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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 13  |  Issue : 3  |  Page : 143-149

SARS CoV-2-related multisystem inflammatory syndrome in adults: An observational case series from tropics


Department of Internal Medicine, Vardhman Mahavir Medical College and Associated Safdarjung Hospital, New Delhi, India

Date of Submission20-Feb-2022
Date of Decision22-Feb-2022
Date of Acceptance22-Feb-2022
Date of Web Publication13-Jul-2022

Correspondence Address:
Dr. Sameer Gulati
Department of Internal Medicine, Vardhman Mahavir Medical College and associated Safdarjung Hospital, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/injms.injms_22_22

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  Abstract 


Background: Extrapulmonary multisystemic manifestations in children were recognized, early in the pandemic, Multisystem Inflammatory Syndrome in Children (MIS-C). Of late, similar manifestations have been reported in adults (Multisystem Inflammatory Syndrome in adults - MIS-A) in too. As new variants of SARS-CoV 2 emerge and fade away, MIS-A needs to be recognized at the most opportune time. Besides, we hypothesize that MIS-A may also co-exist with other tropical infections to further confuse diagnostic scenario. Methodology: A series of five cases of MIS-A is presented. Their demographic, comorbidities, and clinical data were noted. Besides, the clinical and laboratory parameters of patients with and without tropical infections were compared. Results: Patients presented with diverse heterogenous clinical manifestations. The cardiovascular, hematological, and abdominal systems were most commonly involved along with high inflammatory markers. Three of our patients in the present series had tropical infections along with MIS-A. There was no statistically significant difference between clinical manifestations and laboratory parameters among MIS-A patients with and without tropical infections. All the five patients improved on treatment and were discharged home. Conclusions: A high index of suspicion is required to diagnose MIS-A, especially in tropical areas where background rate of other infections is also high. Moreover, these tropical infections may co-occur along with MIS-A, further confusing the diverse heterogenous clinical presentations. Patients with MIS-A may be critically ill, but outcomes are good if lifesaving immunosuppressive therapy is initiated on time.

Keywords: Coronavirus, COVID-19, MIS-A, MIS-C, tropical diseases


How to cite this article:
Gulati S, Jagtap AB, Porwal YC, Kathuria P, Chikara A. SARS CoV-2-related multisystem inflammatory syndrome in adults: An observational case series from tropics. Indian J Med Spec 2022;13:143-9

How to cite this URL:
Gulati S, Jagtap AB, Porwal YC, Kathuria P, Chikara A. SARS CoV-2-related multisystem inflammatory syndrome in adults: An observational case series from tropics. Indian J Med Spec [serial online] 2022 [cited 2022 Nov 26];13:143-9. Available from: http://www.ijms.in/text.asp?2022/13/3/143/350774




  Introduction Top


Since the beginning of the pandemic, coronavirus disease 2019 (COVID-19) has thrown challenges to clinicians in managing the disease and its complications. The extrapulmonary multisystemic manifestations have been recognized in children as a multisystemic inflammatory syndrome (MIS-C).[1] A similar presentation is being reported in adults lately.[2],[3] It is anticipated that heterogenous presentations of hyperinflammatory multisystemic syndrome may create confusing clinical scenarios in febrile patients, especially in tropical countries. The prevalent tropical infectious diseases often present with multisystemic manifestations similar to those of MIS-A. Besides, co-infections may further complicate the diagnostic process. A high index of suspicion may be required to recognize and initiate lifesaving therapies in multisystem inflammatory syndrome of adults (MIS-A). The aim of the present article is to sensitize the readers to MIS-A so that this life-threatening disorder is not missed. Herein we present a case series of five patients, with hyper-inflammatory syndrome who fulfilled the criteria for clinical definition of MIS-A.


  Methodology Top


A series of five cases of MIS-A, in tropical settings, is presented. The quantitative and qualitative data is presented as median ± interquartile range (IQR) and as frequencies, respectively. The quantitative and qualitative data are compared among patients with or without tropical infections with the help of Mann–Whitney and Fisher exact test. The statistical data analysis and visualization have been done with the help of freely available R software version 4.1.0.

