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REVIEW ARTICLE

Consequence of COVID-19 on allergic asthma outcomes: a systematic review and meta-analysis

Xiaoqing Lia#, Dandan Shengb#, Kai Chena, Qiao Wangc*

aDepartment of Infectious Diseases, Ningbo Yinzhou No. 2 Hospital, Ningbo Zhejiang, 315000, China

bDepartment of Tuberculosis, Yantai Qishan Hospital, Yantai Shandong, 264001, China

cDepartment of Respiratory and Critical Care Medicine, Huzhou Traditional Chinese Medicine Hospital, Huzhou, Zhejiang, 313000, China

#X. Li and D. Sheng are co-first authors.

Abstract

Asthma is a common chronic lung disease, and COVID-19 pandemic as a respiratory viral disease led to lung infection and resulted in millions of deaths. So, the impact of COVID-19 on asthma outcomes and the risk of being infected or hospitalized should be clarified. Systematic review and meta-analysis on the outcomes and risk of asthma for people with COVID-19 was done by searching electronic databases between 1 December 2019 and 31 July 2023. A total of 48 studies from 27 countries spread across all continents were included in the review. The prevalence of asthma among COVID-19 patients was 7.9%, and the analysis demonstrated a 16.5% reduction in the risk ratio for acquiring COVID-19 among subjects with asthma compared to those without asthma. There was no statistically significant difference in hospitalization risk, ICU admission risk, and death risk for COVID-19 patients with no asthma compared to those with asthma. The risk of death from COVID-19 was similar between nonasthmatics and asthmatics. The findings indicated that subjects with asthma may be at a lower risk of having infection with COVID-19 compared to those without asthma, but they have a similar risk of hospitalization and mortality.

Key words: COVID-19, Allergy, Asthma, SARS-Cov2, Risk

*Corresponding author: Qiao Wang, Department of Respiratory and Critical Care Medicine, Huzhou Traditional Chinese Medicine Hospital, Huzhou, Zhejiang, 313000, China; Email addresses: [email protected]; [email protected]

Received 24 April 2024; Accepted 27 May 2024; Available online 1 July 2024

DOI: 10.15586/aei.v52i4.1116

Copyright: Li X, et al.
License: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/

Introduction

Asthma is the most common chronic adversity of the lungs, and its prevalence was globally estimated to be in up to 350 million people.14 Asthma, which has no complete cure, leads to several fatalities and involves significant expenses for its prevention and control.2,3 The new coronavirus disease 2019 (COVID-19) pandemic had an impact on one and all, and it spread rapidly across the globe with millions of deaths. Individuals with asthma may be more affected with this virus and were at an increased risk of acquiring the disease or experiencing poor outcomes.4,5

The cohort studies and individual case series were reported with conflicting results in subjects with asthma on the vulnerability to and risk of COVID-19 mortality. There are different reports on the vulnerability of asthma patients to COVID-19 based on various national- or local-level case series and analyses, and the conclusions reached were constrained by the inclusion of cases of COVID-19 and their related analyses that confer significant selection bias of asthma.6,7 The maximum focus was on mortality and not on other important parameters such as admission to an intensive care unit (ICU), risk of being infected, hospitalization, and most importantly ventilator use when admitted.810 A comprehensive understanding of the risk of COVID-19 among subjects with asthma is crucial globally as countries lift lockdown. The relationship between COVID-19 and asthma and also the impact of this virus on symptoms of asthma needs to be analyzed. The risk of SARS-Cov-2 (severe acute respiratory syndrome coronavirus 2) infection affecting people with asthma, hospitalization, ICU admission, and ventilator use should be recognized.4,5,11,12

In this study, detailed searches with new analyses were done and therefore, the research question is that are subjects with asthma at a higher risk of being infected or hospitalized or vulnerable to weaker clinical outcomes from COVID-19? And, what is COVID-19’s impact on asthma outcomes? Consequently, the objective was to conduct a comprehensive systematic review and meta-analysis of the morbidity and mortality of COVID-19 among subjects with asthma.

Methods

Search strategy and also selection criteria

The systematic review and meta-analysis touch upon the risk of asthma in people with COVID-19. Also, it includes publications on the pandemic’s early stages, and the protocol used was from published studies, systematic reviews, and meta-analyses; the preferred reporting items were employed in the reporting of this study.13 A comprehensive search of electronic databases, including the Cochrane Database of Systematic Reviews, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, the World Health Organization COVID-19 Database, Embase, CINAHL, and PEDro, were conducted between 1 December 2019 and 31 July 2023. Also, a hand search of relevant systematic review references was conducted. All studies (primary controlled) reporting on adults with confirmed COVID-19 were included, with a pre-existing asthma diagnosis that was published in the English language, and the screenings were checked and confirmed by three independent reviewers.

