Highlights d A standardized, ultra-high-throughput clinical platform for serum and plasma proteomics d Platform enables high precision quantification of 180 human proteomes per day at low cost d 27 biomarkers are differentially expressed between WHO severity grades for COVID-19 d Biomarkers include proteins not previously associated with COVID-19 infection

Author contributions DCJ coordinated all analyses, isolated DNA for sequencing, analysed and filtered SNP calls, conducted diversity analysis and GWAS and drafted the manuscript. CR produced phenotype data for growth on various solid media and growth rates in liquid media. AR conducted analysis of dating using mitochondrial data. DS conducted GWAS. MP analysed all phenotype data. TM identified LTR transposon insertions and analysed transposon insertion data. FXM conducted crosses for analysis of spore viability ZI produced indel calls with Cortex. WL conducted analysis of recombination rate, linkage disequilibrium decay and PCA for distance between strains. TMKC assisted with phenotype and population analysis. RP analysed Cortex and GATK indel calls. MM conducted amino acid profiling. JLDL and AC produced automated measures of cell morphology. SB aligned reads and produced GATK SNP calls. GH analysed population structure using fineSTRUCTURE. BO'F estimated the TMRCA from the nuclear genome using ACG. TK identified LTR transposon insertions JTS produced de novo assemblies. LB developed the custom Workspace workflow Spotsizer. BT assisted with sequence analysis. DAB assisted with analysis of novel genes. TS assisted with strain verification. SC produced images of wild strains and assisted with strain verification. JEEUH assisted with SNP validation. LvT and MT assisted with LTR validation. LJ and JL assisted with manual measures of cell morphology and FACS. SA produced gene expression data. MF, KM and ND assisted with sequencing. WB initiated and assisted with strain collection. JH coordinated manual measures of cell morphology and FACS. RECS coordinated automated measures of cell morphology. MR coordinated amino acid profiling. NM conducted analysis of recombination, linkage disequilibrium and advised on aspects of diversity and GWAS. DJB advised on GWAS. RD facilitated sequencing. JB contributed to the initiation and development of the project and financed the JB laboratory. AccessionsSequence data are archived in the European Nucleotide Archive (www.ebi.ac.uk/ena/), Study Accessions PRJEB2733 and PRJEB6284 (Supplementary Table 7). All SNPs and indels were submitted to NCBI dbSNP (www.ncbi.nlm.nih.gov/SNP/). Accessions are 974514578-974688138 (SNPs) and 974702618-974688139 (indels). Europe PMC Funders Group AbstractNatural variation within species reveals aspects of genome evolution and function. The fission yeast Schizosaccharomyces pombe is an important model for eukaryotic biology, but researchers typically use one standard laboratory strain. To extend the utility of this model, we surveyed the genomic and phenotypic variation in 161 natural isolates. We sequenced the genomes of all strains, revealing moderate genetic diversity (π = 3 ×10 −3 ) and weak global population structure. We estimate that dispersal of S. pombe began within human antiquity (~340 BCE), and ancestors of these strains reached the Americas at ~1623 CE. We quantified 74 traits, revealing substantial heritable phenotypic diversity. We cond...

Derailed cytokine and immune cell networks account for organ damage and clinical severity of COVID-19 [1][2][3][4] . Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and accompanied by a senescence-associated secretory phenotype (SASP), composed of pro-inflammatory cytokines, extracellular matrix-active factors and pro-coagulatory mediators [5][6][7] . COVID-19 patients displayed markers of senescence in their airway mucosa in situ and elevated serum levels of SASP factors. Mirroring COVID-19 hallmark features such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue 1,8,9 , in vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, neutrophil extracellular trap (NET) formation as well as activation of platelets and the clotting cascade in response to supernatant of VIS cells, including SARS-CoV-2-induced senescence. Senolytics such as Navitoclax and Dasatinib/Quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-driven hamster and mouse models. Our findings mark VIS as pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest senolytic targeting of virus-infected cells as a novel treatment option against SARS-CoV-2 and perhaps other viral infections.The pandemic human pathogenic SARS-CoV-2 coronavirus causes upper respiratory infections and subsequently COVID-19 lung disease that may get further complicated by septic multi-organ failure and comes with significant mortality 10,11 . Escalating immune activation with massive cytokine release seems to drive severe COVID-19 1-3 , possibly more than the virus infection itself. Mechanisms of viral

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