Case report 1

An obese18-year-old female presented with low-grade fever associated with bilateral lower limb swelling, weakness, body ache, painful swelling in neck and difficulty in swallowing and speech for 10 days. Besides, she complained of 2–3 episodes of vomiting along with dull aching diffuse abdominal pain a day before presentation. There was a significant past history of cervical lymph node tuberculosis. There was no history suggestive of recent COVID-19 infection or contact. On presentation, the patient was dehydrated and hypotensive. Her peripheral arterial saturation was 95% at room air. Apart from palpable bilateral level 3 and 4 cervical lymph nodes and mild abdominal tenderness, other examination findings were normal. Laboratory findings have been summarized in [Table 1]. Her inflammatory biomarkers were significantly raised and COVID-19 serology was positive. All other infectious causes of fever were ruled out by relevant investigations. She was started on intravenous broad-spectrum antibiotics along with fluid boluses followed by inotropes and hydrocortisone. Her hemodynamic status improved along with gradual regression of cervical lymph nodes. The inflammatory biomarkers also declined along with clinical improvement. A diagnosis of MIS-A was entertained in view of hyperinflammatory fever with multisystemic involvement along with evidence of recent COVID-19 infection. She was discharged and remains under our follow-up.
Table 1: Comparative investigative profile of multisystem inflammatory syndrome of adults patients

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Case report 2

A 54-year-old female presented with low-grade fever, diffuse chest pain, abdominal discomfort, nausea, and generalized weakness for 10 days. She was a diagnosed case of hypothyroidism on regular hormonal supplementation for the last 5 years. Significantly, she had a positive contact history with COVID-19 4 weeks back, but there was no history suggestive of recent acute COVID-19 infection. On presentation, the patient was hypotensive, had normal peripheral arterial saturation at room air and had mild diffuse abdominal tenderness. Results of laboratory investigations are summarized in [Table 1]. Electrocardiogram revealed ST-segment depression and T wave inversions in chest leads. Troponin I levels were also raised (3.2 ng/ml). A provisional diagnosis of acute coronary syndrome was made in the emergency room and she was initiated on anti-platelets, hypolipidemic, heparin, and inotropes. A hyperinflammatory state was also suspected and an appropriate work up was planned. There was an improvement in hemodynamic status of the patient along with normalization of electrocardiographic findings. However, she became hypoxic with worsening kidney function tests. Her inflammatory biomarkers were significantly raised and COVID-19 serology was positive. All other infectious causes of fever were ruled out by relevant investigations. She was started on oral methylprednisolone (MP) and anticoagulants. Thereafter, a rapid improvement in clinical parameters was recorded with normalization of peripheral arterial oxygen saturation and biochemical and hematological parameters. A diagnosis of MIS-A was entertained in view of hyperinflammatory fever with multisystemic involvement along with evidence of recent COVID-19 infection. She was discharged and remains under our follow-up.

Case report 3

A 74-year-old female presented with a history of fever, breathlessness, vomiting, and diffuse dull aching abdominal pain for 10 days. Significantly, she had received the first dose of COVID-19 vaccine (COVISHIELD-Astra Zeneca (ChAdOx 1 nCoV-19) about a month back. She had received antitubercular therapy for pulmonary tuberculosis 35 years back. There was no history suggestive of recent COVID-19 infection or contact. On presentation, the patient was tachypneic, normotensive and had tachycardia. The patient was hypoxic and was maintaining a peripheral arterial oxygen saturation of 94% with oxygen at 6 L/min. Clinical examination revealed bilateral basal crepitations, diffuse abdominal tenderness, and bilateral pedal edema. Chest X ray at the time of presentation was normal. As the ultra-sonogram revealed nonruptured right-sided subcapsular liver abscess, intravenous metronidazole and ceftriaxone were started. A contrast enhanced computed tomography (CECT) abdomen revealed a sub-capsular liver abscess in segments VI and VII along with right hepatic vein and infra-vena cava thrombosis. Results of laboratory investigations are summarized in [Table 1]. Her inflammatory biomarkers were significantly raised, and COVID-19 serology was positive. The patient was started on oral MP and anticoagulants in view of hyper-inflammatory status. A CECT chest, planned subsequently to rule out pulmonary embolism, was normal. There was a rapid improvement in clinical status of the patient with normalization of peripheral arterial oxygen saturation, inflammatory biomarkers, and hematological parameters. A diagnosis of MIS-A was entertained in view of hyperinflammatory fever with multisystemic involvement along with evidence of recent COVID-19 infection. However, along with a positive COVID-19 serology, our patient also had a right lobe liver abscess. The patient was discharged and remains under our follow-up.

