Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19 (2024)

Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19 (1) https://doi.org/10.1093/cid/ciad780 · Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19 (2)

Видання: Clinical Infectious Diseases, 2024

Видавець: Oxford University Press (OUP)

Автори:

  1. Neil R Aggarwal
  2. Jacquie Nordwall
  3. Dominique L Braun
  4. Lucy Chung
  5. Jordan Coslet
  6. Tatyana Der
  7. Nnakelu Eriobu
  8. Adit A Ginde
  9. Awori J Hayanga
  10. Helene Highbarger
  11. Mark Holodniy
  12. Juan P Horcajada
  13. Mamta K Jain
  14. Kami Kim
  15. Sylvain Laverdure
  16. Jens Lundgren
  17. Ven Natarajan
  18. Hien H Nguyen
  19. Sarah L Pett
  20. Andrew Phillips
  21. Garyphallia Poulakou
  22. David A Price
  23. Philip Robinson
  24. Angela J Rogers
  25. Uriel Sandkovsky
  26. Katy Shaw-Saliba
  27. Jeffrey M Sturek
  28. Barbara W Trautner
  29. Michael Waters
  30. Cavan Reilly
  31. David Sahner
  32. John Tierney
  33. Susan E Vogel
  34. Betsey R Herpin
  35. Mary C Smolskis
  36. Laura A McKay
  37. Kelly Cahill
  38. Page Crew
  39. Ratna Sardana
  40. Sharon Segal Raim
  41. Lisa Hensely
  42. Johsua Lorenzo
  43. Rebecca Mock
  44. Judith Zuckerman
  45. Negin Atri
  46. Mark Miller
  47. David Vallee
  48. Lucy Chung
  49. Nayon Kang
  50. Kevin Barrett
  51. Stacey J Adam
  52. Sarah Read
  53. Ruxandra Draghia-Akli
  54. Judy Currier
  55. Eric Hughes
  56. Rachel H Harrigan
  57. Laura Amos
  58. Amy Carlsen
  59. Anita Carter
  60. Gary Collins
  61. Bionca Davis
  62. Eileen Denning
  63. Alain duch*ene
  64. Kate Eckroth
  65. Nicole Engen
  66. Alex Frase
  67. Greg Gandits
  68. Birgit Grund
  69. Merrie Harrison
  70. Nancy Hurlbut
  71. Payton Kaiser
  72. Joseph Koopmeiners
  73. Gregg Larson
  74. Sue Meger
  75. Shweta Sharma Mistry
  76. Thomas Murray
  77. Ray Nelson
  78. Kien Quan
  79. Siu Fun Quan
  80. Cavan Reilly
  81. Lianne Siegel
  82. Greg Thompson
  83. David Vock
  84. Jamie Walski
  85. Annetine C Gelijns
  86. Alan J Moskowitz
  87. Emilia Bagiella
  88. Ellen Moquete
  89. Karen O'Sullivan
  90. Mary E Marks
  91. Evan Accardi
  92. Emily Kinzel
  93. Sarah Burris
  94. Gabriela Bedoya
  95. Lola Gupta
  96. Jessica R Overbey
  97. Milerva Santos
  98. Marc A Gillinov
  99. Marissa A Miller
  100. Wendy C Taddei-Peters
  101. Kathleen Fenton
  102. Uriel Sandkovsky
  103. Robert L Gottlieb
  104. Michael Mack
  105. Mezgebe Berhe
  106. Clinton Haley
  107. Emma Dishner
  108. Christopher Bettacchi
  109. Kevin Golden
  110. Erin Duhaime
  111. Madison Ryan
  112. Sarah Burris
  113. Catherine Tallmadge
  114. Lorie Estrada
  115. Felecia Jones
  116. Samatha Villa
  117. Samatha Wang
  118. Raven Robert
  119. Tanquinisha Coleman
  120. Laura Clariday
  121. Rebecca Baker
  122. Mariana Hurutado-Rodriguez
  123. Nazia Iram
  124. Michelle Fresnedo
  125. Allyson Davis
  126. Kiara Leonard
  127. Noelia Ramierez
  128. Jon Thammavong
  129. Krizia Duque
  130. Emma Turner
  131. Fisher Tammy
  132. Dianna Robinson
  133. Desirae Ransom
  134. Nicholas Maldonado
  135. Erica Lusk
  136. Aaron Killian
  137. Palacious Adriana
  138. Edilia Solis
  139. Janet Jerrow
  140. Matthew Watts
  141. Heather Whitacre
  142. Elizabeth Cothran
  143. Peter K Smith
  144. Christina E Barkauskas
  145. Andrew M Vekstein
  146. Emily R Ko
