Title : Rapid resolution of post-covid-19 inflammatory syndrome in an adult with targeted inhibition of interleukin-1b
Abstract:
PURPOSE:
Multisystem Inflammatory Syndrome (MIS) is a severe inflammatory response, that occurs days to weeks following the infection of SARS-CoV2, the virus responsible for COVID -19. Initially known in children and named MIS-C, recently several cases of MIS in adults have been reported to CDC, leading to the recognition of a new disease MIS in adults (MIS-A). The current treatment options include high-dose steroids, IVIG, and immunosuppressive therapy. However, the pharmacologic approach remains limited to case reports and pending official guidelines to treat cases with MIS-A.
We present a case of an adult patient who had a severe inflammatory state following COVID-19 infection, who was treated with IL-1 antagonist therapy with a successful outcome.
CASE PRESENTATION:
Our patient is a 38-year-old male with a history of asthma, and Type-2 Diabetes Mellitus who presented with fever, dyspnea, productive cough, and myalgias. He was previously admitted for COVID-19 pneumonia and was discharged after treatment completion. Soon after discharge, he started developing high-grade fever and worsening dyspnea.
On presentation, labs revealed significantly elevated inflammatory markers (Table 1), however infectious work-up was negative. Despite the initiation of broad-spectrum antibiotic therapy, he continued to deteriorate. In the light of recent SARS CoV-2 infection, patient was suspected to have post-COVID-19 multisystem inflammatory syndrome in adults (MIS-A) (Table 2). He was started on Interleukin-1B antagonist therapy, Anakinra. This resulted in marked improvement in his clinical symptoms co-relating to an almost 50% decrease in his inflammatory markers within a few days. His dyspnea and mental status improved, strength returned, and myalgias resolved over a course of 1-2 weeks.
|
Lab findings |
Initial labs |
After treatment |
|
WBC count (4000-9000/uL) |
25,000/uL |
6,300/uL |
|
CRP (<8.0 mg/dL) |
187.4 mg/L |
6.8 mg/L |
|
ESR (0-15 mm/hr) |
122 mm/hr |
87 mg/dL |
|
Ferritin (24 - 336 ng/mL) |
12740ng/mL |
1772 ng/mL |
|
D-dimer (<0.5 mg/dL) |
15.17 mg/L |
6.19 mg/dL |
|
Fibrinogen (172-483 mg/dL) |
789 mg/dL |
428 mg/dL |
|
Pro-calcitonin (<0.5 ng/ml) |
6.2 ng/ml |
0.82 ng/ml |
|
SARS CoV-2 PCR and IgG |
Positive |
- |
Table 1. Laboratory findings in the presented case
|
Case Definition of MIS-A |
Present in this case |
|
Patient aged ≥21 years hospitalized for ≥24 hours |
Yes |
|
Exclusion of alternative diagnosis (e.g., bacterial sepsis, exacerbation of a chronic medical condition) |
Yes |
|
Fever (≥38.0 C) for ≥24 hours prior to hospitalization or within the first THREE days of hospitalization |
Yes |
|
Clinical Criteria |
|
|
|
|
|
Primary clinical criteria |
|
|
Severe cardiac illness (myocarditis, pericarditis, coronary artery dilatation/aneurysm, or new-onset right or left ventricular dysfunction (LVEF<50%), 2nd/3rd degree A-V block, or ventricular tachycardia) |
No |
|
Rash and non-purulent conjunctivitis |
No |
|
|
|
|
Secondary clinical criteria |
|
|
New-onset neurologic signs and symptoms (encephalopathy, seizures, meningeal signs, or peripheral?neuropathy) |
Yes |
|
Shock or hypotension not attributable to medical therapy |
No |
|
Abdominal pain, vomiting, or diarrhea |
No |
|
Thrombocytopenia (platelet count <150,000/ microliter) |
No |
|
|
|
|
Laboratory evidence |
|
|
Elevated levels of at least TWO of the following: C-reactive protein, ferritin, IL-6, erythrocyte sedimentation rate, procalcitonin |
Yes |
|
A positive SARS-CoV-2 test for current or recent infection by RT-PCR, serology, or antigen detection |
Yes |
Table 2. Centers for Disease Control and Prevention Criteria for Multisystem Inflammatory Syndrome in Adults (MIS-A)
CONCLUSION:
We report a case of post-COVID-19 inflammatory syndrome which displayed robust clinical improvement with anakinra. Interleukin-1B (IL-1B) has been identified as one of the key cytokines mediating the hyper-inflammatory state associated with COVID-19 infection. Anakinra is a recombinant IL-1B receptor antagonist that has been used as a pharmacotherapeutic option in children with MIS-C, although there is a lack of data demonstrating its efficacy.
Our report describes rapid improvement of post-COVID-19 inflammatory syndrome with anakinra monotherapy in an adult patient. This report serves as evidence of another option to treat post-COVID-19 inflammatory in adults, especially in patients who may have a contraindication or could be intolerant to steroid therapy, such as our patient who had uncontrolled Diabetes Mellitus.
REFERENCES:
Feldstein LR, Rose EB, Horwitz SM, et al.: Multisystem inflammatory syndrome in US children and adolescents. New England Journal of Medicine. 2020, 23:334-46. 10.1056/NEJMoa2021680
Brown LM, Semler MW, Hansen M, Person AK, Kelly SG: Multisystem inflammatory syndrome in an adult with COVID-19. Infectious Diseases in Clinical Practice (Baltimore, Md. 2021, 29:174. 10.1097/IPC.0000000000000996
Centers for Disease Control and Prevention. Multisystem inflammatory syndrome in adults (MIS-A): case definition.
Cogan E, Foulon P, Cappeliez O, et al.: Multisystem inflammatory syndrome with complete Kawasaki disease features associated with SARS-CoV-2 infection in a young adult. A case report. Frontiers in Medicine. 2020, 14:428. 10.3389/fmed.2020.00428
Cattaneo P, Volpe A, Cardellino CS, et al.: Multisystem inflammatory syndrome in an adult (MIS-A) successfully treated with anakinra and glucocorticoids. Microorganisms. 2021, 28:1393. 10.3390/microorganisms9071393
Aggarwal A, Cohen E, Figueira M, et al.: Multisystem Inflammatory Syndrome in an Adult With COVID-19—A Trial of Anakinra: A Case Report. Infectious Diseases in Clinical Practice (Baltimore, Md. 2021, 29:420.
Keywords: COVID-19, Multisystem Inflammatory Syndrome, Interleukin 1-B, Anakinra
