Association of Multisystem Inflammatory Syndrome Temporally Associated with COVID-19 (MIS-C) with Coinfections: A Retrospective Cross Sectional Analytical Study from Northern India

Abstract

Introduction: Multisystem Inflammatory Response Syndrome in Children (MIS-C) temporally associated with Coronavirus Disease 2019 (COVID-19) is characterized by fever, raised inflammatory markers, multisystem involvement with evidence of COVID-19 infection (positive RT-PCR or serology). It occurs concurrently or after 4-6 weeks of acute COVID infection.It has wide range of clinical presentation ranging from mild asymptomatic infection to severe life-threatening illness. Clinical presentation of MIS-C has considerable overlapping features with other tropical infections. During peak wave of COVID-19, when large proportion of population has been affected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), contracting other infections during and within four weeks of active COVID-19 is inevitable. Despite of this concern, only few researchers have studied co-infection and they explained a complex interaction between COVID-19 and other infections like tuberculosis and dengue. They demonstrated how one infection augments the severity of other. To the best of our knowledge no pediatric population-based study explained the interaction of acute COVID-19 & MIS-C with other infections so far. Aim: To determine the association of MIS-C with co-infections in SARS-CoV-2 positive children of 1 month to less than 18 years of age. Materials and Methods: A retrospective review of the medical records of pediatric patients with SARS-CoV-2 infection, treated from September 2020 to February 2021, was performed.All the patients who fulfilled World Health Organization (WHO) criteria of MIS-C were included. Detailed demographic, clinical, laboratory parameters and associated co-infections were recorded.The severe and non severe MIS-C groups were compared. Sample ‘t’ test, Wilcoxon test and Chi-squared test were used for statistical analysis. Results: A total of 44 children fulfilled the diagnostic criteria of MIS-C and were included in the study. Out of 44 , 20 children (45.4%) had severe disease and 24 had non severe disease. The mean age of children with severe MIS-C was 7.38±5.39 years, as compared to 4.37±4.61 years in the non severe group (p-value= 0.044). Males were predominantly affected in both the groups (Male: Female =1.22:1 in severe MIS-C and 2.4:1 in non severe MIS-C). The gastrointestinal system was most commonly affected in both groups. Associated co-infection was noted more in severe MIS-C group (11 vs 1 patient in severe vs non severe group, p-value=<0.001). Tuberculosis was found to be associated in three patients, followed by complicated enteric fever, and severe dengue in two patients each. The odds ratio for developing severe MIS-C in the presence of co-infections was 10.5(CI=2.33- 47.27) while in its absence it was 0.10(0.02-0.43). Conclusion: The findings of this study support that concurrent infections in COVID-19 can exacerbate the severity of COVID19 illness and may lead to severe MIS-C.