  147. Grace R Dreyer
  148. Neil Stafford
  149. Megan Brooks
  150. Tatyana Der
  151. Marie Witte
  152. Ruwan Gamarallage
  153. John Franzone
  154. Noel Ivey
  155. Rebecca H Lumsden
  156. Nilima Mosaly
  157. Ahmaad Mourad
  158. Thomas L Holland
  159. Mary Motta
  160. Kathleen Lane
  161. Lauren M McGowan
  162. Jennifer Stout
  163. Heather Aloor
  164. Kennesha M Bragg
  165. Barvina Toledo
  166. Beth McLendon-Arvik
  167. Barbara Bussadori
  168. Beth A Hollister
  169. Michelle Griffin
  170. Dana M Giangiacomo
  171. Vicente Rodriguez
  172. Gordon Bokhart
  173. Sharon M Eichman
  174. Patrick E Parrino
  175. Stephen Spindel
  176. Aditya Bansal
  177. Katherine Baumgarten
  178. Johnathan Hand
  179. Derek Vonderhaar
  180. Bobby Nossaman
  181. Sylvia Laudun
  182. DeAnna Ames
  183. Shane Broussard
  184. Nilmo Hernandez
  185. Geralyn Isaac
  186. Huan Dinh
  187. Yiling Zheng
  188. Sonny Tran
  189. Hunter McDaniel
  190. Nicolle Crovetto
  191. Emerson Perin
  192. Briana Costello
  193. Prasad Manian
  194. M Rizwan Sohail
  195. Alexander Postalian
  196. Punit Hinsu
  197. Carolyn Watson
  198. James Chen
  199. Melyssa Fink
  200. Lydia Sturgis
  201. Kim Walker
  202. Kim Mahon
  203. Jennifer Parenti
  204. Casey Kappenman
  205. Aryn Knight
  206. Jeffrey M Sturek
  207. Andrew Barros
  208. Kyle B Enfield
  209. Alexandra Kadl
  210. China J Green
  211. Rachel M Simon
  212. Ashley Fox
  213. Kara Thornton
  214. Amy Adams
  215. Vinay Badhwar
  216. Sunil Sharma
  217. Briana Peppers
  218. Paul McCarthy
  219. Troy Krupica
  220. Arif Sarwari
  221. Rebecca Reece
  222. Lisa Fornaresico
  223. Chad Glaze
  224. Raquel Evans
  225. Fang Di
  226. Shawn Carlson
  227. Tanja Aucremanne
  228. Connie Tennant
  229. Sutton Lisa Giblin
  230. Sabrina Buterbaugh
  231. Roger Williams
  232. Robin Bunner
  233. Jay H Traverse
  234. Frank Rhame
  235. Joshua Huelster
  236. Rajesh Kethireddy
  237. Irena Davies
  238. Julianne Salamanca
  239. Christine Majeski
  240. Paige Skelton
  241. Maria Zarambo
  242. Andrea Sarafolean
  243. Michael E Bowdish
  244. Zea Borok
  245. Noah Wald-Dickler
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  248. Mary Lee
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  251. Linda Sher
  252. Aniket Sharma
  253. Anna P Olds
  254. Chris Justino
  255. Edward Loxano
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  260. Luke Hamilton
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  262. Brad Leshnower
  263. William Bender
  264. Milad Sharifpour
  265. Jeffrey Miller
  266. Woodrow Farrington
  267. Kim T Baio
  268. Mary McBride
  269. Michele Fielding
  270. Sonya Mathewson
  271. Kristina Porte
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  275. Christine Spainhour
  276. Susan Rogers
  277. Derrick Tyler
  278. Ronson J Madathil
  279. Joseph Rabin
  280. Andrea Levine
  281. Kapil Saharia
  282. Ali Tabatabai
  283. Christine Lau
  284. James S Gammie
  285. Maya-Loren Peguero
  286. Kimberly McKernan
  287. Mathew Audette
  288. Emily Fleischmann
  289. Kreshta Akbari
  290. Myounghee Lee
  291. Andrew Chi
  292. Hanna Salehi
  293. Alan Pariser
  294. Phuong Tran Nyguyen
  295. Jessica Moore
  296. Adrienne Gee
  297. Shelika Vincent
  298. Richard A Zuckerman
  299. Alexander Iribarne
  300. Sara Metzler
  301. Samantha Shipman
