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Research Article
Revised

Clinical spectrum and short-term outcome of post-COVID multisystem inflammatory syndrome in children after the 2019 pandemic: a longitudinal cohort study

[version 2; peer review: 3 not approved]
Sudesh Kumar
https://orcid.org/0000-0003-4716-3416
1, Piyali Bhattacharya1, Nikhil Arya1, Anamika Kumari1, Nandita Chattopadhyay1
Sudesh Kumar
https://orcid.org/0000-0003-4716-3416
1, Piyali Bhattacharya1, [...] Nikhil Arya1, Anamika Kumari1, Nandita Chattopadhyay1
PUBLISHED 05 Jul 2024
Author details Author details
OPEN PEER REVIEW
REVIEWER STATUS

This article is included in the Emerging Diseases and Outbreaks gateway.

Abstract

Background

As a post-COVID complication in children, multisystem inflammatory syndrome in children (MIS-C) is important because of its varied and life-threatening manifestations. With this background, this study attempts to focus on MIS-C cases in an underprivileged rural setting in north-eastern India, with most patients being treated with methylprednisolone rather than intravenous immunoglobulin due to financial constraints.

Methods

In this prospective longitudinal cohort study at MGM Medical College, 27 MIS-C cases diagnosed following WHO criteria were included. Laboratory and radiological investigations, including echocardiography, were performed as required for diagnosis and to assess prognosis. Most patients were treated with methylprednisolone. A follow-up assessment was done six weeks after discharge for any residual impairment.

Results

The most frequently affected age group was 5–10 years (59.28%), while respiratory (48.14%) and cardiac (40.74%) were the most commonly involved systems. Logistic regression studies established a significant association between serum ferritin level and prolonged hospital stay (coefficient 0.0674, p=0.0041), possibly due to greater complications in cases with high ferritin levels. Organ impairment was found to increase the need for inotrope use (coefficient 3.8797, p=0.00584). Most cases were treated with methylprednisolone alone (85.18%) with a favourable response and no death occurred.

Conclusion

The favourable response in cases treated with methylprednisolone only affirms the effectiveness of the drug as a cheaper alternative in a resource-poor setting. The study highlights that higher ferritin levels in complicated cases leads to prolonged hospitalisation and the increased need for inotropes in cases with organ impairment.

Keywords

Ferritin; Methylprednisolone; MODS; SARS-COV-2 infection

Corresponding author: Anamika Kumari
Competing interests: No competing interests were disclosed.
Grant information: The author(s) declared that no grants were involved in supporting this work.
Copyright:  © 2024 Kumar S et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: Kumar S, Bhattacharya P, Arya N et al. Clinical spectrum and short-term outcome of post-COVID multisystem inflammatory syndrome in children after the 2019 pandemic: a longitudinal cohort study [version 2; peer review: 3 not approved]. F1000Research 2024, 11:1293 (https://doi.org/10.12688/f1000research.127200.2) First published: 11 Nov 2022, 11:1293 (https://doi.org/10.12688/f1000research.127200.1) Latest published: 05 Jul 2024, 11:1293 (https://doi.org/10.12688/f1000research.127200.2)

Revised Amendments from Version 1

We have re-written the Methodology and made some corrections in the Results according to reviewer suggestions.

See the authors' detailed response to the review by Anita Dhanrajani
See the authors' detailed response to the review by Dr Jigna N Bathia

Introduction

Studies on COVID-19-related complications in children were first reported in April 2020 when healthy children presented with either cardiogenic shock or a Kawasaki disease (KD)-like condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection.1–3 Subsequently, the World Health Organization (WHO) and Center for Disease Control and Prevention (CDC) proposed a case definition for multisystem inflammatory syndrome in children (MIS-C).4–6 MIS-C occurs due to dysregulation of the innate immune system 4–6 weeks following severe acute respiratory syndrome (SARS) infection.7–9 The clinical spectrum varies from mild disease to multi-organ dysfunction syndrome (MODS) which leads to death.10–12 In the largest case series of MIS-C from the USA, the mortality rate was 2%.13 Coronary artery abnormalities developed in 8–24% of cases.14 Most cases were treated with either intravenous immunoglobulin (IVIG) alone or along with methylprednisolone (MP).15,16 As in many other bacterial and viral infections, serum ferritin levels were significantly raised in COVID and post-COVID, along with other inflammatory mediators including tumour necrosis factor alpha (TNFa), interleukin-1 (IL-1), interleukin-8 (IL-8), and type I interferon (IFN). Ferritin plays a crucial role in decreasing iron availability, intracellular sequestration, taming inflammatory reactions, and protecting host cells from oxidative damage.

