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Prognosis of COVID-19 in respiratory allergy: a systematic review and meta-analysis



Do underlying allergic respiratory diseases such as asthma and rhinitis predispose to a severe coronavirus (COVID-19) infection? We conducted this systematic review to map out and synthesize evidence of published literature.

Main body of the abstract

We searched five bibliographic databases for articles published between 1 January and 15 November 2020 using keywords: “COVID” AND “Allergic disease,” “Prognosis and COVID-19,” “SARS-CoV-2,” “Asthma,” “Allergic rhinitis.” We synthesized 32 eligible articles from a total of 11,376 articles retrieved from the search process. The profile of allergic respiratory conditions was identified, and only seven studies reported on the treatment administered. No significant difference was observed concerning the prevalence of COVID-19 in individuals with allergic asthma and those with non-allergic asthma (RR = 0.61, p = 0.08). The mortality rate significantly decreased in COVID-19-infected patients with asthma than patients without asthma (RR = 0.63, p = 0.04).

Short conclusion

There is little evidence available on the role of asthma medications and risk factors influencing the prognostic outcomes for COVID-19 individuals with respiratory allergies, which invites further research.


Respiratory allergy, which infers that IgE-mediated allergic reaction is the major underlying pathophysiology in the upper and lower airways, includes allergic rhinitis and asthma [1,2,3]. In allergic individuals, airways exposure to an allergen will provoke allergic rhinitis and asthmatic reaction [4]. As is typical of most respiratory viruses, the main entry point in the human body by the on-going novel coronavirus disease (COVID-19), announced a global pandemic, is through the nose and nasopharynx airway passage [5]. The main clinical features of COVID-19 are such that respiratory allergic diseases like allergic rhinitis and asthma mimic symptoms of COVID-19, runny nose and headache, are common symptoms of allergic rhinitis, while cough and dyspnea are shared with asthma [6]. Furthermore, one of the prevailing comorbidity conditions identified in individuals infected with COVID-19 is chronic respiratory diseases like respiratory allergies [3].

The chronic allergic disease is linked to the tissue remodeling process, and persistent inflammation with characteristic CD4 T helper 2 (Th2) polarization can impair the efficient antiviral immune response [7]. In that regard, Th2 cytokines have been implicated in the viral progression due to their suppressive effect on physical, humoral barriers against viruses [8]. Further findings have shown the role of Th2 cytokines in coronavirus recognition and infection through modulation of the angiotensin-converting enzyme-2 (ACE2) in the airways and transmembrane protease, serine2 (TMPRSS2) [9, 10].

However, it is still unclear whether respiratory allergies such as asthma and rhinitis predispose one to rapid infection with COVID-19, or whether COVID-19 raises the risk of distressing respiratory allergies [11]. In addition to this research gap on the causal relationship between COVID-19 and respiratory allergies, there is currently no internationally approved therapies or vaccine for clinical trials that can be used to effectively manage COVID-19 infection particularly in adults and children with respiratory allergies [12]. Although informed severity of COVID-19 in children is minimal compared to adults, there is no evidence that allergic rhinitis and asthma medicines currently available, including inhaled corticosteroids (ICSs), antihistamines, and bronchodilators, increase the severity of COVID-19 infection in both adults and children with respiratory allergies [11].

Likewise, there is limited published evidence on the prognostic outcomes for COVID-19 in individuals with respiratory allergies [12]. One of the few available evidences is that from a nationwide cohort study from South Korea, which demonstrated that both allergic rhinitis and asthma were associated with worse clinical findings in individuals infected with COVID-19. Remarkably, patients with non-allergic asthma had a greater risk of testing positive for SARS-CoV-2 test and having a severe prognosis than patients with allergic asthma [13]. Given these uncertainties and limited evidence on clinical outcomes for COVID-19 in individuals with respiratory allergies, we conducted this systematic review to map out evidences and report findings from the synthesis of published literatures. Our review question and objective are outlined below.

Main text

Review questions

  1. 1.

    Does underlying respiratory allergic disease increase risk of COVID-19 infection?

  2. 2.

    What are the prognostic outcomes of COVID-19 infection in individuals with respiratory allergic diseases? Does Allergy medication affect the prognostics?

