key: cord-0942449-htv2ot5y
authors: Smith, Steven J.; Busby, John; Heaney, Liam G.; Pfeffer, Paul E.; Jackson, David J.; Yang, Freda; Fowler, Stephen J.; Menzies-Gow, Andrew; Idris, Elfatih; Brown, Thomas; Gore, Robin; Faruqi, Shoaib; Dennison, Paddy; Dodd, James W.; Doe, Simon; Mansur, Adel H.; Priyadarshi, Radhika; Holmes, Joshua; Hearn, Andrew; Al-Aqqad, Hamsa; Loewenthal, Lola; Cooper, Angela; Fox, Lauren; Selvan, Mayurun; Crooks, Michael G.; Thompson, Alison; Higbee, Daniel; Fawdon, Michelle; Nathwani, Vishal; Holmes, LeanneJo; Chaudhuri, Rekha
title: The impact of the first COVID-19 surge on Severe Asthma Patients in the UK. Which is worse: The virus or the lockdown?
date: 2020-11-19
journal: ERJ Open Res
DOI: 10.1183/23120541.00768-2020
sha: 72a534d0067c145599c78b66bbd33219aa800250
doc_id: 942449
cord_uid: htv2ot5y

Respiratory viral infections are a significant cause of morbidity in asthma [1]. Patients with severe asthma were assumed to be at greater risk from novel coronavirus-2 (COVID-19) infection. In the global response to the COVID-19 pandemic, multiple countries enacted social containment policies. In the UK a countrywide lockdown occurred in March 2020, with stringent self-isolation (“shielding”) advice for high-risk patients, including people with severe asthma.

In the UK a countrywide lockdown occurred in March 2020, with stringent self-isolation ('shielding') advice for high-risk patients, including people with severe asthma.

Subsequently; ISARIC reported 14% of UK patients hospitalised with COVID-19 had an underlying diagnosis of asthma, but they did not associate asthma with higher mortality (2) . The OpenSAFELY study of COVID-19-related deaths identified severe asthma as a factor associated with mortality [HR 1.13 [1.01-1.26] (3). However, 'severe asthma' was defined as anyone with asthma and a course of oral corticosteroids (OCS) in their records in the past year (3) . Their analysis of inhaled corticosteroid (ICS) use showed increased mortality risk from COVID-19 in asthma patients on high dose versus no ICS, attributed to unrecorded health differences between the two groups (4) . The Italian Severe Asthma Registry reported infrequent incidence of COVID-19 infection, based on participating centres reporting cases of confirmed/highly suspected COVID-19 with severe asthma and, as 21/26 cases were on anti-IL5/IL-5R biologics, they speculated that asthma biologics may modulate the risk of COVID-19 (5). To our knowledge, there is no information on the burden of social isolation (shielding) in people with severe asthma. There is a need for information on the impact of COVID-19 on a wellcharacterised severe asthma population in the community, effects of shielding and any association between asthma medication and COVID-19.

The UK Severe Asthma Registry (UKSAR) performed an audit in June 2020 across 14 centres, of patient adherence with shielding advice, potential COVID-19 infection and outcomes and asthma control since 1 st March 2020. UKSAR centres with >100 registry patients used randomly generated lists to reduce potential bias. Where available, electronic hospital records were checked to confirm hospital admissions and COVID-19 swab/serology results. Permission was obtained by centres as per local audit requirements and all patients had previously consented to use of their anonymised Registry data.

Confirmed COVID-19 was defined as those with a positive PCR/serology test. Suspected COVID-19 was defined as typical symptoms, managed clinically as COVID-19, without a negative test.

Ambulatory and hospitalised patients were labelled as 'mild' and 'severe' COVID-19, respectively.

Audit data were combined with clinical data from the UKSAR. We used data from the most recent visit, and imputed missing values with data collected at previous visits. Univariate analyses were conducted using independent t-tests, Mann-Whitney U tests or chi-square tests as appropriate.

Multivariate analyses were undertaken using logistic regression adjusting for age, gender, ethnicity, BMI, site, cardiac disease, diabetes and hypertension. In summary; the majority of patients reported receiving and following shielding advice, 47% of shielding patients reported worsening of mental health, higher than the Office of National Statistics analysis of shielding patients in England (35%), with similar higher incidence in female and younger patients (6) .

We found that monoclonal antibodies for asthma were not associated with increased risk of mild or severe COVID-19 infection. This agrees with other emerging findings of low incidence of COVID-19 in the severe asthma population and biologics not affecting clinical outcome (7) . Poor asthma control increases the risk of severe viral exacerbations, so disease stability from biologics may be protective in itself (8) .

Although numbers were small, there was an association seen with high dose ICS and reduced hospitalisation from COVID-19. The RECOVERY trial demonstrated that dexamethasone reduced mortality and progression to ICU in hospitalised patients (9) . In vitro studies have suggested ICS can reduce viral replication whilst pre-treatment with ICS has been shown to reduce the risk of ARDS in hospitalised patients (10, 11) . Further studies are required, but our findings support continued use of ICS at an appropriate dose for asthma control.

The strength of this study is the multicentre inclusion of well-characterised severe asthma patients.

In addition to studying the impact of COVID-19 and effect of asthma medications, we enquired about the burden of shielding; a consideration when planning for the second wave. Limitations are the small number of patients hospitalised with COVID-19 preventing detailed analyses for risk factors.

We also note that this study cannot separate out the risk of COVID-19 in an unshielded severe asthma population and that adherence to shielding was self-reported. Unfortunately, COVID-19 testing was not widely available in the early months of the pandemic, hence, despite including only patients reporting symptoms distinct from their usual asthma, the natural symptom overlap between poor asthma control and mild COVID-19 limits robust conclusions in the 'suspected COVID-19' group.

In conclusion, hospitalisation and death occurred in small numbers of this UK severe asthma population. Adherence to shielding guidance may have contributed to this, but led to worsening of mental health in our patents. Within our limited numbers of cases, biologic agents for asthma were not associated with increased risk of COVID-19 infection or hospitalisation. 

Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness

Features of 20 133 UK patients in hospital with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study

Factors associated with COVID-19-related death using OpenSAFELY

Inhaled corticosteroid use and risk COVID-19 related death among 966,461 patients with COPD or asthma: an OpenSAFELY analysis

COVID-19 in Severe Asthma Network in Italy (SANI) patients: clinical features, impact of comorbidities and treatments

Office for National Statistics. Statistical Bulletin: Coronavirus and Shielding in Clinically Extremely Vulnerable People in England: 28 May to 3

Early experiences of SARS-CoV-2 infection in severe asthmatics receiving biologic therapy

The influence of asthma control on the severity of virus-induced asthma exacerbations

Dexamethasone in Hospitalized Patients with Covid-19 -Preliminary Report

Inhaled corticosteroids in virus pandemics: a treatment for COVID-19? The Lancet Respiratory Medicine

The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15

Stephen Fowler is supported by the NIHR Manchester Biomedical Research Centre