Long COVID (LC), also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) or post-COVID condition (PCC), is characterized by worsening or newly emerging symptoms following an acute SARS-CoV-2 infection. Although there are several competing definitions, the World Health Organization (WHO) Delphi Consensus defines LC as a condition appearing in individuals with confirmed or probable SARS-CoV-2 infection, typically present at least three months after the onset of COVID-19, with symptoms lasting for at least two months. These symptoms may resolve over time or persist for months or years, encompassing neurological issues (e.g., sleep disturbances and "brain fog"), respiratory problems (e.g., dyspnea and cough), cardiac complications (e.g., palpitations and chest pain), and systemic symptoms (e.g., malaise and fatigue) [1]. Although not all symptoms following an episode of COVID-19 are necessarily attributable to SARS-CoV-2 infection (there is some background rate of spontaneous symptom development in healthy individuals), hundreds of symptoms have been associated with LC [2], and the field is still too immature to definitively exclude any symptom from the case definition at this point.

LC is most frequent after severe COVID-19 [3], [4], but the vast majority of cases follow clinically mild COVID-19 [5]. Incidence and prevalence estimates are highly divergent, reflecting varying case definitions and the various biases inherent to how cases are ascertained in different settings. Initial studies often reported high proportions (>50%) of people with Long COVID after SARS-CoV-2 infection, likely reflecting a variety of biases inflating the prevalence estimate [6]. Most population-based studies, however, have settled on estimates between 5% and 20%, with more recent estimates on the lower end of this spectrum [7], [8], [9], [10]. For example, a recent population-based study in Scotland that adjusted for background symptoms in the uninfected population suggested a prevalence of 6.5% at 12 months [11], similar to prevalence estimates within the U.S. population [12]. Within the ongoing pandemic, the epidemiology is also dynamic. While vaccination reduces the risk of LC, it does not offer complete protection [13], and even following Omicron infection in vaccinated individuals, the estimated prevalence of LC is 4.5% [14]. Ultimately, it is estimated that at least 65 million people worldwide currently suffer from LC, and this number could rise to up to 400 million assuming that 10% of acute cases lead to LC and considering that infections are vastly underreported [2], [15]. Even with more conservative estimates, the potential scale of the problem is huge in the context of a still-ongoing pandemic, and on par with the scope of other high-priority health conditions like heart disease, cancer, and HIV [16]. Given these figures, understanding LC and developing effective prevention and treatment strategies is a pressing public health priority.