Fatal multisystem inflammatory syndrome in a 78-year-old adult after severe COVID-19 pneumonia during 2022 Omicron variant epidemic in Shanghai, China

Abstract

Multisystem inflammatory syndrome adult type (MIS-A) is a rare type of post-acute COVID-19 syndrome which more frequently occurred in younger population. Here we present a 78-year-old Chinese female, the oldest case reported, diagnosed with MIS-A who had severe SARS-CoV-2 infection. She was diagnosed with severe COVID-19 and experienced an unexpected sudden hemodynamic collapse in the recovery period within three weeks. Her platelet count was sharply dropped, accompanied with sustained cardiac, kidney and liver injury. She was diagnosed with MIS-A according to criteria established by Center of Disease Control and Prevention. Though her condition was improved under administrating with high dose of methylprednisolone and intravenous immunoglobulin, methylprednisolone was unable to withdraw till two weeks as her partial pressure of oxygen/fraction of inspiration oxygen ratio and platelet count dropped on the heels of decreasing dosage. Unfortunately, the patient’s condition gradually deteriorated with the development of severe nosocomial pneumonia. We presented this rare case in order to emphasize that MIS-A could occur in the elderly and the management of this population might be more difficult as the condition of the elderly with SARS-CoV-2 infection and MIS-A might be more severe.

Case presentation

Multisystem inflammatory syndrome (MIS) after respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is considered as a special type of post-acute coronavirus disease-19 (COVID-19) syndrome [1], usually occurred within 4 ± 3 weeks after polymerase chain reaction (PCR) test positive [2]. Though commonly occurred in children and adolescents, increasing cases of MIS in adults (MIS-A) has been reported [3], [4], [5], [6], [7], [8], [9], [10]. Here we present a case of fatal MIS-A in a 78-year-old female during 2022 Omicron variant epidemic in Shanghai, China.

The patient was admitted to hospital with SARS-CoV-2 PCR test positive, with a chief complaint of chest distress and shortness of breath for two weeks which aggravated with generalized fatigue, mild cough and allotriogeustia within three days before admission. On admission, her partial pressure of oxygen (PaO2) was only 66 mmHg and fraction of inspiration oxygen (FiO2) was 80 % with an oxygen mask, and chest computed tomography revealed typical features of viral pneumonia (Shown in Supplementary Fig. 1). She was then transferred to intensive care unit for further treatment.

Initial treatment includes nirmatrelvir/ritonavir, empirical antibiotics of meropenem and moxifloxacin, intravenous methylprednisolone (80 mg/d (∼1 mg/kg/day)), and supportive treatment. Repeated culture of her blood and sputum showed no growth of bacterial colony. Next generation sequencing of blood and alveolar lavage fluid sample revealed no common pathogen. Four days after treatment, her PaO2/FiO2 ratio was improved to 230–280 and methylprednisolone tapered to 40 mg/d (∼0.5 mg/kg/day).

Nevertheless, on the fifth day a sudden hemodynamic collapse occurred that her blood pressure dropped to 75/40 mmHg. After immediate resuscitation, her body temperature rose to 38.3 ℃ and she presented severe diarrhea. Meanwhile, blood biochemical assay revealed multisystem injury including surge in myocardial injury markers, serum creatinine and liver transaminase (shown in Supplementary Fig. 2). Besides, platelet count was sharply dropped and venous thrombus was found in her right lower extremity. The clinical course, change of her blood cell count and inflammatory cytokines was depicted in Fig. 1 . The patient was diagnosed with MIS-A and was administrated with intravenous methylprednisolone and immunoglobulin, and continuous renal replacement therapy was applied.

Fig. 1.

Overall clinical course (A), change of inflammatory cells (B, C), serum inflammatory biomarkers (D) and viral load (E). Dashed line indicates the date of shock, while arrow indicates critical clinical time points. Surges in CRP, PCT (B), IL-4, IL-17 IL-1β, IL-6 and IL-8 (D), and drops in platelet count (B) and Ct value after shock can be observed. * Lymphocyte count was displayed by its original value multiplying 100.

After her condition was stabilized for 4 days, her respiratory failure was deteriorated and platelet count dropped again on the heels of methylprednisolone taper. Therefore, she was kept treated with methylprednisolone 80 mg/day and immunoglobulin. Unfortunately, her blood and sputum culturing detected Acinetobacter Baumanii and Klebsiella pneumoniae indicating nosocomial infection. Eventually, she passed away due to severe pneumonia and multiple organ failure.

Discussion

We presented this fatal case of MIS-A in order to emphasize that the management of the elderly with SARS-CoV-2 infection and MIS-A might be more difficult to be controlled, as the elderly might be more vulnerable and outcome of might be poorer than the younger population.