Case report 4

A 65-year-old female presented with fever, breathlessness, nonproductive cough, vomiting, and abdominal pain. There was no history suggestive of recent COVID-19 infection or contact. She has been taking thyroid hormone supplementation for hypothyroidism for 5 years. On presentation, the patient was normotensive, tachypneic, hypoxic and had tachycardia. Peripheral arterial oxygen saturation was 85% at room air. Systemic examination revealed diffuse abdominal tenderness along with bilateral infra-axillary crepitations. A chest X ray was suggestive of right middle zone consolidation. A subsequent contrast enhanced CT chest revealed diffuse ground-glass opacities in left lung along with consolidation, pleural effusion and bronchiectatic changes in right lung. A cavity of size 2 cm × 2.2 cm and wall thickness of 6 mm anterior segment of left upper lobe was also observed. The laboratory parameters have been summarized in [Table 1]. The patient was initiated on broad-spectrum intravenous antibiotics along with other supportive treatment. However, there was a rapid worsening in clinical status of patient with an increase in oxygen requirement from 4 to 10 L/min. The inflammatory biomarkers were also raised along with a positive COVID serology. MP pulses were started along with oral anticoagulants, in view of the hyperinflammatory status. MP pulses were followed by oral steroids. There was a rapid improvement in clinical status with a decline in oxygen requirements along with normalization of hematological parameters. Subsequently, sputum examination for acid–fast bacilli was positive. There was a further improvement after starting antitubercular therapy. The patient was weaned off oxygen and was discharged home. A diagnosis of pulmonary tuberculosis was made. However, a diagnosis of MIS-A was also entertained in view of multisystemic hyperinflammatory state along with evidence of recent COVID-19 infection.

Case report 5

A 28-year-old female presented with fever and multiple episodes of generalized clonic and tonic seizures for the past 1 month. This was associated with complaints of insomnia, agitation, screaming episodes, and decreased speech. She had a past history of having poliomyelitis at the age of 8 years with residual paralysis in the left lower limb. There was no history suggestive of recent COVID-19 infection or contact. On presentation, the patient was normotensive and had normal peripheral arterial oxygen saturation. Significantly she was not following verbal commands and had a vacant stare with a left red eye suggestive of nonpurulent conjunctivitis. Systemic examination was noncontributory except for a left foot drop. Laboratory parameters have been summarized in [Table 1]. She was started on empirical treatment for febrile encephalopathy with broad-spectrum antibiotics, antimalarials, and intravenous acyclovir. Subsequently, as the cerebrospinal fluid evaluation returned, normal acyclovir was stopped. Contrast enhanced magnetic resonance imaging (MRI) head was suggestive of Calcified right frontal granuloma without perilesional edema. The inflammatory biomarkers were raised along with a positive COVID serology. MP pulses were started along with oral anticoagulants, in view of the hyper-inflammatory status. MP pulses were followed by oral steroids. There was a rapid improvement in clinical status with improvement in neuropsychiatric manifestations and a decline in inflammatory biomarkers. The blood culture sensitivity confirmed  Salmonella More Details Typhi growth. Malaria, leptospira, scrub typhus, and dengue serologies were negative. Hence, the antibiotics were changed as per the culture sensitivity report. Significantly, the patient developed left upper lid retraction and proptosis during her hospitalization. A cranial nerve examination at this point of time was normal. There was no evidence of central venous thrombosis on evaluation of MRI head. A thyroid function test was suggestive of thyrotoxicosis and she was promptly started on anti-thyroid medications along with beta-blockers. Thyrotoxicosis and/or Salmonella Typhi could explain the neurological symptoms and signs of our patient, however, there was a coexisting multisystemic hyper-inflammatory state on background of a positive COVID-19 serology. Hence, a diagnosis of MIS-A was also entertained. The patient was discharged and remains under our follow-up.