The affordability of IVIG is an issue in this remote, underprivileged area in North-Eastern India, prompting us to perform this study.

Aims & objective

To study the different clinical presentations of post COVID 19 across age groups, immediate and short-term outcomes and parameters associated with disease severity.

Methods

Study design and setting

This was a prospective longitudinal cohort study conducted at MGM Medical College and LSK Hospital, Bihar, India. From 1st June 2021 to 30th April 2022, the study included recruitment, follow-up, and data collection. Informed consent was taken from participant attendants and ethical clearance was obtained by Ethical committee of institute. IEC No. MGM/PRI-880/22.

Inclusion criteria

Children up to the age of 18 years admitted to MGM Medical College & Hospital with a clinical diagnosis of MIS-C according to WHO criteria, were included in the study after taking informed written consent of parents.17 Additionally Children who were fulfilling the MIS-C criteria according to WHO and COVID-19 antibody IgG and IgM positive, qualitative testing which were done in all cases (method: Enzyme Linked Fluorescent Assay Technique on instrument of the VIDAS family) were included in intervention group. Children who were suffering from either active COVID-19 (diagnosed by nasopharyngeal rapid antigen test) and other including dengue, scrub typhus, and bacterial sepsis were excluded by appropriate investigations.

Data collection

For the children who were prospectively enrolled , demographics, clinical signs and symptoms, laboratory parameters, echocardiography, and coronary findings (at admission and at six-week follow-up), duration of ICU stay, medication (with special emphasis on immunomodulators and inotropes), mechanical ventilation, and mortality data were collected by trained resident doctors in a preformed abstraction form with pretested standardized questionarry during the hospital stay and on follow-up after six weeks of discharge.

At the time of admission, detailed clinical history and examination were conducted to determine precipitating factors, associated comorbidity, measurement of vitals & shock with illness and reach a clinical diagnosis. Necessary investigations for the diagnosis of MIS-C and evaluation of organ impairment at the time of discharge & follow-up were conducted. Laboratory markers including erythrocyte sedimentation rate, C-reactive protein, neutrophil/lymphocyte ratio, serum ferritin, D-dimer, liver and renal function tests, prothrombin time, and activated partial thromboplastin time (APTT) were done at the time of admission before starting immune-modulator therapy. Creatinine phosphokinase (CPK-MB) and troponin-1 were not included as they were not done routinely at this hospital. Common tropical infection like enteric fever, malaria, dengue, scrub typhus was ruled out. Chest X-rays, high-resolution chest computed tomography and ECG were done. Recruited children were treated as per standard national guidline.18 The choice of immunomodulators for treatment was decided by the treating team based on affordability for the patient and guidelines for the management of COVID-19 provided by the Ministry of Health and Family Welfare, Government of India. Patients who were treated with methylprednisolone received a pulse dose of 30 mg/kg/day for three days, followed by 2 mg/kg/day for a week or until their CRP value normalised. Steroids were tapered off over the next 2–3 weeks. Children treated with IVIG received 2 gm/kg as a continuous infusion over 8–12 hours. In case of unresponsiveness or detoriation repeat IVIG was not given due to affordability. Along with immunomodulator, antimicrobial, supportive therapy like oxygen, inotropes, NIV was used, preferably in PICU. All prospectively enrolled children were followed up till outcome. Once symptoms subsided, methylprednisolone were replaced with oral equivalent dose of prednisolone and gradually tapered over 2-3 weeks. 2D echocardiography were performed in all patients with shock (patients needed more than 20 mL/kg of IV fluid or an inotrope to keep their blood pressure above the 5th centile) at admission and again six weeks after discharge in case of residual cardiac impairment. Left ventricular ejection fraction (LVEF), coronary artery abnormality with a Z-score of >2.5, and other features like myocarditis, dilated cardiomyopathy, pericardial effusion, and arrhythmia were asses at the time of admission and at the time of follow-up.19

After six weeks, the children were reassessed with a clinical evaluation and lab tests.

Categorization of children with MIS-C

The patients were categorized into three groups according to age: <5 years, 5–10 years, and >10 years for subgroup comparison. All patients were further categorised based on hospital stay (duration) and organ impairment (fully recovered or partial recovery).

Sampling method

Samples were taken using a simple random sampling method technique.

Sample size

Based on a 95% confidence interval, a 5% alpha error, and the fact that MIS-C occurs in 2% of cases,2 the sample size was calculated to be 32 by online Epi Info software.

