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1.
Lancet Respir Med ; 9(7): 699-711, 2021 07.
Article in English | MEDLINE | ID: covidwho-1337033

ABSTRACT

BACKGROUND: Studies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use. METHODS: We analysed data from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study. All patients admitted to hospital with COVID-19 across England, Scotland, and Wales between Jan 17 and Aug 3, 2020, were eligible for inclusion in this analysis. Patients with asthma, chronic pulmonary disease, or both, were identified and stratified by age (<16 years, 16-49 years, and ≥50 years). In-hospital mortality was measured by use of multilevel Cox proportional hazards, adjusting for demographics, comorbidities, and medications (inhaled corticosteroids, short-acting ß-agonists [SABAs], and long-acting ß-agonists [LABAs]). Patients with asthma who were taking an inhaled corticosteroid plus LABA plus another maintenance asthma medication were considered to have severe asthma. FINDINGS: 75 463 patients from 258 participating health-care facilities were included in this analysis: 860 patients younger than 16 years (74 [8·6%] with asthma), 8950 patients aged 16-49 years (1867 [20·9%] with asthma), and 65 653 patients aged 50 years and older (5918 [9·0%] with asthma, 10 266 [15·6%] with chronic pulmonary disease, and 2071 [3·2%] with both asthma and chronic pulmonary disease). Patients with asthma were significantly more likely than those without asthma to receive critical care (patients aged 16-49 years: adjusted odds ratio [OR] 1·20 [95% CI 1·05-1·37]; p=0·0080; patients aged ≥50 years: adjusted OR 1·17 [1·08-1·27]; p<0·0001), and patients aged 50 years and older with chronic pulmonary disease (with or without asthma) were significantly less likely than those without a respiratory condition to receive critical care (adjusted OR 0·66 [0·60-0·72] for those without asthma and 0·74 [0·62-0·87] for those with asthma; p<0·0001 for both). In patients aged 16-49 years, only those with severe asthma had a significant increase in mortality compared to those with no asthma (adjusted hazard ratio [HR] 1·17 [95% CI 0·73-1·86] for those on no asthma therapy, 0·99 [0·61-1·58] for those on SABAs only, 0·94 [0·62-1·43] for those on inhaled corticosteroids only, 1·02 [0·67-1·54] for those on inhaled corticosteroids plus LABAs, and 1·96 [1·25-3·08] for those with severe asthma). Among patients aged 50 years and older, those with chronic pulmonary disease had a significantly increased mortality risk, regardless of inhaled corticosteroid use, compared to patients without an underlying respiratory condition (adjusted HR 1·16 [95% CI 1·12-1·22] for those not on inhaled corticosteroids, and 1·10 [1·04-1·16] for those on inhaled corticosteroids; p<0·0001). Patients aged 50 years and older with severe asthma also had an increased mortality risk compared to those not on asthma therapy (adjusted HR 1·24 [95% CI 1·04-1·49]). In patients aged 50 years and older, inhaled corticosteroid use within 2 weeks of hospital admission was associated with decreased mortality in those with asthma, compared to those without an underlying respiratory condition (adjusted HR 0·86 [95% CI 0·80-0·92]). INTERPRETATION: Underlying respiratory conditions are common in patients admitted to hospital with COVID-19. Regardless of the severity of symptoms at admission and comorbidities, patients with asthma were more likely, and those with chronic pulmonary disease less likely, to receive critical care than patients without an underlying respiratory condition. In patients aged 16 years and older, severe asthma was associated with increased mortality compared to non-severe asthma. In patients aged 50 years and older, inhaled corticosteroid use in those with asthma was associated with lower mortality than in patients without an underlying respiratory condition; patients with chronic pulmonary disease had significantly increased mortality compared to those with no underlying respiratory condition, regardless of inhaled corticosteroid use. Our results suggest that the use of inhaled corticosteroids, within 2 weeks of admission, improves survival for patients aged 50 years and older with asthma, but not for those with chronic pulmonary disease. FUNDING: National Institute for Health Research, Medical Research Council, NIHR Health Protection Research Units in Emerging and Zoonotic Infections at the University of Liverpool and in Respiratory Infections at Imperial College London in partnership with Public Health England.


