The association between COVID‐19 and asthma: A systematic review and meta‐analysis

Abstract

To the Editor, Recently, the associations between COVID-19 and its comorbidities including hypertension, diabetes, obesity, cardiovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, immunosuppression and other diseases have been reported in the many studies.1 However, there is no clear evidence about whether patients with asthma were at a higher risk of severe or fatal COVID-19. Respiratory viral infections are one of the most common triggers for asthma exacerbations. Some studies have provided data about the prevalence of asthma in severe or fatal COVID-19 patients.2-5 Higher levels of evidence are required to investigate the association between severe or fatal COVID-19 and asthma. Thus, we performed this systematic review and meta-analysis. We systematically conducted an electronic literature search in PubMed, EMBASE, Cochrane library, Web of Science and China National Knowledge Infrastructure (CNKI), using the keywords “asthma” or “respiratory diseases” AND “2019-nCoV” or “novel coronavirus” or “coronavirus disease 2019” or “SARS-CoV-2” or “COVID-19” from their inception up to 5 August 2020. The search was not restricted by language. Studies were selected if they fulfilled the following entry criteria: (a) patients must be diagnosed with COVID-19 infection and (b) provided information of asthma with severe or non-severe or between death and survivors. Abstracts, letters, case reports, literature review articles, letters to the editor and/or editorials were excluded. For each study, the following data were abstracted: name of the first author, country where the cohort was conducted, size of the cohort, numbers of males and females, age range or mean and outcomes of interest. The severity of the disease was mainly determined on the basis of symptom (eg patients with pulse oxygen saturation less than 90%, or required mechanical ventilation, or with acute respiratory distress syndrome, or admitted to intensive care unit). For non-random controlled studies, a nine-item Newcastle-Ottawa Scale (NOS) was used as an assessment tool for selection, comparability and outcome assessment by two investigators (YW and GA). A total score of ≥7 indicated a high-quality study, whereas a total score of <7 was considered to a low-quality study. If necessary, the primary authors were contacted to retrieve further data. The literature search, eligible study selection and data extraction were performed independently by two authors (YW and GA). Any disagreements were resolved with a third investigator or by consensus. Review Manager 5.3 (Cochrane Collaboration) was used to calculate the individual and pooled odds ratio (OR) with their relative 95% confidence interval (95% CI). Heterogeneity among studies was assessed with Cochran's Q test and the I2 statistic, with an I2 < 25%, 25%-50% and greater than 50% represented low, moderate and high heterogeneity, respectively. In addition, sensitivity analysis was conducted to evaluate the stability of the outcome and was performed by excluding 1 study at a time. P < .05 was considered statistically significant. This study is registered with PROSPERO, number CRD42020203058. In total, the search strategy retrieved 457 studies based on our search criteria. After exclusion of duplicate records and studies that did not fulfil our inclusion criteria, 72 articles remained and we further evaluated the full texts of these 72 literatures. Of these, we excluded 58 studies owing to lack of sufficient information for estimation of OR and not an outcome of interest. Finally, a total of 14 publications representing data from 17 694 participants were included in this meta-analysis.1-14 The sample size of patients ranged from 69 to 9946. Six studies were from America, two studies from Mexico, two studies from China and four studies from other countries. Asthma is defined according to the patient's medical history. All studies were published in English. The details of each included study are presented in Table 1. The NOS scores of these studies ranged from 7 to 9, which indicated that all data sets were of high quality (Table S1). The meta-analysis showed that patients with severe COVID-19 disease were not associated with an increased risk of asthma than non-severe COVID-19 patients (OR = 1.36, 95% CI: 0.79-2.34, P = .27; I2 = 77%) (Figure 1A). Moreover, asthma was not associated with increased risk of mortality in patients with COVID-19 (OR = 1.03, 95% CI: 0.55-1.93, P = .92; I2 = 76%) (Figure 1B). The subgroup analysis based on countries suggested no significant relationship between asthma and risk of severe COVID-19 disease in America (OR = 1.30, 95% CI: 0.57 to 2.98, P = .53; I2 = 84%). Sensitivity analyses by omitting each study at a time did not significantly alter the direction of the overall estimates. COVID-19 is a global pandemic infectious disease caused by infection with severe acute respiratory syndrome coronavirus 2. Asthma was associated with more severe diseases during influenza epidemics. Although respiratory viruses are well-recognized as important causes of acute exacerbations of asthma in children and adults, these viruses are not the same and may have different effects on asthma. Our meta-analysis did not identify that asthma had a higher risk of becoming seriously ill and mortality of COVID-19 disease. As with any meta-analysis, our study shares several limitations of the original studies. Our results are based on observational studies, which are susceptible to design bias, selection bias and residual confounding. In addition, results were analysed on study-level data; thus, we could not assess whether all baseline characteristics were balanced across groups. Besides, our results were based on the unadjusted estimates, and more accurate outcomes would result from adjustments for other confounders such as age, gender and comorbidities. Another limitation in this study was that heterogeneity across the studies was substantial, which could be attributed to a different definition of severity used or sample size. Despite these limitations, this meta-analysis provides information on the association between asthma and COVID-19 infection with regard to disease severity and mortality. We should not relax our focus on the COVID-19 patients with asthma. More well-designed studies are needed to provide a better understanding of the impact of asthma and other allergic disorders on susceptibility and severity of COVID-19. The authors declare no conflict of interest. The data that support the findings of this study are openly available in PubMed and medRxiv. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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