The pandemic of COVID-19 has been lasting for about three years. According to report from World Health Organization, from 1st January 2020–31 th December 2021 the mortality associated with COVID-19 was 14.91 million globally, and 15,529 in China [11]. Although cases of severe condition caused by current dominant variant Omicron is scarce, surging reports of MIS after SAS-CoV-2 infection attract the attention of researchers.

First identified in April 2020, MIS seemed to happen more commonly to children. However, recent studies on MIS showed that MIS also occurred in 9.9 % of the infected adults age > 21 [12], and thus the diagnosis of adult type (MIS-A) was established. As previously reported and our case presented, MIS-A commonly occur during the period of recovery after SARS-CoV-2 infection. Typical symptoms of MIS-A include a sudden and massive inflammatory response in more than two extra-pulmonary systems, such as myocarditis, gastroenteritis, acute kidney injury and liver dysfunction.

According to previous study, the median age of patients with MIS-A after COVID-19 was 21, with inter-quartile range of 19–34 [13], showing that MIS-A more commonly occurs in young and middle aged adults. While cases of MIS-A in aged patients were emerging. Kerkerian et al. reported a 60-year-old male diagnosed with MIS-A showing conjunctivitis, lymphadenopathy and edema [14]; Boby et al. presented a case of 55-year-old female diagnosed as MIS-A with multiple ischemic strokes [15]; Hiroshi et al. presented a fatal case of 72-year-old male diagnosed as MIS-A with arterial thrombosis and ischemia [7]; Julius et al. reported a fatal case of 59-year-old female diagnosed as MIS-A with shock and multisystem failure [8]. And our present case of a 78-year-old female, to the best of our knowledge, is the oldest reported case diagnosed with MIS-A.

Notably, MIS-A in the elder patients seems to be more severe and fatal. According to literature, 3 out of 5 cases of MIS-A in the elder adults (age>50) were fatal, presenting as multisystem failure. Information of fatal cases of MIS-A are listed in Table 1 (detailed information was listed in Supplementary Table 1). We consider that the worse prognosis of MIS-A in the elderly could be explained from two aspects. On one hand, the elderly patients have worse general condition and compromised immune function, which render them vulnerable to viral and inflammatory attack. On the other hand, the elderly are prone to complications following anti-viral and anti-inflammatory treatment. Therefore, MIS-A should be paid attention to in the elderly after COVID-19 and the management of those elder patients should be specifically evaluated.

Table 1.

Reported deceased cases of MIS-A following COVID-19 infection.

Authors (year)	Demographics	Involved extra-pulmonary organ	Treatment
Y. Su, et al. (2022)	A 78-year-old female, Asian	Heart, liver, kidney, bowel	Methylprednisolone, immunoglobulin
Y. Elouardi, et al. (2022)	A 28-year-old female, Caucasian	Heart, liver, kidney	methylprednisolone, plasmapheresis
T. Nonaka, et al. (2022)	A 68-year-old male, Asian	Heart, liver, bowel	methylprednisolone, ECMO
	A 62-year-old male, Asian
K. Vannella, et al. (2021)	A 26-year-old male	Heart	Colchicine, ECMO
H. Grome, et al. (2021)	A male in 30 s	Heart, liver, kidney	Immunoglobulin, corticosteroids, ECMO
H. Kobe, et al. (2021)	A 72-year-old male	Heart, vessels	NA
M. Julius, et al. (2021)	A 59-year-old female, Caucasian	Liver, kidney	Hydrocortisone, plasmapherasis
S. Fox et al. (2020)	31-year-old female, African- American	Heart	NA
S. Morris et al. (2020)	46-year-old male, African-American	Heart, liver	NA

ECMO denotes extracorporeal membrane oxygenation.

Currently, treatment for MIS-A includes immunoglobulin and corticosteroids. However, such regimen might not be easily applicable to the elderly. Importantly, the dosage of corticosteroids is hard to be tapered in the melieu of worse general condition of the elderly. Early and sudden tapered dosage might not effectively suppress the overreacted inflammation, while prolonged use of corticosteroids could bring serious side effects that worsen prognosis. As shown in our case, platelet count drop immediately after the dosage of methylprednisolone was tapered, and prolonged high dose methylprednisolone impairs the immunity and predispose the patient to fatal nosocomial infection. Hence, management of MIS-A in the elderly could be more challenging, it is urgent to establish comprehensive management strategy as well as search for better treatment for the elderly against MIS-A.

Appendix A. Supplementary material

Supplementary material

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