Statistical analysis

We used R software, version 3.4 (RRID:SCR_001905), for statistical analysis. All continuous variables were summarised using the mean (SD) or median (IQR). Categorical variables were expressed in counts (%). Age group and laboratory findings and complication mean were compared by ANOVA test and categorical frequency were compared by Chi squared test. Logistic regression analysis was used to assess the significant association between complications and laboratory findings. P value less than 0.05 was considered significant.

Results

Demographic characteristics

A total of 42 participants were enrolled in the study, but 10 individuals had active cases of COVID-19 (rapid antigen test positive) and 5 were serologically negative and hence were excluded. Among the 27 patients with confirmed MIS-C, 14 (51.9%) were male and 13 (48.1%) were female. The median age of patients was 8 years (range 2–16 yrs.). The most common age group of MIS-C was 5–10 years (59.28%). Three (11.11%) patients had comorbidities such as cerebral palsy, seizure disorder, and pulmonary tuberculosis. A temporal association with COVID-19 infection was identified with serological testing of COVID-19 IgG and IgM. All patients were serologically COVID-19 IgG positive and four (14.81%) were IgM positive.

Clinical characteristics

A fever was present in 26 (96.29%) cases, and one patient was afebrile (Table 1). The most common system involved was the respiratory system, with 13 patients displaying complications of this kind (48.14%). Dyspnea (100%) and cough (38.4%) were the most common symptoms of the respiratory system. Table 1 gives the demographic, clinical characteristics, and the outcome of MIS-C cases across age groups.

Table 1. Demographic, clinical characteristic, and outcome of MIS-C cases across age groups.

Total (n=27) No. (%)<5 years (n=5) No. (%)5–10 years (n=16) No. (%)>10 years (n=6) No. (%)
1. SexMale14 (51.9)3 (60.0)10 (62.5)1 (16.7)
Female13 (48.1)2 (40.0)6 (37.5)5 (37.5)
2. ComorbiditiesTotal comorbidity number3 (11.11)03 (11.11)0
Cerebral palsy1 (6.3)01 (6.3)0
Pulmonary TB1 (6.3)01 (6.3)0
Seizure disorder1 (6.3)01 (6.3)0
3. Fever26 (96.29)5 (18.51)16 (59.25)5 (18.51)
4. Organ involved
GI5 (18.51)3 (60.0)1 (20.0)1 (20.0)
Pain abdomen3 (60.0)1 (33.33)1 (33.33)1 (33.33)
Diarrhoea4 (80.0)3 (75.0)1 (25.0)0
Nausea/vomiting2 (40.0)2 (100.0)
CVS11 (40.7)2 (18.18)9 (81.81)
Shock11 (100.0)2 (18.18)9 (81.81)
Hypotension11 (100.0)2 (18.18)9 (81.81)
Tachycardia1 (9.09)1 (100.0)
Respiratory13 (48.14)2 (15.3)9 (69.23)2 (15.3)
Dyspnoea13 (48.14)3 (23.07)8 (61.53)2 (15.3)
Cough5 (38.46)1 (20.0)2 (40.0)2 (40.0)
Mucocutaneous7 (25.9)1 (14.28)4 (57.12)2 (28.57)
Rash6 (85.71)1 (16.6)4 (66.6)1 (16.6)
Lymph node1 (14.28)1 (100.0)
Petechiae1 (14.28)1 (100)
Conjunctivitis2 (28.57)1 (50)1 (50)
Oropharyngeal1 (14.28)1 (100)
CNS7 (25.92)1 (14.28)4 (57.14)2 (28.57)
Seizure4 (57.14)1 (25)2 (50)1 (25)
Altered sensorium6 (85.71)1 (16.66)4 (66.66)1 (16.66)
Headache2 (33.3)1 (50)1 (50)
LiverHepatitis2 (7.40)2 (100.0)
5. Treatment
Inotropes11 (45.83)2 (1.1)9 (81.8)0
Methyl prednisolone23 (85.1)4 (80.0)13 (81.25)6 (100.0)
IVIG4 (14.8)1 (20.0)3 (75.0)0
Non-invasive ventilation16 (59.3)2 (12.5)10 (62.5)4 (25.0)
Mechanical ventilation4 (16.66)03 (75.0)1 (20.0)
6. Course
PICU stay in cases24 (88.8)4 (16.6)15 (62.5)5 (20.8)
Duration of PICU stay in days, median (range)6.5 (2–15)5.5 (3–7)6 (2–12)7 (3–15)
Duration of hospital stay (days), median (range)14 (7–34)12 (7–18)14.5 (8–34)14 (7–30)
7. Outcome
Full recovery14 (51.85)3 (21.42)7 (50.0)4 (28.57)
Organ impairment13 (48.14)2 (15.38)9 (69.23)2 (15.38)
CVS10 (76.9)2 (20.0)8 (80.0)0
CNS201 (50.0)1 (50.0)
Respiratory1001 (100.0)
8. Follow up at six weeks
Fully recovered16484
Organ impairment11 (40.74)2 (18.18)7 (63.63)2 (18.18)
1. CVS9 (81.81)3 (33.33)5 (55.55)1 (11.11)
2. CNS2 (18.18)1 (50)1 (50)
3. RESP0