  302. Haley Johnson
  303. Crystallee Newton
  304. Doug Parr
  305. Leslie Miller
  306. Beth Schelle
  307. Sherry McLean
  308. Howard R Rothbaum
  309. Michael S Alvarez
  310. Shivam P Kalan
  311. Heather H Germann
  312. Jennifer Hendershot
  313. Karen Moroney
  314. Karen Herring
  315. Sharri Cook
  316. Pam Paul
  317. Rebecca Walker-Ignasiak
  318. Crystal North
  319. Cathryn Oldmixon
  320. Nancy Ringwood
  321. Ariela Muzikansky
  322. Richard Morse
  323. Laura Fitzgerald
  324. Haley D Morin
  325. Roy G Brower
  326. Lora A Reineck
  327. Karen Bienstock
  328. Jay H Steingrub
  329. Peter K Hou
  330. Jay S Steingrub
  331. Mark A Tidswell
  332. Lori-Ann Kozikowski
  333. Cynthia Kardos
  334. Leslie DeSouza
  335. Sarah Romain
  336. Sherell Thornton-Thompson
  337. Daniel Talmor
  338. Nathan Shapiro
  339. Konstantinos Andromidas
  340. Valerie Banner-Goodspeed
  341. Michael Bolstad
  342. Katherine L Boyle
  343. Payton Cabrera
  344. Arnaldo deVilla
  345. Joshua C Ellis
  346. Ana Grafals
  347. Sharon Hayes
  348. Conor Higgins
  349. Lisa Kurt
  350. Nicholas Kurtzman
  351. Kimberly Redman
  352. Elinita Rosseto
  353. Douglas Scaffidi
  354. Nathan Shapiro
  355. Michael R Filbin
  356. Kathryn A Hibbert
  357. Blair Parry
  358. Justin Margolin
  359. Brooklynn Hillis
  360. Rhonda Hamer
  361. Kelsey Brait
  362. Caroline Beakes
  363. Brenna McKaig
  364. Eleonore Kugener
  365. Alan E Jones
  366. James Galbraith
  367. Utsav Nandi
  368. Rebekah Peaco*ck
  369. Gregory Hendey
  370. Kirsten Kangelaris
  371. Kimia Ashktorab
  372. Rachel Gropper
  373. Anika Agrawal
  374. Kimberley J Yee
  375. Alejandra E Jauregui
  376. Hanjing Zhuo
  377. Eyad Almasri
  378. Mohamed Fayed
  379. Kinsley A Hubel
  380. Alyssa R Hughes
  381. Rebekah L Garcia
  382. George W Lim
  383. Steven Y Chang
  384. Gregory Hendey
  385. Michael Y Lin
  386. Julia Vargas
  387. Hena Sihota
  388. Rebecca Beutler
  389. Trisha Agarwal
  390. Jennifer G Wilson
  391. Rosemary Vojnik
  392. Cynthia Perez
  393. Jordan H McDowell
  394. Jonasel Roque
  395. Henry Wang
  396. Ryan M Huebinger
  397. Bela Patel
  398. Elizabeth Vidales
  399. Timothy Albertson
  400. Erin Hardy
  401. Richart Harper
  402. Marc A Moss
  403. Amiran Baduashvili
  404. Lakshmi Chauhan
  405. David J Douin
  406. Flora Martinez
  407. Lani L Finck
  408. Jill Bastman
  409. Michelle Howell
  410. Carrie Higgins
  411. Jeffrey McKeehan
  412. Jay Finigan
  413. Peter Stubenrauch
  414. William J Janssen
  415. Christine Griesmer
  416. Olivia VerBurg
  417. Robert C Hyzy
  418. Pauline K Park
  419. Kristine Nelson
  420. Jake I McSparron
  421. Ivan N Co
  422. Bonnie R Wang
  423. Jose Jimenez
  424. Norman Olbrich
  425. Kelli McDonough
  426. Shijing Jia
  427. Sinan Hanna
  428. Michelle N Gong
  429. Lynne D Richardson
  430. Rahul Nair
  431. Brenda Lopez
  432. Omowunmi Amosu
  433. Obiageli Offor
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  436. Sabah Boujid
  437. Jarrod M Mosier
  438. Cameron Hypes
  439. Elizabeth Salvagio Campbell
  440. Billie Bixby
  441. Boris Gilson
  442. Anitza Lopez
  443. Christian Bime
  444. Sairam Parthasarathy
  445. Ariana M Cano
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  448. Herbert P Wiedemann
  449. Kristin Hudock
  450. Hammad Tanzeem
  451. Harshada More
