I am grateful for the additional insights provided by Professor Yon and Ha et al. in response to my editorial comment [1,2]. The authors reported that the incidence of gastrointestinal disease, hepatobiliary disease, and other digestive abnormalities increased in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the post-acute phase from three large-scale population-based cohorts [3]. The strength of this study is that it showed the risk of post-acute sequelae of COVID-19 (PASC) for the digestive organs across diverse disease entities, coronavirus disease 2019 (COVID-19) severity, changes over time and the presence or absence of vaccination.

In this study, the risk of gastrointestinal disease remained high after 6 months of COVID-19 infection, although the hazard ratio tended to decrease with time. A recent metaanalysis reported that the pooled prevalence estimates for PASC involving various organs were 45.06%, 41.30% and 41.32%, respectively, when the follow-up or assessment timepoint was categorized as ≥3rd, ≥6th, and ≥12th months after the index date [4]. Another recent study on the risk of PASC over a longer period has been published [5]. This study analyzed the risk of death and PASC over 3 years from a cohort of 135,161 people with SARS-CoV-2 infection and 5,207,835 controls from the US Department of Veterans Affairs. They showed that the risk of PASC decreased over the 3 years, but three organ systems still showed an increased risk in the third year, including neurologic, pulmonary and gastrointestinal disorders. The pathophysiology of PASC is not fully understood, but it was associated with several factors, including viral persistence, organ damage, inflammation, and immune dysregulation [6]. In addition, socioeconomic factors, pre-existing comorbidities, assess to health-care and the consequences of critical illness may influence the risk of PASC. These complex factors can act together to cause PASC over a short or longer period of time. The diagnosis of PASC is based on the history and clinical symptoms, excluding other diseases. Therefore, it is necessary to take a careful history, keeping in mind that there may be long-term effects of PASC for digestive system-related symptoms or signs.

So date, there is no standard treatment for PASC. There have been studies on the alleviation of gastrointestinal manifestations of PASC with vaccination and antiviral therapy [7-10]. As Professor Yon and Ha, et al commented, It would be premature to make a definitive statement regarding the protective effect of vaccination on gastrointestinal manifestations during post-COVID. However, several studies have shown the safety of COVID-19 vaccination and positive results in alleviating gastrointestinal manifestations during post-COVID [7-9]. Therefore, vaccination should not be hindered or discouraged. Another study presented a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2–3 months later), integrated with clinical data and patient-reported symptoms [10]. The authors suggested that the importance of detectable virus at clinical diagnosis as a PASC factor may suggest antivirals administered early in the disease course may be beneficial not only for treating acute COVID-19, but also for reducing later PASC.

PASC is a complex and poorly understood condition, that can affect people for 2 weeks, months, or even years after their initial COVID-19 infection. Future research is needed to better understand the pathogenesis of PASC and multidisciplinary intervention may be required to provide a personalized treatment and rehabilitation.