be COVID-19 positive. Maternal outcomes included intensive care unit admission and death related to COVID-19 infection. The infant outcomes of interest included respiratory distress syndrome, intraventricular hemorrhage, neurodevelopmental delay, and death, and were assessed along with maternal and infant quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were used to evaluate model assumptions.
Results: In our theoretical cohort of 10,000 women with COVID-19 infection and preterm prelabor rupture of membrane between 24 and 32 weeks, corticosteroid administration resulted in 2,200 women admitted to the ICU and 110 maternal deaths at each gestational age. No antenatal corticosteroid use resulted in 1,500 ICU admissions and 75 maternal deaths at each gestational age. Antenatal corticosteroid administration also resulted in fewer cases of respiratory distress syndrome, intraventricular hemorrhage, and infant death. Overall, we found that between 24 and 30 weeks of gestation, administering antenatal corticosteroids was the optimal management strategy as it resulted in higher combined QALYs than no corticosteroid use. For 31 and 32 weeks of gestation, antenatal corticosteroid administration resulted in lower combined QALYs. On sensitivity analyses, we found that with increasing gestational age, the probability which antenatal corticosteroids was the optimal management strategy decreased.
Conclusion: Administration of antenatal corticosteroids was an effective management strategy compared to no corticosteroid administration at gestational ages less than 31 weeks. These results provide data for clinicians to utilize when counseling pregnant patients hospitalized with PPROM and have a COVID-19 infection.
Background: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses.
Methods: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects.
Results: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia.
Interpretation: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.
Background and aims: Administration of corticosteroids is common in obstetric practice. In this concise review we queried on the effects of corticosteroids in pregnancies complicated by SARS-CoV-2.
Methods: We performed a literature search on PubMed, regarding the use of corticosteroids in patients with SARS-CoV-2 infection, in pregnancies complicated by SARS-CoV-2, as well as their impact on glycemia in pregnant women with or without diabetes. Furthermore, we searched for effects of SARS-CoV-2 and of other coronaviridae on insulin secretion and glycemia.
Results: SARS-CoV-2 infection appears to be a risk factor for complications in pregnancy. Corticosteroids may not be recommended for treating SARS-CoV-2 pneumonia but they may be needed for at-risk pregnancies. Corticosteroids in pregnancy have a diabetogenic potential. SARS-CoV-2 and other coronaviridae may have effects on glycemia.
Conclusions: Caution should be exercised while using corticosteroids in pregnant women with COVID-19 requiring preterm delivery.