To the editor
In their recent manuscript, Lippi et al1 addressed some fundamental issues concerning the post-COVID syndrome, which made us debate how to more precisely define the terms post-COVID and long-COVID. We are persuaded that this still represents a fundamental concern for medicine.1 Recently, Antony Fauci2 introduced the concept of post-COVID in its simplest meaning, that is, something coming “after” COVID-19, yet recalling many symptomatic features of the COVID-19 itself. In this context, the term long-COVID, which suggests the existence of “long haulers” of COVID-like symptoms, was introduced by the World Health Organization and later the Centers for Disease Control, to describe a syndrome with a COVID-like pattern, yet with symptoms lasting for 6 months or longer.
Notwithstanding, in our opinion, Lippi et al1 reported a rather simplistic classification of post-COVID and long-COVID. The authors represented the terms in a graph, leading the readers to believe that if a difference does exist, it simply consists in the length of time for which the symptoms persisted following a SARS-CoV-2 infection. Post-COVID is a preliminary term, referring to a simple observation of COVID-like symptoms immediately following COVID-19. Its use among experts spread over, because the pandemic ceased very recently. To consider the concept of long-COVID, with reference to time, we need at least several months passing from the end of the pandemic. However, Lippi et al1 allowed us to expand the debate on a conceptual terminological bias, which we consider worth discussing.
Some authors state that the difference between post-COVID and long-COVID is blurred,3 and to come up with clear definitions of post-COVID or long-COVID, we should consider the persistence of symptoms either directly linked to a current SARS-CoV-2 infection or the symptoms indicating extended damage caused by previous and resolved SARS-CoV-2 infections. Controversies regarding the definitions of such post-acute sequelae following COVID-19 still exist, because patients may suffer from several SARS-CoV-2 infections throughout their life, which may overlap with a clinical landscape of post-COVID symptomatology.4 With reference to that, Mantovani et al5 suggested the persistence of a SARS-CoV-2 infection in some cases of post-COVID.
A definition of long-COVID as a permanent, even chronic, systemic pathology, causing fatigue, brain fog, cognition impairment, musculoskeletal pain, sleep disorder, and general weakness, may help clinicians to discern real post-acute sequelae of COVID-19 from permanent COVID-19, even though some authors did not address this issue deeply enough.1 It is possible to distinguish typical symptoms associated with COVID-19, such as fever, dyspnea, persistent cough, gastrointestinal disorders, ageusia / dysgeusia, or anosmia from typical post-COVID manifestations, such as fatigue, impaired usual activity, generalized weakness, sleep impairment, depression, and musculoskeletal pain. The latter are usually intertwined with COVID-19 symptoms, and subsequently reach a symptomatology pattern mostly including fatigue, weakness, brain fog, pain, and cognition impairment upon a negative SARS-CoV-2 swab test.3 This is a very simple approach to introduce possible discrimination between COVID-19 and post-COVID syndrome. However, this simplistic approach, used to distinguish between a long-lasting mild COVID-19 and a clear long-COVID syndrome, can be disproved by symptoms erroneously attributed only to COVID-19, such as persistent dyspnea not related to cardiopulmonary impairments.6 According to some authors, at least 53% of patients suffering from SARS-CoV-2 infection and mild COVID-19 might in fact suffer from long-COVID, and about 60% of these patients suffered from post-COVID dyspnea.6 As respiratory impairments are typical features of COVID-19, probably a diagnostic test discriminating between cardiopulmonary and other types of dyspnea can help clinicians to correctly diagnose a post-COVID syndrome and discern it from a permanent COVID-19 inflamed status. Moreover, it could be recommended to discern real post-COVID by assessing the symptomatic patients during a periodic immunological follow-up (eg, serum specific receptor binding domain for spike protein, immunoglobulin M / immunoglobulin G) for the 6 months following the latest SARS-CoV-2 negative swab to prevent the occurrence of statistic confounders, for example, from newly acquired SARS-CoV-2 infections. A patient having any single or multiple symptoms, such as fatigue, weakness, sleep disorders, cognitive impairments, brain fog, and musculoskeletal pain for as long as 6 months without any contact with newly incoming coronaviruses, may be included in a post-COVID pattern of systemic pathology.
Correct discrimination between a prolonged form of mild, persistent COVID-19, due to the persistence of SARS-CoV-2 allergens or anti-idiotypic antibodies, and post-COVID associated with systemic damage to microcirculation and immune regulation after the virus disappeared, is still challenging, and scientists should take this into account to shape and promote proper therapy.
Salvatore Chirumbolo, PhD, Senior Researcher, Department of Engineering for Innovation Medicine, University of Verona, strada Le Grazie 9, 37134 Verona, Italy, phone: +39 0458027456, email: email@example.com
May 23, 2023.
Salvatore Chirumbolo, Umberto Tirelli (SC: Department of Engineering for Innovation Medicine, University of Verona, Verona, Italy; UT: Tirelli Medical Group, Pordenone, Italy)
Chirumbolo S, Tirelli U. Post-COVID or long-COVID? That is the question. Pol Arch Intern Med. 2023; 133: 16506. doi:10.20452/pamw.16506
- Lippi G, Sanchis-Gomar F, Henry BM. COVID-19 and its long-term sequelae: what do we know in 2023? Pol Arch Intern Med. 2023; 133: 16402.Crossref
- Spectrum News. Dr. Fauci: Long COVID still a risk with omicron despite milder illness. https://www.ny1.com/nyc/all-boroughs/news/2021/12/29/fauci-interview-long-covid-still-a-risk-with-milder-omicron-cases. Accessed March 2023.
- Mumoli N, Conte G, Evangelista I, et al. Post-COVID or long-COVID: two different conditions or the same? J Infect Public Health. 2021; 14: 1349-1350.Crossref
- Bowe B, Xie Y, Al-Aly Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nat Med. 2022; 28: 2398-2405.Crossref
- Mantovani A, Morrone MC, Patrono C, et al; Covid-19 Commission of the Accademia Nazionale dei Lincei. Long Covid: where we stand and challenges ahead. Cell Death Differ. 2022; 29: 1891-1900.Crossref
- Beaudry RI, Brotto AR, Varughese RA, et al. Persistent dyspnea after COVID-19 is not related to cardiopulmonary impairment; a cross-sectional study of persistently dyspneic COVID-19, non-dyspneic COVID-19 and controls. Front Physiol. 2022; 13: 917886.Crossref