The second most common organ involvement was the cardiac system, which was affected in 11 patients (40.74%). Shock and hypotension were noted in all cases and one patient suffered from cardiac arrhythmia in the form of sinus tachycardia. The incidence of shock was highest in the age group of 5–10 years (81.18%). Mucocutaneous involvement was seen in seven (25.92%) children, among whom a macular-papular rash over the trunk and extremities was evident in six of them (85.71%). Two patients (28.57%) had non-purulent conjunctivitis, and one each had petechia and oropharyngeal congestion. Seven (25.92%) patients had CNS affection, including six (85.71%) with altered sensorium, four (57.14%) with seizures, and two (28.57%) with headaches. Gastrointestinal involvement was seen in five (18.51%) children, of which diarrhoea was reported in four (80%), followed by abdominal pain in three (60%), and nausea and vomiting in two (40%). Two patients (7.4%) suffered from hepatitis C.

Laboratory investigations and cardiac assessment

At the time of admission, anaemia (below 2 standard deviations for age and sex) was found in 14 (51.85%) children. Four (14.8%) had thrombocytopenia (1.5 lakh/mm3) and four (14.8%) had leucopenia (5000 mm3).

Among inflammatory markers, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were raised in all cases, with an average mean value of 15.89 and 25.59, respectively. Serum ferritin (mean value of 942.04 ng/mL) and dimer (3255 ng/mL) levels were also raised in all cases. Prothrombin time/activated partial thromboplastin time (PT/APTT) was abnormal in two (7.4%) cases and transaminase values were raised in three (11.11%) patients (Table 2).

Table 2. Laboratory findings in MIS-C cases.

ParametersTotal Mean±S.D<5 years (n=5) Mean±S.D5-10 years (n=16) Mean±S.D>10 years (n=6) Mean±S.D
COVID-19 IgG14.5804±43.564425.1020±4.425007.5231±8.1009241.2983±92.46887
COVID-19 IgM1.2875±0.06714801.5650±0.304061.0100±0.97581
TLC (/mL)10577.41±4409.6111430.00±2996.58110455.63±4411.00610191.67±5882.59
Platelet (/mL)213788.52±78989.78223018.00±24358.81210175.00±80868.68215733.33±110541.33
N/L Ratio3.597±2.65182.050±1.88943.604±2.74264.867±2.6113
CRP (mg/L)15.89±9.34515.40±18.43417.25±6.75812.67±5.164
ESR (mm/hr)25.59±9.44320.60±4.45025.38±9.52130.33±11.130
Ferritin (ng/mL)942.042±560.9147756.20±295.241078.00±653.20747.20±424.14
D-dimer (ng/mL)3445.77±3591.862482.31±3072.533273.23±3457.053296.32±3439.86

Echocardiography (ECHO) was done in 11 patients in which myocarditis (54.54%), global hypokinesia (18.18%), severely decreased left ventricular ejection fraction (LVEF) less than 30% was 18.18%, moderately decreased LVEF [30–55%] was 45.45%, and one patient pulmonary embolism were noted.

Clinical course, treatment, and outcome

Twenty-four (88.88%) patients required intensive care, and the median duration of PICU stay was 6.5 days (range 2–15). Four patients (16.66%) required mechanical ventilation and 11 (45.83%) required inotropic support.

Twenty-three patients (85.18%) were treated with methylprednisolone, and four (14.8%) patients were treated with IVIG. Of the patients treated with IVIG, one patient had a complete recovery and three had residual organ impairment (clinically improve but radiologically structure abnormality persists) at the time of discharge (95% CI, 25–75%; p=0.239). One patient who suffered from a pulmonary embolism was given anticoagulant therapy.

At the time of discharge, 14 (51.85%) children had fully recovered, and 13 (48.14%) patients suffered from organ impairment, of which 10 had cardiovascular involvement (76.9%), two had CNS involvement (15.38%), and one had respiratory involvement (7.6%). The average median hospital stay duration was 13.5 days (range 7–34). No patients had expired.