Main objective

To determine risk factors for COVID-19 and the prognostic outcome in patients with respiratory allergic conditions.


Study design

This systematic review and meta-analysis were conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [14] and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) [15] guidelines. The registration number for this review protocol in the International Prospective Register of Systematic Reviews (PROSPERO) is CRD42020198329.

Search sources and strategy

We carried out a comprehensive search on PubMed/MEDLINE, Web of Science, Google Scholar, and EBSCO using a search strategy that was developed by two of our reviewers (AAES and BA). The search strategy contained medical subject headings (MeSH) and keywords that include “COVID” AND “Allergic disease,” “Prognosis and COVID-19,” “2019-nCoV,” “coronavirus,” “SARS-CoV-2,” “Asthma,” “Allergy,” “Allergic rhinitis,” and “COPD”. The time frame for the search process was between 1 January 2019 and 15 November 2020.

Database screening

The database retrieved from the search process was reviewed for the removal of duplicates by AAES. The initial search process was conducted in June 2020 and thereafter, another search was conducted 15 November 2020. Two other authors (AS and AH) independently carried out the title and abstract screening of the articles in the first database while AAES and RA independently screened the newly retrieved database. To ensure that the methodological rigor is maintained during the screening process, NBHD independently reviewed the database after the title and abstract screening has been carried out. Lastly, full text of identified eligible studies from the title and abstract screening process were evaluated to determine articles were finally selected for data synthesis.

Study selection process

The titles and abstracts were screened and evaluated for selection into the study using our eligibility criteria which included the population (patients with respiratory allergic conditions infected with COVID-19), exposure (respiratory allergic diseases and their medication), comparison (if data available-compare outcome among COVID-19 infected individuals with or without respiratory allergy diseases), and outcomes (risk factors for COVID-19 and prognostic outcomes) (PECO) framework. To suit the context of our study, we replaced I (Intervention) in the usual PICO with E (exposures). In addition to the PECO inclusion criteria, only peer-reviewed published articles irrespective of language were included. Study designs of articles selected for further review and synthesis included case reports, case series, case-control, cross-sectional, cohort studies, and randomized control trials. Primary articles deemed eligible were also identified from the results section of systematic reviews in the database and selected for further review in our study. Articles were excluded if they involved other types of allergies (food allergy, drug allergy, skin allergy) and articles (reviews, book chapters, editorials, letters, and conference abstracts).

Quality assessment/critical appraisal

Two reviewers independently evaluated the quality of the eligible articles using the appropriate quality assessment tools for each study design of these articles. The NIH Quality Assessment Tool for observational studies [16] was used for the study that was case series, case-control, cross-sectional, and cohort. Furthermore, the Joanna Briggs Institute (JBI) checklist [17] was used to appraise the case reports. Other two reviewers (KEO and NBHD) reviewed the critically appraised articles for any discrepancies. There were no disagreements between the reviewers during the assessment process.

Data extraction

The data extraction process was done according to the list of items detailed in the design in a data extraction rubric. The data extracted include author, year of publication, geographical setting, study objectives, study design, study population such as respiratory allergic patients, sample size, treatment for COVID-19 and respiratory allergy, and treatment outcomes/useful statistical findings in the study. There were no scenarios of missing information or difficulty with the retrieval of full text for eligible articles. The PRISMA flow diagram (Fig. 1) provides summaries of the methodological steps performed in this review.

Fig. 1
figure 1

PRISMA flow diagram illustrating the search process which eligible articles were identified for data synthesis

Data synthesis

The data synthesis first involved a summary of findings synthesized from the data extracted from eligible articles and presented in a tabular form ( Tables 1 and 2). To further quantitatively determine the prognosis of COVID-19 in patients with respiratory diseases, we carried out a meta-analysis to report point estimates and the confidence interval. The meta-analysis was performed using a random effects model because of heterogeneity in the eligible studies that were synthesized. Heterogeneity of individual studies was evaluated using the I2 statistics and was graphically presented using a forest plot.

