ABSTRACT
Background: Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory, multisystem syndrome temporally associated with SARS-CoV-2, is a rare but serious complication of SARS-CoV-2 infection in children that typically occurs 2-6 weeks after SARS-CoV-2 infection. The pathophysiology of MIS-C is unknown. MIS-C, first recognized in April 2020, is characterized by fever, systemic inflammation, and multi-system organ involvement. Post-vaccination adverse effects have increased with COVID-19 vaccinations, and MIS linked to immunization with COVID-19 vaccines has also been observed. Case Report: An 11-year-old Chinese girl presented with a high-grade fever, rash, and dry cough for 2 days. She had her 2nd SARS-CoV-2 inactivated vaccination dose five days before hospital admission. On day 3 & 4, she experienced bilateral conjunctivitis, hypotension (66/47â mmHg), and a high CRP level. She was diagnosed with MIS-C. The patient's condition deteriorated rapidly, necessitating intensive care unit admission. The patient's symptoms improved after intravenous immunoglobulin, methylprednisolone, and oral aspirin therapy. She was discharged from the hospital after 16 days as her general condition, and laboratory biomarkers returned to normal. Conclusion: Inactivated Covid-19 vaccination might trigger MIS-C. Further research is needed to evaluate whether a correlation exists between COVID-19 vaccination and MIS-C development.
ABSTRACT
Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human coronavirus causing severe disease and mortality. MERS-CoV infection failed to elicit robust IFN response, suggesting that the virus might have evolved strategies to evade host innate immune surveillance. In this study, we identified and characterized type I IFN antagonism of MERS-CoV open reading frame (ORF) 8b accessory protein. ORF8b was abundantly expressed in MERS-CoV-infected Huh-7 cells. When ectopically expressed, ORF8b inhibited IRF3-mediated IFN-ß expression induced by Sendai virus and poly(I:C). ORF8b was found to act at a step upstream of IRF3 to impede the interaction between IRF3 kinase IKKε and chaperone protein HSP70, which is required for the activation of IKKε and IRF3. An infection study using recombinant wild-type and ORF8b-deficient MERS-CoV further confirmed the suppressive role of ORF8b in type I IFN induction and its disruption of the colocalization of HSP70 with IKKε. Ectopic expression of HSP70 relieved suppression of IFN-ß expression by ORF8b in an IKKε-dependent manner. Enhancement of IFN-ß induction in cells infected with ORF8b-deficient virus was erased when HSP70 was depleted. Taken together, HSP70 chaperone is important for IKKε activation, and MERS-CoV ORF8b suppresses type I IFN expression by competing with IKKε for interaction with HSP70.