  Results Top


All the patients in our case series were females and their median age was 54 years (IQR = 28–65), with a range of 18–74 years. One patient was obese and two other patients had hypothyroidism as comorbidities. The bar plot depicting the heterogeneous clinical presentations is presented in [Figure 1]. Three of the patients in the present series also had other tropical infections (pulmonary tuberculosis, liver abscess, and typhoid fever) along with COVID-related MIS-A. The difference in various systems involvement in MIS-A patients with or without tropical infections was not statistically significant (Fisher exact test). The odds ratios (OR) for respiratory and renal systems involvement in MIS-A with tropical infections were 1.73 and 0.58, respectively. High inflammatory markers (C-reactive protein [CRP], ferritin and interleukin [IL] 6), hematological abnormalities (lymphopenia, neutrophilia, and thrombocytopenia) and deranged D Dimer levels were documented in all the patients. Even though echocardiography could not be done for our patients, NT proBNP levels were markedly elevated in 100%. Box plots in [Figure 2] present the distribution of high inflammatory markers and deranged hematological parameters. The various hematological parameters (total leucocyte counts, absolute neutrophil counts, absolute lymphocyte counts, and platelet counts), inflammatory markers (CRP, NT proBNP, and serum albumin) and liver transaminase (SGOT and SGPT) were compared between MIS-A patients with and without tropical infections by Mann Whitney test. No significant differences were found between these laboratory parameters. All the patients were started on broad-spectrum antibiotics and oral anticoagulants. Inotropic support, fluid boluses, and specific therapies for tropical infections were provided wherever indicated. Other than the first patient, who was started on hydrocortisone, all others were initiated on MP pulses or oral MP. Second and third patients received oral MP and the remaining received 500-1 g MP pulse for 3 days followed by 80 mg/day and 40 mg/day MP for 3 days and 4 days, respectively. The fifth patient was also managed for thyrotoxicosis. All the five patients improved on treatment and were discharged home.
Figure 1: Bar plots highlighting heterogenous clinical presentations. All the patients presented with fever with four (80%) of them having abdominal complaints (nausea, vomiting, and abdominal pain/discomfort). One patient (20%) had mucocutaneous involvement in the form of nonpurulent conjunctivitis. Breathlessness and/or hypoxia was observed in three (60%) patients. Neurological manifestations (seizures) were seen in one (20%) and two patients (40%) presented to the hospital with shock. Two patients (20%) developed azotemia during the course of hospitalization. Hematological abnormalities (lymphopenia, neutrophilia, and thrombocytopenia), very high NT proBNP, and deranged D Dimer levels were documented in all the patients

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Figure 2: Box plots for TLC, Platelet, C-reactive protein, NT proBNP, Ferritin and IL 6 distributions in MIS-A patients of our series. The median (interquartile range) TLC, Platelet, C-reactive protein, Ferritin, interleukin 6 and NT proBNP were 20,700 (15,900–28,000), 84,000 (55,000–92,000), 48 (48–134) mg/L, 580 (512.5–637.9) mcg/L, 161.4 (118.2–204.2) pg/ml and 5173 (5000–5578) pg/ml, respectively

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  Discussion Top


A multisystem inflammatory syndrome, similar to macrophage activation syndrome (MAS), Kawasaki disease and toxic shock syndrome, was being reported in children since the very beginning of COVID-19 pandemic.[1] As the pandemic progressed, Western countries have also reported a similar syndrome in adults.[2],[3] The exact incidence and etiopathogenesis of this multisystemic inflammatory presentation are unknown. For a while, a clinical case definition for MIS-A was adapted from that of MIS-C, so that this clinical entity is not missed.[3] Lately, the Centers for Disease Control and Prevention has updated the case definition based on certain clinical and laboratory criteria.[4] Moreover, not many cases of MIS-A have been reported from tropical countries so far. Hence, this case definition needs to be validated in tropical settings. We present here a series of five cases who presented to a tertiary hospital of Delhi with hyperinflammatory fever, soon after the peak of COVID cases was settling down.

All our patients were females with a median age of 54 years. Davogustto et al. have previously reported that out of 15 MIS-A patients, 66.7% (10/15) were male, and 33.3% (5/15) were females.[2] The mean age reported in one series of 51 cases is 29.4 years and median age reported in another of 15 cases is 45.1 years.[2],[5] The difference in age profiles in all these series indicates that MIS-A may involve any age group. As far as gender is concerned, our series was very small to bring out any notable differences.

