Follow-up study on pulmonary function and radiological changes in critically ill patients with COVID-19.

Dear Editor

The clinical manifestations of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), range from asymptomatic, mild pneumonia to acute respiratory distress syndrome (ARDS). An epidemiological study with 72,314 patients has reported that around 4.7% of patients with COVID-19 developed ARDS, and the mortality rate in these patients was up to 49%. Most patients surviving from ARDS caused by other coronaviruses like SARS-CoV and Middle East respiratory syndrome coronavirus suffered from impaired pulmonary function and radiological abnormalities. , Up till now, follow-up data regarding critically ill COVID-19 survivors is rare. To facilitate the understanding of the prognosis of these patients, we here present a follow-up study of two COVID-19 patients with severe ARDS up to 3 months after the illness onset.

Two patients with COVID-19 who developed severe ARDS in The Second People's Hospital of Fuyang (Anhui, China) were enrolled. Institutional review board approval and written informed consent were obtained.

Patient 1 was a 20-year old female working in Wuhan and returned to Fuyang to celebrate the Spring Festival with her family. She presented in the hospital with fever, dry cough, and deteriorated dyspnea for 10 days on 29 January 2020. On admission, her vital signs were unstable (temperature 39 °C, heart rate 112 beats per minute, respiratory rate 32 breaths per minute, blood pressure 104/65 mmHg) with obvious dyspnea (SpO2 89% under conventional oxygen therapy of 40% FiO2). Laboratory results indicated leukopenia (2.65 × 109/L), lymphopenia (0.45 × 109/L), elevated C-reactive protein (CRP) (102 mg/L), IL-6 (62 pg/ml) and d-dimer (1.06 mg/L). Arterial blood gas analysis (ABGA) reported impaired oxygenation of PaO2/FiO2 at 213 mmHg. The diagnostic RT-PCR on a nasopharyngeal swab specimen was positive for SARS-CoV-2 and a chest CT scan illustrated bilateral pneumonia (Fig. 1 a). Lopinavir-ritonavir (500 mg, twice per day) was administrated immediately. Her condition progressed rapidly on illness day 12 and she required intubation and mechanic ventilation because of severe ARDS (PaO2/FiO2 92 mmHg). On illness day 17, both oxygenation (PaO2/FiO2 348 mmHg) and chest CT significantly improved (Fig. 1b), and she was then weaned from mechanical ventilation. She was discharged on illness day 21 with mild lung abnormalities on chest CT images (Fig. 1c). One month later after discharge, both chest CT scan (Fig. 1d) and pulmonary function test (forced vital capacity (FVC) of predicted 103.7%, FEV1/FVC 84.64%, carbon monoxide diffusing capacity (DLCO) of predicted 94%) indicated no-abnormalities.

Fig. 1

Transverse serial CT scans from a 20-year-old woman with COVID-19. (a) On admission (Day 10 from onset of symptoms): multiple areas of consolidation in bilateral lungs with peripheral and basal distribution. (b) On the day weaned from mechanical ventilation (Day 17): opacifications being dissipated into ground-glass opacities and irregular linear opacities. (c) On the day discharged from hospital (Day 21): ground-glass opacities and consolidations with decreased extent. (d) One month after discharge (Day 50): no abnormalities presented.