Subject(s)
Asthma/complications , Asthma/mortality , COVID-19/complications , COVID-19/mortality , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/mortality , Adolescent , Adult , Clinical Protocols , Cohort Studies , Female , Hospital Mortality , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , Risk Assessment , United Kingdom , World Health Organization , Young Adult
2.
Front Pharmacol ; 12: 670170, 2021.
Article in English | MEDLINE | ID: covidwho-1268276

ABSTRACT

Background: Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed. The real role of corticosteroid use in COVID-19 has long been of interest and is disputable. Methods: We aimed to quantitatively reevaluate the efficacy of corticosteroids on COVID-19. Databases were searched for eligible meta-analyses/systematic reviews with available outcome data. For each association, we estimated the summary effect size with fixed- and random-effects models, 95% confidence intervals, and 95% prediction intervals. Heterogeneity, Egger's test, evidence of small-study effects and excess significance bias, and subgroup analyses were rigorously evaluated. Results: Intended outcomes of 12 eligible studies were mortality, clinical improvement, hospitalization, mechanical ventilation (MV), adverse events (AEs), intensive care unit (ICU) stay, hospital stay, virus clearance time (VCT), and negative conversion. Corticosteroid administration was associated with a 27% risk reduction in MV [hazard ratio (HR): 0.73 (0.64-0.83)] and a 20% reduction in mortality of critically ill/severe COVID-19 patients [HR: 0.80 (0.65-0.98)]. Interestingly, shorter ICU stays and, conversely, potentially longer hospital stays, a longer VCT, and a longer time to negative conversion were associated with corticosteroid use. There was no significant impact of different corticosteroid doses on mortality. Only one study showed slightly excess significant bias. Caution should be applied given the weak nature of the evidence, and it has been confirmed by sensitivity analyses too. Conclusion: This umbrella study found benefits from corticosteroids on MV and especially the mortality of critically ill/severe patients with shorter ICU stays but prolonged hospital stays and VCT. The benefits and harms should be reevaluated and balanced before corticosteroids are cautiously prescribed in clinical practice.

3.
Clin Infect Dis ; 72(11): e914, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1261035
4.
J Allergy Clin Immunol Pract ; 9(6): 2262-2271.e2, 2021 06.
Article in English | MEDLINE | ID: covidwho-1209057

ABSTRACT

BACKGROUND: Basic studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can affect chronic rhinosinusitis (CRS), but there is unclear real-world evidence regarding the association of underlying CRS with the risk for SARS-CoV-2 infection and severe coronavirus disease 19 (COVID-19). OBJECTIVE: We aimed to determine whether CRS is associated with increased risk for SARS-CoV-2 infection and severe COVID-19. METHODS: Altogether, 219,959 adult patients who tested for SARS-CoV-2 in South Korea from January 1 to May 15, 2020 (excluding self-referral) were identified in this nested case-control study with propensity score matching. Data on SARS-CoV-2 test results and COVID-19 worsened outcomes (ie, the need for oxygen therapy, intensive care, or mechanical ventilation, and death) were obtained from the Health Insurance Review and Assessment Service of Korea. RESULTS: In this matched cohort, 380 of 12,217 patients with CRS (3.1%) tested positive for SARS-CoV-2 infection, compared with 310 patients without CRS (2.5%; adjusted odds ratio = 1.22; 95% confidence interval, 1.04-1.42). Moreover, 60 of 286 COVID-19 patients with CRS (21.0%) had severe COVID-19 outcomes, compared with 38 without CRS (13.3%; adjusted odds ratio = 1.71; 95% confidence interval, 1.09-2.71). Subgroup analysis identified that CRS patients with an absence of nasal polyps, prior intranasal corticosteroid use, or nonatopic type had a greater risk for SARS-CoV-2 infection and severe COVID-19 outcomes. CONCLUSIONS: In patients with CRS, prior intranasal corticosteroid use, the absence of nasal polyps, or nonatopic type was associated with increased risk for SARS-CoV-2 infection and severe COVID-19 in the Korean nationwide cohort. Clinicians should be cautious in determining prognosis and care for patients with CRS amid the COVID-19 pandemic.


Subject(s)
COVID-19 , Pandemics , Adult , Case-Control Studies , Cohort Studies , Humans , Republic of Korea/epidemiology , SARS-CoV-2
5.
J Clin Invest ; 130(12): 6417-6428, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-1112385

ABSTRACT

BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P < 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P < 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P < 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (>200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , COVID-19/drug therapy , COVID-19/mortality , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/mortality , Aged , COVID-19/complications , Disease-Free Survival , Female , Humans , Male , Middle Aged , Respiratory Distress Syndrome/etiology , Retrospective Studies , Severity of Illness Index , Survival Rate
6.
Front Med (Lausanne) ; 8: 604263, 2021.
Article in English | MEDLINE | ID: covidwho-1106028

