Convalescent Plasma Treatment for SARS-CoV-2 Infected High-risk Patients - a Matched Pair Analysis to the LEOSS Cohort (preprint)

Background: Establishing the optimal treatment for COVID-19 patients remains challenging. Specifically, immunocompromised and pre-diseased patients are at high risk for severe disease course and face limited therapeutic options. Convalescent plasma has been considered as therapeutic approach, but reliable data are lacking, especially for high-risk patients. Methods: We performed a retrospective analysis of 55 hospitalized COVID-19 patients with high risk for disease progression, primarily due to immunosuppression from cancer, solid organ transplantation, autoimmune disease, dialysis. A matched-pairs analysis (1:4) was performed with 220 patients from the Lean European Open Survey on SARS-CoV-2-infected Patients (LEOSS) who were treated or not treated with convalescent plasma. Results: Both cohorts, had high mortality (UKD 41.8%, LEOSS 34.1%). A matched-pairs analysis showed no significant effect on mortality. CP administration before the formation of pulmonary infiltrates showed the lowest mortality in both cohorts (10%), whereas mortality in the complicated phase was 27.8%. CP administration during the critical phase revealed the highest mortality; UKD 60.9%, LEOSS 48.3%. Conclusion: In our cohort of SARS-CoV-2 infected patients with severe comorbidities CP did not significantly reduce mortality in a retrospective matched pairs analysis. However, our data supports the concept that a reduction in mortality is achievable when CP is administered early.

Association of HLA and Mutated CCR5 With the Clinical Course of the Disease in Subjects With mild / moderate disease following COVID-19 infection (preprint)

COVID-19, the pandemic infection caused by SARS-CoV-2, may take highly variable clinical courses, ranging from symptom-free and pauci-symptomatic to fatal disease. The goal of the current study was to assess the association of COVID-19 clinical courses controlled by patients’ adaptive immune responses without progression to severe disease with patients’ Human Leukocyte Antigen (HLA) genetics, the presence or absence of near-loss-of-function delta 32 deletion mutant of C-C chemokine receptor type 5 (CCR5) and AB0 blood group antigens. We further analyzed the association of these immunogenetic background characteristics with patients’ humoral antiviral immune response patterns, assessed longitudinally. The study enrolled 157 convalescent adult patients followed up for up to 250 days. Univariate HLA analyses identified putatively protective HLA alleles (HLA class II DRB1*01:01 and HLA class I B*35:01, with a trend for DRB1*03:01) associated with reduced durations of disease and decreased (rather than increased) total anti-S IgG levels providing virus neutralizing capacity comparable to non-carriers. Conversely, analyses also identified HLA alleles (HLA class II DQB1*03:2 und HLA class I B*15:01) not associated with such benefit in the patient cohort of this study. Hierarchical testing by Cox regression analyses confirmed the significance of the protective effect of the HLA alleles identified (when assessed in composite) in terms of disease duration, whereas AB0 blood group antigen heterozygosity was found to be significantly associated with disease severity (rather than duration) in our cohort. A seeming association of a heterozygous CCR5 delta 32 mutation with prolonged disease duration suggested by univariate analyses was not confirmed by hierarchical multivariate testing.In conclusion, the current study shows that the presence of certain "protective" HLA alleles is of even stronger association with reduced duration of mild and moderate COVID-19 than age or any other potential risk factor assessed. Prospective studies in larger patient populations assessing the impact of HLA genetics on the capacity of mounting protective vaccination responses may be warranted.