  452. Jamie Martinkovic
  453. Susan Sellers
  454. Judy Houston
  455. Mary Burns
  456. Simra Kiran
  457. Tammy Roads
  458. Sarah Kennedy
  459. Abhijit Duggal
  460. Nirosshan Thiruchelvam
  461. Kiran Ashok
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  466. Donald M Yealy
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  471. Catherine L Hough
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  475. Mistry Kinjal
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  477. Raju Reddy
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  479. Milad K Jouzestani
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  481. Rupali Deshmukh
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  483. Bryce H Robinson
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  495. Devin Fine
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  564. Jenna Lumpkin
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  589. Anjana Pillai
  590. Jean Daniel
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  592. Balavenkatesh Kanna
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  1396. Debi Hogarty
  1397. Lynda Huber
  1398. Gary Krauss
  1399. Eileen Lake
  1400. Meryan Manandhar
  1401. Erin Rudzinski
  1402. Jen Sandrus
  1403. Connie Suders
  1404. Ven Natarajan
  1405. Adam W Rupert
  1406. Michael Baseler
  1407. Danielle Lynam
  1408. Tom Imamichi
  1409. Sylvain Laverdure
  1410. Ashley McCormack
  1411. Sharada Paudel
  1412. Kyndal Cook
  1413. Kendra Haupt
  1414. Ayub Khan
  1415. Allison Hazen
  1416. Yunden Badralmaa
  1417. Kenneth Smith
  1418. Bhakti Patel
  1419. Amanda Kubernac
  1420. Robert Kubernac
  1421. Marie L Hoover
  1422. Courtney Solomon
  1423. Marium Rashid
  1424. Joseph Murphy
  1425. Craig Brown
  1426. Nadine DuChateau
  1427. Sadie Ellis
  1428. Adam Flosi
  1429. Lisa Fox
  1430. Les Johnson
  1431. Rich Nelson
  1432. Jelena Stojanovic
  1433. Amy Treagus
  1434. Christine Wenner
  1435. Richard Williams
  1436. for the ACTIV-3/TICO Study Group

Анотація

Abstract <jats:sec> Background Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials. </jats:sec> <jats:sec> Methods A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti–SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models. </jats:sec> <jats:sec> Results Viral Ag ≥4500 ng/L (vs &amp;lt;200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29–3.34), viral RNA (&amp;lt;35 000 copies/mL [aHR, 2.42; 1.09–5.34], ≥35 000 copies/mL [aHR, 2.84; 1.29–6.28], vs below detection), respiratory support (&amp;lt;4 L O2 [aHR, 1.84; 1.06–3.22]; ≥4 L O2 [aHR, 4.41; 2.63–7.39], or noninvasive ventilation/high-flow nasal cannula [aHR, 11.30; 6.46–19.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29–2.42), and IL-6 &amp;gt;5.8 ng/L (aHR, 2.54 [1.74–3.70] vs ≤5.8 ng/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time. </jats:sec> <jats:sec> Conclusions Baseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease. </jats:sec>

Джерела фінансування

  1. National Institute of Allergy and Infectious Diseases
  2. National Institutes of Health
  3. National Cancer Institute
  4. National Heart, Lung, and Blood Institute
  5. University of Minnesota

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Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19 (2024)
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