FIRST, SECOND AND THIRD COVID-19 PANDEMIC WAVES AND THEIR DIFFERENT IMPACTS ON STROKE CARE: EVIDENCES FROM THE TUSCANY STROKE NETWORK

Background and aims: We aim at describing the impact of the first, second and third waves of the COVID-19 pandemic on stroke services in Tuscany. We measured the global impact of the COVID-19 pandemic on the volumes of both intracranial hemmorhage (ICH) and acute ischemic stroke (AIS) hospitalizations, as well as of reperfusion treatments throughout the pandemic years 2020-21 (January1, 2020 -June 30, 2021) compared with the year 2019 control period. Methods: Retrospective, observational, multicenter study, across 3 huband- spoke stroke systems, and 22 stroke hospitals. The diagnoses were identified by their ICD-9 CM codes and/or classifications in stroke databases at participating centers. Results: In comparison with the same periods of 2019, the hospitalization volumes for ICHs and for AIS declined by 26% and 30.1% respectively during the fist pandemic wave, by 11% and 24.6% during the second wave, and by 2.5% and 4% during the third wave. Reperfusion treatments decreased by 15% during the first wave, and by 11.4% and 0.3% during the second and third waves respectively. Treated patients' functional outcome at 90days did not vary throughout the pandemic waves. Casefatality at 30days increased from 10.3% to 10.8% for AIS, and from 26.5% to 27.6% for ICH before and after the COVID-19 outbreak. Conclusions: The COVID-19 pandemic waves were associated with a decreasing decline in the volume of stroke hospitalizations, nevertheless fewer and probably the most severe patients were able to reach the hospital within the therapeutic windows. We observed different pattern of variations across the three hub-and-spoke systems.

Role and Experience of a Subintensive Care Unit in Caring for Patients with COVID-19 in Italy: The CO-RESP Study

Objective: This retrospective and prospective cohort study was designed to describe the characteristics, treatments, and outcomes of patients with SARS-CoV-2 infection (COVID-19) admitted to subintensive care units (SICU) and to identify the variables associated with outcomes. SICUs have been extremely stressed during the pandemic, but most data regarding critically ill COVID-19 patients come from intensive care units (ICUs). Studies about COVID-19 patients in SICUs are lacking. Setting and participants: The study included 88 COVID-19 patients admitted to our SICU in Cuneo, Italy, between March and May 2020. Measurements: Clinical and ventilatory data were collected, and patients were divided by outcome. Multivariable logistic regression analysis examined the variables associated with negative outcomes (transfer to the ICU, palliation, or death in a SICU). Results: A total of 60 patients (68%) had a positive outcome, and 28 patients (32%) had a negative outcome;69 patients (78%) underwent continuous positive airway pressure (CPAP). Pronation (n=37 [42%]) had been more frequently adopted in patients who had a positive outcome vs a negative outcome (n=30 [50%] vs n=7 [25%];P=.048), and the median (interquartile range) Pao2/Fio2 ratio after 6 hours of prone positioning was lower in patients who had a negative outcome vs a positive outcome (144 [140-168] vs 249 [195-268], P=.006). Independent predictors of a negative outcome were diabetes (odds ratio [OR], 8.22;95% CI, 1.50-44.70;P=.015), higher D-dimer (OR, 1.28;95% CI, 1.04-1.57;P=.019), higher lactate dehydrogenase level (OR, 1.003;95% CI, 1.000-1.006;P=.039), and lower lymphocytes count (OR, 0.996;95% CI, 0.993-0.999;P=.004). Conclusion: SICUs have a fundamental role in the treatment of critically ill patients with COVID-19, who require long-term CPAP and pronation cycles. Diabetes, lymphopenia, and high D-dimer and LDH levels are associated with negative outcomes.

UNESCO Global Geoparks in the "World after": a multiple-goals roadmap proposal for future discussion

The new challenges posed to UNESCO Global Geoparks (UGGps), resulting from the COVID-19 pandemic, require a guiding reflection and the presentation of a proposal for a roadmap, to be discussed and implemented in the short -medium term. The proposal presented in this work is the result of careful reflection and discussion among the authors, with the purpose of providing the UGGps with tools and lines of action that will allow them to face the new reality of the "World after". These proposals are aligned with the new global dynamics, mainly with those that are seen as strategic for these territories. It is also based on the SDGs of the 2030 Agenda, with particular emphasis on Climate Action. The new reality must therefore also include a para-digm shift and a strengthening of networking activities, which should include a new dynamic of participation and sharing, appropriate to the more frequent use of tools for effective long-distance teamwork.

