Discussions
The main finding of this study was that the CT findings and symptoms
(especially effort dyspnea, fatigue and muscle weakness) may not be
totally resolved 6 months after the onset of symptoms in patients who
require ICU admission. Also, some of these patients may encounter
impaired pulmonary function tests and decreased exercise capacity.
Impairment of quality of life was comparable between ICU and non-ICU
patients.
Chest CT has been frequently used as a diagnostic tool during the
COVID-19 outbreak and CT severity scores were related to disease
severity25. In our study patients who were admitted to
ICU had higher CT scores than patients admitted to the medical ward and
this result was consistent with previous studies25,26.
At the follow-up visit patients who were discharged from ICU had higher
CT scores than patients who were discharged from the medical ward (6 vs
0). CT findings were totally resolved in most non-ICU patients, but most
ICU patients had abnormal CT findings at the follow-up visit. In a
previous study most of the CT findings were resolved in non-severe
COVID-19 patients within 4 weeks after discharge16,27.
However, as the severity of disease increases the recovery time may be
longer. In a large cohort, patients with increased disease severity had
higher CT scores at follow-up visits28. We found
two-thirds of ICU patients had at least one of the CT findings at
follow-up visits; irregular lines, subpleural lines and GGO were the
most common patterns in chest CT. We also found advanced age and higher
CT scores at admission were risk factors for having abnormal CT findings
at the follow-up visit. Disease severity was found to be an independent
risk factor for percentage change of CT score in the previous
study28. Positive pressure ventilation or higher
levels of fraction of inspired oxygen (FiO2), which are
frequently used in serious patients, may themselves cause lung damage
and may inhibit complete recovery29–31.
We found PFT impairment was more frequent in individuals who were
discharged from ICU. Patients with severe disease were more prone to PFT
impairment at the early convalescence phase and
long-term27,28. Patients with PFT impairment had
higher CT scores at the follow-up visit despite these patients having
had lower CT scores at admission (Table-4). It is difficult to associate
changes in pulmonary function tests with COVID-19, since the baseline
pulmonary function status of patients is not fully known. Nevertheless,
patients with impaired PFT had higher scores at the follow-up CT,
suggesting a relationship between partial improvement in CT findings and
PFT impairment.
Median distance of 6-min walk was similar in both the patients
discharged from ICU and from the medical ward, and these results are
consistent with a previous study28. However, in half
of the patients discharged from the ICU, when the patients were
stratified into age and weight, the 6-minute walk test was found to be
less than 80% of the expected value. Immobilization, severity of
illness, and use of corticosteroids are risk factors for reduced
exercise capacity32. ICU patients had these risk
factors, thus reduced exercise capacity could be expected in these
patients. Prolonged immobilization after hospital discharge and
restrictions to prevent transmission, such as general curfew, may have
limited the mobilization of these patients in the recovery phase.
We found 79% of participants had at least one persistent symptom and
patients with severe disease had a higher percentage of persistent
symptoms. The percentage of residual symptoms in COVID-19 varies from
49% to 79% in previous studies14,28. Effort dyspnea,
fatigue and muscle weakness were the most common persistent symptoms in
our and a previous study28.
Impairment of quality of life was observed in SF-36 categories,
especially social functioning, role limitation due to physical and
emotional problems. Impairment of quality of life was similar in both
ICU and non-ICU patients. This result is consistent with long term
follow up in SARS patients24. The percentage of
residual symptoms and impairment of health status were significantly
higher in female participants. Female survivors were more prone to
depression and anxiety after the previous SARS
outbreak33. Severity of disease and female gender were
found to be risk factors for persistent psychological
symptoms28. Not just disease-related causes, but also
social restrictions (such as quarantine, and curfew to prevent spread of
the disease), increased stress, anxiety, and depression in
females34. Psychological distress, anxiety and
depression may aggravate persistent symptoms and influence the
impairment of quality of life.
This study has several limitations. This is a single-centre study so
these results cannot be generalized to other centres. Although the
desired number of patients could not be reached in the ICU patients
group, the study has enough power (0.83) to test the difference between
the two groups for the primary outcome. We could not measure diffusion
of carbon monoxide (DLCO), which is frequently impaired in patients with
SARS or COVID-19, due to technical reasons in our pulmonary functional
centre. The baseline data of PFT and 6-min walking distance were unknown
so we cannot directly associate COVID-19 and PFT or 6-min walking
impairment. The fact that the majority of the participants were men may
have affected the results especially the assessment of quality of life.