Data collection

Three reviewers screened abstracts and titles, and excluded irrelevant studies using Rayyan QCRI.14 Independently, full-text publications were subsequently reviewed and disagreement resolved via consensus and also referral to a fourth reviewer. At the full-text review stage, potential overlaps between studies were identified in order to prevent double counting of individual patients. The data were extracted using a standard electronic form, and the quality of the included studies was rated using the Newcastle–Ottawa Scale.15

Outcomes

The outcomes were: (1) the risk of asthma, expressed as the proportion of confirmed asthmatic patients with a diagnosis of COVID-19; (2) risk of hospitalization from asthma with confirmed COVID-19; (3) risk of ICU admission (confirmed COVID-19 patients with asthma); (4) risk of being ventilated (asthmatic individuals with confirmed COVID-19); and (5) risk of death (asthmatic individuals with confirmed COVID-19).

Data analysis

In Table 1, descriptive statistics were utilized to summarize the details of the included studies. It was mentioned that the Newcastle–Ottawa Scale was applied to assess the quality of methodology of the included studies based on the relevant study designs, case–control or cohort. The main sets (two) of meta-analyses were performed. To estimate the prevalence of asthma among individuals with COVID-19, a binomial distribution was employed to model within-study variability. The Wilson score was used to calculate 95% confidence intervals for all the binary outcomes, and a Sidik–Jonkman random-effects meta-analysis was conducted. The degree of quantitative heterogeneity was evaluated through the implementation of a formal test of homogeneity and the estimation of the proportion of variability attributable to heterogeneity. In addition, prespecified subgroup analyses were conducted on the studies’ quality and content, and univariate meta-regression using proportions of current smokers, age, and former smokers as covariates were performed. All pooled results were presented in the results section, and statistical analyses were performed using Stata 16.

Table 1 Detailed summary of the studies.

Refer-ence Country Setting Design COVID-19 positive Age (years) Male Current smokers COPD NOS Score
Asthma Overall
1 26 Argentina Mixed Retrospective cohort study 12,580 207, 079 41 1,03,487 4,074 4,405 9
2 27 Australia Mixed Case series 10 99 54 51 ----- 2 8
3 28 Australia Hospital Case series 22 197 45 94 ----- 4 7
4 29 Belgium Hospital Retrospective cohort study 57 596 58.75 294 ----- ----- 9
5 30 Brazil Hospital Retrospective cohort study 7 114 32.4 0 ----- ----- 7
6 31 China Hospital Retrospective cohort study 244 39,420 55.7 1,9655 ----- ----- 9
7 32 China Hospital Retrospective cohort study 68 562 47 265 ----- ----- 8
8 33 China Hospital Retrospective cohort study 1 290 57 155 10 6 8
9 34 Denmark Mixed Retrospective cohort study 354 5,104 54.6 2,399 ----- 432 9
10 35 France Mixed Retrospective cohort study 814 7,320 43 2,301 790 87 7
11 36 France Hospital Retrospective cohort study 37 112 60 49 ----- ----- 9
12 37 Ghana Hospital Retrospective cohort study 24 307 37.9 174 ----- ----- 7
13 38 Italy Hospital Retrospective cohort study 20 1,043 52.5 704 ----- ----- 9
14 39 Kuwait Hospital Retrospective cohort study 235 3,995 40.4 2,814 140 17 9
15 40 Kuwait Hospital Retrospective cohort study 43 1,096 41 888 44 5 9
16 41 Mexico Hospital Retrospective cohort study 4,942 1,78,306 44.1 88,083 ----- ----- 8
17 42 Mexico Mixed Retrospective cohort study 1,188 38,324 46.9 2,2362 3,277 889 9
18 43 Mexico Hospital Retrospective cohort study 1,448 66,123 52.4 40,124 ----- 2,619 9
19 44 Norway Mixed Retrospective cohort study 515 7,632 33.22 ----- ----- 161 7
20 45 Spain Hospital Retrospective cohort study 113 2,539 62.66 1,275 154 89 9
21 46 Spain Hospital Retrospective cohort study 577 6,310 59 2,983 873 ----- 9
22 47 Spain Mixed Retrospective cohort study 288 10,454 58 4,172 258 180 9
23 48 Spain Mixed Retrospective cohort study 2,330 35,387 38.8 17,172 6,119 1,404 9
24 49 Spain Community Retrospective cohort study 10 376 54 192 ----- ----- 8
25 50 South Korea Community Retrospective cohort study 725 7,340 47.1 2,970 ----- 350 9
26 51 South Korea Community Retrospective cohort study 686 7,272 45.3 2,927 ----- ----- 9
27 52 South Korea Hospital Case–control study 66 2,200 56.71 785 92 30 9
28 53 South Korea Mixed Retrospective cohort study 218 7,372 44.5 3,000 ----- ----- 9
29 54 Sweden Mixed Case–control study 133 1,981 61 14,65 ----- 75 9
30 55 Sweden Mixed Case–control study 4,493 68,575 46 26,808 ----- 2,168 9
31 56 Turkey Hospital Retrospective cohort study 58 767 51.99 374 80 43 8
32 57 UK Hospital Retrospective cohort study 1,557 17,606 67 10,560 231 ----- 9
33 18 UK Mixed Retrospective cohort study 29,792 1,98,420 37.7 93,765 22,134 1,873 9
34 58 UK Hospital Retrospective cohort study 102 617 65 ----- ----- ----- 9
35 59 UK Hospital Retrospective cohort study 12 52 54.82 29 ----- ----- 8
36 60 USA Hospital Retrospective cohort study 105 727 49.46 ----- ----- ----- 8
37 61 USA Hospital Retrospective cohort study 18 242 ----- 123 ----- 30 8
38 62 USA Hospital Retrospective cohort study 41 113 50 53 2 57 9
39 63 USA Hospital Retrospective cohort study 272 6,245 ----- 3,060 ----- ----- 8
40 64 USA Mixed Prospective cohort study 163 1,298 52 762 55 ----- 9
41 65 USA Hospital Case–control study 562 3,248 ----- 911 131 ----- 8
42 66 USA Hospital Retrospective cohort study 4 33 63 22 0 1 8
43 67 USA Hospital Retrospective cohort study 30 529 70 286 39 36 7
44 22 USA Hospital Retrospective cohort study 468 10,523 58.35 5,707 ----- 286 9
45 68 USA Hospital Case–control study 88 1,045 64.6 352 ----- 18 8
46 69 USA Hospital Retrospective cohort study 951 4,558 60.5 ----- ----- ----- 9
47 70 USA Hospital Retrospective cohort study 598 5,596 38.4 2,635 123 88 9
48 71 USA Hospital Retrospective cohort study 220 1,526 53.3 654 43 ----- 9