A case of Vaccine-Induced Thrombotic Thrombocytopenia (VITT) with thrombosis of the superior mesenteric artery after ChAdOx1 nCov-19 COVID-19 Vaccine

We describe the case of a 64 years-old woman admitted to the Emergency Department of the ASST-Spedali Civili of Brescia with fever and gastrointestinal symptoms 10 days after the first dose of ChAdOx1 nCov-19 vaccine. Laboratory investigations showed severe thrombocytopenia and high D-dimer, while an abdominal CT scan reported a partially occluding thrombosis of the superior mesenteric artery. Following treatment with fondaparinux, immunoglobulins and high dosage steroid therapy, we observed a rapid improvement of patient's conditions. An ELISA assay showed the presence of antibodies against heparin PF4-complex. Subsequent abdominal CT-scan showed the superior mesenteric artery thrombosis resolution, and the patient was finally discharged after 12 days of hospitalization. Several reports pointed to the venous system as the main district affected by Vaccine-Induced Thrombotic Thrombocytopenia (VITT), while a peculiar feature of this report is the involvement of the mesenteric arterial system. Further investigation of VITT's pathophysiological mechanisms is mandatory to develop preventive strategies and effective treatments.

Early echocardiographic and cardiac MRI findings in multisystem inflammatory syndrome in children (MIS-C)

Introduction: Multisystem Inflammatory Syndrome in Children (MISC) is a known severe condition affecting children previously exposed to SARS-CoV-2. Cardiovascular manifestations in MIS-C are quite common and include myocardial dysfunction, coronary artery dilation or aneurysms, arrhythmias, conduction abnormalities, pericarditis and valvulitis. Severe cases can present even with cardiogenic shock. To date, little is known about the very early myocardial abnormalities in pediatric patients with MIS-C. The Speckle Tracking Echocardiography (STE) and cardiac MRI (cMRI) have shown to be potential candidate for identifying regional ventricular dysfunctions in early stages of inflammatory COVID-related conditions [1,2]. Objectives: To describe the early cardiac findings in patients with MIS-C, evaluated by two advanced cardiovascular imaging, STE and cMRI. Methods: Consecutive patients with MIS-C underwent standard transthoracic echocardiography (TTE), speckle-tracking echocardiography (STE) with analysis of left ventricle (LV) global longitudinal strain (GLS) and cardiac MRI (cMRI). Clinical and laboratory data, including markers of systemic inflammation, Troponin I (TnI) and Brain Natriuretic Peptide (BNP) were also collected at onset and during follow up. All patients received intravenous immunoglobulins (IVIGs), intravenous corticosteroids (methylprednisolone) and antiplatelet therapy (aspirin). The use of biological agents (Anakinra) was reserved to patients with severe or critical illness. The need for Intensive Care Unit (ICU) was based on clinical and hemodynamic status at presentation. Results: Twenty-three patients (13M, 10F), mean age 8.1±4years (range 5.4-15.7), all with positive clinical and/or serological evidence of previous SARS-COV2 infection, entered the study. The majority (78.2%) was caucasian. All presented high degree fever, gastrointestinal symptoms and rash. Conjunctivitis and cardiovascular symptoms, as hypotension, thoracic pain or dysrhythmia, were present in 10 (43.5%). Nine children (39.1%) shared Kawasaki Disease-like symptoms. Four patients (17.4%) needed ICU admission and 3 required inotropic support. Short-term survival was 100%. All patients showed an hyperinflammatory state with elevated CRP, ESR, and D-Dimer. Tn- I was abnormal (>34 ng/L) in 15 patients (65.2%), BNP was significantly elevated in 20 (86.9%). Median time to STE evaluation was 8 days and to cMRI was 18 days since fever onset. Mean LVEF and RVEF were respectively 59±10% and 45±7%. Coronary dilation was observed in 6 (26.1%) patients. STE showed reduced mean LVGLS (-17±4.3%). LVEF on cMR was 60±13%, LGE with non-ischemic pattern was evident in 6/16 patients (37.5%) and pericardial effusion in 2 (12.5%). Conclusion: MIS-C can occur in a small but not negligible proportion of children previously affected by COVID-19 and affects the heart in a significant proportion of them. STE and cMRI were shown to be very sensitive tools to evaluate and monitor the early cardiac dysfunctions in patients with MIS-C. The elevation of myocardial necrosis markers, the myocardial injury confirmed by reduced LVGLS and presence of LGE on cMR in about a quarter of the patients support the pathogenetic hypothesis of a post-viral immuno-mediated myocarditis.

