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Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time. HLA-DR hi CD11c hi inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DR lo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.

We performed a genome-wide association study (GWAS) in 1,713 Caucasian patients with Parkinson’s disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, two strong association signals were observed: in the α-synuclein gene(SNCA) (rs2736990, OR=1.23, p=2.24×10−16) and at the MAPT locus (rs393152, OR=0.77, p=1.95×10−16). We exchanged data with colleagues performing a GWAS in Asian PD cases. Association at SNCA was replicated in the Asian GWAS1, confirming this as a major risk locus across populations. We were able to replicate the effect of a novel locus detected in the Asian cohort (PARK16, rs823128, OR=0.66, p=7.29×10−8) and provide evidence supporting the role of common variability around LRRK2 in modulating risk for PD (rs1491923, OR=1.14, p=1.55×10−5). These data demonstrate an unequivocal role for common genetic variability in the etiology of typical PD and suggest population specific genetic heterogeneity in this disease.

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