Background: Cytokine release storm is the most fearsome complication associated with worse outcomes in COVID-19 patients with severe acute respiratory failure. In COVID-19 patients, interleukin-6 (IL-6) levels are significantly elevated. Blocking IL-6 preliminarily resulted in the improvement of this hyperinflammatory state. Objectives: To define if the serum level of IL-6 early tested after tocilizumab treatment could be useful to distinguish non-survivors from survivors in patients with severe respiratory failure due to COVID-19 pneumonia. Methods: This prospective cohort study was conducted at two referral hospitals for management of COVID-19 in Basilicata region, Italy: San Carlo Hospital, Potenza and Madonna delle Grazie Hospital, Matera. All consecutive patients with COVID-19 confirmed by RT-PCR testing of a naso-oropharyngeal swab. The enrollement period was from the 23rd of February to the 15th of August. 37 patients between all 124 underwent tocilizumab 8 mg/kg intravenously at baseline and after 24h. All patients were tested for serum IL-6, 24 hours before and 72 hours after tocilizumab infusion. Comparisons between survivors (Sv) and nonsurvivors (NSv) were performed. Results: 21 patients were discharged, while 16 patients died. The main clinical or laboratory differences (p < 0.001) between the two groups at baseline were mean diseases duration before ward admission and serum troponine levels. IL-6 was not different at baseline (p = 0.01), while 72 hours post-tocilizumab IL-6 serum levels were significantly higher in non-survivors than in survivors [(Sv 21.1%)vs(NSv 64%) p < 0.001)]. Serum IL-6 post-tocilizumab could be considered a good predictor to discriminate Sv from NSv. At multivariate stepwise analysis including disease duration at admission, baseline serum troponine levels and IL-6 post TCZ) were independent predictors of not survival Conclusion: Our data confirm the results of Quartuccio et al. In fact the highest burden of inflammation may be revealed by IL-6 levels after tocilizumab. Therefore repeated measurement of the serum level of IL-6 early after tocilizumab could be useful to distinguish non-survivors from survivors and support the choice of deeper targeting IL-6 in COVID-19 pneumonia. References: [1]Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020; 395(10229): 1033- 1034. [2]Toniati P, Piva S, Cattalini M, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in Brescia, Italy. Autoimmun Rev. 2020; 19:102568 [3]McGonagle D, Sharif K, O’Regan A, Bridgewood C. The role of cytokines including interleukin 6 in COVID19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020; 19(6):102537. [4]Chakraborty C, Sharma AR, Bhattacharya M, Sharma G, Lee SS, Agoramoorthy G. COVID19: consider IL6 receptor antagonist for the therapy of cytokine storm syndrome in SARS CoV2 infected patients. J Med Virol 2020 [5]Quartuccio L, Sonaglia A, Pecori D,et al. Higher levels of IL-6 early after tocilizumab distinguish survivors from nonsurvivors in COVID-19 pneumonia: A possible indication for deeper targeting of IL-6. J Med Virol.2020;92:2852–2856 Disclosure of Interests: None declared

Background:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology.Objectives:We report a case of multisystem inflammatory syndrome in children (MIS-C) in patient with SARS-CoV-2 infection and Enteropathogenic Escherichia coli (EPEC) sepsis due to acute enteritis, observed at end of December 2020 to a tertiary-care center (San Carlo Hospital), in Basilicata region (Italy).Methods:This healthy 12-year- old male patient was tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Clinical presentations was characterized by fever, abdominal pain, gastrointestinal complaints and evanescent rash. Laboratory values were remarkable for high levels of procalcitonin, C-reactive protein (CRP), D-dimers, B-type natriuretic peptide (BNP), and troponin. He also had low albumin levels. Autoantibodies tests were negative. Chest tomography showed ground-glass opacities in less than 25% of the lungs, small bilateral pleural effusion and increased cardiac area; abdominal tomography showed enlargement of the lymphnodes and ascites. Evaluation for other infectious etiologies showed molecular test positivity on fecal samples for EPEC E. coli. He received broad spectrum intravenous antibiotics (macrolids and quinolones and then carbapenems). On the seventh day the enteritis resolved and procalcitonin normalized, however he continued to have lymphopenia, thrombocytopenia, hypoalbuminemia, elevated levels of CRP, D-dimers, ferritin, troponin, and increased BNP. On the ninth day he was feverish again and developed severe cardiac and respiratory failure requiring advanced respiratory support and admission to the intensive care unit. He received IVIG (intravenous immunoglobulin at 2 g/Kg, glucocorticoids (Methylprednisolone 1mg/kg) and enoxaparin.Results:The patient was discharged asymptomatic at home after 28 days of hospital stay.Conclusion:We observed multisystem inflammatory syndrome in children (MIS-C) in a previously healthy patient with SARS-CoV-2 infection and E.coli sepsis, who became critically ill with multisystem involvement. In this case viral and bacterial infections could be considered as a double hit for the etiopathogenesis of MIS-C. The trend of procalcitonin was better than C-reactive protein for differentiating bacterial from non-bacterial phase of systemic inflammatory response syndrome (SIRS) in this critically ill child. Although the accuracy of both tests is moderate. Diagnostic accuracy could be enhanced by combining these tests with bedside clinical judgment.References:[1]Consiglio CR, Cotugno N, Sardh et al. The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19. Cell. 2020 Nov 12;183(4):968-981.e7. doi: 10.1016/j.cell.2020.09.016. Epub 2020 Sep 6. PMID: 32966765; PMCID: PMC7474869.[2]Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management. Children (Basel). 2020 Jul 1;7(7):69. doi: 10.3390/children7070069. PMID: 32630212; PMCID: PMC7401880.[3]Simon L, Saint-Louis P, Amre DK, Lacroix J, Gauvin F. Procalcitonin and C-reactive protein as markers of bacterial infection in critically ill children at onset of systemic inflammatory response syndrome. Pediatr Crit Care Med. 2008 Jul;9(4):407-13. PMID: 18496408.Disclosure of Interests:None declared