PET-MRI for the detection of minimal residual disease in MIS-C: A long-term prospective study

Introduction: Multisystem Inflammatory Syndrome in Children (MISC) is an emerging clinical condition, similar to the hyperinflammatory response seen in adults with COVID-191. To date, little is known about the natural history of the disease and the long-term monitoring of MIS-C patients. Positron emission tomography PET/MRI is actually used to identify active inflammatory or neoplastic sites using [18F]fluorodeoxyglucose (FDG) due to the high glycolytic metabolism of inflammatory/neoplastic tissues2. Therefore, it could be indicated to evaluate and monitor the inflammatory disease state2. Objectives: To describe the PET/MRI findings for the evaluation of the minimal residual disease in a cohort of patients with MIS-C. Methods: Consecutive patients with MIS-C underwent a whole body FDG PET/MRI by 2 weeks, when possible, and at 6 weeks after the onset of fever. Each patient, after a 36 hours of fasting and high-fat low carbohydrate (<5g/day) diet preparation, was scanned using 3 MBq/kg FDG to minimize the radiation exposure. Clinical and laboratory data were also collected at onset and during follow up. Results: Ten patients (7M, 3F), mean age 10.2 years (range 5.4-17.7), all with positive clinical and/or serological evidence of previous SARS-COV2 infection, entered the study. All presented high degree fever, gastrointestinal symptoms and rash. Conjunctivitis and cardiovascular involvement, as hypotension, significant myocardial dysfunction and increased myocardiolysis markers, were also present in half of them. Only one patient needed intensive care support for five days. Systemic inflammatory and prothrombotic markers were elevated in all patients on admission (mean CRP 166.3 mg/L;procalcitonin 11.8 ug/L;D-dimer 2348 ug/L, ferritin 1135 ng/L). All patients were treated, 4.5 (± 1.5) days from fever onset with pulse IVIG (2 g/ kg) and IV methyprednisone (MPDN 2 mg/kg/day, max 80 mg) for 2 weeks then with oral PDN tapered down to 0 in further 4 weeks. PET/MRI was performed 13.3 days (± 1.5) after fever onset in three patients and 48 days (± 10.6) in 8. During the acute phase, all patients showed pelvic effusion and edema of the abdominal wall tissues at the total body MRI, not seen in patients during the late phase. Lymph node involvement was present in 81% of MRI findings. The cervical district appeared to be the most involved one as compared to the thoracic, mesenteric and retroperitoneal ones (72% vs 45, 36 and 45% respectively). However, a residual mesenteric lymphadenopathy was exclusive to the late phase (5/8 patients). Conclusion: PET/MRI confirms the good metabolic response to treatment in patients with MIS-C. The abdominal region is more intensively involved in the early stage of the disease, likely related to the hyperinflammatory state. A slow normalization through the lymph node compartment is present in the late stage. PET/MRI is a highly sensitive and specific tool for assessing minimal residual disease in MIS-C and should be indicated for patients with incomplete clinical response to treatment.

Non convulsive status epilepticus as ongoing symptom of multisystem inflammatory syndrome in children (MIS-C)

