INTRODUCTION

Coronavirus disease (COVID-19), caused by the SARS-CoV-2 virus, is a public health problem with almost 658 million confirmed cases and more than six million deaths by December 2022 ¹. As a result, different risk factors associated with a worse prognosis of the disease were studied during the pandemic, in an effort to design strategies for early intervention and to avoid hospitalizations and deaths. These factors include being male, advanced age, smoking ², diabetes mellitus ³, arterial hypertension (HT), cardiovascular disease, obesity, chronic respiratory disease and cancer ⁴. In addition, allergic rhinitis has been suggested to be a potential predictor of worse clinical outcomes in infected patients, although the evidence is controversial ^5,6.

A systematic review reported that patients with COVID-19 and allergic rhinitis are less prone to severe disease and hospitalization ⁷. However, the included studies did not specify whether patients had comorbidities that might influence severity of illness, and definitions of severe illness were heterogeneous ⁷. Although the reasons for this association are not entirely clear, elevated concentrations of eosinophilic cationic protein, IL-17 and IL-33 are found in patients with allergic rhinitis ⁸, the latter being present in patients with severe COVID-19 ⁹, which could partially explain this association. Since allergic rhinitis is a common disease, with an incidence of 10 to 40% of the world population ¹⁰, its possible role as a risk factor for a worse clinical outcome of COVID-19 should be considered.

Peru is one of the countries with the highest mortality rates due to COVID-19 worldwide. As of March 10, 2023, reports showed 4,487,553 confirmed cases and 219,539 deaths nationwide ¹. Likewise, in Peru, the prevalence of allergic rhinitis can reach up to 23% in Lima ¹¹, above the average in Latin America ¹², due to factors like air pollution ¹³. In this sense, identifying a possible association with pulmonary involvement in infected patients could be relevant. Although some studies attempted to estimate the role of allergic rhinitis as a possible predictor of adverse outcomes in COVID-19 patients, these did not include relevant control variables and used several outcomes ⁷. The tomographic score (TS) is a surrogate variable for pulmonary involvement in infected patients and its increase is associated with increased mortality and disease severity ¹⁴. In addition, it predicts hospital stay and need for intubation ^15,16, so we consider it a good marker to assess the association. Therefore, this study aimed to estimate the association between allergic rhinitis and the degree of pulmonary involvement by COVID-19 in adults from a Peruvian general hospital.

MATERIALS AND METHODS

Design and study population

This is an observational, analytical and cross-sectional study. We included the medical records of hospitalized patients with COVID-19 from the Cayetano Heredia Hospital during the period 2020-2021.

We assessed the medical records of adult patients (18 to older) diagnosed with COVID-19 by clinical evaluation, molecular or antigen testing, or by computed tomography. The history of allergic rhinitis was defined according to the medical records. Patients whose medical records were illegible or who provided incomplete information on the variables of interest were excluded. Similarly, patients diagnosed with COVID-19 by rapid antibody test were excluded.

Of 434 eligible medical records, we found 245 patients with COVID-19 and complete information regarding the variables of interest; Figure 1 shows the selection flow chart.

Figure 1 Sample selection flow chart. 

RESULTS

We assessed 434 medical records. The patients were mostly male, over 60 years of age with no significant medical history; 56.2% had a history of allergic rhinitis and 43.1% had moderate to severe pulmonary involvement. Other characteristics are shown in Table 1.

The bivariate analysis showed statistically significant differences between the presence or absence of allergic rhinitis and age groups (p<0.001), history of HT (p=0.017) and chronic consumption of corticoids (p=0.010). Patients with allergic rhinitis had lower mean age (59.2 vs. 66.7), a higher prevalence of uncontrolled HT (73.9% vs. 26.1%), chronic corticosteroid use (68.1% vs. 31.9%) and pulmonary involvement (63.2% vs. 36.8%), compared to those who did not have allergic rhinitis (Table 1).

Statistically significant differences were found during the bivariate analysis between pulmonary involvement and the variables age (p=0.015) and chronic corticosteroid use (p=0.020). Those with moderate to severe pulmonary involvement had a higher mean age (64.4 vs. 61.1) and higher frequency of chronic corticosteroid consumption (53.9% vs. 46.2%) compared to those with mild involvement (Table 2).

