Inhaled corticosteroids and COVID-19: a systematic review and clinical perspective

Halpin, David; Singh, Dave; Hadfield, Ruth M.

doi:10.1183/13993003.01009-2020

Cited by 264 publications

(276 citation statements)

References 29 publications

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“…New data are emerging daily, rapidly updating our understanding of this novel coronavirus, but it is crucial that patients with asthma and other allergic diseases such as allergic rhinitis maintain their controller medication,from inhaled corticosteroids to biologics [51, 59, 60], including allergen immunotherapy [61], without making any dose adjustments on their own or stopping medication, which may lead to a higher risk of asthma exacerbations, increased OCS use, and a higher probability of the need for emergency room access and hospitalization (risk factors for coronavirus exposure and spread). Likewise, it is important to maintain well-controlled rhinitis and rhinosinusitis, together with other known risk factors for asthma exacerbations [62].…”

Section: Discussionmentioning

confidence: 99%

Asthma and the Coronavirus Disease 2019 Pandemic: A Literature Review

Morais‐Almeida

Pité

Aguiar

et al. 2020

Int Arch Allergy Immunol

106

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Even though respiratory viruses are one of the most common triggers for asthma exacerbations, not all of these viruses affect patients equally. There is no strong evidence supporting that patients with asthma have a higher risk of becoming seriously ill from coronavirus disease 2019 (CO-VID-19), although recent reports from the USA and the UK suggest that asthma is much more common in children and adults with mild to severe COVID-19 than has previously been reported in Asia and in Europe. As in previous severe acute respiratory syndrome (SARS) outbreaks, patients with asthma, especially children, appear to be less susceptible to the coronavirus with a low rate of asthma exacerbations. A different expression of viral receptors and T2 inflammation can be responsible for different outcomes. Future studies focused on asthma and on other allergic disorders are needed to provide a greater understanding of the impact of underlying asthma and allergic inflammation on COVID-19 susceptibility and disease severity. However, for the moment, it is crucial that asthmatic patients maintain their controller medication, from inhaled corticosteroids to biologics, without making any dose adjustments on their own or stopping the medication. New data are emerging daily, rapidly updating our understanding of this novel coronavirus.

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Section: Discussionmentioning

confidence: 99%

Asthma and the Coronavirus Disease 2019 Pandemic: A Literature Review

Morais‐Almeida

Pité

Aguiar

et al. 2020

Int Arch Allergy Immunol

106

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“… 5 , 6 These findings have led to speculation that treatments for respiratory disease, specifically inhaled corticosteroids (ICSs), might have a protective effect against SARS-CoV-2. 8 , 9 , 10 , 11 …”

Section: Introductionmentioning

confidence: 99%

“… 19 , 20 A systematic review of the role of ICS use in SARS-CoV-2, severe acute respiratory syndrome coronavirus 1, and Middle East respiratory syndrome coronavirus identified no relevant articles addressing this question, and whether ICS use could influence either the risk of becoming infected with SARS-CoV-2 or the clinical prognosis of COVID-19 is unclear. 9 Two ongoing randomised controlled trials are investigating whether the clinical course of COVID-19 is affected by ICS use ( NCT04331054 , NCT04330586 ); however, these trials will not address the role of regular ICS use on the risk of SARS-CoV-2 infection and outcomes among people who have an indication for ICS use, and, specifically, whether such use might have been responsible for the under-representation of people with chronic respiratory disease in early epidemiological descriptions of COVID-19. To answer this question, we aimed to explore the association between current ICS use and COVID-19-related death among people with COPD and asthma using the OpenSAFELY platform, which runs across linked primary care electronic health record (EHR) data for approximately 40% of the population in England, UK.…”

Section: Introductionmentioning

confidence: 99%

Risk of COVID-19-related death among patients with chronic obstructive pulmonary disease or asthma prescribed inhaled corticosteroids: an observational cohort study using the OpenSAFELY platform

