Severe multisystem inflammatory syndrome in a vaccinated adult with COVID-19

  1. Vijairam Selvaraj ,
  2. Arkadiy Finn ,
  3. Michael Santos and
  4. Kwame Dapaah-Afriyie
  1. Division of Hospital Medicine, Department of Medicine, Warren Alpert Medical School at Brown University, Providence, Rhode Island, USA
  1. Correspondence to Dr Vijairam Selvaraj; vijairam.selvaraj@lifespan.org

Publication history

Accepted:17 Apr 2022
First published:26 Apr 2022
Online issue publication:26 Apr 2022

Case reports

Case reports are not necessarily evidence-based in the same way that the other content on BMJ Best Practice is. They should not be relied on to guide clinical practice. Please check the date of publication.

Abstract

The ability of SARS-CoV-2 to trigger hyperinflammatory response in children and adults is increasingly recognised. However, the detailed features that distinguish severe COVID-19-associated hyperinflammation from multisystem inflammatory syndrome in adults (MIS-A) is not yet known. We describe a young, vaccinated patient with no prior SARS-CoV-2 exposure who developed COVID-19 and MIS-A. We also provide a review of the current literature on MIS-A and COVID-19-associated hyperinflammation.

Background

COVID-19 continues to pose a global public health crisis. Yet, its full clinical and pathophysiological characterisation is still not clearly defined. In May 2020, multisystem inflammatory syndrome in children (MIS-C) was described.1 2 The illness was characterised by cardiac dysfunction, shock, severely elevated inflammatory markers and positive SARS-CoV-2 serology. In October 2020, an illness referred to as multisystem inflammatory syndrome in adults (MIS-A) was described.3 Recently, there have been a few case reports of multisystem inflammatory syndrome following SARS-CoV-2 vaccination (MIS-V).4 5 Here, we describe a unique case of a patient vaccinated against SARS-CoV-2, presenting with COVID-19 and MIS-A and provide a review of the current literature regarding this complex presentation.

Case presentation

A healthy man in his late 20s presented to the hospital after being found down unconscious. He tested positive for SARS-CoV-2, 3 weeks prior to admission. He endorsed cough, fevers and chills. He was unable to walk unassisted due to generalised weakness. He became increasingly tachypneic and lost consciousness. He was noted to become rigid and lost bladder continence. He had no prior history of seizures. He did not take any medications at home. He had received two doses of mRNA-1273 (Moderna) SARS-CoV-2 mRNA vaccine for SARS-CoV-2, 9 months prior to presentation. He did not receive a booster dose.

En route to the hospital, he developed supraventricular tachycardia with a heart rate of the 200 beats per minute on cardiac monitor. He was given 12 mg of intravenous adenosine with improvement in heart rate. At the time of admission, his temperature was 100.7F, heart rate 125 beats/min, BP 62/28 mm Hg and respiratory rate of 30 breaths/min. His body mass index was 44.85 kg/m2. His Glasgow Coma Scale was noted to be 3 and underwent endotracheal intubation for airway protection. Physical examination was remarkable for comatose state, mydriasis of pupils, and coarse, rhonchorous breath sounds throughout all lung fields. Conjunctivitis and skin rash were not identified. Extremities were cool to touch. Initial labs were notable for elevated lactate of 5.6 mEq/L, acute kidney injury, transaminitis and SARS-CoV-2 positivity (table 1). He was started on norepinephrine for management of shock and admitted to the medical intensive care unit. His urine drug screen was positive for fentanyl. CT scan of the chest showed low lung volumes with dependent bilateral airspace disease suspicious for atelectasis or aspiration.

