Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4) : a randomised, double-blind, double placebo-controlled trial
Copyright © 2022 Elsevier Ltd. All rights reserved..
BACKGROUND: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.
METHODS: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168.
FINDINGS: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012).
INTERPRETATION: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered.
FUNDING: National Institute of Allergy and Infectious Diseases.
| Errataetall: |
CommentIn: Ann Intern Med. 2022 Oct;175(10):JC115. - PMID 36191322 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
The Lancet. Respiratory medicine - 10(2022), 9 vom: 15. Sept., Seite 888-899 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wolfe, Cameron R [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 08.09.2022 Date Revised 14.02.2024 published: Print-Electronic ClinicalTrials.gov: NCT04640168 CommentIn: Ann Intern Med. 2022 Oct;175(10):JC115. - PMID 36191322 Citation Status MEDLINE |
|---|
| doi: |
10.1016/S2213-2600(22)00088-1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM341403229 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM341403229 | ||
| 003 | DE-627 | ||
| 005 | 20240214232520.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/S2213-2600(22)00088-1 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1292.xml |
| 035 | |a (DE-627)NLM341403229 | ||
| 035 | |a (NLM)35617986 | ||
| 035 | |a (PII)S2213-2600(22)00088-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wolfe, Cameron R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4) |b a randomised, double-blind, double placebo-controlled trial |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.09.2022 | ||
| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04640168 | ||
| 500 | |a CommentIn: Ann Intern Med. 2022 Oct;175(10):JC115. - PMID 36191322 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier Ltd. All rights reserved. | ||
| 520 | |a BACKGROUND: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19 | ||
| 520 | |a METHODS: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168 | ||
| 520 | |a FINDINGS: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012) | ||
| 520 | |a INTERPRETATION: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered | ||
| 520 | |a FUNDING: National Institute of Allergy and Infectious Diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 7 | |a Azetidines |2 NLM | |
| 650 | 7 | |a Purines |2 NLM | |
| 650 | 7 | |a Pyrazoles |2 NLM | |
| 650 | 7 | |a Sulfonamides |2 NLM | |
| 650 | 7 | |a Dexamethasone |2 NLM | |
| 650 | 7 | |a 7S5I7G3JQL |2 NLM | |
| 650 | 7 | |a baricitinib |2 NLM | |
| 650 | 7 | |a ISP4442I3Y |2 NLM | |
| 650 | 7 | |a Oxygen |2 NLM | |
| 650 | 7 | |a S88TT14065 |2 NLM | |
| 700 | 1 | |a Tomashek, Kay M |e verfasserin |4 aut | |
| 700 | 1 | |a Patterson, Thomas F |e verfasserin |4 aut | |
| 700 | 1 | |a Gomez, Carlos A |e verfasserin |4 aut | |
| 700 | 1 | |a Marconi, Vincent C |e verfasserin |4 aut | |
| 700 | 1 | |a Jain, Mamta K |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Otto O |e verfasserin |4 aut | |
| 700 | 1 | |a Paules, Catharine I |e verfasserin |4 aut | |
| 700 | 1 | |a Palacios, Guillermo M Ruiz |e verfasserin |4 aut | |
| 700 | 1 | |a Grossberg, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Harkins, Michelle S |e verfasserin |4 aut | |
| 700 | 1 | |a Mularski, Richard A |e verfasserin |4 aut | |
| 700 | 1 | |a Erdmann, Nathaniel |e verfasserin |4 aut | |
| 700 | 1 | |a Sandkovsky, Uriel |e verfasserin |4 aut | |
| 700 | 1 | |a Almasri, Eyad |e verfasserin |4 aut | |
| 700 | 1 | |a Pineda, Justino Regalado |e verfasserin |4 aut | |
| 700 | 1 | |a Dretler, Alexandra W |e verfasserin |4 aut | |
| 700 | 1 | |a de Castilla, Diego Lopez |e verfasserin |4 aut | |
| 700 | 1 | |a Branche, Angela R |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Pauline K |e verfasserin |4 aut | |