Introduction: Since April 2020, Multisystem inflammatory syndrome in children (MIS-C) has been reported worldwide and associated with a different spectrum of symptoms. Although mild neurological manifestations in SARS-Cov2 infection and MIS-C have been reported, severe involvement with brain abnormalities, is rare 1. Objectives: Describe a child with MIS-C presenting non-convulsive status epilepticus associated with abnormal cerebral magnetic resonance (MR), never previously reported. Methods: Case report. Results: A previously healthy 19-month-old girl presented to our emergency department after a prolonged febrile seizure involving the right side of her body lasting about 25 minutes. She presented with fever lasting more than 24 hours. On physical examination, abdominal distention and tenderness and altered mental status with irritability were detected. RT-PCR for SARS-CoV-2 on nasal swab was negative but her parents had SARS-CoV-2 infection four weeks earlier. Laboratory showed elevated CRP (35 mg/L), while all microbiological analyses in blood, urine and CSF were negative. Computerized tomography (TC) showed a doubtful left temporal hypointensity, and cerebral MRI displayed cytotoxic oedema in left temporal mesial area of the brain on diffusion-weighted imaging (DWI). Few day later, her clinical conditions worsened with irritability and drowsiness associated with persistent abdominal distention, diarrhoea, and high fever. The EEG revealed a pattern suggestive for non-convulsive status epilepticus responsive to benzodiazepines and loading dose of Levetiracetam. Consensually, an increase of inflammatory markers (CRP 153 mg/L, procalcitonin 114 ug/L) was observed. Chest X-ray, EKG, troponin and BNP levels were normal, whereas echocardiogram demonstrated left ventricular diastolic dysfunction and mild pericardial effusion. In the suspicion of MIS-C with abdominal, cardiac and neurological involvement, she was treated with intravenous immunoglobulin (2g/kg), methylprednisolone (2 mg/kg) and acetylsalicylic acid (5mg/kg). Serum SARS-Cov2 antibody test resulted positive for previous infection, confirming the diagnosis of MIS-C. Neuronal antibodies for immune-mediated CNS disorders tested negative. Within 36 hours from therapy start, a significant improvement in general conditions, along with stable apyrexia and decreasing in inflammatory markers were observed. She was discharged two weeks later on oral steroids, ASA and Levetiracetam;the physical examination was normal, and EEG showed a global improvement in brain electrical activity. Conclusion: Neurological symptoms secondary to SARS-Cov2 infection and MIS-C have been reported in children (1) but only a few present severe neurological complications such as status epilepticus. Non-convulsive status epilepticus has been previously described in an adult with acute COVID192 but has never been reported as presenting sign of MIS-C. The current case illustrates the need of a careful neurological evaluation in children with MIS-C, as CNS involvement can represent the main clinical presentation thus underlining the need of an appropriate diagnostic and therapeutic approach.

Particle Number Emissions of a Euro 6d-Temp Gasoline Vehicle under Extreme Temperatures and Driving Conditions

With the introduction of gasoline particulate filters (GPFs), the particle number (PN) emissions of gasoline direct-injection (GDI) vehicles are below the European regulatory limit of 6 x 10(11) p/km under certification conditions. Nevertheless, concerns have been raised regarding emission levels at the boundaries of ambient and driving conditions of the real-driving emissions (RDE) regulation. A Euro 6d-Temp GDI vehicle with a GPF was tested on the road and in the laboratory with cycles simulating congested urban traffic, dynamic driving, and towing a trailer uphill at 85% of maximum payload. The ambient temperatures covered a range from -30 to 50 degrees C. The solid PN emissions were 10 times lower than the PN limit under most conditions and temperatures. Only dynamic driving that regenerated the filter passively, and for the next cycle resulted in relatively high emissions although they were still below the limit. The results of this study confirmed the effectiveness of GPFs in controlling PN emissions under a wide range of conditions.

Severe cardiac involvement with myocardial dysfunction and arrhythmias in SARS-COV-2-related Kawasaki-like disease

