The Relation between Persistent Poor Health after COVID-19 and Respiratory Complications or Initial Disease Severity

To the Editor:

We read with interest the recent article by Townsend and colleagues that described respiratory recovery and self-reported health at the time of outpatient attendance after coronavirus disease (COVID-19) infection (1). The authors graded participants into three groups by initial severity (not requiring admission, requiring hospital admission, and requiring intensive care unit [ICU] care) by an analysis of chest radiography, a 6-minute walk test (6MWT), fatigue, frailty, subjective return to health, and some inflammatory markers (1). The authors concluded that none of the measures of persistent respiratory disease were associated with initial disease severity (1).

Because self-reported health and symptoms such as fatigue have an essentially subjective basis, the study is limited by its analysis of only a chest radiograph. This study should be complemented with computed tomography (CT) or lung function, as the follow-up protocols of scientific societies include lung function among their main evaluations (2). This takes on particular importance because, in Townsend and colleagues’ study, persistent chest radiograph abnormalities attributable to COVID-19 were seen in only 4% of patients (5/115) (1), but other authors have shown approximately 70% persistence of altered CT at 3-month follow-up (3).

We believe that lung function should be incorporated into this type of analysis to allow an assessment of how the respiratory system is working. A recent meta-analysis has shown that altered diffusion persists in 36% of patients with nonsevere COVID-19 and 66% of patients with severe COVID-19 between 1 and 3 months after infection (4). A recent study has reported a reduced diffusion capacity in 22% of patients without oxygen requirements and in 56% of patients with ICU requirements 6 months after the infection (5). These results reinforce the picture of greater functional respiratory compromise in the most severe patients. Without lung function assessment, it is particularly difficult to establish a strong relationship between respiratory complications and poor post–COVID-19 health.

One of the most relevant assessments in the follow-up of patients after COVID-19 is physical capacity, and the 6MWT is a useful instrument that is widely used in healthy subjects and for studying many diseases (6). This test provides useful information not only about physical capacity but also about exertional desaturation (6). The authors used this test, but only 71% of the subjects were able to perform it (1). One wonders what happened to those who could not perform the test, whether they suffered the most severe cases, and how many of them were in the ICU. This information is relevant as recent studies of patients after COVID-19 have reported a significant reduction in the distance walked in the 6MWT and a significant connection between the number of patients with scores less than the lower limit and the severity of the disease (5). It would also be useful to see the score as a percentage of the recommended reference values (6).

Finally, the common characteristic of the studies described above is that they have a significant number of patients across the entire spectrum of severity (3–5). In Townsend and colleagues, of the 487 patients who were offered a follow-up appointment, only 153 (31.4%) accepted, of whom only 19 (3.9%) had been in the ICU. It is difficult to establish how representative this group is of the COVID-19 population, which represents the clear possibility of selection bias.

The study by Townsend and colleagues is an important step in investigating the possible causes of the persistence of symptoms and the functional sequelae after COVID-19, but future investigations should incorporate lung function or CT and use a more representative sample so that the consequences after COVID-19 infection can be analyzed while minimizing the risk of misinterpretation.