The crude model analysis showed that a history of allergic rhinitis decreased the severity of COVID-19 (PR: 0.69; 95%CI: 0.56-0.86; p<0.001). This association maintained its direction and magnitude in the regression model adjusted for sex, age, tobacco use, comorbidities and chronic corticosteroid use (aPR: 0.70; 95%CI: 0.56-0.88; p=0.002) (Table3). The complete crude and adjusted regression models are presented in the Supplementary Material.

DISCUSSION

We found that a history of allergic rhinitis was associated with a 30.0% lower prevalence of moderate to severe pulmonary involvement in patients with COVID-19.

Our findings are similar to those from a systematic review of nine studies, which found that patients with COVID-19 and allergic rhinitis are less prone to severe disease (odds ratio [OR ]: 0.79, 95% CI: 0.52-1.18; p=0.250) and hospitalization (OR: 0.23, 95 %CI: 0.02-2.67; p≤0.001) than patients without allergic rhinitis ⁷. However, the authors point out that the analyzed studies did not assess other comorbidities such as advanced age, diabetes or cardiovascular disease, which, being factors associated with worse outcomes in these patients ¹⁹, may limit the interpretation of their results. In this sense, our study, by including several comorbidities, provides a more robust analysis of the association. In addition, unlike the studies included in the systematic review, we used TS as a clinical outcome. TS has been described as a useful surrogate predictor of mortality, disease severity ¹⁴, hospital stay and need for intubation ¹⁵, therefore, it is a marker that can be used in clinical practice to assess disease severity.

Although the reasons why a history of allergic rhinitis is a protective factor for moderate to severe pulmonary involvement in patients with COVID-19 are unclear, some hypotheses have been proposed. One study found that cat nasal allergen produced a reduction in angiotensin-converting enzyme-2 (ACE2) mRNA expression in the nasal cilia of adult patients with allergic rhinitis who were allergic to cats ²⁰. This is relevant, as COVID-19 uses a host cell ACE2 receptor for entry, which can be found on the oral mucosa and the airways ⁷. Furthermore, this receptor plays a notable role in the development of the disease, associated pulmonary lesion and severity of the disease ²¹. Similarly, it has been proposed that exposure to IL-13 would reduce the expression of ACE2 in airway epithelial cells of atopic individuals ²². In this sense, it is possible that ACE2 mRNA expression may decrease in cases of allergic rhinitis, which could explain this presumed protection. Additionally, it is possible that the history of rhinitis is not the cause of this protective effect, but rather the drugs used for its treatment, as some studies have suggested. Thus, some research suggests a direct antiviral activity against SARS-CoV-2 virus in H1 receptor antagonists by interfering with the first steps of viral replication or by binding to ACE2 ²³. Therefore, patients taking these drugs had a significantly lower risk of SARS-CoV-2 infection ²⁴. According to previous studies, the prevalence of allergic rhinitis in patients positive to COVID-19 is 57.4% ⁶ which is very similar to our results.

Although our findings are preliminary, they encourage further research on the mechanisms by which a history of allergic rhinitis could be a possible protective factor for adverse clinical outcomes in infected patients. Understanding this potential mechanism could identify therapeutic targets that would allow the development of drugs to treat new infecting variants or other similar viral infections.

The limitations of our study include the use of non-probabilistic sampling and the fact that the results cannot be applied to other populations. Since we used self-reported information, recall bias may have affected our data. Asking about the history of allergic rhinitis is not part of the normal evaluation, so there is a possibility that some physicians may inquire about it and others may not. Relevant variables such as history of asthma, its severity or treatment were not included in the study. In addition, information about the diagnosis of allergic rhinitis did not include the exact time of the disease, severity, treatment or time from the onset of symptoms until the imaging tests. In almost every case, the CT scans may have been taken when pulmonary involvement had not yet reached its maximum extent. No information was collected on time of hospitalization, intensive care unit (ICU) requirement, mechanical ventilation or death. Our study uses pulmonary involvement by TS as a surrogate variable to assess the severity of the clinical picture by COVID-19. Nevertheless, the results suggest a potential factor whose mechanisms should be explored in future research.

In conclusion, more than half of the patients had a history of allergic rhinitis and four out of ten had moderate to severe pulmonary involvement. The history of allergic rhinitis could have a protective effect on moderate to severe pulmonary involvement due to COVID-19. This information will be useful to carry out studies with greater scientific rigor such as cohorts and cases and control studies, in addition to studies that may help explaining the biochemical and molecular mechanism of the protective effect of rhinitis. If the mechanism is found, it could be used for pharmacological purposes.