Worsening of asthma control after recovery from mild to moderate COVID-19 in patients from Hong Kong

Study design and data sources

There are approximately 950 patients with asthma that is regularly followed up in asthma clinic in Queen Mary Hospital, and potentially eligible subjects were identified from this clinic during the enrolment period from 24th May 2022 to 1st November 2022. Eligible subjects were adults aged ≥ 18 years with asthma. The subjects who had scheduled follow-up in asthma clinic were recruited. Patients who had ad hoc or emergency visits in asthma clinic after COVID-19 were excluded to avoid selection bias. Those who had mild to moderate COVID-19 30 to 270 days before the date of assessment were classified into the COVID-19 group, while equal number of controls that did not have COVID-19 that were matched based on age, gender, smoking status, asthma severity and lung function were included and classified in non-COVID-19 group. Mild disease is defined as patients who have any of the various signs and symptoms of COVID-19 (e.g., fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell) but who do not have shortness of breath, dyspnea, or abnormal chest imaging. Moderate illness is defined as patients who show evidence of lower respiratory disease during clinical assessment or imaging and who have an oxygen saturation measured by pulse oximetry (SpO2) ≥ 94% on room air at sea level [13]. In Hong Kong, for non-hospitalized patients with COVID-19 need to have at least 7 days home quarantine if they completed COVID-19 vaccine. The quarantine period is at least 14 days among those who have not completed COVID-19 vaccination. They are not allowed to leave their residence until the quarantine order is off. This is reinforced by the use of Leave Home Safe apps which will incorporate both the vaccination record and the infection record. As such, they will not be able to attend the asthma clinic in Queen Mary Hospital during the quarantine period. All patients who were included in this study were all from the asthma clinic, which the patients attending were all out of the acute infection who are allowed to go to hospital by law. Patient with asthma-COPD overlap, history of severe COVID-19 that required oxygen therapy, mechanical ventilation or intensive care unit admission were excluded. The diagnosis of COVID-19 was confirmed by laboratory-confirmed positive reverse transcription–polymerase chain reaction (RT-PCR) test, or positive rapid antigen test (RAT), as documented on the designated COVID-19 data platform on Clinical Management System (CMS) of Hong Kong Hospital Authority. Patients’ records were accessed through the electronic patient record (ePR) of the Hong Kong Hospital Authority, which consisted of the records of all patients with out-patient clinic attendances and hospital admissions. The information available included patient demographics, clinical notes, investigation results and treatment records. Demographic data (age, gender, smoking status) and clinical data / investigations (ACT score, asthma medication, comorbidities, spirometry results, date of COVID-19, hospitalization and complications from COVID-19, date and dose of COVID-19 vaccination, type of COVID-19 vaccines) were identified from clinical records. The past ACT score, asthma medication, comorbidities, spirometry results and COVID-19 vaccination details were collected from a retrospective database. ACT scores range from 5 (poor control of asthma) to 25 (complete control of asthma), and the minimally important difference (MID) is 3 points [14]. Asthma is classified as well controlled if ACT score is 20 or above, partially controlled if ACT score is 16 to 19 and uncontrolled if ACT score is 15 or below [15, 16]. Spirometry was performed with CareFusion Vmax® Encore 22 system. Spirometry data was interpreted with the updated spirometric reference values for adult Chinese in Hong Kong [17]. The study was approved by the Institutional Review Board of the University of Hong Kong and Hospital Authority Hong Kong West Cluster (UW 22-110).

Outcomes

The primary outcome was the deterioration in asthma control defined as a reduction in ACT score by three or more point from “the immediate prior visit” to “enrolment visit”. The secondary outcomes include the magnitude of change in ACT score at enrolment visit, the proportion of patients with ACT score at or below 15 at enrolment visit and the need for escalation of asthma maintenance therapy.

Statistical analysis

The demographic and clinical data were described in actual frequency, mean ± SD or median (interquartile range). Baseline demographic and clinical data were compared between the patients with or without COVID-19 by Chi-squared test or Fisher’s exact test as appropriate. Continuous variables are expressed as mean ± standard deviation (SD) and compared using the student’s t test. The risks of worsening asthma control between patients with or without COVID-19 will be compared by binary logistic regression. Multiple logistic regression modeling was used to account for potential confounders including age, gender, smoking status, baseline FEV1 (% predicted), COVID-19 vaccination status, ACT score at prior visit 12 months before and GINA step of medication at baseline. The statistical significance was determined at the level of p < 0.05. All the statistical analyses will be done using the 26th version of SPSS statistical package.

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