Addressing standardized definitions of post-COVID and long-COVID

Although the clinical burden of coronavirus disease 2019 (COVID-19) has undergone a substantial decline over time [1], the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remain substantial worldwide, persuading the World Health Organization (WHO) to reiterate the status of public health emergency of international concern [2]. Besides the still important clinical burden of an acute infection, especially in the most vulnerable parts of the general population, several concerns have emerged regarding the medium- and long-term impact on health and fitness, a still vague syndromic condition that is shared by many viral infections and may involve between 9 and 63 % of all COVID-19 patients [3], especially those who experienced more severe COVID-19 illness (e.g., hospitalized or needing intensive care), patients with underlying health conditions and who did not receive COVID-19 vaccination.

There is still large confusion and open debate as to what should be defined as a “pathological continuum of symptoms after recovering from an acute SARS-CoV-2 infection”, including confusion over appropriate terminology, such as differentiating between “post-COVID” and “long-COVID” (notably, other terminology could be used, including “long-haul COVID”, “post-acute COVID”, “post-acute sequelae of SARS CoV-2 infection (PASC)”, “long-term effects of COVID”, “chronic COVID” and so forth). Notably, a specific ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) has been developed for defining the constellation of clinical signs and symptoms that may persist after recovering from an acute SARS-CoV-2 infection, classified as “Diagnosis Code U09.9 (Post COVID-19 condition, unspecified)” [4] and, as detailed in the ICD-10-CM website, refers to the definition endorsed by WHO, summarized in Table 1. This operative description, where post-COVID and long-COVID are used almost interchangeably, requires that suggestive symptoms continue or newly develop at least 3 months after an acute SARS-CoV-2 infection, with persistence of such symptoms for not less than 2 months and with no other reasonable justifications [5]. The US Centers for Disease Control and Prevention (CDC) uses a different approach. While also failing to operate a substantial demarcation between post-COVID and long-COVID, the CDC prefer to define both conditions as persistence or newly onset of suggestive signs and symptoms after (at least) 4 weeks from an acute SARS-CoV-2 infection [6]. Thus, the timeline is considerably short compared to that endorsed by the WHO, contributing to confusion and uncertainty. To this end, recent data published by the Consortium for Clinical Characterization of COVID-19 by HER (4CE), showed the many issues emerging from the only partial overlap between these two definitions, with a rate of misclassification and/or misdiagnosis exceeding 25 % when one or the either definitions are used [7].

Understandably, the challenges arising from the inappropriate usage of the ICD-10-CM code U09.9 – reflecting poor worldwide standardization of diagnostic criteria – not only complicates diagnosis and treatment of patients with prolonged illness, but also generates a substantial impact on laboratory medicine, whereby we expect that the search for predictive and/or diagnostic biomarkers of post-COVID and/or long-COVID will exponentially grow in the nearby future [8]. We are hence providing here a tentative (operative) definition, where we suggest to define “post-COVID” as continuation of signs, symptoms or even radiologic/laboratory abnormalities of an initial SARS-CoV-2 infection, irrespective of their duration, whilst we prefer to reserve the definition of “long-COVID” to those people with persistence of signs, symptoms or even radiologic/laboratory abnormalities of an initial SARS-CoV-2 infection for more than 3 months (Table 1, Figure 1). We hope that this definition could help harmonize the classification of patients with any type of post-COVID condition for both clinical and research purposes.

Figure 1:

Timeline of the available definitions for classifying post-COVID signs, symptoms or even laboratory abnormalities.