Binding of phosphatidylserine-positive microparticles by PBMCs classifies disease severity in COVID-19 patients (preprint)

SUMMARY Infection with SARS-CoV-2 is associated with thromboinflammation, involving thrombotic and inflammatory responses, in many COVID-19 patients. In addition, immune dysfunction occurs in patients characterized by T cell exhaustion and severe lymphopenia. We investigated the distribution of phosphatidylserine (PS), a marker of dying cells, activated platelets, and platelet-derived microparticles (PMP), during the clinical course of COVID-19. We found an unexpectedly high amount of blood cells loaded with PS + PMPs for weeks after the initial COVID-19 diagnosis. Elevated frequencies of PS + PMP + PBMCs correlated strongly with increasing disease severity. As a marker, PS outperformed established laboratory markers for inflammation, leucocyte composition, and coagulation, currently used for COVID-19 clinical outcome prognosis. PS + PMPs preferentially bound to CD8 + T cells with gene expression signatures of proliferating effector rather than memory T cells. As PS + PMPs carried programmed death-ligand 1 (PD-L1), they may affect T cell expansion or function. Our data provide a novel marker for disease severity and show that PS, which can trigger the blood coagulation cascade, the complement system, and inflammation, resides on activated immune cells. Therefore, PS may serve as a beacon to attract thromboinflammatory processes toward lymphocytes and cause immune dysfunction in COVID-19.

Emergence of multiple SARS-CoV-2 mutations in an immunocompromised host (preprint)

Prolonged shedding of infectious SARS-CoV-2 has recently been reported in a number of immunosuppressed individuals with COVID-19. Here, we describe the detection of high levels of replication-competent SARS-CoV-2 in specimens taken from the respiratory tract of a B-cell depleted patient up to 154 days after initial COVID-19 diagnosis concomitant with the development of high mutation rate. In this patient, a total of 11 nonsynonymous mutations were detected in addition to the Y144 deletion in the spike protein of SARS-CoV-2. Virus evolution studies revealed a dramatic diversification in viral population coinciding with treatment with convalescent plasma and clinical respiratory deterioration. Our findings highlight the urgent need for continuous real-time surveillance of genetic changes of SARS-CoV-2 adaptation alongside immunological investigations in patients with severely compromised humoral responses who may shed infectious virus over prolonged periods of time.