Introduction: During SARS-COV-2 pandemic, different reports have been published regarding children who developed hyperinflammatory syndrome with certain or probable relationship with SARS-COV-2. These patients presented incomplete or atypical manifestations of Kawasaki disease (KD), particularly abdominal pain, myocarditis and macrophage activation syndrome features. Objectives: To report a case of SARS-COV-2-related Kawasaki-like disease with severe cardiac involvement. Methods: case report description. Results: A 10-year-old previously healthy girl presented progressively worsening abdominal pain, high grade fever for 3 days and vomiting. Lab tests showed WBC 11680/mmc, N 9370/mmc, Creactive protein (CRP) 329 mg/L, procalcitonin (PCT) 0,74 ug/L, PT-INR 1,35 and elevated D-dimer and fibrinogen levels (817 ug/L and 9,45 g/L respectively). Abdomen ultrasound revealed lymphadenopathies and hyperechogenic mesentery in the right lower quadrant, although the appendix was not visualized. She underwent laparoscopy showing moderate quantity of free fluid and appendectomy was performed. Thereafter she continued to complain of high-grade fever, abdominal pain and diarrhoea, despite broad-spectrum antibiotics. Blood, urine and stool cultures were negative. Bilateral non-exudative conjunctivitis was present. Moreover, the lab tests showed persistent marked elevation of CRP (370 mg/L), WBC 15590/mmc, N 14070/mmc, hypoalbuminemia (23 g/L), elevated ferritin and triglycerides (458 ug/L and 221 mg/dl). By taking into consideration the concomitant SARS-COV-2 pandemic, nasopharyngeal and rectal swabs were taken with negative results. Conversely, serological test showed anti-SARS-COV-2 IgG antibodies and absence of IgM. The family medical history showed that the mother had presented fever, cough, ageusia and anosmia one month before, preceded by a contact with a SARS-COV-2 positive case, while the patient was asymptomatic at that time. Suspecting a KD-like disease she was referred to our Paediatric Rheumatology Unit: cardiological assessment revealed negative Twaves in V4-V5-V6 on EKG while standard and advanced echocardiography showed mild mitral and tricuspid insufficiencies, mild dilatation of the left main coronary artery (LMCA, z score +2), normal global function (FEVS 2D 58%) but reduced longitudinal strain (GLS-16%). Lab tests confirmed myocardial injury with troponin (TnI) 100,1 ng/l and brain natriuretic peptide (P-BNP) 593 ng/L. A single infusion of intravenous immunoglobulin 2 g/kg associated with methylprednisolone (1 mg/kg/day) led to a rapid clinical improvement with apyrexia and resolution of abdominal pain and conjunctivitis. Blood test confirmed gradual normalization of inflammatory markers, ferritin, troponin and BNP and EKG showed positive T-waves. Shortly after the discharge, while she was on prednisone 0.5 mg/kg/day and acetylsalicylic acid 100 mg/day, she referred some episodes of heart pounding, lasting about ten minutes with spontaneous resolution. Three weeks after onset, cardiac MRI was normal, however, speckle tracking echocardiography showed persistent dilatation of LMCA and reduction of global longitudinal strain (GLS-14%). 24-hour EKG-Holter detected episodes of supraventricular tachycardia and several ventricular and supraventricular extrasystoles. Thus, oral atenolol therapy was started. Conclusion: In our patient SARS-COV-2 induced a possible postinfectious antibody or immune-complex mediated reaction that led to KD-like disease with acute surgical abdomen presentation and persistent myocardial damage and arrythmias. Speckle tracking echocardiography appears more reliable than MRI in early detection of myocardial damage in patients with preserved left ventricular ejection fraction.

Life-threatening macrophage activation syndrome with fulminant myocarditis successfully rescued by high dose intravenous Anakinra

Introduction: Macrophage activation syndrome (MAS) is a rare, potentially life-threatening complication of some rheumatologic diseases1. Objectives: We report the case of a child with systemic onset Juvenile Idiopathic Arthritis (sJIA) complicated by severe MAS and acute myocarditis, needing veno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO), successfully rescued by high dose intravenous Anakinra (HDIV-ANA). Methods: Case report's description Results: A two-year-old boy presented with one month history of fever associated with limping gait, cervical lymphadenopathy and skin rash. Laboratory tests showed elevation of inflammatory markers and ferritin. By exclusion criteria, sJIA was diagnosed and steroid therapy started. After a soft tissue bacterial infection, fever relapsed and laboratory tests were consistent with MAS (day 1): Hb 8.5 g/dL, PLT 44000/mm3;FDP 1522 ug/L, CRP 100 mg/L, ferritin 2200 ug/L. High doses intravenous metilprednisolone and oral Cyclosporin A (CSA) were started. On day 2 he presented a Systemic Capillary Leak Syndrome and acute myocarditis. He was admitted into the pediatric intensive care unit (PICU) where intravenous immunoglobulin and subcutaneous Anakinra (ANA) were added. On day 4, due to an episode of cardiac arrest, VA-ECMO was started and we tried high dose intravenous ANA (HDIV-ANA, 8 mg/Kg/day q6h). This treatment brought immediate benefit: echocardiography showed progressive resolution of myocarditis so that VA-ECMO was definitely weaned off in six days. Laboratory test showed isolated neutropenia (PMNs 0-100/mm3). Suspecting a iatrogenic cause, HDIV-ANA was gradually reduced to the maintenance dose without benefit. On day 22, ANA was stopped and neutropenia resolved. Analysis of PRF1 gene revealed a mutation (c.[272C>T] p.[Ala91Val]) in heterozygosis. 49 days after admission he was discharged on oral prednisone and CSA. Neither neurological nor other organ consequences related to MAS were reported. A few months later, on tapering down of therapy, he relapsed. ANA was restarted with rapid improvement and no side effects, including neutropenia. Currently, after 12 months, the disease is in clinical remission on medication. Conclusion: MAS is a rare life-threatening complication of sJIA, triggered by infections in up to one-third of the patients 2. It is the result of a cytokine storm that lead to a dysregulated inflammatory activation of the immune system, with rapid progression to multiorgan failure. Treatment usually includes high dose corticosteroids and immunosuppressive agents. Recently, the use of selective cytokine inhibitors has been suggested. No standardized guidelines are available to date, but the use of ANA has been already reported, pointing out the need for a higher doses regimen in refractory cases. MAS in our patient appeared after a soft tissue infection which could have act as triggering factor in a patient with sJIA and genetic predisposing pattern. The choice of intravenous administration of ANA was partly due to the generalized edema and partly to the severe discoaugulopathy. Considering the higher doses needed for rapidly suppressing the cytokine storm and ANA pharmacokinetics, we split the daily dose into four administrations. No major adverse events were reported, except for a transient neutropenia, already reported 6. Based on our experience, HDIV-ANA is a safe and effective treatment for refractory life-threatening sJIA-related MAS. This therapeutic approach may be also considered in the current pandemic COVID-19 emergency where recent evidence showed IL1-driven MAS-like complication triggered by SARS-COV-2 virus as predictor of bad outcome7.