All of these hospitalized patients had positive COVID serology with no history of any past acute illness attributable to SARS-CoV infection. Hence, a gap between acute SARS-CoV infection and the hyperinflammatory multisystemic presentation cannot be determined in our series. An average gap of 2–5 weeks has been documented between acute infection and MIS-A by Morris et al.[3] The mean time interval between positive polymerase chain reaction results to symptoms of MIS in their series was 31.25 ± 13.03 days. Similarly, Davogustto et al. have also documented median interval between COVID-19 and MIS-A admissions to be 23 days (IQR-16–24.5 days).[2] When compared to adults, this difference may not be apparent in children as the acute illness is by and large mild or asymptomatic.[1] It may be noted that in adults with severe acute illness, the hyperinflammatory state may closely follow the acute illness and may be clinically inseparable. In fact, Davogustto et al. reported that 60% of the MIS-A patients in their series had overlapping acute COVID-19 symptoms.[2] Thus, the possibility of MIS-A in acute COVID-19 patients should be always suspected so that lifesaving treatment may be initiated in the optimal time window.

Hypothyroidism and obesity were found in 40% and 20% of our patients, respectively, as a comorbidity. All the patients with comorbidities had a favorable outcome in our series. In comparison, Davogustto et al. reported comorbidities (hypertension, diabetes, obesity, coronary artery disease, cancer, and chronic kidney disease) in 66.7% of the patients. All of these patients survived.[2] However, more data is needed to determine the effect of comorbidities on the severity and outcome of MIS-A.

These patients had a heterogeneous multisystemic presentation, with varied involvement of gastrointestinal, renal, cardiac, mucocutaneous, respiratory, and hematological systems. Fever was present in 100% of the patients in our series in comparison to 80.4% in another.[5] Most common complaints in our series were abdominal (80%). Respiratory involvement was next common, with 60% of them presenting with breathlessness and/or hypoxia. Azotemia was noted in 40% of patients. Notably, 40% were hypotensive on presentation and required resuscitation with fluid boluses and inotropic support. Neurological and mucocutaneous involvements were not very frequent and were seen only in 20% of the patients. Echocardiography was not done, but all the five cases (100%) had very high NT proBNP levels pointing toward a possible myocarditis. All the patients (100%) had hematological involvement in the form of neutrophilia, lymphopenia and thrombocytopenia. Bastug et al. have reported 2 patients and they included another 49 patients reported till February 2021 to analyze demographic and clinical characteristics of MIS-A.[5] They concluded that cardiovascular system was most frequently involved (82.4%) in the form of global hypokinesis and decreased left ventricular ejection fraction. This was followed by gastrointestinal symptoms in 72.5% of patients. Dermatological, respiratory, conjunctival involvement, and lymphadenopathy were seen in 54.9%, 39.2%, 35.3%, and 17.6% of patients, respectively. Notably, vasopressor support was required in 44% of these 51 patients. Davogustto et al. also reported that most commonly gastrointestinal system was involved (80%) in their series. This was followed by the hematological and renal involvement (66.7%). Cardiovascular and respiratory systems were involved in 53.3% of the patients. Mucocutaneous and neurological systems were involved in just one patient each out of 15 reported. Almost one-third of the patients required intensive care unit (ICU) care for vasopressor support, hemodynamic monitoring or noninvasive ventilator support in his series.[2] On the basis of these observations, it may be concluded that there is a heterogeneous multisystemic involvement with fever in MIS-A with gastrointestinal, hematological, and cardiac involvements seen most commonly. Such a febrile multisystemic presentation of MIS-A may be easily confused with that of any tropical infection. A significant number of patients may be critically ill on presentation and may require ICU support. Different phenotypes have been noticed in children according to their ages, with mucocutaneous involvement common in younger children and myocarditis and gastrointestinal symptoms more common in elder adolescents.[6] Our series, along with others, reiterates that an adult phenotype of multisystemic inflammatory syndrome, just as that of adolescents, may have cardiac and gastrointestinal involvement more commonly than other systems.