Follow-up at six weeks after discharge

All discharged patients remained clinically stable, and no new symptoms or deterioration were noted. In patients with partial recovery, improvement in terms of increased LVEF, Z scores, and respiratory findings was noted. However, hemiparesis and facial palsy persisted in children with CNS involvement. Multiple logistic regression was done to predict the effect of laboratory markers on the likelihood of occurrence of organ impairment and prolongation of hospital stay in which only serum ferritin level [Coefficient 0.00674; p = 0.0041] was significant for prolongation of hospitalization possibly due to its positive association with greater organ impairment (Tables 3, 4, 5 and Figure 1).

Table 3. Correlation matrix (Pearson) multiple linear regression.

Hospital stayIgGTLCCRPESRFerritin ng/mLD-dimer
Hospital stay10.014680−0.31849−0.049480.20800.5336790.150493
COVID-19 IgG0.01468010.17860−0.093460.302770.085098−0.04881
TLC−0.318490.17860110.2064670.105805−0.166420.24277
CRP−0.04948−0.0934610.206461−0.0969770.006771−0.01158
ESR0.2080190.302770.10580−0.0969771−0.0887350.18174
Ferritin ng/mL0.5336790.08509−0.166420.006771−0.0887310.493638
D-dimer0.150493−0.048810.242772−0.011580.1817440.4936381

Table 4. Coefficient table iteration 1 (adjusted R-squared=0.276).

CoefficientSEt-statisticStandard coefficientp value
b05.5896195.7458570.97280900.342268
COVID-19 IgG−0.01966090.0298619−0.658392−0.124630.517794
TLC−0.0002828340.000307531−0.91969−0.1814760.368695
CRP0.003395650.1340340.02533430.004414670.980039
ESR0.2600310.1359161.9131770.3572990.0701504
Ferritin ng/mL0.008095510.002765192.9276540.6409380.00832336
D-dimer−0.0003689120.000431029−0.855888−0.1928110.402198

Table 5. Coefficients table: 0 related to 1 binary logistic regression.

CoefficientSEz-statisticlower z0.025upper z0.975exp(b)p value
b0−2.52141.0646−2.3684−4.6079−0.43480.080350.01786
Inotropes3.87971.40742.75661.12126.638148.40810.005840
Organ impairment2.26551.28251.7664−0.24824.77939.63630.07732
14f11ff2-e04a-4d04-9d22-a852891dc68c_figure1.gif

Figure 1. Incidence of systemic complications related to hospital stay.

CVS (cardiovascular system), CNS (central nervous system), RESP (respiratory system).

Discussion

The present study shows a favourable outcome in MIS-C treated with methylprednisolone therapy. In this study, the median age was 8 years old and the most common age group was 5–10 years. Fever was a universal symptom (96.29%). The most common systems of involvement were respiratory (48.14%) and cardiac (40.74%). Shock mainly occurred in the age group of 5–10 years. Mucocutaneous involvement occurred in 25.92% of cases and CNS involvement in 25.92% of cases.

In a recent multicentre observational study of 134 cases, Nayak S et al. have shown that fever was a universal finding. In 50.7% and 39.6% of the cases, gastrointestinal and respiratory symptoms were observed, respectively. Shock was noted in 35% of cases.20 Sugnan S et al. found that the median age of patients with MIS-C was 7.5 years and the most common symptoms were gastrointestinal (84%) and cardiac (91%).21 In our study gastrointestinal symptom was not such a common presentation as GI cases with relatively milder symptoms, did not come to the tertiary center and commonest age presentation similar to the study by Sugnan S et al.

Laboratory parameters showed a trend toward lower lymphocytes and a high N/L(neutrophil/lymphocyte) ratio. Inflammatory markers such as CRP, ESR, D-dimer, and serum ferritin were high in all cases in our study population. Lacuna–Rangel found an association with having a high white blood cell count, low lymphocyte count, low platelet count, and elevated CRP with increased mortality and severity of disease.22 Tiwari Arun et al. showed that inflammatory markers (CRP, ESR, D-dimer, and ferritin) were elevated in all cases.23 In our study, as in the study by Tiwari et al., these inflammatory markers were elevated.

In our study, cardiac evaluation by echocardiography revealed myocarditis (54.54%) as a prominent finding, which is higher than a Brazilian study which reported myocarditis in only 27% of cases and a Turkish study that found that a 22.4% incidence of myocardial dysfunction in MIS-C may be due to the fact that mostly referral patients were included in the study.24,25 Thrombosis was not reported in any Indian study but was observed in our studies, and was also documented in studies conducted in the United States and the United Kingdom.26,27

In our study, 88.88% of cases required intensive care, and the median duration of pediatric intensive care unit (PICU) stay was 6.5 days; 16.66% of PICU patients required MV. In our study, the PICU admission rate was high compared with the subsequently discussed literature due to patients who were critically ill and mostly referred from other hospital.

