Type I interferon response and vascular alteration in chilblain-like lesions during the COVID-19 outbreak.

BACKGROUND: The outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear. OBJECTIVES: To study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus. METHODS: This observational study was conducted during 9-16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included. RESULTS: Histological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic-natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL. CONCLUSIONS: Our findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations.

Prolonged positive SARS-CoV-2 RT-PCR in cancer outpatients requires specific reorganization of cancer centres

Background: Patients with cancer are more susceptible to infection because of immunosuppressive treatment given to cure cancer. Several guidelines published at the beginning of the COVID-19 pandemic recommend delaying systemic anticancer treatment until complete resolution of COVID-19 symptoms. In addition, it is important to segregate patients with cancer from patients with COVID-19 to avoid transmission. Nevertheless, some patients will present both diseases, and the duration of eviction from cancer units and delay of cancer treatment after COVID-19 remains unclear. Notably the duration of viral excretion after COVID-19 is a concern in immunosuppressed patients. Methods: We tested all patients with a confirmed initial diagnosis of COVID-19 who needed to receive cancer or immunosuppressive treatment for a solid tumour, haematological or inflammatory disease in our centre from April 1st to May 15th 2020. We have repeated SARS-COV2 RT-PCR until negative viral shedding. Results: We tested 49 consecutive patients: 53% had solid tumours, 37% haematological disease and 10% inflammatory disease. 59% were under 65 years. Overall, 82% of patients had a positive RT-PCR from day 14 to 20 after the initial diagnosis of COVID-19 infection, 60% from day 21 to 27 and 30% from day 28 to 34. Only 4/37 patients evaluated remained with a positive RT-PCR after day 35. No predictive factors were associated with a positive RT-PCR but our results suggest that patients treated for inflammatory disease had a shorter duration of positive RT-PCR. 18 patients had their treatment delayed according to guideline recommendations and 17 patients received their treatment in a dedicated COVID-19 outpatient unit. No symptomatic COVID-19 recurrence was observed during follow-up in patients who had received chemotherapy despite persistent positive RT-PCR. Conclusions: We report here the first assessment of SARS-CoV2 RT-PCR kinetic in cancer patients. A prolonged viral excretion is observed in patients treated for cancer. A systematic retest is needed after day 14 if RT-PCR remains positive. A specific unit dedicated to outpatients with persistent positive RT-PCR allows urgent anticancer treatment and avoids the risk of viral exposure for other immunodepressed patients. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.