Table 1

Lab values on the day of presentation, peak values and post intervention

Labs On presentation Peak value Post intervention
White blood cell count (3.5–11.0×109/L) 4.2 12.7 8.5
Platelets (150–400×109/L) 112 000 15 000 87 000
Aaspartate aminotransferase (10–42 IU/L) 56 2008 209
Alanine aminotransferase (6–45 IU/L) 114 1399 942
Ferritin (22–322 NG/ML) >16 500 >16 500 1707
C reactive protein (0–10 MG/L) 223.88 223.88 46.21
D dimer (0–230 NG/ML) 6692 12 574 3249
High-sensitive troponin (3–57 NG/L) 5298 11 295 1712
Creatine kinase (20–210 IU/L) 722 1337 174

Outcome and follow-up

He improved neurologically and was able to follow some commands although remained persistently weak due to critical illness myopathy. He remained on a gradual tapering regimen of methylprednisolone.

Discussion

Current adult models of COVID-19 disease typically involve three clinical phases. First, there is an initial viral response phase where patients mostly have mild constitutional symptoms, followed by a pulmonary phase where there is an overlap of host inflammatory response and viral replication effects. Lastly, there is a hyperinflammatory phase where the pathophysiology is driven by the host immune response. Such progression occurs within 1–2 weeks of SARS-CoV-2 infection.6 MIS-A may be a late sequela of the hyperinflammatory phase or a delayed inflammatory phase, driven by a dysregulated immune response or autoimmunity. Unlike MIS-A, COVID-19 hyperinflammatory syndrome (cHIS) does not have a defined clinical presentation and may exhibit a mix of features of severe COVID-19 disease, multi-inflammatory syndrome (MIS) and other known hyperinflammatory syndromes such as haemophagocytic lymphohistiocytosis, macrophage activation syndrome and cytokine release syndrome. Differentiation of severe COVID-19 infection and cHIS versus MIS remains a challenge.

The true incidence of MIS-A is not known. MIS-A is likely underdiagnosed due to overlapping symptoms with severe, acute biphasic COVID-19 disease and cHIS. cHIS is more difficult to define clinically and likely has a more heterogeneous presentation. Although both are similar in terms of fever, extremely elevated inflammatory markers and multiorgan dysfunction, they are clinically distinct syndromes. MIS-A likely has a more severe presentation, involving severe multiorgan failure, shock and cardiac involvement, additionally it typically occurs some time (1+ weeks) after the initial infection. The onset of cHIS is also heterogenous: it may be concurrent with COVID-19 or take more of a delayed course. MIS-A and cHIS should be considered on a spectrum of hyperinflammation concurrent with or following after SARS-CoV-2 infection. Table 2 details differences between severe COVID-19/cHIS and MIS-A.7–11 Differential diagnoses should also include Kawasaki disease, hemophagocytic lymphohistiocytosis, toxic shock syndrome, macrophage activation syndrome and severe Kawasaki shock. It is critical to distinguish MIS-A from alternative diagnoses as the clinical management can differ significantly. A thorough history and physical examination, laboratory workup and high clinical suspicion can provide a degree of clinical certainty.

Table 2

Differences between severe COVID-19/cHIS and MIS-A

Differences Severe COVID-19/cHIS MIS-A
cHIS, COVID-19 hyperinflammatory syndrome; MIS-A, multisystem inflammatory syndrome in adult.
Age Tend to be older patients Tend to be younger patients
Comorbidities Diabetes, hypertension, obesity Usually healthy, minimal comorbidities
Timing after initial SARS-CoV-2 exposure 1–2 weeks 2–5 weeks
Severity of SARS-CoV-2 infection Moderate to severe Asymptomatic or mild
Common clinical presentation Respiratory symptoms with thrombotic sequelae Gastrointestinal, cardiologic, neurologic symptoms
Diagnosis SARS-CoV-2 PCR tests SARS-CoV-2 serologic assays, PCR tests
Management Dexamethasone, remdesivir, tocilizumab, baricitinib Intravenous immunoglobulin, corticosteroids, anakinra, tocilizumab
Mortality Variable Low

Ethics statements

Patient consent for publication

Footnotes

  • Twitter @Vj235

  • Contributors VS was involved in obtaining consent and drafting the original document. AF revised the manuscript, did literature review and discussion. MS was involved in direct care of the patient, revised manuscript and edited tables and case presentation. KD-A supervised, reviewed and edited the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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