| 700 | 1 | |a Mehta, Aneesh K |e verfasserin |4 aut | |
| 700 | 1 | |a Short, William R |e verfasserin |4 aut | |
| 700 | 1 | |a McLellan, Susan L F |e verfasserin |4 aut | |
| 700 | 1 | |a Kline, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Iovine, Nicole M |e verfasserin |4 aut | |
| 700 | 1 | |a El Sahly, Hana M |e verfasserin |4 aut | |
| 700 | 1 | |a Doernberg, Sarah B |e verfasserin |4 aut | |
| 700 | 1 | |a Oh, Myoung-Don |e verfasserin |4 aut | |
| 700 | 1 | |a Huprikar, Nikhil |e verfasserin |4 aut | |
| 700 | 1 | |a Hohmann, Elizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Kelley, Colleen F |e verfasserin |4 aut | |
| 700 | 1 | |a Holodniy, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Eu Suk |e verfasserin |4 aut | |
| 700 | 1 | |a Sweeney, Daniel A |e verfasserin |4 aut | |
| 700 | 1 | |a Finberg, Robert W |e verfasserin |4 aut | |
| 700 | 1 | |a Grimes, Kevin A |e verfasserin |4 aut | |
| 700 | 1 | |a Maves, Ryan C |e verfasserin |4 aut | |
| 700 | 1 | |a Ko, Emily R |e verfasserin |4 aut | |
| 700 | 1 | |a Engemann, John J |e verfasserin |4 aut | |
| 700 | 1 | |a Taylor, Barbara S |e verfasserin |4 aut | |
| 700 | 1 | |a Ponce, Philip O |e verfasserin |4 aut | |
| 700 | 1 | |a Larson, LuAnn |e verfasserin |4 aut | |
| 700 | 1 | |a Melendez, Dante Paolo |e verfasserin |4 aut | |
| 700 | 1 | |a Seibert, Allan M |e verfasserin |4 aut | |
| 700 | 1 | |a Rouphael, Nadine G |e verfasserin |4 aut | |
| 700 | 1 | |a Strebe, Joslyn |e verfasserin |4 aut | |
| 700 | 1 | |a Clark, Jesse L |e verfasserin |4 aut | |
| 700 | 1 | |a Julian, Kathleen G |e verfasserin |4 aut | |
| 700 | 1 | |a de Leon, Alfredo Ponce |e verfasserin |4 aut | |
| 700 | 1 | |a Cardoso, Anabela |e verfasserin |4 aut | |
| 700 | 1 | |a de Bono, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Atmar, Robert L |e verfasserin |4 aut | |
| 700 | 1 | |a Ganesan, Anuradha |e verfasserin |4 aut | |
| 700 | 1 | |a Ferreira, Jennifer L |e verfasserin |4 aut | |
| 700 | 1 | |a Green, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Makowski, Mat |e verfasserin |4 aut | |
| 700 | 1 | |a Bonnett, Tyler |e verfasserin |4 aut | |
| 700 | 1 | |a Beresnev, Tatiana |e verfasserin |4 aut | |
| 700 | 1 | |a Ghazaryan, Varduhi |e verfasserin |4 aut | |
| 700 | 1 | |a Dempsey, Walla |e verfasserin |4 aut | |
| 700 | 1 | |a Nayak, Seema U |e verfasserin |4 aut | |
| 700 | 1 | |a Dodd, Lori E |e verfasserin |4 aut | |
| 700 | 1 | |a Beigel, John H |e verfasserin |4 aut | |
| 700 | 1 | |a Kalil, Andre C |e verfasserin |4 aut | |
| 700 | 0 | |a ACTT-4 Study Group |e verfasserin |4 aut | |
| 700 | 1 | |a Wahid, Lana |e investigator |4 oth | |
| 700 | 1 | |a Walter, Emmanuel B |e investigator |4 oth | |
| 700 | 1 | |a Belur, Akhila G |e investigator |4 oth | |
| 700 | 1 | |a Dreyer, Grace |e investigator |4 oth | |
| 700 | 1 | |a Patterson, Jan E |e investigator |4 oth | |
| 700 | 1 | |a Bowling, Jason E |e investigator |4 oth | |
| 700 | 1 | |a Dixon, Danielle O |e investigator |4 oth | |
| 700 | 1 | |a Hewlett, Angela |e investigator |4 oth | |
| 700 | 1 | |a Odrobina, Robert |e investigator |4 oth | |
| 700 | 1 | |a Pupaibool, Jakrapun |e investigator |4 oth | |
| 700 | 1 | |a Mocherla, Satish |e investigator |4 oth | |
| 700 | 1 | |a Lazarte, Suzana |e investigator |4 oth | |
| 700 | 1 | |a Cayabyab, Meilani |e investigator |4 oth | |
| 700 | 1 | |a Hussein, Rezhan H |e investigator |4 oth | |
| 700 | 1 | |a Golamari, Reshma R |e investigator |4 oth | |
| 700 | 1 | |a Krill, Kaleigh L |e investigator |4 oth | |
| 700 | 1 | |a Rajme, Sandra |e investigator |4 oth | |
| 700 | 1 | |a Riska, Paul F |e investigator |4 oth | |
| 700 | 1 | |a Zingman, Barry S |e investigator |4 oth | |
| 700 | 1 | |a Mertz, Gregory |e investigator |4 oth | |
| 700 | 1 | |a Sosa, Nestor |e investigator |4 oth | |
| 700 | 1 | |a Goepfert, Paul A |e investigator |4 oth | |
| 700 | 1 | |a Berhe, Mezgebe |e investigator |4 oth | |