Table 1 Summary description of study population in the synthesized articles
Table 2 Summary of findings and implications in synthesized articles


The literature search retrieved 11,376 articles and 4541 duplicate studies were removed. After screening of titles and abstracts of the total 6835 articles after duplicates have been removed, we excluded 6487 studies that were not relevant to our inclusion criteria. We further conducted a full-text screening of the remaining 348 articles and, this resulted in the identification of 32 studies as eligible for inclusion in our systematic review (Fig. 1).

Characteristics and quality of included studies

The summary and baseline characteristics of synthesized studies and the therapeutic management for respiratory allergic patients infected with COVID-19 are shown in Tables 1 and 2, respectively. According to the NIH Quality Assessment tool [16], the quality assessment of the included studies ranged between good and fair quality.

The prevalence of respiratory allergy in COVID-19 patients

The prevalence of asthma in COVID-19 patients more than 11 years old was reported in 21 studies with 40,422 COVID-19 patients, under random effect model, the overall prevalence of asthma was 9.5% of COVID-19 patients with 95%, CI = 0.063, 0.128, P < 0.001. While the prevalence of asthma in COVID-19 patients under 11 years old was reported in 4 studies with 656 COVID-19 patients, under random effect model, the overall prevalence of asthma was 15.5% of COVID-19 patients with 95%, CI = − 0.002, 0.311, P < 0.054. The pooled results for the prevalence of asthma in COVID-19 patients above and under 11 years old are presented in Figs. 2 and 3, respectively. In addition to this, the pooled effect estimate demonstrated that there is no significant difference in association between COVID-19 with allergic asthma and non-allergic asthma (RR = 0.61, 95% CI 0.35, 1.06, p = 0.08), and this pooled result was homogenous (P = 0.05, I2 = 47%) as illustrated in Fig. 4. The prevalence of allergic rhinitis between COVID-19 patients was reported in 4 studies with 9237 COVID-19 patients, under random effect model; the overall prevalence of allergic rhinitis was 23% of COVID-19 patients (95%, CI = − 0.073, 0.532, P < 0.136) as displayed in Fig. 4.

Fig. 2
figure 2

The prevalence of asthma in old COVID-19 patients

Fig. 3
figure 3

The prevalence of asthma in young COVID-19 patients

Fig. 4
figure 4

The prevalence of allergic rhinitis in COVID-19 patients

The prognostic outcomes for COVID-19 infection in asthmatic patients

Nine (9) studies with 7880 COVID-19 patients reported that the mean duration of hospitalization time in COVID-19 patients was (estimated mean = 7.039, 95%, CI = 4.589, 9.489, P < 0.001), under the random effect model. the pooled result was heterogeneous (I2 = 99.68%, P < 0.001) (Fig. 5). Five (5) studies with 869 COVID-19 patients reported that the mean duration of ICU staying time in COVID-19 patients was (estimated mean = 10.37, 95%, CI = 6.928, 13.815, P < 0.001), under the random effect model. the pooled result was heterogeneous (I2 = 98.64%, P < 0.001) (Fig. 6). The pooled effect estimate showed that mortality rate significantly reduced by 30% in COVID-19 patients with asthma than in patients without asthma (RR = 0.63, 95% CI 0.40, 0.97, p = 0.04). There is no significant difference in associated between COVID-19 with allergic asthma and non-allergic asthma (RR = 0.61, 95% CI 0.35, 1.06, p = 0.08). These pooled results were homogenous (P = 0.05, I2 = 47%) (Fig. 7a).

Fig. 5
figure 5

The hospitalization time in COVID-19 patients

Fig. 6
figure 6

The intensive care unit time in COVID-19 patients

Fig. 7
figure 7

a The prevalence of COVID-19 in allergic and non-allergic asthmatics patients. b The mortality rate in asthmatics COVID-19 patients compared with non-asthmatics COVID-19 patients. c The hospitalization time in asthmatics COVID-19 patients compared with non-asthmatics COVID-19 patients

The pooled effect estimate showed that hospitalization time significantly increased with asthmatic patients more than non-asthmatic patient (mean difference = 0.88, 95% CI 0.21, 1.56, p = 0.01). The pooled results for mortality rate and hospitalization time for COVID-19 infection in asthmatic patients were homogenous as presented in Fig. 7b, c, respectively.