Results

The searches resulted in 41,392 citations. After removing of duplications, 17,831 abstracts and titles were screened, and 17,027 publications were excluded. From the remaining 804 manuscripts, 756 were excluded after reviewing the full text and a total of 48 studies were included in the review (Figure 1). Studies involving overlapping patient populations were excluded from the analysis if they reported identical outcomes.

Figure 1 Summary of the results of the screening and evaluation of the publications and citations searched.

Descriptive characteristics

This review is based on a pooled sample of patients diagnosed with COVID-19 who reported information related to asthma. Most of these hospital-based studies were from 27 countries spread across Europe, South America, Asia, North America, Africa, and Australia (Table 1).

The mean ± SD age of COVID-19 patients was 49.2 ± 13.6 years; 43.9% were male and 56.1% were female; and 6.6% were current smokers and 7.9% were former smokers. The asthma prevalence among those infected with the novel coronavirus (COVID-19) was 7.9%, and 2.8% also had COPD.

Risk of results’ bias

According to the Newcastle–Ottawa scores, all of the studies had scores of more than 7 and were of high quality.

Meta-analysis of the risk of acquiring COVID-19

The pooled analysis of studies demonstrated a 16.5% reduction in the risk ratio for acquiring COVID-19 among individuals with asthma compared to those without asthma. There was considerable heterogeneity across the studies and meta-regression by age revealed that the older ages was associated with enhanced risk of COVID-19 in individuals with asthma. However, the current smoker group did not demonstrate a statistically significant association.

Meta-analysis of the risk of hospitalization

There was no statistically significant difference with regard to the risk of hospitalization for COVID-19 individuals with and without asthma, and there was considerable heterogeneity observed across the studies. A meta-regression by age and current smoking status revealed no significant association between asthma and the risk of hospitalization due to COVID-19.

Meta-analysis of the risk of ICU admission

There was a no statistically significant difference in the ICU admission risk for subjects with asthma compared to those without asthma in a pooled analysis, and substantial heterogeneity was observed across the studies. A meta-regression analysis, with age and current smoking status as moderators, did not yield statistically significant results.

Meta-analysis of the risk of ventilator use when admitted in the ICU

In relation to the probability of mechanical ventilation, a statistically significant difference was not observed in the likelihood of being treated with a ventilator once admitted to the ICU for asthma compared to those with no asthma. Considerable heterogeneity was observed across the studies and a meta-regression analysis was conducted to determine the relationship between age and current smoking status. However, the results were not statistically significant.

Meta-analysis of the risk of death

The analysis revealed no statistically significant difference in the risk of death from COVID-19 between individuals with and without asthma, and considerable heterogeneity was observed across the studies. Including age as a moderator in the meta-regression analysis yielded no significant reduction in the risk of death, nor did it reveal any significant association with the current smoking status.