Nayak S et al. reported that 55.2% of patients required intensive care and the median PICU stay was four days. MV was required in 27.38% of cases and the median stay in a hospital was 8.09 days.20

In our study, most patients were treated with methylprednisolone. At the time of discharge, 51.85% had recovered completely and there was no mortality. The remaining 48.15% went home with some residual impairment. In earlier studies, mortality due to MIS-C was reported to be 1.2–2%.27,28 Godfred-Cato S et al. reported a favourable short-term outcome response to IVIG and steroids.28

In our study multiple logistic regression showed high serum ferritin level was significantly associated with longer duration of hospital stay which is consistent with study of Mercks J et al. Clinically, it was evident that no systemic complications were seen in cases within one week of hospital stay, though in most cases, greater organ impairment was the underlying cause of the prolonged hospital stay. So, it may be inferred that higher ferritin levels were associated with organ impairment, which led to a prolonged hospital stay. A study by Merck J et al. showed that age and high ferritin were associated with more severe MIS-C.29

In binary logistic regression, another significant finding was that organ impairment necessitated a greater requirement for inotropes.

It is thus observed that our patients, mostly treated with methylprednisolone, had a similar outcome compared with studies from other parts of the country and abroad. In a resource-poor setting, this was an effective and affordable mode of treatment.

Limitations

  • 1. Being a tertiary center, only patients in more serious condition were admitted, and hence the overall clinical spectrum of MIS-C may not have been truly reflected in the study population.

  • 2. Due to the small sample size, the results may not be representative of the general population.

What this study adds to our knowledge

  • 1. Use of pulse methylprednisolone therapy as a first-line treatment for MIS-C had favourable immediate and short-term outcomes.

  • 2. High serum ferritin levels are associated with severe systemic complications leading to prolonged hospitalisation.

  • 3. Greater organ infliction, as reflected by residual organ impairment, is associated with increased use of inotropes.

Conclusions

In patients with MIS-C with severe organ impairment, IV methylprednisolone pulse therapy was associated with favourable immediate and short-term follow-up outcomes. High serum ferritin can predict severe systemic complications and hence prolonged hospitalisation. This study demonstrates that cases with eventual residual organ impairment require greater use of inotropes. Further studies and longer follow-ups of patients diagnosed with MIS-C are required to improve treatment and follow-up criteria.

Informed consent

Written informed consent was obtained from the parents of all participants under the age of 18 years old.

Ethical approval

Ethical clearance was obtained by the Institutional Ethics Committee. IEC No: MGM/PRI-880/22.

Data availability

Underlying data

Figshare: MISC. https://doi.org/10.6084/m9.figshare.21523530.v1. 30

The project contains the following underlying data:

  • - MISC Data Entry.xlsx (raw data).

  • - MISC questionnaire.docx (raw questionnaire).

Reporting guidelines

Figshare: STROBE checklist for ‘[Clinical spectrum and short-term outcome of post-COVID multisystem inflammatory syndrome in children after the 2019 pandemic: a longitudinal cohort study.]’. https://doi.org/10.6084/m9.figshare.21523530.v1. 30

Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).

