Asthmatic patients and COVID-19: Different disease course?

We read with great interest the article ‘‘Asthma and COVID‐19: Is asthma a risk factor for severe outcomes?’’ by Johnston about the possible implications of asthma asthma treatment and coronavirus disease 2019 (COVID‐19).

COVID‐19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the number of SARS‐CoV‐2–infected patients with asthma is consistent with the asthma incidence in the population despite the virus outbreak. There are few reports of COVID‐19 in asthmatic patients. Therefore we aimed to investigate the disease course of COVID‐19 in asthmatic patients from hospitalization until COVID‐19 resolution.

Patients were recruited at the Hospital das Clinicas—University of São Paulo (HCFMUSP). Asthma patients were selected based on the previous asthma diagnoses. COVID‐19 was confirmed by the nasopharyngeal detection of SARS‐CoV‐2 by reverse transcriptase polymerase chain reaction. Patients were evaluated daily until SARS‐CoV‐2 clearance and hospital discharge. This study was approved by the Ethics Committee of HCFMUSP (No. 30 800 520.7.0000.0068‐2020).

We recruited 215 COVID‐19–infected patients. Among those 5 (2.32%) had asthma and systemic arterial hypertension (SAH) a common comorbidity associated with asthma. A total of 7 patients without comorbidities were included in the study: 3 patients were in the general ward with moderate COVID‐19 infection (MODERATE) and 4 were in the intensive care unit with severe COVID infection (SEVERE). Seventy‐four patients had SAH (34.4%) as a comorbidity and only 10 (4.65%) were included in the study. The other 64 patients presented other comorbidities or secondary infections that could influence COVID‐19 disease course. All patients with SAH underwent regular daily usage of losartan (50 mg). There was no sex difference between groups and patients were hospitalized between 3 and 4 days after COVID‐19 symptom onset. All patients in this study survived (Table 1). Statistical analyses were performed using the Kruskal‐Wallis test with Dunn's multiple comparison and the data are shown as the mean ± standard error of the mean. P‐value of < .05 was considered to be statistically significant.

TABLE 1

Clinical characteristics and fate of COVID‐19 patients included in the study

Group	Patient	Age (y)	Sex	SAH	Diabetes	Smoking	Secondary bacterial infection	Death	Hospitalization time (d)
Moderate	#1	63	Male	No	No	No	No	No	6
	#2	67	Male	No	No	No	No	No	13
	#3	51	Female	No	No	No	No	No	16
Severe	#1	50	Female	No	No	No	No	No	20
	#2	61	Male	No	No	No	No	No	20
	#3	43	Male	No	No	No	No	No	18
	#4	65	Male	No	No	No	No	No	18
Asthma + SAH	#1	43	Male	Yes	No	No	No	No	14
	#2	61	Female	Yes	No	No	No	No	8
	#3	64	Male	Yes	No	No	No	No	18
	#4	41	Male	Yes	No	No	No	No	5
	#5	61	Female	Yes	No	No	No	No	8
SAH	#1	74	Male	Yes	No	No	No	No	13
	#2	45	Female	Yes	No	No	No	No	15
	#3	47	Male	Yes	No	No	No	No	13
	#4	59	Male	Yes	No	No	No	No	44
	#5	67	Female	Yes	No	No	No	No	11
	#6	74	Male	Yes	No	No	No	No	19
	#7	52	Male	Yes	No	No	No	No	19
	#8	72	Female	Yes	No	No	No	No	18
	#9	69	Female	Yes	No	No	No	No	18
	#10	53	Male	Yes	No	No	No	No	41

Abbreviations: Moderate, nonasthmatic and non‐SAH patients in the general ward with moderate COVID‐19; Severe, nonasthmatic and non‐SAH patients in the intensive care unit with severe COVID‐19; SAH, SAH patients in the intensive care unit; asthma + SAH, asthmatic and SAH patients in the intensive care unit.

Viral infections are associated with asthma exacerbations and can modulate the expression of angiotensin‐converting enzyme 2 (ACE2) the most described SARS‐CoV‐2 entry receptor. Nevertheless SARS‐CoV‐1 did not increase asthma exacerbations.

Asthma is a complex respiratory syndrome that compresses different inflammatory profiles which could influence the immune response to SARS‐CoV‐2 and ACE2 expression differently. A caveat of this investigation is that all asthmatic patients were previously diagnosed and we could not determine their asthma endotype.

Inhaled corticosteroid (IC) and anti‐asthma (AA) drugs could act as possible modulators of SARS‐CoV‐2 infection which could reduce the incidence of COVID‐19 in asthma patients but in our cohort asthma patients did not regularly use IC or AA drugs. Although the number of cases was low our asthma patients also presented SAH a risk factor for COVID‐19 but no difference was verified in the hospitalization time between all groups (Figure 1A).

FIGURE 1

Daily clinical features of COVID‐19 patients. (A) hospitalization time, (B) ratio of neutrophils to lymphocytes, (C) neutrophils, (D) creatinine, (E) C‐reactive protein, and (F) platelets. MODERATE, nonasthmatic and non‐SAH patients in the general ward with moderate COVID‐19; SEVERE, nonasthmatic and non‐SAH patients in the intensive care unit with severe COVID‐19; SAH, SAH patients in the intensive care unit; asthma + SAH, asthmatic and SAH patients in the intensive care unit. #P < .05 difference from MODERATE in relation to all other groups. **P < .01 for asthma + SAH in relation to SAH. ****P < .001 for asthma + SAH in relation to SAH. The Kruskal‐Wallis test with Dunn's multiple comparison. Data collected between March 1, 2020, and July 24, 2020

The MODERATE group presented a lower ratio of neutrophils to lymphocytes and neutrophils in the blood which are relevant COVID‐19 severity markers in relation to the other groups (Figure 1B‐C).

Asthma patients showed reduced levels of creatinine C‐reactive protein and platelets in comparison with SAH patients (Figure 1D‐F). Our data indicate that asthmatic patients did not present an increase in hospitalization time or COVID‐19 severity; in contrast asthmatic patients exhibited a reduction in some of the COVID‐19 severity‐associated markers.

We hypothesize that type 2 cytokines produced in eosinophilic asthma may downregulate ACE2 expression or counteract type 1 cytokines released in COVID‐19 therefore presenting as a protective factor; however patients with asthma are not immune to COVID‐19.

Our university hospital is a referral unit for moderate or severe cases of COVID‐19; hence this profile may not be present in mild COVID‐19 cases. Our study is the first asthma‐related report in the Brazilian population but further investigation is needed to better understand the influence of asthma on COVID‐19.

CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest.

Funding information

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) grants: 17/18199‐9 and 19/02679‐7 and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) grant: 88887.503842/2020‐00.