ABSTRACT

Corticosteroid is commonly used to reduce damage from inflammatory reactions in coronavirus disease 2019 (COVID-19). We aim to determine the outcomes of corticosteroid use in critically ill COVID-19 patients. Ninety six critically ill patients, hospitalized in 14 hospitals outside Wuhan from January 16 to March 30, 2020 were enrolled in this study. Among 96 critical patients, 68 were treated with corticosteroid (CS group), while 28 were not treated with corticosteroids (non-CS group). Multivariable logistic regression were performed to determine the possible correlation between corticosteroid use and the treatment outcomes. Forty-six (68%) patients in the CS group died compared to six (21%) of the non-CS group. Corticosteroid use was also associated with the development of ARDS, exacerbation of pulmonary fibrosis, longer hospital stay and virus clearance time. On admission, no difference in laboratory findings between the CS and the non-CS group was observed. After corticosteroid treatment, patients treated with corticosteroids were associated with higher counts of white blood cells, neutrophils, neutrophil-to-lymphocyte ratio, alanine aminotransferase level and Sequential Organ Failure Assessment score. In conclusion, corticosteroid use in critically ill COVID-19 patients was associated with a much higher case fatality rate. Frequent incidence of liver injury and multi-organ failure in corticosteroid treated patients may have contributed to the adverse outcomes. The multi-organ failure is likely caused by more persistent SARS-CoV-2 infection and higher viral load, due to the inhibition of immune surveillance by corticosteroid.

7.
Respir Med ; 176: 106275, 2021 01.
Article in English | MEDLINE | ID: covidwho-947438

ABSTRACT

BACKGROUND: The effects of chronic inhaled and systemic corticosteroids use on COVID-19 susceptibility and severity are unclear. Since many patients with chronic pulmonary diseases rely on corticosteroids to control disease, it is important to understand the risks of their use during the pandemic. We aim to study if the use of inhaled or systemic corticosteroids affects the likelihood of developing COVID-19 infection. METHODS: We used the National Jewish Health electronic medical record research database to identify a cohort of all subjects who were tested for suspected COVID-19 between March 11 - June 23, 2020. Testing results, medication use, and comorbidities were obtained from the medical record. Following a comparison of different propensity score weighting methods, overlap propensity score weighting was used to analyze the association between medication use and COVID-19 diagnosis. RESULTS: The cohort consisted of 928 patients, of which 12% tested positive. The majority (66%) of patients had a history of chronic pulmonary diseases. There was no significant association between inhaled corticosteroid use and testing positive for COVID-19. Interestingly, systemic corticosteroid use was associated with a lower odds ratio (0.95, 95% CI: 0.91-0.99) of testing positive for COVID-19. Similar results were noted when the analysis was restricted to those with any chronic pulmonary diseases, with asthma or with chronic obstructive pulmonary disease (COPD). CONCLUSIONS: Our study supports the recommendation that patients with chronic pulmonary diseases, including asthma and COPD who require treatment with either inhaled or systemic corticosteroids, should continue their use during the COVID-19 pandemic.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Asthma/drug therapy , COVID-19/epidemiology , Pulmonary Disease, Chronic Obstructive/drug therapy , Administration, Inhalation , Adult , Aged , Asthma/complications , Asthma/diagnosis , COVID-19/diagnosis , Cohort Studies , Female , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Propensity Score , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/diagnosis , Risk Factors
8.
J Comp Eff Res ; 9(18): 1247-1254, 2020 12.
Article in English | MEDLINE | ID: covidwho-948021

ABSTRACT

Dexamethasone was shown to decrease the mortality in coronavirus disease-2019 (COVID-19) recently. Use of corticosteroids was harmful in other coronavirus infections previously. WHO recommended against routine use of corticosteroids in COVID-19. In view of these, we reviewed the evidence about the use of corticosteroids in virus-induced acute respiratory distress syndrome (ARDS). Corticosteroids are beneficial in ARDS regardless of etiology. However, they increased the mortality rate in influenza-associated ARDS. In SARS and the Middle East respiratory syndrome, corticosteroids increased the mortality, delayed the viral clearance and increased the length of hospital stay. In the case of COVID-19, the available evidence from retrospective and observational studies is inconclusive about the corticosteroid use. Low-dose therapies appear to be effective. Evidence from a randomized control study found dexamethasone is effective in decreasing mortality in severe COVID-19 cases. More studies are needed to validate the benefit of corticosteroids in COVID-19.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/diagnostic imaging , Dexamethasone/therapeutic use , Pneumonia, Viral/drug therapy , Female , Humans , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
9.
Headache ; 60(8): 1558-1568, 2020 09.
Article in English | MEDLINE | ID: covidwho-638748

ABSTRACT

OBJECTIVE: To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. BACKGROUND: The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic. METHODS: A detailed search of the scientific and popular literature was performed. RESULTS: There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. CONCLUSION: Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.


