If you, like the skeptical cardiologist, suffer from asthma you may be wondering if you are at a higher risk of contracting Covid-19 or developing more severe respiratory complications from the disease once infected.
There are 25 million asthma sufferers in the United States, about 8% of the population and many of us are using as primary treatment a combination of inhaled beta-agonists (for immediate relief) and inhaled corticosteroids (ICS) (for long-term conditioning of the lung).
How are these treatments influencing our risks during the Covid-19 pandemic?
A commentary published online in Lancet Respiratory medicine suggested that there is a lower prevalence of asthma in patients with Covid-19. However, the sum of evidence from this commentary and elsewhere is insufficient to say asthma is protective.
When there is an absence of evidence, as we saw with hypertension as a risk factor and hydroxychloroquine as a treatment, the tendency of journalists is to obtain a quote from a physician who has treated patients with Covid-19 to buttress a particular argument. Quotes which say something like “we don’t know” or “there is not enough evidence right now” are highly unlikely to be published whereas anecdotal speculation is always intriguing (but often misleading.). The New York Times published this quote on the topic:
“We’re not seeing a lot of patients with asthma,” said Dr. Bushra Mina, a pulmonary and critical care physician at Lenox Hill Hospital in New York City, which has treated more than 800 Covid cases. The more common risk factors, he added, are “morbid obesity, diabetes and chronic heart disease.”
A major problem in sorting out asthma as an independent risk factor is that many papers are lumping all “chronic respiratory diseases” together which puts asthma in a bucket with chronic obstructive pulmonary disease (COPD) and interstitial lung disease like pulmonary fibrosis. There are striking differences in the demographics and prognosis of these diseases. For example, patients with COPD are older and much more likely to have smoked cigarettes, two factors clearly associated with Covid-19 risk.
In addition, asthma in older adults is highly associated with obesity, a well-recognized independent risk factor Covid-19 complications.
Among adults aged 60 and over, there was a significant trend of increasing asthma prevalence with weight status: 7.0% among normal weight adults; 9.1% among overweight adults; 11.6% among adults with obesity.
In addition, almost no data is available on asthma stratified by severity and treatment. The severe asthma patient who requires oral corticosteroids is markedly different from the mild asthmatic whose only treatment is intermittent inhaled beta-agonists.
These data, like the data on hypertension, should be taken with a grain of salt, but at a minimum, we can say there is no signal that asthma by itself increases the risk of Covid-19 infection.
Inhaled Corticosteroids and Covid-19
The authors* of the commentary in Lancet which implied asthma (and chronic respiratory disease) was protective against Covid-19 infection also concluded that
“the possibility that inhaled corticosteroids might prevent (at least partly) the development of symptomatic infection or severe presentation of COVID-19 cannot be ignored”
They cited some very preliminary data to support this contention:
in in-vitro models, inhaled corticosteroids alone or in combination with bronchodilators have been shown to suppress coronavirus replication and cytokine production. Low- quality evidence also exists from a case series in Japan, in which improvement was seen in three patients with COVID-19 requiring oxygen, but not ventilatory support,
Personally, I have always worried that my use of ICS put me at a higher risk of respiratory infections because corticosteroids are potent immunosuppressives, potentially lowering my immune response to bacterial, viral, or fungal infections. This 2019 meta-analysis in Infection found a 24% higher rate of upper respiratory tract infection in patients using ICS.
Due to these concerns, when the pandemic began I purposely cut back on my Advair usage. Fortunately, my asthma has been very mild since I started taking Dupixent for eczema 3 years ago. Since then, Dupixent has been approved for treatment of asthma. (By the way, although dupilumab is a targeted biologic therapy that inhibits signaling of interleukin-4 (IL-4) and interleukin-13 (IL-13), two key proteins that may play a central role in type 2 inflammation that underlies atopic dermatitis and several other allergic diseases we have no idea if it increases or decreases Covid-19 risks or complications.)
Does ICS usage increase or lower our risk of Covid-19 outcomes?
This figure from a review of the topic shows where in the process ICS could influence Covid-19, either increasing or decreasing risk of 1) initial infection 2) progression to pneumonia or 3) progression to ARDS and death once pneumonia is established.
There are theoretical arguments to suggest the use of ICS could either improve or worsen all 3 stages.
The review of 59 publications on Covid-19 concluded:
Following examination of the full texts including translations of those in Chinese, no publications were identified as having data on prior ICS use in patients with SARS, MERS or COVID-19 infection. No data were available for either a qualitative or narrative answer to the review question.
The bottom line right now is that we don’t know if ICS use is an important risk factor in Covid-19 outcomes.
Should ICS Stay or Go?
The recommendations of the CDC, and all pulmonary/asthma societies at this point is to stick to your current asthma action plan. If that includes taking an ICS, keep on taking it at current levels.
In fact, the AAAAI and other major asthma or pulmonary organization emphasize that patients should remain on their current medications because experiencing an exacerbation event and the need for hospitalization, in those who become poorly controlled, could actually increase patient exposure and the risk of infection.
I’ve gone back to taking my ICS at pre-pandemic levels and I don’t consider that my asthma puts me at any higher risk during the pandemic.
N.B. Common inhaled corticosteroids include:
- Beclomethasone (QvarTM)
- Budesonide (Pulmicort FlexhalerTM)
- Ciclesonide (AlvescoTM)
- Flunisolide (AerospanTM)
- Fluticasone (Flovent Diskus TM, Flovent HFATM, Arnuity ElliptaTM)
- Mometasone (AsmanexTM)
ICS are commonly combined with long-acting beta agonists. The “purple circle” Advair is one such combination.
N.B. The authors of the Lancet commentary seem to have heavy ties to companies that stand to profit from sales of ICS
DMGH has received personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, and Sanofi, and non-financial support from Boehringer Ingelheim and Novartis, outside of the submitted work. RF has received grants from GlaxoSmithKline and Menarini, outside of the submitted work. AA has received grants from AstraZeneca, GlaxoSmithKline, and Menarini, and personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, and Menarini, outside of the submitted work. OS and JRB declare no competing interests
Here are the references they cited suggested ICS might be beneficial against coronavirus.
- Yamaya M, Nishimura H, Deng X, et al. Inhibitory effects of glycopyrronium, formoterol, and budesonide on coronavirus HCoV-229E replication and cytokine production by primary cultures of human nasal and tracheal epithelial cells. Respir Investig 2020; published online Feb 21. DOI:10.1016/j.resinv.2019.12.005.
- Matsuyama S, Kawase M, Nao N, et al. The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15. bioRxiv 2020; published online March 12. DOI:10.1101/2020.03.11.987016 (preprint).
- Iwabuchi K, Yoshie K, Kurakami Y, Takahashi K, Kato Y. Morishima T. COVID-19. Three cases improved with inhaled ciclesonide in the early to middle stages of pneumonia. 2020. http://www.kansensho.or.jp/uploads/ files/topics/2019ncov/covid19_casereport_200310.pdf (accessed March 27, 2020; in Japanese).