Characteristics and outcomes of asthmatic patients with COVID-19 pneumonia who require hospitalisation

Clinical characteristics of patients hospitalised for COVID-19 pneumonia

Among 768 hospitalised COVID-19 patients, 37 (4.8%) reported a history of asthma. Thirty-one asthmatics had positive SARS-CoV-2 RT-PCR on nasopharyngeal swab (84%). The remaining six were diagnosed on the basis of clinical presentation and radiological patterns [7].

Asthmatic patients were mainly female (70%), non-smokers (85%), with a median age of 54 years (42–67) and a median body mass index (BMI) of 28.3 kg·m⁻² (26.8–31.5). In 85% of cases the diagnosis of asthma had been previously confirmed by a pulmonologist. Eleven patients (30%) were GINA step 5, receiving high doses inhaled CS (ICS) with long-acting-beta agonists (LABA), associated with low dose oral CS in one case, and long-term omalizumab therapy in two (Supplementary Table 1).Thirty-one asthmatics (84%) had a BMI ≥25 kg·m⁻². Twenty-two (59%) had at least one major comorbidity. The most common comorbid conditions were obesity (36%), hypertension (27%) and diabetes (19%). Fifteen (41%) had multimorbidities (table 1).

The median time from onset of symptoms to admission in the emergency room was 6 days (3–8). Fifty percent of patients had an initial peripheral oxygen saturation below 95% while breathing room air and 25% had a respiratory rate above 30/min. None of them presented with an asthma exacerbation. Wheezing, mostly reported as mild, was reported at admission in only 6 cases (16%) (table 2).

Non-asthmatic controls are presented in tables 1 and 2. All differences pointed to worst COVID-19 pneumonia in non-asthmatics, as evidenced by older age, higher male/female gender rate, and a trend to more comorbidities.

Biological findings at inclusion

Laboratory values in the emergency room are summarised in table 3. Among asthmatics, lymphopenia was a frequent finding (median 1205/mm3, IQR 738–1476) (fig. 1a). Patients also presented with a marked eosinopenia, 78% having a blood eosinophils count equal to zero (fig. 1b). N-terminal pro–B-type natriuretic peptide (NT-pro BNP) was measured in 21 patients and normal value (<300 ng·L⁻¹) was found in 81% of cases. Of 31 available data, 6 patients (19%) had increased high-sensitive cardiac troponin T (≥14 ng·L⁻¹); however, none of these patients demonstrated consistent evidence of serious myocardial injury. Elevation of D-dimers was commonly observed (median 810 µg·L⁻¹, IQR 483–1180), as well as increased CRP levels (median CRP 51 mg·L⁻¹, IQR 27–116). Arterial blood gas while breathing room air was available in 29 patients : hypoxaemia was a common finding (median arterial partial pressure of oxygen (PaO₂) 68 mmHg, IQR 62–83) with hypocapnia (median arterial partial pressure of carbon dioxide (PaCO₂) 34 mmHg, IQR 32–38).

Non-asthmatic controls are presented in table 3. There was a trend for more pronounced lymphopenia and worst CRP, D-dimers, LDH, liver transaminases levels, with more severe hypoxemia.

Radiological findings

All asthmatics underwent a CT of the chest (table 4). Peripheral or mixed ground glass opacities were the most frequent CT patterns (95% of cases), expanding over more than 10 percent of lung parenchyma in 76% of cases. Consolidations were observed in 26 patients (70%) and crazy-paving pattern in 13 patients (35%). In 51% of cases, lesions predominated in inferior lobes. Based on clinical judgement or prediction rules [9], four patients had initial CT pulmonary angiography (CTPA), demonstrating two cases of acute pulmonary embolisms (PE) at admission. Eight additional CTPA were performed during hospital stays for clinical deterioration, leading to another acute PE diagnosis. In this small cohort of patients, higher inhaled corticosteroid exposure was not associated with higher proportion of severe radiological pneumonia; mild pneumonia tended to be more frequent in asthmatics with higher doses of ICS (Supplementary Figure 2).

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FIGURE 2

Outcomes of patients with COVID-19 pneumonia.

All non-asthmatic controls had imaging of the chest at admission (66 CT and 9 chest X ray). The results of CT of the chest are presented in table 4. As compared to asthmatics, there was more sereve-to-critical radiological presentation in the non-asthmatics.

Management and outcomes

As shown in table 5, 30 (81%) asthmatics received oxygen with use of high-concentration masks in 10 patients. When nasal oxygen was used, the median oxygen flow-rate was 2 L·min⁻¹. In two patients, oxygen had to be maintained after discharge. Thirty-one (84%) received at least one antibiotic. SABA as needed was prescribed using a pressurised metered-dose inhaler (p-MDI) with a spacer chamber and previous inhaled treatments were maintained. Five patients received oral CS before admission, one of them in the context of self-medication. Three additional patients received intravenous CS during hospital stay: refractory ARDS was the main cause of CS prescription in two cases and bronchospasm occurring in the context of mechanical ventilation in one case. Eleven patients were admitted in ICU, six of them requiring invasive mechanical ventilation. There was a trend for more aged and comorbid patients among patients admitted in ICU (table 6). A flowchart of the main outcomes is presented in figure 2. As shown in figure 3, asthmatics without multimorbidities were discharged at home earlier.