Principal findings

The present systematic review collects evidence from 32 studies that provide information about the prognostic outcome of COVID-19 in respiratory allergic patients (asthma & allergic rhinitis. The pooled results display no significant difference between the prevalence of COVID-19 with allergic asthma and non-allergic asthma. Asthma is characterized by chronic inflammation, hyper responsiveness of respiratory airways, mucus overproduction, and remodeling [49]. Allergy has been involved in 50–80% of asthma and the roughly 50% of severe asthma [50], though non-allergic asthma has been implicated in 10–33% of asthmatic individuals. The mechanism of allergic asthma has largely been associated with TH2 inflammation that is exemplified by high levels of eosinophils, IgE, and cytokines, such as IL-4, IL-5, IL-13, and IL-9 [51]. Compared with this allergic mechanism, TH1 response which involves the stimulation of neutrophils and mast cells has been characterized nonallergic asthma [52]. Together respiratory infections, failure in resolution of inflammation, and stimulation of IL-17 pathway attribute to neutrophilic inflammation [53]. In the included Korean nationwide cohort, allergic asthma patients were not diagnosed by their medical history, including laboratory data (e.g., IgE levels) but they were defined by International Classification of Disease codes, which may have miscaptured data, and allergic asthma was demarcated as asthma with at least one further allergic disorder (atopy or allergic rhinitis), while asthma without any atopic disorder was defined as nonallergic asthma [13].

Strengths and limitations

This review affords up-to-date results of the risk of respiratory allergic disease in patients with COVID-19. To the best of our knowledge, this is the first systematic review focused on the prevalence and outcome of COVID-19 infection in allergic asthma and allergic rhinitis patients. These studies were generated from several countries. However, this meta-analysis had some limitations. First, while only two studies described the phenotype of asthmatic patients, others offered no information. Also, there were no data on asthma control due to a lack of lung function tests which were not performed due to restrictions recommended during COVID-19. Second, data on allergic rhinitis was sourced only from three studies, other studies combined this data with other allergies (food allergy, eczema). Third, there is no detailed information on asthma severity, systemic antihistamines, leukotriene antagonists, and allergen immunotherapy displayed in the identified studies which keep us from further conclusions about their role in COVID-19 prognosis. Fourth, the pooled results of the prevalence of allergic rhinitis and asthma between COVID-19 patients were heterogenous. This might be related to methodological discrepancies in the sampling criteria and study design across the studies included in this part of the analysis.

Comparison with other studies

Regarding the outcome of COVID-19 infection in asthmatics patients, the pooled effect estimate showed that mortality rate was significantly reduced by 30% in COVID-19 patients with asthma than in patients without asthma (RR = 0.63, 95% CI 0.40, 0.97, p = 0.04). Our study findings are similar to results from a previously published meta-analysis which reported the risk of mortality in patients with COVID-19 with asthma was (RR = 0.87, 95% CI 0.69, 1.09, p = 0.24) [54]. Their results were not significant as they included only three studies and used random effect model. On the other hand, no significant effect was reported by Wang et al. [55] (4 studies) for the mortality risk (OR = 0.96; 95% CI 0.70–1.30; I2 = 0%; p = 0.79). Among the four included studies in the current analysis, Desir et al. weighted 45.4%, noted that the prevalence of asthma as a comorbidity in severe COVID-19 seems to be parallel to that of coexistent conditions such as hypertension, diabetes, and hyperlipidemia.

There are various justifications for this result. Earlier, the overall prevalence of asthma in COVID-19 patients under 11 years old and more than 11 years old patients were 15.5% and 9.5% respectively. The second explanation is that asthmatic patients were adherent to home isolation precaution during the COVID-19 epidemic as they were known as a high-risk group. Moreover, the hospitalized asthmatic patients were presented early to the hospital and were received an aggressive and timely management. The low prevalence of asthma may be attributed to the low risk of asthmatic patients to COVID-19 infection. Jackson et al. observed that allergic asthmatic patients have reduced expression of ACE2 in respiratory epithelial cells [56]. This can be attributed to the TH2 inflammatory pathway and asthmatic medications (ICS alone or with bronchodilators) which inhibit viral replication [57, 58]. These observations may explain the low mortality risk in asthmatics patients with COVID-19 infection.