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  • 4.  World Health Organization (WHO): Multisystem inflammatory syndrome in children and Adolscent with COVID-19: scientific Brief2020. Reference Source
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  • 10.  Hoste L, Van Paemel R, Haerynck F: Multisystem Inflammatory Syndrome in Children Related to COVID-19: A Systematic Review. Eur. J. Pediatr. 2021; 180(February): 2019–2034. PubMed Abstract | Publisher Full Text
  • 11.  Bagri NK, Deepak RK, Meena S, et al.: Outcomes of Multisystem Inflammatory Syndrome in Children Temporally Related to COVID-19: A Longitudinal Study. Rheumatol. Int. 2021; 42(October): 477–484. PubMed Abstract | Publisher Full Text
  • 12.  Tang Y, Li W, Baskota M, et al.: Multisystem Inflammatory Syndrome in Children during the Coronavirus Disease 2019 (COVID-19) Pandemic: A Systematic Review of Published Case Studies. Transl. Pediatr. 2021; 10(January): 121–135. PubMed Abstract | Publisher Full Text
  • 13.  Son MBF, Murray N, Friedman K, et al.: Multisystem Inflammatory Syndrome in Children — Initial Therapy and Outcomes. N. Engl. J. Med. June 2021; 385: 23–34. Publisher Full Text PubMed Abstract |
  • 14.  Valverde I, Singh Y, Sanchez-de-Toledo J, et al.: Acute cardiovascular manifestations in 286 children with multisystem inflammatory syndrome associated with COVID-19 infection in Europe. Circulation. 2021 Jan 5; 143(1): 21–32. PubMed Abstract | Publisher Full Text
  • 15.  Verdoni L, Mazza A, Gervasoni A, et al.: An Outbreak of Severe Kawasaki-like Disease at the Italian Epicentre of the SARS-CoV-2 Epidemic: An Observational Cohort Study. Lancet. 2020; 395(June): 1771–1778. PubMed Abstract | Publisher Full Text | Free Full Text
  • 16.  Abrams JY, Godfred-Cato SE, Oster ME, et al.: Multisystem Inflammatory Syndrome in Children Associated with Severe Acute Respiratory Syndrome Coronavirus 2: A Systematic Review. J. Pediatr. November 2020; 226: 45–54.e1. PubMed Abstract | Publisher Full Text
  • 17.  World Health Organisation: Multisystem Inflamatory Syndrome in Children and adolescents with COVID-19.Published May 15, 2020. Reference Source
  • 18.   www.mohfwgov.in/pdf/guidelines for Management of Covid 19 in children. (18th June 2021)
  • 19.  McCrindle BW, Rowley AH, Newburger JW, et al.: Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017; 135(April): e927–e999. PubMed Abstract | Publisher Full Text
  • 20.  Nayak S, Panda CP, Biswal B, et al.: Eastern India Collaboration on Multisystem Inflammatory Syndrome in Children (EICOMISC): A Multicentre Observational Study of 134 Cases. Front. Pediatr. 11 March 2022. Publisher Full Text
  • 21.  Sugunan S, Bindusha S, Geetha S, et al.: Clinical Profile and Short-Term Outcome of Children With SARS-CoV-2 Related Multisystem Inflammatory Syndrome (MIS-C) Treated With Pulse Methylprednisolone. Indian Pediatr. 2021; 58(April): 718–722. PubMed Abstract | Publisher Full Text | Free Full Text
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Kumar S, Bhattacharya P, Arya N et al. Clinical spectrum and short-term outcome of post-COVID multisystem inflammatory syndrome in children after the 2019 pandemic: a longitudinal cohort study [version 2; peer review: 3 not approved]. F1000Research 2024, 11:1293 (https://doi.org/10.12688/f1000research.127200.2)
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ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
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Reviewer Report 27 Dec 2024
Victor Irungu Mwangi, Universidade do Estado do Amazonas, Manaus, Brazil;  DENPE, Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, MANAUS, AMAZONAS, Brazil 
Not Approved
VIEWS 3
https://doi.org/10.5256/f1000research.168728.r350467
  1. The aims/objective needs to be concise. In its current form, it is open to erroneous interpretations.
  2. Refine Outcome Metrics: Define full recovery, partial recovery, and organ impairment clearly and consistently. Consider using standardized scoring systems
... Continue reading
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Mwangi VI. Reviewer Report For: Clinical spectrum and short-term outcome of post-COVID multisystem inflammatory syndrome in children after the 2019 pandemic: a longitudinal cohort study [version 2; peer review: 3 not approved]. F1000Research 2024, 11:1293 (https://doi.org/10.5256/f1000research.168728.r350467)
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Reviewer Report 30 Sep 2024
Dr Jigna N Bathia, Institute of Child Health, Kolkata, West Bengal, India 
Not Approved
VIEWS 5
https://doi.org/10.5256/f1000research.168728.r312453
Thank you for incorporating the suggested changes. 
Following are my observations:
1) Syntax needs to be improved significantly. 
2) Definition of partial and full recovery is  still not clear. As the outcome was distributed system wise, hence ... Continue reading
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Bathia DJN. Reviewer Report For: Clinical spectrum and short-term outcome of post-COVID multisystem inflammatory syndrome in children after the 2019 pandemic: a longitudinal cohort study [version 2; peer review: 3 not approved]. F1000Research 2024, 11:1293 (https://doi.org/10.5256/f1000research.168728.r312453)