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FIGURE 3

Proportion of asthmatics discharged at home at 30 days according to the number of their comorbidities.

CS: corticosteroids; DPI: dry powder inhaler; IQR: interquartile range; IV: intravenous; pMDI: pressurised metered-dose inhaler; SABA: short-acting bronchodilators.

Two deaths occurred at one-month follow-up and one additional death was later noted, thus leading to a mortality rate of 8.1% in asthmatics (as compared to 14.6% in non-asthmatics, p=0.381). The first patient was a 68 year-old woman treated for asthma by her pulmonologist with fluticasone/salmeterol 500/50 µg daily (medium doses, GINA step 4). She had several comorbidities including obesity (BMI=31.2 kg·m⁻²), diabetes, current chemotherapy for ovarian cancer, dyslipidemia and sleep apnea syndrome. At admission, no wheezing was reported, she was eosinopenic (0/mm³), had positive nasal SARS-CoV-2 RT-PCR and presented with mild extent of pulmonary lesions on CT of the chest. 5 days after symptoms had started, she was transfered in ICU for acute respiratory failure. No acute PE was detected on CTPA. Due do an extremely poor prognosis, it was decided to restrict advanced life support, including intubation. She died on day 9. The second patient was a 67 year-old woman with a diagnosis of asthma confirmed by a pulmonologist and treated with inhaled beclometasone/formoterol 200/12 µg daily (low doses, GINA step 3). She also displayed severe obesity (BMI=43 kg·m⁻²), hypertension, renal failure requiring chronic dialysis and primary biliary cirrhosis. Mild wheezing was noted at admission along with positive nasal SARS-CoV-2 RT-PCR, eosinopenia (0/mm³) and severe extent of pulmonary lesions on CT of the chest. 10 days after symptoms had started, she was intubated in ICU for acute respiratory failure. She died at day 15 from refractory ARDS. The third patient was a 75 year-old hypertensive and overweight woman (BMI=29.4) treated for asthma with budesonide/formoterol 1200/36 µg daily (high doses, GINA step 5). At admission in the emergency room, no wheezing was reported; she was eosinopenic (0/mm³), had positive nasal SARS-CoV-2 RT-PCR and presented with very severe extent of radiological lesions (50–75%). She was intubated 4 days later. Bronchospasm occurred during mechanical ventilation and systemic corticosteroids were administrated at day 12. Withdrawal of mechanical ventilation was not possible: she died at day 45 from respiratory failure.

Evolution of asthmatics treated with biologics

Two patients were treated with anti-immunoglobulin E monoclonal antibody (omalizumab) for severe allergic asthma. The first one was a 53 year-old woman treated with budesonide/formoterol 800/12 µg daily, montelukast 10 mg·j⁻¹ and subcutaneous omalizumab at a monthly dose of 300 mg. She had no sign of asthma exacerbation before admission, but took a short course of oral prednisone (40 mg·day⁻¹) during 5 days as self medication that was stopped at admission. She had positive nasal SARS-CoV-2 RT-PCR, eosinopenia (0/mm³) and a moderate extent of lesions on CT of the chest. She had no evidence of asthma exacerbation nor respiratory failure, allowing discharge at home on day 5.

The second patient was a 78 year-old overweight woman with severe allergic asthma and allergic bronchopulmonary aspergillosis, treated with budesonide/formoterol 800/12 µg daily, oral prednisone 5 mg·j⁻¹ and subcutaneous omalizumab 300 mg twice monthly. She also suffered from hypothyroidism, lumbar spinal stenosis and depression. Initial presentation included crackles and minor wheezing, with positive nasal SARS-CoV-2 RT-PCR, blood eosinophil count of 50/mm³ and severe extent of pneumonia on CT at admission (fig. 4a). 9 days after the beginning of symptoms, she was admitted in ICU for acute respiratory failure. Oro-tracheal intubation was needed and mechanical ventilation was well tolerated with no evidence of bronchospasm. After 8 days of mechanical ventilation, acute bronchospasm appeared for the first time. Aspergillus fumigatus was detected in bronchial secretions. Segmental acute PE was diagnosed 12 days after admission (fig. 4b). Other treatments included anticoagulation, bronchodilator nebulizations, intravenous CS and voriconazole. The next omalizumab injection has been administrated as planned, when she was under mechanical ventilation. No adverse events were observed and successful extubation was possible 5 days later. She was discharged of ICU after 23 days. At day 75, she was well and alive, still undergoing rehabilitation.

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FIGURE 4

Computed tomography of the chest of the same patient with severe allergic asthma at day 1 (a) and day 12 (b) of hospitalisation. a) Typical extended ground glass opacities with crazy-paving pattern (solid arrow) and nodular consolidations (dashed arrow). b) Computed tomography with pulmonary angiography revealing acute pulmonary embolism in the right lower lobe pulmonary artery (white arrow).