Analyses of the subgroup

Subgroup analyses by continent revealed substantial differences in the risk of acquisition of COVID-19 between the continents. The lowest risk was observed in Asia, while no major differences in hospitalization were found between continents. Nevertheless, significant discrepancies were observed in ICU admission rates across continents, and the maximum risk was found to be in Asia and the lowest in South America. In addition, the risk of ventilator use had significant differences across the continents, and the maximum risk was found in Europe. Similarly, the risk of death was found to vary considerably across the continents. The maximum risk was observed in Asia.

Discussion

The objective of this meta-analysis was to assess the vulnerability of patients with asthma who are infected with COVID-19. This discrepancy can be attributed to the more rigorous inclusion criteria employed, which excluded case series and single-arm cohort studies. The focus was on including only studies published by the nonasthma control group. Moreover, the prevalence rate was found to be lower than the global prevalence of self-reported symptoms of asthma. In this meta-analysis, the proportion estimated was less than in the recent UK studies which reported prevalence in those who were infected with the variant of B.1.1.7; lower prevalence rates were reported in other studies in Turkey and in Italy.1618 The current study found a significant decrease in the risk of acquiring COVID-19.

The study reported lower rates of positivity for COVID-19 test in asthma patients compared to those without asthma.19 Moreover, a community study demonstrated a lower prevalence of asthma in individuals who tested positive for the COVID-19 test compared to those who had negative COVID-19 test results.20,21 Several mechanisms may contribute to the lower risk of acquiring COVID-19 in subjects with asthma compared to individuals with no asthma. A retrospective study demonstrated that asthma is associated with poor outcomes and lower risk, and that both in those with and without asthma, the presence of eosinophilia is associated with reduced risk of mortality. Although not statistically significant, a greater proportion of individuals with asthma exhibited eosinophilia compared to those without asthma.22 Subgroup analyses by continent revealed statistically significant differences in the risk of contracting the novel coronavirus (COVID-19) between the continents. The lowest risk was observed in Asia, followed by America and Europe. In addition, it was observed that there was consistent risk reduction in three out of the four regions, and all countries with a large testing regime may account for this variance between regions. Furthermore, it is crucial to acknowledge that the outcome may not be representative of other countries where testing protocols have been less comprehensive.

Furthermore, the lower risk of acquiring COVID-19 may be attributed to the angiotensin-converting enzyme 2 receptor expression that is significantly lower in asthmatic patients compared to healthy controls,23 which supports the result of the current study analysis. The data demonstrated a clear correlation between increasing age and elevated risk of contracting the novel coronavirus. In a final directive, health authorities advised asthmatic patients to practice social distancing and to take particular care to avoid contracting the novel coronavirus. Furthermore, the pooled point estimate indicates a potential enhanced risk of hospitalization for COVID-19 for subjects with asthma, with a considerable degree of uncertainty. Similarly, the pooled point estimate indicates a potential increased risk of ICU admission due to COVID-19 for subjects with asthma, although this is not statistically significant.

It was reported that inhaled budesonide administration in early stage reduced the likelihood of urgent medical care and also time to recovery from COVID-19. The study demonstrated that the budesonide group exhibited a more rapid recovery compared to the usual care group.24,25 A main finding of the current study was the similar risk of death between nonasthmatics and asthmatics from COVID-19. The information provided was limited on smoking that limits our ability to assess the impact of smoking.

Furthermore, reported were details of both nonasthma and asthma patients wherein COVID-19 infection status was used, and there was no access to information to determine if individuals with asthma were disproportionately represented among cases of mild or asymptomatic illness that did not undergo testing. This would suggest that there may be a need for further investigation into the potential underdiagnosis of asthma in this population. The findings from this analysis indicated that individuals with allergic asthma may be at a lower risk of COVID-19 infection compared to those without asthma but have a similar risk of ICU admission, ventilator use, hospitalization, and mortality. In light of the rapid evolution of the COVID-19 virus and the emergence of variants globally, it is imperative to exercise caution for individuals with asthma. Moreover, further research is necessary to ascertain the precise risk profile.

Ethics Approval and Consent to Participate

Not Applicable.

Consent for Publication

Not Applicable.

Availability of Data and Materials

Not Applicable.

Conflict of Interest

There is no conflict of interest.

Funding

Not Applicable.

Authors’ contributions

X.L., D.S., K.C., and Q.W. searched the literature, screened the inclusion/exclusion reviews, extracted data, did quality assessment, and contributed to writing the review. All of them performed the statistical analysis and oversaw the study from inception to completion. X.L. and D.S. are co-first authors, and they contributed equally to this work. QW is the corresponding author.

Acknowledgements

Not Applicable.

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