Since SARS-CoV-2 outbreak in March 2020, several studies have been carried out to analyse physical, mental and pulmonary consequences in patients with COVID-19 infection after discharge.
The present study aimed to assess the quality of life in our population after an average observation time of 3 months. Our cohort reveals that the mean EQ-5D and E-VAS index scores decreased with hospitalization time, the number of days spent in IRCU units and the level of dyspnoea at the beginning of the hospitalization period. A lower average in E-VAS is also associated to higher LDH serum levels.
The previous outbreaks of SARS and MERS used SF-36 to measure QoL, and showed a significantly low quality of life at 1 year in affected patients, lower than the quality of life of those with chronic pathologies (using normative data) (2)
Current literature suggests similar postdischarge symptoms. Halpin et al. found that patients admitted to ICU had a greater prevalence of symptoms in almost all reported symptom domains, despite being a younger and less comorbid group (15). This is in keeping with the well- characterized post‐intensive care syndrome (16).
Another study showed that the quality of life of COVID-19 survivors showed mean scores that are substantially lower than those of healthy people (17).
Anxiety/depression was the most frequently reported symptom (40,3% of our population). Those who are younger than 57 dropped to a level of below average, and it is correlated with ICU/IRCU admission, the need of ventilatory support and the need of oxygen therapy after discharge.
Two Chinese studies found that anxiety or depression were common, even at 6 months follow-up after symptom onset, being the severity of illness a risk factor for persistent psychological symptoms (18, 19). The underlying mechanism of the psychiatric consequences of COVID-19 is likely to be multifactorial and might include the direct effects of viral infection, the immunological response, corticosteroid therapy, ICU stay and social isolation (20).
Mobility and pain were other reported problems in a proportion close to anxiety/depression. We found that pain was associated with higher levels of LDH and D-dimer, which is consistent with other studies which found a correlation between pain/discomfort and clinical severity (21,22). Around 29% presented pain after 3 months.
Breathlessness was a significant problem both after 3 month and 10 months after discharge. Those which presented more dyspnoea at admission have greater dyspnoea at 3 months (measured by mMRC scale). After 10 months, those who had more dyspnoea at admission continued to have greater dyspnoea, as well as those who had a poorer quality of life (poorer result in EQ5D index). Regarding dyspnoea on exertion (by Borg) after 10 months, it is associated with those who spent more days in ICU, higher severity index and worse quality of life measured 3 months after hospital admission.
Our results are comparable to those demonstrated in a multicentre cross-sectional cohort study in Spain, which reports that dyspnoea as persistent symptom was significantly associated with number of days at hospital, number of medical comorbidities and number of symptoms at hospitalization (23). Another study described that those needing ICU admission and respiratory support, premorbid lung problems, higher age, higher BMI, and BAME ethnicity are more likely to experience breathlessness postdischarge (13), being comparable to those reported in the meta-analysis study of 11–45% of survivors having breathlessness even up to one year (2)
We also analysed the radiological features after 3 and 10 months. Radiological abnormalities (presented predominantly in lower lobes and women) in patients 10 months after discharge were more frequent in those which had previous higher CXR scores (at admission and at 3 months follow-up) and a higher value in mMRC dyspnoea scale. Therefore, a poorer result in CXR score at 3 months precedes long-term pulmonary sequelae.
An Italian study including 119 patients showed that the radiological abnormalities were present in about half patients 3 months after discharge, which had higher age, previous higher CXR scores and longer hospitalization. Days of hospitalization and previous CXR scores were independent factors for predicting the CXR at three months (24). Based on a scoring system the authors used, they suggested this finding could help prioritize patients with more severe clinical and radiological findings.
In a review of 59 patients with SARS-CoV-2 pneumonia admitted to a hospital in Madrid, Spain, who had abnormalities on chest X-ray at hospital discharge, none of the X-ray performed at 8–12 weeks were normal (25). In contrast, a recent publication describes a lower rate (12%) of radiological sequelae in 110 post-COVID-19 patients at 8–12 weeks after hospital admission (26) probably due to differences in the method of quantifying lung affectation and differences in the severity of illness. Most patients will have abnormalities on chest X-ray when discharged from hospital and it has been proposed that after 3 months is a good time to perform follow-up and assess the resolution of this condition (27).
The results of lung function assessment in our study showed that a considerable part of the participants had abnormalities regarding lung capacity and diffusion. We found that higher average at mMRC scale at 3 months is associated with a lower FVC in a long-term follow-up (10 months) and predisposing factors for a FVC < 80% after 10 months are the high levels of ferritin and lymphopenia at admission. Regarding DLCO, high D-dimer levels on admission predict poorer long-term diffusion capacity (DLCO < 70%).
Zhao et al. reported that at 3-months after discharge, residual abnormalities of pulmonary function were observed in around 25% of their cohort, mostly demonstrated diffusion reductions in DLCO (5). In the following-up studies for the patients rehabilitating from SARS, impaired lung function could last for months or even years (28). At 6, 9 and 12 months after discharge, the same phenomenon can be noted (29).
D-dimer elevation has been determined as an important laboratory finding in COVID-19 patients. The level of D-dimer was an important prognostic factor for abnormal DLCO. Thus, for those patients who have high D-dimer content, pulmonary rehabilitation should be needed subsequently (5), whereas Méndez et al. and Sibila et al. observed that patients with impaired DLCO also showed 3 months after discharged higher values of C-reactive protein (CRP), D-dimer and lactate dehydrogenase (LDH) (30,31), which is consistent with the data of our study. In addition, prolonged ICU and hospital stay and breathlessness were also associated with reduced DLCO (29). Abnormalities in DLCO indicate pulmonary fibrosis or a late phase in the course of recovery.
In the Swiss national cohort, lower lung volumes (FVC and FEV1) 4 months after severe/critical COVID-19 were demonstrated in several patients; the higher FEV1/FVC ratio in the severe/critical subgroup suggests a tendency toward a restrictive physiology, and there was a negative correlation between the duration of mechanical ventilation during the acute disease and pulmonary function at 4-month follow-up (32).
However, there are several limitations in this study. It does not include COVID-19 survivors who were not hospitalized and it is likely that non‐hospitalized COVID‐19 survivors will have different rehabilitation needs to those who were hospitalized, so this needs further investigation. Moreover, the presence of different comorbidities in some of our patients may have impacted on symptoms reported in quality of live questionnaires. We carried out a single center study with a limited number of cases, being difficult to assess risk factors for disease severity and mortality with multivariable adjusted methods.