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We discuss a case of a young woman, presenting a constellation of clinical and biochemical features meeting the current case definition of multisystem inflammatory syndrome in adults (MIS-A), 18 days after receiving her first dose of the Oxford/AstraZeneca vaccine. Therapy by means of intravenous immunoglobulins was initiated, leading to clinical and biochemical recovery. Although a relationship between MIS-A and the preceding vaccination cannot be confirmed, it can also not be excluded, given the temporal association and the fact that there were no indicators of a preceding SARS-CoV-2 infection.

Introduction: There is evidence to suggest that patients delayed seeking urgent medical care during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. A delay in health-seeking behavior could increase the disease severity of patients in the prehospital setting. The combination of COVID-19-related missions and augmented disease severity in the prehospital environment could result in an increase in the number and severity of physician-staffed prehospital interventions, potentially putting a strain on this highly specialized service., Study Objective: The aim was to investigate if the COVID-19 pandemic influences the frequency of physician-staffed prehospital interventions, prehospital mortality, illness severity during prehospital interventions, and the distribution in the prehospital diagnoses., Methods: A retrospective, multicenter cohort study was conducted on prehospital charts from March 14, 2020 through April 30, 2020, compared to the same period in 2019, in an urban area. Recorded data included demographics, prehospital diagnosis, physiological parameters, mortality, and COVID-status. A modified National Health Service (NHS) National Early Warning Score (NEWS) was calculated for each intervention to assess for disease severity. Data were analyzed with univariate and descriptive statistics., Results: There was a 31% decrease in physician-staffed prehospital interventions during the period under investigation in 2020 as compared to 2019 (2019: 644 missions and 2020: 446 missions), with an increase in prehospital mortality (OR = 0.646; 95% CI, 0.435 - 0.959). During the study period, there was a marked decrease in the low and medium NEWS groups, respectively, with an OR of 1.366 (95% CI, 1.036 - 1.802) and 1.376 (0.987 - 1.920). A small increase was seen in the high NEWS group, with an OR of 0.804 (95% CI, 0.566 - 1.140); 2019: 80 (13.67%) and 2020: 69 (16.46%). With an overall decrease in cases in all diagnostic categories, a significant increase was observed for respiratory illness (31%; P = .004) and cardiac arrest (54%; P < .001), combined with a significant decrease for intoxications (-58%; P = .007). Due to the national test strategy at that time, a COVID-19 polymerase chain reaction (PCR) result was available in only 125 (30%) patients, of which 20 (16%) were positive., Conclusion: The frequency of physician-staffed prehospital interventions decreased significantly. There was a marked reduction in interventions for lower illness severity and an increase in higher illness severity and mortality. Further investigation is needed to fully understand the reasons for these changes.

Background: The peak of the global COVID-19 pandemic has not yet been reached, and many countries face the prospect of a second wave of infections before effective vaccinations will be available. After an initial phase of viral replication, some patients develop a second illness phase in which the host thrombotic and inflammatory responses seem to drive complications. Severe COVID-19 disease is linked to high mortality, hyperinflammation, and a remarkably high incidence of thrombotic events. We hypothesize a crucial pathophysiological role for the contact pathway of coagulation and the kallikrein-bradykinin pathway. Therefore, drugs that modulate this excessive thromboinflammatory response should be investigated in severe COVID-19., Methods: In this adaptive, open-label multicenter randomized clinical trial, we compare low molecular weight heparins at 50 IU anti-Xa/kg twice daily-or 75 IU anti-Xa twice daily for intensive care (ICU) patients-in combination with aprotinin to standard thromboprophylaxis in hospitalized COVID-19 patients. In the case of hyperinflammation, the interleukin-1 receptor antagonist anakinra will be added on top of the drugs in the interventional arm. In a pilot phase, the effect of the intervention on thrombotic markers (D-dimer) will be assessed. In the full trial, the primary outcome is defined as the effect of the interventional drugs on clinical status as defined by the WHO ordinal scale for clinical improvement., Discussion: In this trial, we target the thromboinflammatory response at multiple levels. We intensify the dose of low molecular weight heparins to reduce thrombotic complications. Aprotinin is a potent kallikrein pathway inhibitor that reduces fibrinolysis, activation of the contact pathway of coagulation, and local inflammatory response. Additionally, aprotinin has shown in vitro inhibitory effects on SARS-CoV-2 cellular entry. Because the excessive thromboinflammatory response is one of the most adverse prognostic factors in COVID-19, we will add anakinra, a recombinant interleukin-1 receptor antagonist, to the regimen in case of severely increased inflammatory parameters. This way, we hope to modulate the systemic response to SARS-CoV-2 and avoid disease progressions with a potentially fatal outcome., Trial Registration: The EU Clinical Trials Register 2020-001739-28 . Registered on April 10, 2020.