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Reviewer Report 05 Jun 2024
Dr Jigna N Bathia, Institute of Child Health, Kolkata, West Bengal, India 
Not Approved
VIEWS 14
https://doi.org/10.5256/f1000research.139679.r261166
I appreciate your work; however, I don’t find it suitable for approval. Following are my observations:
1) Aims and Objectives not mentioned.
2) Methods, Procedure not very clear.
3) Outcome measures are vague, clear cut outcome measures ... Continue reading
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HOW TO CITE THIS REPORT
Bathia DJN. Reviewer Report For: Clinical spectrum and short-term outcome of post-COVID multisystem inflammatory syndrome in children after the 2019 pandemic: a longitudinal cohort study [version 2; peer review: 3 not approved]. F1000Research 2024, 11:1293 (https://doi.org/10.5256/f1000research.139679.r261166)
The direct URL for this report is:
https://f1000research.com/articles/11-1293/v1#referee-response-261166
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  • Author Response 05 Jul 2024
    sudesh kumar, pediatrics, MGM MEDICAL COLLEGE AND LIONS SEVA KENDRA HOSPITAL, kishanganj, 855107, India
    05 Jul 2024
    Author Response
    Respected Sir/Ma'am, I have tried to correct your queries.
    Competing Interests: No competing interests were disclosed.
    Report a concern
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COMMENTS ON THIS REPORT
  • Author Response 05 Jul 2024
    sudesh kumar, pediatrics, MGM MEDICAL COLLEGE AND LIONS SEVA KENDRA HOSPITAL, kishanganj, 855107, India
    05 Jul 2024
    Author Response
    Respected Sir/Ma'am, I have tried to correct your queries.
    Competing Interests: No competing interests were disclosed.
    Report a concern
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Reviewer Report 24 Jan 2024
Anita Dhanrajani, Department of Pediatrics, Tulane University (Ringgold ID: 5783), New Orleans, Louisiana, USA 
Not Approved
VIEWS 22
https://doi.org/10.5256/f1000research.139679.r231102
I am not seeing a section for aims of the study.
Methods are very vaguely described. Specifically need to include detailed descriptions of the control group and intervention group along with treatment protocols used for this group. Not sure ... Continue reading
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HOW TO CITE THIS REPORT
Dhanrajani A. Reviewer Report For: Clinical spectrum and short-term outcome of post-COVID multisystem inflammatory syndrome in children after the 2019 pandemic: a longitudinal cohort study [version 2; peer review: 3 not approved]. F1000Research 2024, 11:1293 (https://doi.org/10.5256/f1000research.139679.r231102)
The direct URL for this report is:
https://f1000research.com/articles/11-1293/v1#referee-response-231102
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Report a concern
  • Author Response 22 Mar 2024
    sudesh kumar, pediatrics, MGM MEDICAL COLLEGE AND LIONS SEVA KENDRA HOSPITAL, kishanganj, 855107, India
    22 Mar 2024
    Author Response
    Thanks for guiding and promoting me.
    Competing Interests: no
    Report a concern
  • Author Response 05 Jul 2024
    sudesh kumar, pediatrics, MGM MEDICAL COLLEGE AND LIONS SEVA KENDRA HOSPITAL, kishanganj, 855107, India
    05 Jul 2024
    Author Response
    Respected Sir/Ma'am, I have tried to correct your queries.
    Competing Interests: No competing interests were disclosed.
    Report a concern
  • Respond or Comment
COMMENTS ON THIS REPORT
  • Author Response 22 Mar 2024
    sudesh kumar, pediatrics, MGM MEDICAL COLLEGE AND LIONS SEVA KENDRA HOSPITAL, kishanganj, 855107, India
    22 Mar 2024
    Author Response
    Thanks for guiding and promoting me.
    Competing Interests: no
    Report a concern
  • Author Response 05 Jul 2024
    sudesh kumar, pediatrics, MGM MEDICAL COLLEGE AND LIONS SEVA KENDRA HOSPITAL, kishanganj, 855107, India
    05 Jul 2024
    Author Response
    Respected Sir/Ma'am, I have tried to correct your queries.
    Competing Interests: No competing interests were disclosed.
    Report a concern

Comments on this article Comments (0)

Version 2
VERSION 2 PUBLISHED 11 Nov 2022
Comment

Open Peer Review

Reviewer Status

Alongside their report, reviewers assign a status to the article:

Approved
The paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations
A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved
Fundamental flaws in the paper seriously undermine the findings and conclusions

Reviewer Reports

Invited Reviewers
1 2 3
Version 2
(revision)
 05 Jul 24 		read read
Version 1
11 Nov 22 		read read
  1. Anita Dhanrajani, Tulane University (Ringgold ID: 5783), New Orleans, USA
  2. Dr Jigna N Bathia, Institute of Child Health, Kolkata, India
  3. Victor Irungu Mwangi, Universidade do Estado do Amazonas, Manaus, Brazil; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, MANAUS, Brazil

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    Alongside their report, reviewers assign a status to the article:
    Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
    Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
    Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
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