A Clinical Riddle: Post-COVID Inflammatory Syndrome in Adults

Adults with multi-system inflammatory syndrome (MIS-A) following COVID-19 illness had a wide variety of organ involvement, a retrospective single-center study found.

In an analysis that included nearly 700 COVID-19 patients, the median number of involved organ systems among the 15 patients admitted for MIS-A was four, with the kidneys, hematologic, and gastrointestinal systems most commonly affected, reported Giovanni Davogustto, MD, of Vanderbilt University Medical Center in Nashville, and colleagues.

Overall, nine of the MIS-A patients had experienced acute COVID-19 illness, with three requiring hospital admission for COVID-19 prior to being admitted for MIS-A, the authors wrote in JAMA Network Open.

“These data suggest that, although uncommon, MIS-A has a more heterogeneous clinical presentation than previously appreciated and is commonly underdiagnosed,” they added.

Incidence of MIS is unknown and is suggestive of being an uncommon post-acute COVID-19 complication, the authors said. Previously, post-acute COVID-19 complications have been described in children (MIS-C), but Davogustto and colleagues sought to investigate how MIS-A presents after a SARS-CoV-2 infection.

“Unlike adult cases of acute COVID-19, most pediatric patients experience asymptomatic infection or mild COVID-19 symptoms, thus allowing a contrast between the diagnoses of acute COVID-19 and MIS-C,” Eric Chow, MD, of the University of Washington in Seattle, wrote in an accompanying editorial.

“However, Davogustto et al laid the groundwork for future studies by offering an initial framework by which MIS-A cases could be identified systematically in future research studies,” he added.

Davogustto’s team analyzed cases of adults diagnosed with subacute or convalescent COVID-19 at the Vanderbilt University Medical Center to understand their clinical outcomes. This study took place from March to September 2020, initially including 7,196 adults over age 21 who had laboratory-confirmed COVID-19.

Selection criteria required patients admitted to the hospital only between 14 and 84 days after receiving a positive COVID-19 RT-PCR test or admitted at 15 days before or after given a positive COVID-19 serologic test result.

Overall, 839 patients (11.7%) were admitted with a SARS-CoV-2 infection, with 683 classified as having acute COVID-19. Of the remaining patients, 15 met the criteria for MIS-A.

In the end, there were 698 patients included in the analysis, 683 with acute COVID-19 and 15 with MIS-A. Median age was about 56, a little over half were men and almost 60% were white. Patients with MIS-A tended to be younger (median age 45) and more likely to have evidence of SARS-CoV-2 infection via serologic testing.

Median interval between acute COVID-19 admission and MIS-A admission was 23 days. All MIS-A patients showed elevated ferritin lab results, with most MIS-A patients showing D-dimer elevation, C-reactive protein, and erythrocyte sedimentation rate elevation.

In addition, five patients needed intensive care treatment, three for hemodynamic monitoring, and one apiece for vasopressors or non-invasive ventilation support. There were 20% of patients with MIS-A who experienced shock.

Among the 15 MIS-A admissions, three patients were formally diagnosed with MIS-A, immunosuppressive therapy was required for four, and antibiotic therapy was required for seven patients. No deaths were reported.

Authors noted the primary clinical team was unable to initially identify most patients who met the MIS-A criteria.

Limitations of this study include an underestimation of MIS-A incidence and that not all COVID-related admissions were given comprehensive screening assessments for MIS-A.

The authors highlighted the need for additional investigations to enroll more MIS-A patients for diagnostic and treatment improvement.

“Not only does MIS have important implications for our understanding of SARS-CoV-2 pathology, but it also has the potential to offer new insights in how our immune system functions and its role in hyperinflammation,” editorialist Chow wrote. “MIS-A is yet another important piece to the ever expanding SARS-CoV-2 puzzle.”