Higher rates of COVID-19 but less severe infections reported for patients on Dupilumab: a Big Data analysis of the World Health Organization VigiBase.

OBJECTIVE: Dupilumab (Dupixent®) is a monoclonal antibody that inhibits IL-4 and IL-13 signaling used for the treatment of allergic diseases. Whilst biologic therapy is traditionally regarded as immunosuppressive and capable to increase the infectious risk, Dupilumab does not display these characteristics and may be even protective in certain cases. We investigated the link between Dupilumab therapy and SARS-CoV-2 infection. MATERIALS AND METHODS: We carried out a comprehensive data mining and disproportionality analysis of the WHO global pharmacovigilance database. One asymptomatic COVID-19 case, 106 cases of symptomatic COVID-19, and 2 cases of severe COVID-19 pneumonia were found. RESULTS: Dupilumab treated patients were at higher risk of COVID-19 (with an IC0.25 of 3.05), even though infections were less severe (IC0.25 of -1.71). The risk of developing COVID-19 was significant both among males and females (with an IC0.25 of 0.24 and 0.58, respectively). The risk of developing COVID-19 was significant in the age-group of 45-64 years (with an IC0.25 of 0.17). CONCLUSIONS: Dupilumab use seems to reduce COVID-19 related severity. Further studies are needed to better understand the immunological mechanisms and clinical implications of these findings. Remarkably, the heterogenous nature of the reports and the database structure did not allow to establish a cause-effect link, but only an epidemiologically decreased risk in the patients subset treated with dupilumab.

Chest pain mimicking pulmonary embolism may be a common presentation of COVID-19 in ambulant patients without other typical features of infection.

BACKGROUND: Radiological and pathological studies in severe COVID-19 pneumonia (SARS-CoV-2) have demonstrated extensive pulmonary immunovascular thrombosis and infarction. This study investigated whether these focal changes may present with chest pain mimicking pulmonary emoblism (PE) in ambulant patients. METHODS: CTPAs from outpatients presenting with chest pain to Leeds Teaching Hospital NHS Trust 1st March to 31 May 2020 (n = 146) and 2019 (n = 85) were compared. Regions of focal ground glass opacity (GGO), consolidation and/or atelectasis (parenchymal changes) were determined, and all scans were scored using British Society for Thoracic Imaging (BSTI) criteria for COVID-19, and the 2020 cohort was offered SARS-CoV-2 antibody testing. RESULTS: Baseline demographic and clinical data were similar between groups with absence of fever, normal lymphocytes and marginally elevated CRP and D-Dimer values. Evidence of COVID-19 or parenchymal changes was observed in 32.9% (48/146) of cases in 2020 compared to 16.5% (14/85) in 2019 (P = 0.007). 11/146 (7.5%) patients met BSTI criteria for COVID-19 in 2020 compared with 0/14 in 2019 (P = 0.008). 3/39 patients tested had detectable COVID-19 antibodies (2 with parenchymal changes and 1 with normal parenchyma) however 0/6 patients whose CTPA met BSTI criteria "likely/suspicious for COVID-19" and attended antibody testing were SARS-CoV-2 antibody positive. CONCLUSIONS: 32.8% ambulatory patients with suspected PE in 2020 had parenchymal changes with 7.5% diagnosed as COVID-19 infection by imaging criteria, despite the absence of other COVID-19 symptoms. These findings suggest that localized COVID-19 pneumonitis with immunothrombosis occurs distal to the bronchiolar arteriolar circulation, causing pleural irritation and chest pain without viraemia, accounting for the lack of fever and systemic symptoms.