Kawasaki disease complicated by macrophage activation syndrome and parvovirus b19 infection: Which relationship?

Introduction: Macrophage activation syndrome (MAS) is characterized by massive production of cytokines leading to macrophage activation and haemophagocytosis presenting with prolonged fever, rash, hepatosplenomegaly, pancytopenia, liver dysfunction, hypertriglyceridemia, hyperferritinemia and coagulopathy that can complicate rheumatic conditions such as Systemic Juvenile Idiopathic Arthritis (sJIA) and Systemic Lupus Erythematosus (SLE). Incidence of MAS in Kawasaki Disease (KD) has been estimated in about 1.1% patients but subclinical MAS may be detected in 30-40% of KD. Objectives: Case description Methods: A previously healthy 10 years-old girl presented high grade fever for 4 days, pharyngitis and vomiting. After 24 hours, she developed diffuse maculo-papular rash and oedema on extremities. She presented progressive worsening of general conditions and bilateral bulbar conjunctivitis, mucositis with strawberry-like tongue and left cervical lymph nodes enlargement. On admission remarkable laboratory tests were increased C reactive protein (CRP), neutrophilic leucocytosis, low sodium and albumin, increased gGT and gallbladder hydrops on abdominal ultrasound. Suspecting Kawasaki disease 2 gr/kg IVIG were administered with salicylic acid (50 mg/kg/day). Nevertheless, she presented persistent remitting fever, low consciousness, diffuse vasculitic rash, worsening of mucositis and pericardial and pleural effusion. Lab tests showed low haemoglobin, platelets and fibrinogen (9,3 g/L, 65.000/ml and 1.05 g/L, respectively), ferritin 16.492 g/L, SGOT 487 U/L, SGT 351 U/L, triglycerides 345 mg/dl, Ddimers 10.353 microgr/L and soluble interleukin-2 receptor (sIL-2R), 6464 kU/L. Active haemophagocytosis was retrieved in bone marrow and cerebrospinal fluid (CSF) so MAS was diagnosed. Three consecutive iv methylprednisolone pulses (30 mg/kg) were administered followed by dexamethasone 10 mg/m2/day and cyclosporin A 2 mg/kg/day as well as plasma infusions and oxygen supplementation (6 l/min) for 48 hours. Parvovirus B19 (HPVB19) DNA was found in peripheral blood, bone marrow and CSF, while other microbiological analysis (EBV, CMV, HHV6, VZV, Influenza A-B, Measles, Adenovirus, HSV) were negative. The patient progressively improved with reduction of fever, oedema of extremities and skin rash and after 6 days presented extensive desquamation on hands, feet and limbs. Lab tests slowly improved and normal values were achieved on day 23. Echocardiogram did not show any coronary aneurism or dilatation, cerebral MRI was normal and neurological impairment gradually disappeared. Primary HLH mutations for UNC13D, STXBP2, STX11, RAB27a, SH2D1A, XIAP were not found. Corticosteroids and Ciclosporin were gradually tapered and discontinued after 7 and 12 months respectively, whilst acetylsalicylic acid was stopped after 2 months. Results: MAS is a relatively infrequent complication in KD and may be associated with severe course and poor outcome. Several potential infectious agents have been suggested as trigger factors of both MAS and KD, such as Epstein Barr virus, Influenza virus etc. and, more recently, the SARS-COV-2 epidemic has been associated with severe forms of systemic inflammatory syndrome resembling KD and MAS. Conclusion: To the best of our knowledge, this is the first case in which demonstration of HPVB19 DNA in peripheral blood, bone marrow and CSF during acute phase strongly suggests a direct role of the virus in triggering both KD and MAS rather than an antibody or immune-complex mediated mechanism.