Reply.

To the Editor:

The article by Marco et al titled “Asthmatic patients in COVID-19 outbreak: few cases despite many cases” discusses the prevalence of asthma in patients with coronavirus disease 2019 (COVID-19) in the Northeast of Italy. The low prevalence of asthma in patients with COVID-19 in Italy was consistent with what we observed in our study, but was much lower than those from the United States and Dublin. The reasons behind the regional difference in the prevalance of asthma with COVID-19 are worth discussion.

We searched PubMed and Medline database for articles published up to May 20, 2020, using the keywords “SARS-COV-2,” “COVID-19,” and “asthma.” As shown in Table I ,1, 2, 3, 4, 5, 6, 7 the prevalence of asthma with COVID-19 in each country was listed as well as the prevalence of asthma in the general population of the corresponding region.

Table I

Regional differences in the prevalence of asthma in patients with COVID-19

Country	Percentage of asthma with COVID-19 (n/n)	Prevalence of asthma in the general population	References
China	0.9% (5/548)	6.4%	Li et al2
Italy	1.92% (20/1043)	6.1%	Caminati et al1
Mexico	3.6% (270/7497)	5.0%	Solís et al5
USA	9.0% (479/5700)	10.1%	Richardson et al3
Ireland	8.8% (17/193)	7.0%	Butler et al4
France	8.5% (3/35)	11%	Belhadjer et al6
Australia	25% (1/4)	13.9%	Ibrahim et al7

The studies from China, Italy, and Mexico confirmed the lower rates of asthma patients with COVID-19 when compared with the prevalence of asthma in the corresponding general population (0.9%, 1.92%, and 3.6%, compared with 6.4%, 6.1%, and 5.0%, respectively). , , However, recent data released from New York and Dublin indicated the high rates of asthma in COVID-19, which were similar or a little higher than the prevalence of asthma in the general population (9.0% and 8.8%, compared with 10.1% and 7%, respectively). , The other 2 small cohorts from France and Australia also manifested the high rates of comorbidity of asthma in pediatric patients with COVID-19. ,

The reasons for the regional differences may partially be attributed to the variety in the strictness of prevention and control measures, the public awareness of self-protection, and the detection strategy of SARS-COV-2. However, we also notice that the risk of patients with asthma to COVID-19 in the regions with a low prevalence of asthma seems lower than that in regions with a high prevalence of asthma. The recent study suggested that TH2 cytokine may decrease the expression of angiotensin-converting enzyme 2 (ACE2) in epithelial cells, but increase another SARS-COV-2 entry protein transmembrane protease serine 2 (TMPRSS2) gene expression. The regulation on the expressions of ACE2 and TMPRSS2 in TH2-high patients with asthma differed from that in TH2-low patients with asthma. Therefore, we may speculate that the difference in phenotype and genotype of asthma may contribute to the differential regulation of ACE2 and TMPRSS2 and be partially responsible for the variety in susceptibility of patients with asthma to COVID-19 among different regions.

The other concern is the various clinical characteristics of patients with asthma in the different regions; for example, high body mass index in patients with asthma is more common in the United States than in China and Italy. Obesity is related to an increased risk of COVID-19. Obese patients are also prone to have hypertension, which is a predisposing factor for COVID-19. The different comorbidities with patients with asthma may also be one of the reasons for the regional differences in the prevalence of asthma in COVID-19.

Asthma is a disease with marked heterogeneity. It would be intriguing to investigate and understand how the heterogeneity of asthma is attributable to the variability in susceptibility and clinical course of asthma with COVID-19.