The hospitalization time significantly increased with asthmatic patients more than non-asthmatic patient (MD = 0.88, 95% CI 0.21, 1.56, p = 0.01). Our finding could be clarified by the fact that the symptoms of asthma are exacerbated by respiratory viral infections and the management of asthma becomes more complicated during the COVID-19 pandemic [49]. The respiratory viruses penetrate the epithelium of the respiratory airway and elicit local inflammation, which disrupts the bronchial defense system [59]. There are several cytokines induced by a viral infection that play role in the exacerbation of asthma. Secretion of IL-25 and IL-33 in epithelial cells stimulates TH2 pathways to cause increased mucin production, eosinophilia, and secretion of proinflammatory cytokines (i.e., IL-4, IL-5, and IL-13) [60]. Interferons (IFNs) engage in a pivotal role in antiviral and allergic responses. Earlier studies have revealed that IFN secretion by respiratory epithelial cells and plasmacytoid dendritic cells (pDCs) is reduced in asthma [61]. Additionally, IgE cross-linking reduces antiviral responses through inhibition of pDC maturation, IFN-α response, and TLR-7 upregulation [62].

Concerning hospitalization and mortality in allergic rhinitis patients with COVID-19 infection, we could not do analysis as there is not enough data. Only included cohort studies assumed that allergic rhinitis showed a trend toward lower hospitalization, although not statistically significant (RR, 0.83;95%CI,0.64-1.07) [44]. There were seven synthesized articles that mentioned corticosteroids, bronchodilators, leukotriene antagonist therapy, and their outcome in asthmatic COVID-19 patients. They included 2 case reports and 1 case series that noted that prognostic outcome of COVID-19 infection can be attributed to underlying comorbid conditions and hidden causes other than COVID-19 in patients with concurrent COVID-19 and respiratory allergy [18, 19, 24]. In a French cohort study, they concluded that that the risk factors for hospitalization in their asthmatic patients were related more to the risk factors of SARS-CoV-2 pneumonia (e.g., hypertension, obesity, sleep apnea diabetes, smoking) than to asthma [63]. Bhatraju et al. could not draw a conclusion regarding the role of systemic glucocorticoids in patients with Covid-19 infection but recommended further research [25]. However, Chhiba et al., 2020, concluded that the use of ICS with or without systemic corticosteroids was not associated with COVID-19-related hospitalization [44].


Based on current findings, there was little evidence on therapeutic management of respiratory allergic patients infected with COVID-19 and the impact on prognostic outcomes. Consequently, it is critical that asthmatic patients should continue to administer medications prescribed to maintain asthma control regularly, in particular, ICS, long-acting bronchodilators, antileukotrienes drugs to avoid complications as increased hospitalization time. Further investigation is needed to determine the role of asthma medications and immunotherapy in the outcome of COVID-19 infection in asthmatic patients. In addition, the association of severe COVID-19 with other risk factors in asthmatic patients should be the topic of future studies.

Availability of data and materials

Not applicable



T helper 2


Angiotensin-converting enzyme-2


Transmembrane protease, serine2


Inhaled corticosteroids


Prospective Register of Systematic Reviews


Medical Subject Headings


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The authors wish to thank the COVID-19 MENA Response Research Team for providing the conducive platform and support to conduct this review.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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NBHD, AAES, and the MENA COVID-19 response team conceived the study with contributions from all the other authors. NBHD and KEO supervised the review process and manuscript writing, AH carried out the meta-analysis. NBHD, KEO, AAES, and AH constructively reviewed the manuscript for intellectual content. All authors read and approved the final version of the manuscript

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Correspondence to Alia Abdelmonem El Shahawy, Kelechi Elizabeth Oladimeji or Nesrine Ben Hadj Dahman.

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El Shahawy, A.A., Oladimeji, K.E., Hamdallah, A. et al. Prognosis of COVID-19 in respiratory allergy: a systematic review and meta-analysis. Egypt J Bronchol 16, 12 (2022).

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  • COVID-19
  • Prognostic outcomes
  • Respiratory allergy