Schultze

Walker

MacKenna

et al. 2020

The Lancet Respiratory Medicine

239

245

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Background Early descriptions of patients admitted to hospital during the COVID-19 pandemic showed a lower prevalence of asthma and chronic obstructive pulmonary disease (COPD) than would be expected for an acute respiratory disease like COVID-19, leading to speculation that inhaled corticosteroids (ICSs) might protect against infection with severe acute respiratory syndrome coronavirus 2 or the development of serious sequelae. We assessed the association between ICS and COVID-19-related death among people with COPD or asthma using linked electronic health records (EHRs) in England, UK. Methods In this observational study, we analysed patient-level data for people with COPD or asthma from primary care EHRs linked with death data from the Office of National Statistics using the OpenSAFELY platform. The index date (start of follow-up) for both cohorts was March 1, 2020; follow-up lasted until May 6, 2020. For the COPD cohort, individuals were eligible if they were aged 35 years or older, had COPD, were a current or former smoker, and were prescribed an ICS or long-acting β agonist plus long-acting muscarinic antagonist (LABA–LAMA) as combination therapy within the 4 months before the index date. For the asthma cohort, individuals were eligible if they were aged 18 years or older, had been diagnosed with asthma within 3 years of the index date, and were prescribed an ICS or short-acting β agonist (SABA) only within the 4 months before the index date. We compared the outcome of COVID-19-related death between people prescribed an ICS and those prescribed alternative respiratory medications: ICSs versus LABA–LAMA for the COPD cohort, and low-dose or medium-dose and high-dose ICSs versus SABAs only in the asthma cohort. We used Cox regression models to estimate hazard ratios (HRs) and 95% CIs for the association between exposure categories and the outcome in each population, adjusted for age, sex, and all other prespecified covariates. We calculated e-values to quantify the effect of unmeasured confounding on our results. Findings We identified 148 557 people with COPD and 818 490 people with asthma who were given relevant respiratory medications in the 4 months before the index date. People with COPD who were prescribed ICSs were at increased risk of COVID-19-related death compared with those prescribed LABA–LAMA combinations (adjusted HR 1·39 [95% CI 1·10–1·76]). Compared with those prescribed SABAs only, people with asthma who were prescribed high-dose ICS were at an increased risk of death (1·55 [1·10–2·18]), whereas those given a low or medium dose were not (1·14 [0·85–1·54]). Sensitivity analyses showed that the apparent harmful association we observed could be explained by relatively small health differences between people prescribed ICS and those not prescribed ICS that were not recorded in the database (e value lower 95% CI 1·43). Interpretation Our results do not support a major role for regular ICS use in ...

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“…The potential bene t of immunosuppression in such illnesses may stem from their anti-in ammatory effects which could diminish the clinical expression of disease including exaggerated immune response to viral illness. Therefore, it is not surprising that immunosuppressants usage during the COVID-19 pandemic is the centre of interest from several viewpoints with regard to: [1] susceptibility to viral infection, [2] plausibility of atypical presentation and un-recognised spread of infection, [3] their role as a potential therapeutic option, and [5] their impact on prognosis in people who routinely require some form of immunosuppression for their pre-existing conditions.…”

mentioning

confidence: 99%

Routine Use of Immunosuppressants is Associated with Mortality in Hospitalised Patients with COVID-19

Myint

Carter

Barlow-Pay

et al. 2020

Preprint

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Abstract Background: Whilst there is literature on impact of the SARS viruses in the severely immunosuppressed, and those who develop exaggerated immune response, less is known about the link between routine immunosuppressant use and outcome in COVID-19. Consequently, guidelines on their use vary depending on specific patient populations.Methods: The study population was drawn from the COPE Study (COVID-19 in Older People), a multicentre observational cohort study, carried out in UK and Italy. Data were collected between 27th February and 28th April 2020 by trained data collectors and included all unselected consecutive admissions with Covid-19. Load (name/number of medications) and dosage of immunosuppressant were collected along with other covariate data. The primary outcome was time-to-mortality from the date of admission (or) date of diagnosis, if diagnosis was five or more days after admission. Secondary outcomes were Day-14 mortality and time-to-discharge (length of stay). Data were analysed with mixed-effects, Cox proportional hazards and Logistic regression models using non-users of immunosuppressants as the reference group.Results: 1184 patients were eligible for inclusion. The median (IQR) age was 74(62-83), 676(57%) were male, and 299(25.3%) died in hospital (total person follow-up 15,540 days). Most patients exhibited at least one comorbidity, and 113(~10%) were on immunosuppressants. We found that any immunosuppressant use was associated with increased mortality: aHR 1.87,95%CI:1.30,2.69 (time to mortality) and aOR1.71,95%CI:1.01-2.88 (14-day mortality). There also appeared to be a dose-response relationship.Conclusion: Despite the possibility of indication bias, until further evidence emerges we recommend adhering to public health measures stringently, a low threshold to seek medical advice and close monitoring of worsening symptoms in those who take immunosuppressants routinely regardless of their indication.

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Inhaled corticosteroids and COVID-19: a systematic review and clinical perspective

Cited by 264 publications

References 29 publications

Asthma and the Coronavirus Disease 2019 Pandemic: A Literature Review

Asthma and the Coronavirus Disease 2019 Pandemic: A Literature Review

Risk of COVID-19-related death among patients with chronic obstructive pulmonary disease or asthma prescribed inhaled corticosteroids: an observational cohort study using the OpenSAFELY platform

Routine Use of Immunosuppressants is Associated with Mortality in Hospitalised Patients with COVID-19

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