LAUSR

To the Editor, Postcoronavirus disease (COVID) syndrome is a matter of debate for health policy inasmuch severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) infection, and COVID‐19 pandemic may gain a potentially everlasting hallmark as a public health concern. Probably, full awareness about the existence and the impact of postacute sequelae of COVID‐19 (PASC), otherwise known as post‐COVID or long‐COVID, has not yet reached all medical interests. For example, some authors reported that the persistence of a complex of symptoms, which they named post‐COVID conditions (PCCs), should be associated with factors far from the causative SARS‐CoV2 infection, even related to psychological backgrounds. The first question that was raised while reading the paper was how the authors had introduced a novel terminology such as postinfective fatigue syndrome (PIFS) and attached this to references regarding the Fukuda et al.'s CDC classification of chronic fatigue syndrome (CFS); perhaps, the authors intended CFS instead of PIFS. It is a bit misleading when addressing particular symptoms such as fatigue, usually associated with CFS and post‐COVID, inasmuch as fatigue is erroneously intended as a mood disorder in people suffering from the psychological consequences of the COVID pandemic. Despite that a small percentage of very young people can suffer from post‐COVID fatigue, it is particularly burdensome to diagnose fatigue as a consequence of a previous SARS‐CoV2 infection with respect to psychological impairments due to COVID‐19 restrictions. From this perspective, the methods used to recruit and investigate patients are particularly crucial. In a recent paper by Selvakumar et al., for example, it is hard to know the exact number of people suffering from fatigue, as this symptom is commonly associated with post‐COVID and CFS, and our general impression is that controls show confounders due to the introduction of symptoms recalling fatigue of psychic or mood origin, rather than related to COVID‐19. Considering that 184 subjects had PCC among 379 SARS‐ CoV2‐positive individuals, the authors evaluated the presence of PCC with an error of ≥5% (5.03%, 95% confidence interval [CI]), and in SARS‐CoV2‐negative subjects, PCC with a very high margin of error (10.61%, 95% CI). For PIFS, the margin of error was 3.49% (<5%, 95% CI) for SARS‐CoV2‐positive subjects, yet the error was >5% (5.84%, 95% CI) for SARS‐CoV2‐negative subjects. This would mean that the screening of typical symptoms associated with post‐ COVID in subjects without signs of infections was presumptively flawed. By using an SPSS Statistical software (v.24.0), we recalculated the actual relative risk (RR) to associate PCC with the absence of a previous COVID‐19 infection; recalculation was done taking into account the statistical errors (1.1686; 95% CI = 0.8546–1.5980), indicating that PCC may be a collection of symptoms not related to SARS‐CoV2 infections even from the beginning, that is, the authors erroneously included subjects with symptoms resembling a PCC but without any relationship with current SARS‐CoV2‐negative swabs. For PIFS, the recalculated RR in controls was 0.2909 (95% CI = 0.2122–0.3987). We took into account a recently published paper as an outstanding example of how science may dismiss post‐COVID syndrome as a “psychic” rather than an actual, postinfective syndrome with numerous symptomatic similarities with CFS. This evaluation would mean that some authors compared post‐COVID CFS‐like symptom disorders, including fatigue, with symptoms of non‐COVID origin, in particular fatigue. Furthermore, post‐COVID syndrome, particularly if referring to fatigue, is usually considered in mature and older adults, despite the claim that it is widely present in young people as well. Clarifying the term post‐COVID to date is of utmost importance. Any possible debate on post‐SARS‐CoV2 infection symptomatology, should be finely distinguished and properly classified. Psychological ailments and impairments coming from pandemic restrictions cannot be included in a post‐COVID syndrome if a post‐COVID complex of symptoms deals with a postinfectious action on the infected organism, that is, immune dysregulation, immune‐thromboembolic effects on the microvasculature, and so on. By commenting on a paper by Selvakumar, we addressed the issue of shifting the well‐ known term post‐COVID into two definitions, one collecting psychological and sociological or general conditions following COVID‐19 (PCC) and the other considering a PIFS; it is possible to clarify the “real” character of a post‐COVID syndrome. Unfortunately, this approach fails in focusing fatigue as a proper biomarker of a post‐ COVID syndrome due to possible confounders in the research rationale. Fatigue is a typical symptom of CFS, which recalls many features of post‐COVID (due to damages generated by the viral infection), rather than mood disorders. It is important to inform the readers about this fundamental concern, as it affects the immune landscape and immunology interpretation of any possible laboratory analysis of post‐COVID patients. Probably, COVID‐19, as a scary pandemic, is turning to an end but its “poisoning tail” is going ahead through post‐COVID syndrome, which deserves greater attention than before.