medRxiv : the preprint server for health sciences
Authors: Sun K, Cedarbaum E, Hill C, Win S, Parikh NI, Hsue PY, Durstenfeld MS
American journal of respiratory and critical care medicine
Authors: Verma A, Minnier J, Wan ES, Huffman JE, Gao L, Joseph J, Ho YL, Wu WC, Cho K, Gorman BR, Rajeevan N, Pyarajan S, Garcon H, Meigs JB, Sun YV, Reaven PD, McGeary JE, Suzuki A, Gelernter J, Lynch JA, Peterson JM, Zekavat SM, Natarajan P, Dalal S, Jhala DN, Arjomandi M, Gatsby E, Lynch KE, Bonomo RA, Freiberg M, Pathak GA, Zhou JJ, Donskey CJ, Madduri RK, Wells QS, Huang RD, Polimanti R, Chang KM, Liao KP, Tsao PS, Wilson PWF, Hung A, O'Donnell CJ, Gaziano JM, Hauger RL, Iyengar SK, Luoh SW, Million Veteran Program COVID-19 Science Initiative
Journal of clinical microbiology
Authors: Fasching CL, Servellita V, McKay B, Nagesh V, Broughton JP, Sotomayor-Gonzalez A, Wang B, Brazer N, Reyes K, Streithorst J, Deraney RN, Stanfield E, Hendriks CG, Fung B, Miller S, Ching J, Chen JS, Chiu CY
Volume 3 of Issue 7 | Cell reports. Medicine
Authors: Feyaerts D, Hédou J, Gillard J, Chen H, Tsai ES, Peterson LS, Ando K, Manohar M, Do E, Dhondalay GKR, Fitzpatrick J, Artandi M, Chang I, Snow TT, Chinthrajah RS, Warren CM, Wittman R, Meyerowitz JG, Ganio EA, Stelzer IA, Han X, Verdonk F, Gaudillière DK, Mukherjee N, Tsai AS, Rumer KK, Jacobsen DR, Bjornson-Hooper ZB, Jiang S, Saavedra SF, Valdés Ferrer SI, Kelly JD, Furman D, Aghaeepour N, Angst MS, Boyd SD, Pinsky BA, Nolan GP, Nadeau KC, Gaudillière B, McIlwain DR
The biological determinants underlying the range of coronavirus 2019 (COVID-19) clinical manifestations are not fully understood. Here, over 1,400 plasma proteins and 2,600 single-cell immune features comprising cell phenotype, endogenous signaling activity, and signaling responses to inflammatory ligands are cross-sectionally assessed in peripheral blood from 97 patients with mild, moderate, and severe COVID-19 and 40 uninfected patients. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identify and independently validate a multi-variate model classifying COVID-19 severity (multi-class area under the curve [AUC] = 0.799, p = 4.2e-6; multi-class AUC = 0.773, p = 7.7e-6). Examination of informative model features reveals biological signatures of COVID-19 severity, including the dysregulation of JAK/STAT, MAPK/mTOR, and nuclear factor κB (NF-κB) immune signaling networks in addition to recapitulating known hallmarks of COVID-19. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for prevention and/or treatment of COVID-19 progression.
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Frontiers in public health
Authors: Westfall M, Forster M, Golston O, Taylor KD, White K, Reid MJA, Dorian A, Prelip ML, Shafir S
American journal of physiology. Lung cellular and molecular physiology
Authors: Khanna K, Raymond W, Jin J, Charbit AR, Gitlin I, Tang M, Werts AD, Barrett EG, Cox JM, Birch SM, Martinelli R, Sperber HS, Franz S, Duff T, Hoffmann M, Healy AM, Oscarson S, Pöhlmann S, Pillai SK, Simmons G, Fahy JV
JMIR public health and surveillance
Authors: Ayala G, Arreola S, Howell S, Hoffmann TJ, Santos GM
JAMA internal medicine
Authors: Verma A, Huffman JE, Gao L, Minnier J, Wu WC, Cho K, Ho YL, Gorman BR, Pyarajan S, Rajeevan N, Garcon H, Joseph J, McGeary JE, Suzuki A, Reaven PD, Wan ES, Lynch JA, Petersen JM, Meigs JB, Freiberg MS, Gatsby E, Lynch KE, Zekavat SM, Natarajan P, Dalal S, Jhala DN, Arjomandi M, Bonomo RA, Thompson TK, Pathak GA, Zhou JJ, Donskey CJ, Madduri RK, Wells QS, Gelernter J, Huang RDL, Polimanti R, Chang KM, Liao KP, Tsao PS, Sun YV, Wilson PWF, O'Donnell CJ, Hung AM, Gaziano JM, Hauger RL, Iyengar SK, Luoh SW, VA Million Veteran Program COVID-19 Science Initiative
Pathogens & immunity
Authors: Peluso MJ, Anglin K, Durstenfeld MS, Martin JN, Kelly JD, Hsue PY, Henrich TJ, Deeks SG
Volume 7 of Issue 12 | JCI insight
Authors: Kratochvil MJ, Kaber G, Demirdjian S, Cai PC, Burgener EB, Nagy N, Barlow GL, Popescu M, Nicolls MR, Ozawa MG, Regula DP, Pacheco-Navarro AE, Yang S, de Jesus Perez VA, Karmouty-Quintana H, Peters AM, Zhao B, Buja ML, Johnson PY, Vernon RB, Wight TN, Stanford COVID-19 Biobank Study Group, Milla CE, Rogers AJ, Spakowitz AJ, Heilshorn SC, Bollyky PL
Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e., resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We found the percentages of solids and protein content were greatly elevated in COVID-19 compared with heathy control samples and closely resembled levels seen in cystic fibrosis, a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan (HA) were major components of respiratory secretions in COVID-19 and were likewise abundant in cadaveric lung tissues from these patients. COVID-19 secretions exhibited heterogeneous rheological behaviors, with thicker samples showing increased sensitivity to DNase and hyaluronidase treatment. In histologic sections from these same patients, we observed increased accumulation of HA and the hyaladherin versican but reduced tumor necrosis factor-stimulated gene-6 staining, consistent with the inflammatory nature of these secretions. Finally, we observed diminished type I interferon and enhanced inflammatory cytokines in these secretions. Overall, our studies indicated that increases in HA and DNA in COVID-19 respiratory secretion samples correlated with enhanced inflammatory burden and suggested that DNA and HA may be viable therapeutic targets in COVID-19 infection.
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