Patient 2 was a 68-year old man who permanently resides in Fuyang. He visited the hospital because of fever (37.5 °C) and cough for one week on 4 February 2020. The nasopharyngeal swab was positive for SARS-CoV-2 by RT-PCR and a chest CT revealed bilateral ground-glass opacity (Fig. 2 a). Laboratory results indicated leukopenia (3.33 × 109/L), lymphopenia (0.55 × 109/L), elevated CRP (116 mg/L), and IL-6 (357 pg/ml). His-condition was stable on admission, with oxygen saturation of 97% on ambient air. Lopinavir-ritonavir (500 mg, twice per day) was administrated. He reported the history of hypertension and diabetes for around 10 years, blood pressure and glucose were controlled well, no history of chronic respiratory diseases. On illness day 12, he was transferred to the intensive care unit and converted to invasive mechanical ventilation because of worsening oxygenation (PaO2/FiO2 84 mmHg) and progressing abnormalities on chest CT scan with extensive ground-glass opacities and partial consolidation on bilateral lungs (Fig. 2b). His-oxygenation improved slowly, but could not be weaned from mechanic ventilation, hence he received a tracheostomy on illness day 22. During this period, bronchoalveolar lavage culture reported Escherichia coli that was sensitive to carbapenems but resistant against third-generation cephalosporins. Therefore, imipenem was administrated. On illness day 30, oxygenation of the patient suddenly deteriorated, and a chest CT scan revealed right-sided pneumothorax (Fig. 2c). The patient then received thoracic drainage with a closed system which was removed 2 days later. On illness day 35, the oxygenation of the patient improved and he was successfully weaned from mechanic ventilation. He was discharged from hospital on illness day 45 with obvious abnormalities on the chest CT scan (Fig. 2d). Because of the impaired pulmonary function on discharge, he was transferred to a rehabilitation center. Two months after the onset of illness, he went to the hospital for the first follow-up visit. The pulmonary function test indicated restrictive lung function defect, with decreased FVC of predicted (62.3%) and DLCO of predicted (49.6%), but FEV1/FVC was at the normal range of 80.1%, which was consistent with the manifestations on chest CT images (Fig. 2e). On the second follow-up visit (3 months after illness onset), almost all ground-glass opacities were dissolved, but with obvious architectural distortion, bronchial dilatation and volume loss in bilateral lungs suggestive of fibrotic changes on chest CT (Fig. 2f). Lung ventilation was worse than that of the previous month, featured as the restrictive pulmonary disease with decreased FVC of predicted (54%), but diffusion capacity improved significantly, albeit it was still lower than that of the normal range (DLCO of predicted increased from 49.6% to 64.3%). The patient complained of shortness of breath and general weakness (6-minute walking distance was 200 m), and ABGA indicated low PaO2 (61.6 mmHg) on ambient air.

Fig. 2

Transverse serial CT scans from a 68-year-old man with COVID-19. (a) On admission (Day 7 from onset of symptoms): small air space consolidation in right lung, largely peripheral in location. (b) On the day received invasive mechanical ventilation (Day 12): Disease deteriorated with extensive ground-glass opacities, air space consolidation in bilateral lungs, mainly with peripheral and basal distribution. (c) On day 30, right pneumothorax has developed. (d) On the day discharged from hospital (Day 45): still had obvious abnormalities on bilateral lungs with gradually dissolved ground-glass opacities superimposed with irregular linear densities, partially presented as subpleural reticular opacities, cysts and bronchiectasis were also identified. (e) Two months follow-up scan (Day 60): Gradual resolution of bilateral ground-glass opacities and consolidation, with distortion of architectures and bronchiectasis. (f) Three months follow-up scan (Day 90): almost all ground-glass opacities dissolved, showing reticular densities, distortion of architectures and bronchiectasis in bilateral lungs with volume loss suggestive of fibrotic changes.

Discussion

Little is known about the sequelae of COVID-19. The two patients reported in this study showed distinct consequences. The young patient completely recovered with non-abnormality on both chest radiology and function tests, while the older patient manifested with obviously radiological changes and functional defects during the follow-up period. The results of the older patient in this study, suggest that a proportion of severe COVID-19 patients developed fibrosis. Similar fibrotic changes had been reported for SARS, which seem to have the ability of self-rehabilitation as gradual improvements were observed over time. , Nevertheless, the restrictive ventilatory defect and impaired diffusion capacity still affect the patient's physical abilities significantly in the early recovering stage, which suggests the importance of early rehabilitation. The limitation of this study was the short-term follow-up of only two cases; therefore, to understand any long-term effects of COVID-19, long-term follow-up studies with large cohorts of patients are warranted.

Funding

The work was supported by the special fund for coronavirus disease 2019 of Wuhu (grant number 2020dx2-1).

Declaration of Competing Interest

None.