In a rapidly expanding field of knowledge concerning long-term COVID-19 sequela and with heterogeneous patient groups, we contribute demographical data from a population of hospitalised patients. We hypothesized that the initial disease severity could have a lasting impact on the residual function, especially pulmonary. To this end, we divided patients into three groups depending upon the reliance of oxygen to keep them saturated as a surrogate marker of pulmonary disease activity. The main result of this study is that the lung function values were at the lower limit of normal when evaluated with dynamic spirometry at one-year follow-up. There were no significant differences related to initial disease severity in lung function and long-term health status at 12 months. Increased in-hospital mortality was associated with acute biochemical abnormalities, higher age, heart and renal disease.
Previous studies have shown reduced lung function, radiological abnormalities and increased rates of depression or anxiety because of COVID-19. Early follow-up at 4-8 weeks showed fatigue (60-72%), dyspnoea (42-65%) and psychological distress (23-46%), more commonly in patients that needed ICU-level care (18). Similarly, it has been shown that fatigue and dyspnoea were still common at 8-12 weeks, but significant radiological and lung function abnormalities were less frequent especially in patients without respiratory insufficiency in their acute infection (19). Huang et al provided large-scale follow-up data from Wuhan, the initial site of the pandemic, showing reduced diffusing capacity for carbon monoxide (DLCO) and radiological abnormalities (primarily ground glass opacities and irregular lines) at 6 months (8). There was a correlation between oxygen need and the residual pulmonary function and increased tendency of depression and anxiety (8). More recent one-year data from the same cohort showed slight improvement in pulmonary function over time although diffusion impairment, and radiographic abnormalities persisted up to one year especially in patients who were critically ill during their hospital stay (20). Another study showed persistent symptoms associated with post-acute COVID-19 syndrome in 67% of patients requiring hospital care compared to 50% of non-admitted patients (21). One-year radiological follow-up recently showed lingering fibrotic changes with traction bronchiectasis and reticular pattern (22). One of the most reported abnormality is a reduced DLCO (6), which by its nature, is difficult to measure in primary care where most patients with long-lasting symptoms seek medical attention. We focused therefore on pulmonary variables that are more easily obtainable, such as dynamic spirometry and questionnaires.
Collectively, we found a generally reduced, albeit within reference, pulmonary function with lower FEV1% and FVC%. These observations give credit to the possibility of long-lasting lung damage even after one year of the infectious event, even though the current evidence is still a bit speculative.
In the studied population, one can note a substantially more common occurrence of co-morbidities such as diabetes and obesity compared to the general prevalence (23, 24). This is an expected finding since these conditions are well-established risk factors for severe COVID-19. We did not see any increased mortality related to diabetes and obesity in this population. Otherwise, we have confirmed previously reported risk factors for mortality during the acute phase such as hypertension, ischemic heart disease, chronic renal disease, anaemia, rise of troponin and acute kidney injury (25–27). Acute kidney injury, in particular, has been identified as highly prognostic of a poor outcome (28). There is evidence that suggests correlation between acute kidney injury during COVID-19 and microtrombotic disease activity (29). Asthma had a small protective effect, which might seem paradoxical, but has also been reported previously (30). Perhaps this could be due to the use of inhaled corticosteroids (ICS) treatment, as there has been reported that ICS treatment alter the prognosis of COVID-19 in a beneficial fashion (31). Previous reports indicate that prior lung disease, especially advanced COPD, predicts higher mortality (32), which we could not replicate. This could potentially be due to a low prevalence of such patients in our study group, which could imply differences in medical priorities between countries concerning terminal lung disease. The high death toll in the regularly oxygen treated group (group 3) is also heavily skewed due to decisions to withhold advanced life-prolonging treatment in relation to co-morbidities.
In contrary to previous data indicating 26% depression and anxiety rates at 1 year in hospitalised patients (20), only 14 patients (11%) reported clinically relevant depression or anxiety based on the HAD scale, which is calibrated to rather include than exclude. These results could also be influenced by community restrictions, where Sweden as a nation never imposed a formal lock-down. Other studies analyzing the non-COVID mental health issues during the pandemic have not found clinically relevant depression and anxiety symptoms or severe psychological distress in general (33), but there are such findings concerning adolescents (34). And as such perhaps the higher age in our patient cohort has been a confounding factor. It is also a bit surprising that the prevalence of mental health symptoms is as low as it is when compared to reported numbers that reach close to 40% at 1-year follow-up of acute respiratory distress syndrome (ARDS) in the pre-COVID era (35). Probably, there is a protective element in COVID-19 being recognized as a global pandemic.
The rates of re-admissions and subsequent unscheduled medical visits in our group were not correlated to initial disease severity. We noted in addition that even though a large proportion of patients reported dyspnoea as lasting symptoms; many had not done any form of investigation with chest radiology or pulmonary function test outside of the study; suggesting strain on the health care apparatus to adequately follow-up patients and possibly lack of knowledge as well. This also led to relatively few radiological data points and as such, a robust analysis of prolonged radiological changes was not possible.
Obvious limitation of this study is the lack of pre-existing baseline pulmonary function data and the lack of a control group. Nonetheless, reduced lung function is not a recognized risk factor for hospital admission (36). To provide a baseline comparison in general functional level, we used the PCFS-scale where patients were asked to grade themselves retrospectively, though accuracy might have been obscured by the passing of one year. The relatively small number of participants is also a limiting factor, but still, almost 64% of all hospitalised patients were ultimately included, providing excellent regional demographic data.