Subject(s)
Adrenal Cortex Hormones/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , COVID-19/epidemiology , Headache/drug therapy , Pandemics , SARS-CoV-2/drug effects , Adrenal Cortex Hormones/therapeutic use , Angiotensin-Converting Enzyme 2/biosynthesis , Angiotensin-Converting Enzyme 2/genetics , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19/etiology , COVID-19/prevention & control , Contraindications, Drug , Disease Susceptibility/chemically induced , Dogs , Humans , Hypernatremia/chemically induced , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Mass Media , Models, Animal , Neutrophils/drug effects , Practice Guidelines as Topic , Pulmonary Edema/chemically induced , Rats , Receptors, Virus/biosynthesis , Receptors, Virus/genetics , Risk Assessment , SARS-CoV-2/growth & development , SARS-CoV-2/physiology , Up-Regulation/drug effects , Virus Shedding/drug effects
10.
Clin Infect Pract ; 7: 100033, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-343694

ABSTRACT

BACKGROUND: The potential risk of cytokine storm in patients with coronavirus disease 2019 (COVID-19) has been described [1]; we write to share our experience treating a 17-year-old male with haemophagocytic lymphohistiocytosis (HLH) secondary to COVID-19 infection. CASE REPORT: This patient presented with cough, sore throat, anorexia and pyrexia. On examination, he had gross cervical lymphadenopathy and palpable splenomegaly. Nose and throat swab for SARS-CoV-2 was positive and blood tests revealed pancytopaenia with very high ferritin, triglyceride and d-dimer levels. The patient's H-Score [2] was calculated at 220, suggesting probability of HLH of 93-96%. Considering Russell and colleagues' [3] comments about potential harm of corticosteroid use in patients with COVID-19 infection, the patient was commenced on treatment with the selective IL-1 receptor antagonist drug, Anakinra, and a two-day course of intravenous immunoglobulin. RESULTS: The patient responded rapidly to treatment, becoming apyrexial after 24 h. His lymph nodes and spleen began to normalise after the first 48 h, at which time point the ferritin also started to decrease. He was discharged after 11 days feeling fit and well. CONCLUSION: This case certainly illustrates the importance of hyperinflammation syndromes in COVID-19. It also raises the question - is the severe pneumonitis seen in patients with COVID-19 an immunological phenomenon? We know that the viral load of patients with COVID-19 seems to peak in the early stages of illness [4,5]; however, patients deteriorate later in the disease course, at around days 10-14. This patient, who had risk factors for deterioration (male, pancytopaenic), did not develop an oxygen requirement and clinically and biochemically improved rapidly on Anakinra with no adverse events. We might suggest Anakinra to the scientific community as a treatment option in COVID-19 infection.

12.
Am J Perinatol ; 37(8): 809-812, 2020 06.
Article in English | MEDLINE | ID: covidwho-46580

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) pandemic is causing a necessary, rapid adjustment within the field of obstetrics. Corticosteroid use is a mainstay of therapy for those women delivering prematurely. Unfortunately, corticosteroid use has been associated with worse outcomes in COVID-19 positive patients. Given this information, it is necessary that obstetricians adjust practice to carefully weigh the fetal benefits with maternal risks. Therefore, our institution has examined the risks and benefits and altered our corticosteroid recommendations. KEY POINTS: · Corticosteroid use is an important part of prematurity treatment because it provides benefit to the fetus.. · Corticosteroid use may be related with increased morbidity and mortality in novel coronavirus disease 2019 (COVID-19).. · Therefore, during the COVID-19 pandemic, an alteration in current corticosteroid practices is necessary to uniquely weigh the maternal risks and fetal benefits..


Subject(s)
Betamethasone , Coronavirus Infections , Dexamethasone , Fetal Organ Maturity/drug effects , Pandemics , Pneumonia, Viral , Pregnancy Complications, Infectious , Premature Birth/prevention & control , Prenatal Care/methods , Betacoronavirus/isolation & purification , Betamethasone/administration & dosage , Betamethasone/adverse effects , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Female , Gestational Age , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Humans , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Pregnancy , Pregnancy Complications, Infectious/therapy , Pregnancy Complications, Infectious/virology , Risk Assessment , SARS-CoV-2
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