Documentation of elevated levels of any 2 inflammatory markers is a must to support the diagnosis of MIS-A.[4] The median (IQR) CRP, Ferritin, IL6 and NT proBNP in our case series were 48 (48–134) mg/L, 580 (512.5–637.9) mcg/L, 161.4 (118.2–204.2) pg/ml and 5173 (5000–5578) pg/ml, respectively. Other than these, D Dimer levels were also significantly raised [Table 1]. These remarkably raised inflammatory markers (CRP, IL6, and ferritin) support a diagnosis of MIS-A in our patients. Febrile patients with or without diagnosed tropical infections who have atypical natural histories, fail to respond to specific therapies and have very high inflammatory markers along with extreme values of NT proBNP should be evaluated for MIS-A.

Due to the paucity of MIS-A treatment guidelines, clinicians have extrapolated the experience gained in managing multisystem inflammatory syndrome in children to MIS-A. Besides supportive therapy, all patients in our series were managed with steroids (MP pulses, hydrocortisone, or oral MP) along with anticoagulants. All of our patients improved on treatment and were discharged home. The available treatment modalities have been utilized variably in different case series and reports. Bastug et al. reported that steroids, intravenous immunoglobulin, and tocilizumab were used in 60.8%, 37.3%, and 13.7% of patients, respectively, in their series.[5] Another series reported that immunosuppressives were employed to manage 26.7% of the MIS-A patients.[2] Randomized controlled trials will be needed to deduce treatment algorithms, preferably according to disease severity, to optimally manage these patients. Patients with tropical infections who also have MIS-A should be offered these immunomodulatory therapies along with specific antimicrobials as a life-saving measure.

All of these patients fulfilled the case definition of MIS-A, however, three of them also had other tropical infections. One may argue that the presence of tropical infections may favor a diagnosis of MAS rather than that of MIS-A. However, we argue that co-presence of tropical infections and a hyperinflammatory state in a patient with evidence of recent SARS-CoV infection should not rule out a diagnosis of MIS-A. Though MAS and MIS-A are both hyperinflammatory states, they have very fine lines of distinction. It might be possible to differentiate them on the basis of certain clinical and laboratory parameters as outlined recently by Poniecka and Smolewska.[7] The presence of prominent respiratory and abdominal symptoms along with very high levels of CRP, NT proBNP, and lymphopenia in the presence of positive SARS-CoV serology favor a diagnosis of MIS-A in our patients.[7] Our case series underscores the fact that tropical infections may occur along with MIS-A. Hence, the case definition should be revised accordingly. Such a revision will be extremely relevant for settings where probability of coexistence of two conditions is high due to high background rate of tropical infections. The impact of such a coexistence on the clinical presentation and immunopathogenesis of the disease needs to be explored further. We could not elicit any significant difference in clinical presentation and laboratory parameters between MIS-A patients with and without tropical infections.

A Brighton Collaboration case definition for multisystem inflammatory syndrome in children and adults (MIS-C/A) following SARS-CoV-2 vaccination has been proposed so as to monitor this entity as an adverse event following immunization.[8] The third reported case in our series presented with fever, breathlessness, vomiting, and diffuse dull aching abdominal pain for 10 days. This patient was subsequently diagnosed as having liver abscess. A liver abscess, in all likelihood, will present with diffuse abdominal pain and tenderness if it has been complicated with a rupture. We had diligently ruled out a rupture with the help of clinical examination and supportive radio-imaging findings. Hence, we hypothesize that the abdominal complaints in our patient were due to MIS-A rather than rupture of liver abscess. Subsequently, this patient showed remarkable improvement with supportive antibiotics and immunosuppressives. This patient met Brighton Collaboration's level 1 diagnostic certainty of MIS-A, postvaccination. Lymphopenia, deranged NT proBNP levels along with inflammatory fever were against a possibility of thrombosis with thrombocytopenia syndrome due to SARS CoV 2 vaccination.[9],[10]

The fifth patient was an interesting case highlighting the possibility of variable and heterogenous presentation of MIS-A along with Salmonella Typhi infection. Hyper-inflammatory fever, nonpurulent conjunctivitis, positive SARS CoV2 serology, and high NT proBNP levels soon after a recent COVID peak supported the diagnosis of MIS-A. Interestingly, this patient also developed thyrotoxicosis. The THYROCOV study had previously shown that the cytokine storm induced by SARS CoV 2 infection may have led to thyrotoxicosis in 20.2% of the study COVID patients.[11] Higher IL 6 levels were associated with thyrotoxicosis with an OR of 3.25 (95% confidence interval 1.97–5.36).[11] We hypothesize that the hyperinflammatory state may have triggered thyrotoxicosis in our MIS-A patient just as in acute SARS CoV 2 infection.

