Non-MIS-C postacute sequelae of COVID-19, is it autoimmune or autoinflammatory? A systematic review of the reported cases

Introduction:

Coronavirus Disease 2019 (COVID-19) is by far the most world-altering pandemic to ever hit modern humanity. Three years after the very first case emerged in December 2019, the virus continues to bring upon global disarray in the acute phase of the infection as well as months afterwards, causing the virus’s morbidity and mortality to further skyrocket. This systematic literature review was conducted up till December 2022, comprising all the case reports that thoroughly discuss a myriad of non-Multisystem Inflammatory Syndrome In Children (non-MIS-C) post-acute sequalae of COVID-19 (PASC) in the paediatric population, also known as Long COVID Syndrome.  In this review, we aimed to highlight the prevalent time interval between COVID-19 infection and the development of various non-MISC post-infectious sequalae (PIS). 

Methods:

We conducted a holistic literature search on PubMed, Google Scholar, Google Search, and Scopus. Data bases were searched for studies that met our inclusion and exclusion criteria. The systematic review was performed on all case reports containing relevant outcome parameters such as age, sex, the interval between COVID-19 infection and subsequent PASC and, lastly, the need for hospitalization during the course of the disease.

Results: 

We collected a total of 78 case reports discussing the various post-infectious immune sequalae following COVID-19 infection in the paediatric population, consisting of a total of 109 patients. The final screening revealed an equal sex distribution, whereas the two commonest age intervals were school-aged children and adolescents, with 38% of the patients having been older than six years. Interestingly, hospital admission throughout the course of COVID-19 wasn’t a predictor of the subsequent PASC; forty-nine patients (44.9%) were hospitalized while sixty patients (55.1%) were not hospitalized. More importantly, the most predominant time interval between COVID-19 infection and the developing PASC was observed to be within 14 days since the start of COVID-19 infection, accounting for 61% of the cases. 

Conclusion: 

These findings suggest a crucial link is slowly but surely unfolding between COVID-19 and an abundance of systemic post-infectious immune sequalae in the paediatric population, especially amongst children older than six years. Accordingly, meticulous follow-up and prompt management is largely encouraged for the paediatric population in case of unusual symptoms and signs following COVID-19 infection, regardless of COVID-19’s severity.