Review Navigating the Spectrum of Two Pediatric COVID-19 Complications: MIS-C and PASC Infection, 2024, by Parzen-John & Katz

https://www.mdpi.com/2077-0383/13/4/1147

Navigating the Spectrum of Two Pediatric COVID-19 Complications: Multi-System Inflammatory Syndrome in Children and Post-Acute Sequelae of SARS-CoV-2 Infection
by
Simon Parzen-Johnson1*
and
Ben Z Katz
2


1 Section of Infectious Diseases, Biological Sciences Division, University of Chicago, 5841 South Maryland Avenue, MC 6082, Chicago, IL 60637, USA

2 Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, 225 E Chicago Avenue, Chicago, IL 60611, USA

*Author to whom correspondence should be addressed.

J. Clin. Med. 2024, 13(4), 1147; https://doi.org/10.3390/jcm13041147

Submission received: 6 December 2023 / Revised: 28 December 2023 / Accepted: 14 February 2024 / Published: 18 February 2024


Abstract

Purpose:

This review summarizes the current scope of understanding associated with two common post-infectious complications associated with COVID-19 infection: Multi-System Inflammatory Syndrome in Children (MIS-C) and Post-Acute Sequelae of SARS-CoV-2 infection (PASC). It identifies current gaps in the knowledge and issues that may limit the ability to fill these gaps. This review provides a framework to drive continued research.

Methods:

A comprehensive review of the current literature was performed, identifying seminal articles describing the emergence of MIS-C and PASC, and works from the literature focused on the clinical implications and pathophysiologic understanding of these disorders.

Findings:

Although pediatric patients experienced few severe cases of acute COVID-19 infection, the burden of disease from post-infectious sequelae is substantial. Mortality is low, but morbidity is significant. There are still numerous unknowns about the pathophysiology of both MIS-C and PASC; however, with widespread immunity developing after increased vaccination and prior infection, it may be difficult to perform adequate prospective studies to answer pathophysiologic questions. Long-term sequalae of MIS-C seem to be minimal whereas, by definition, PASC is an ongoing problem and may be severe.

Implications:

The rapid sharing of information regarding novel conditions such as MIS-C and PASC are key to interventions related to future post-infectious sequelae outside of those stemming from COVID-19. Although MIS-C seems unlikely to return as a clinical condition in substantial numbers, there is still significant learning that can be gleaned from existing patients about general aspects of epidemiology, equity, and pathophysiology. There is significant morbidity associated with PASC and additional resources need to be dedicated to determining appropriate and effective therapies moving forward.

Keywords:
PASC; COVID-19; pediatrics; MISC; PIM; ME/CFS

 

Quite a number of references to ME/CFS in this review.
Very disappointing to see that graded exercise therapy and CBT are recommended in the last extract. Ben Katz has published on ME/CFS before but I don't think I knew these were his views.

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Similar post-infectious syndromes have been seen following other systemic illnesses, the most common of which is myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) following infectious mononucleosis (IM). Over 10% of patients with IM meet the criteria for ME/CFS 6 months after their bout of IM [30,31,32]. Many experts believe that PCC/PASC is the latest example of a post-infectious fatigue syndrome like ME/CFS [33].

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Another potential pathophysiologic mechanism focuses on perturbations of the microbiome and virome after SARS-CoV-2 infection, as has been postulated to be the case for inflammatory bowel disease, diabetes, and ME/CFS [40,41].

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In longer-term studies of PASC, symptoms diminish with time [60,63], and in one study there were no differences in symptoms between cases and controls after 6–9 months [63]. This diminution of symptoms over time is similar to what is seen in adolescents who meet criteria for CFS following infectious mononucleosis, again supporting the notion that PASC and CFS following IM are related disease processes [32]. In one preliminary study that directly compared 19 children with PASC to 19 age- and gender-matched children with a self-reported diagnosis of ME/CFS, the children with ME/CFS had worse severity and longevity of symptoms, although symptoms in both groups declined over time [64].

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3.3. Treatment and Outcomes

As has been summarized above, whether due to the infection itself or the conditions brought about by the pandemic (e.g., school closures and social isolation), about 15% of children and adolescents will have 3 months or more of symptoms such as fatigue, brain fog, headache, sleep disturbances, behavioral changes and abdominal pain following COVID-19. These symptoms interfere with a child’s daily activities, including school, and these children require help. At present, there is no cure for PASC. However, as symptoms tend to diminish with time there are therapies that have been shown to speed recovery for both CFS following IM and PASC, the most promising of which is cognitive behavioral therapy (CBT). The CBT modalities that have been studied for PASC include a graded exercise component, which whether alone or in combination with CBT appears to offer the best chance of speeding recovery, although studies have found that even graded exercise alone without CBT may be helpful [65,66,67]. A Cochrane review of eight randomized controlled trials in adults with ME/CFS [68] showed benefit to graded exercise, while three randomized controlled trials in adolescents with ME/CFS [69,70,71] also showed the benefit of CBT.

Long-term follow-up for PASC is not yet available since the pandemic first began at the end of 2019. However, again it may be reasonable to extrapolate findings from studies of ME/CFS. One such study on pediatric patients with ME/CFS found that ~65% of patients showed sustained recovery, after a mean follow-up 2.7 years, with online CBT alone [72]. In adults with ME/CFS, 37–70% have sustained recoveries up to 10 years later [73]. These findings are encouraging for patients with PASC. Future long-term follow-up studies focused on this important patient population are certainly warranted.

 

Definitely not encouraging for the 35% who don't, and for the months or years lost to illness for those who do. Especially since there are no treatments and no possibility of making individual prognoses. But I guess that if that doesn't bother you, then it doesn't bother you.

"Good news, there is a 35% chance that life as you know it is over! Possibly more. We don't know! It could be months. It could be years. No one can tell. Have you tried yoga? Ain't that good news?! We are smart people."