Strengths and limitations

The small number of patients is the biggest limitation of our series. Some bias may also have affected our findings because of all our patients being females. A complete follow-up was desirable in order to study the chronic implications of MIS-A. However, our study is the first to stress the importance of not missing a diagnosis of MIS-A in patients with tropical infections. Nonutilization of immunosuppressives in such a setting, along with other specific therapies, may have disastrous consequences.


  Conclusions Top


Multisystem inflammatory syndrome of adults has a heterogeneous clinical presentation. The cardiovascular and gastrointestinal systems get involved most commonly. High index of suspicion is required to diagnose MIS-A, especially in settings where there is a high incidence of tropical infections. Any febrile illness in tropics with prominent abdominal, cardiac and hematological manifestations especially if associated with high inflammatory markers and serological evidence of recent COVID-19 infection should raise suspicion for MIS-A. In fact, coexistence of tropical infections and MIS-A should not discourage an aggressive management plan with immunosuppressives. A diagnosis of MIS-A should not be missed in any febrile patient, with or without tropical infections, as utilization of relevant immunosuppressive therapy may be lifesaving in such instances.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347-58.  Back to cited text no. 1
    
2.
Davogustto GE, Clark DE, Hardison E, Yanis AH, Lowery BD, Halasa NB, et al. Characteristics associated with multisystem inflammatory syndrome among adults with SARS-CoV-2 infection. JAMA Netw Open 2021;4:e2110323.  Back to cited text no. 2
    
3.
Morris SB, Schwartz NG, Patel P, Abbo L, Beauchamps L, Balan S, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection – United Kingdom and United States, March-August 2020. MMWR Morb Mortal Wkly Rep 2020;69:1450-6.  Back to cited text no. 3
    
4.
Multisystem Inflammatory Syndrome in Adults (MIS-A) Case Definition Information for Healthcare Providers. Available from: https://www.cdc.gov/mis/mis-a/hcp.html. [Last accessed on 2021 Jul 15].  Back to cited text no. 4
    
5.
Bastug A, Aslaner H, Aybar Bilir Y, Kemirtlek N, Gursoy FM, Bastug S, et al. Multiple system inflammatory syndrome associated with SARS-CoV-2 infection in an adult and an adolescent. Rheumatol Int 2021;41:993-1008.  Back to cited text no. 5
    
6.
Chow EJ. The multisystem inflammatory syndrome in adults with SARS-CoV-2 infection-another piece of an expanding puzzle. JAMA Netw Open 2021;4:e2110344.  Back to cited text no. 6
    
7.
Poniecka A, Smolewska E. A fine line between macrophage activation syndrome and multisystem inflammatory syndrome in children – Literature review based on two case reports. Reumatologia 2021;59:47-57.  Back to cited text no. 7
    
8.
Vogel TP, Top KA, Karatzios C, Hilmers DC, Tapia LI, Moceri P, et al. Multisystem Inflammatory Syndrome in Children and Adults (MIS-C/A): Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2021;39:3037-49.  Back to cited text no. 8
    
9.
Canadian Case Definition for Thrombosis with Thrombocytopenia Syndrome Following Vaccination. Available from: https://www.princeedwardisland.ca/sites/default/files/publications/case_definition_for_thrombosis_with_thrombocytopenia_syndrome_following_vaccination.pdf. [Last accessed on 2021 Jul 16].  Back to cited text no. 9
    
10.
Proposed Brighton Collaboration Process for Developing a Standard Case Definition for Study of New Clinical Syndrome X, as Applied to Thrombosis with Thrombocytopenia Syndrome (TTS). Available from: https://brightoncollaboration.us/wp-content/uploads/2021/04/TTS-Case-Finding-and-Definition-Process.v9.0-April-16-202115853.pdf. [Last accessed on 2021 Jul 16].  Back to cited text no. 10
    
11.
Lania A, Sandri MT, Cellini M, Mirani M, Lavezzi E, Mazziotti G. Thyrotoxicosis in patients with COVID-19: The THYRCOV study. Eur J Endocrinol 2020;183:381-7.  Back to cited text no. 11
    


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