| 700 | 1 | |a Dishner, Emma |e investigator |4 oth | |
| 700 | 1 | |a Fayed, Mohamed |e investigator |4 oth | |
| 700 | 1 | |a Hubel, Kinsley |e investigator |4 oth | |
| 700 | 1 | |a Martinez-Orozco, José Arturo |e investigator |4 oth | |
| 700 | 1 | |a Bautista Felix, Nora |e investigator |4 oth | |
| 700 | 1 | |a Elmor, Sammy T |e investigator |4 oth | |
| 700 | 1 | |a Bechnak, Amer Ryan |e investigator |4 oth | |
| 700 | 1 | |a Saklawi, Youssef |e investigator |4 oth | |
| 700 | 1 | |a Van Winkle, Jason W |e investigator |4 oth | |
| 700 | 1 | |a Zea, Diego F |e investigator |4 oth | |
| 700 | 1 | |a Laguio-Vila, Maryrose |e investigator |4 oth | |
| 700 | 1 | |a Walsh, Edward E |e investigator |4 oth | |
| 700 | 1 | |a Falsey, Ann R |e investigator |4 oth | |
| 700 | 1 | |a Carvajal, Karen |e investigator |4 oth | |
| 700 | 1 | |a Hyzy, Robert C |e investigator |4 oth | |
| 700 | 1 | |a Hanna, Sinan |e investigator |4 oth | |
| 700 | 1 | |a Olbrich, Norman |e investigator |4 oth | |
| 700 | 1 | |a Traenkner, Jessica J |e investigator |4 oth | |
| 700 | 1 | |a Kraft, Colleen S |e investigator |4 oth | |
| 700 | 1 | |a Tebas, Pablo |e investigator |4 oth | |
| 700 | 1 | |a Baron, Jillian T |e investigator |4 oth | |
| 700 | 1 | |a Levine, Corri |e investigator |4 oth | |
| 700 | 1 | |a Nock, Joy |e investigator |4 oth | |
| 700 | 1 | |a Billings, Joanne |e investigator |4 oth | |
| 700 | 1 | |a Kim, Hyun |e investigator |4 oth | |
| 700 | 1 | |a Elie-Turenne, Marie-Carmelle |e investigator |4 oth | |
| 700 | 1 | |a Whitaker, Jennifer A |e investigator |4 oth | |
| 700 | 1 | |a Luetkemeyer, Anne F |e investigator |4 oth | |
| 700 | 1 | |a Dwyer, Jay |e investigator |4 oth | |
| 700 | 1 | |a Bainbridge, Emma |e investigator |4 oth | |
| 700 | 1 | |a Gyun Choe, Pyoeng |e investigator |4 oth | |
| 700 | 1 | |a Kyung Kang, Chang |e investigator |4 oth | |
| 700 | 1 | |a Jilg, Nikolaus |e investigator |4 oth | |
| 700 | 1 | |a Cantos, Valeria D |e investigator |4 oth | |
| 700 | 1 | |a Bhamidipati, Divya R |e investigator |4 oth | |
| 700 | 1 | |a Nithin Gopalsamy, Srinivasa |e investigator |4 oth | |
| 700 | 1 | |a Chary, Aarthi |e investigator |4 oth | |
| 700 | 1 | |a Jung, Jongtak |e investigator |4 oth | |
| 700 | 1 | |a Song, Kyoung-Ho |e investigator |4 oth | |
| 700 | 1 | |a Kim, Hong Bin |e investigator |4 oth | |
| 700 | 1 | |a Benson, Constance A |e investigator |4 oth | |
| 700 | 1 | |a McConnell, Kimberly |e investigator |4 oth | |
| 700 | 1 | |a Wang, Jennifer P |e investigator |4 oth | |
| 700 | 1 | |a Wessolossky, Mireya |e investigator |4 oth | |
| 700 | 1 | |a Perez, Katherine |e investigator |4 oth | |
| 700 | 1 | |a Eubank, Taryn A |e investigator |4 oth | |
| 700 | 1 | |a Berjohn, Catherine |e investigator |4 oth | |
| 700 | 1 | |a Utz, Gregory C |e investigator |4 oth | |
| 700 | 1 | |a Jackson, Patrick E H |e investigator |4 oth | |
| 700 | 1 | |a Bell, Taison D |e investigator |4 oth | |
| 700 | 1 | |a Haughey, Heather M |e investigator |4 oth | |
| 700 | 1 | |a Moanna, Abeer |e investigator |4 oth | |
| 700 | 1 | |a Cribbs, Sushma |e investigator |4 oth | |
| 700 | 1 | |a Harrison, Telisha |e investigator |4 oth | |
| 700 | 1 | |a Colombo, Christopher J |e investigator |4 oth | |
| 700 | 1 | |a Schofield, Christina |e investigator |4 oth | |
| 700 | 1 | |a Colombo, Rhonda E |e investigator |4 oth | |
| 700 | 1 | |a Tapson, Victor F |e investigator |4 oth | |
| 700 | 1 | |a Grein, Jonathan |e investigator |4 oth | |
| 700 | 1 | |a Sutterwala, Fayyaz |e investigator |4 oth | |
| 700 | 1 | |a Ince, Dilek |e investigator |4 oth | |
| 700 | 1 | |a Winokur, Patricia L |e investigator |4 oth | |
| 700 | 1 | |a Fung, Monica |e investigator |4 oth | |
| 700 | 1 | |a Jang, Hannah |e investigator |4 oth | |
| 700 | 1 | |a Wyles, David |e investigator |4 oth | |
| 700 | 1 | |a Frank, Maria G |e investigator |4 oth | |
| 700 | 1 | |a Sarcone, Ellen |e investigator |4 oth | |
| 700 | 1 | |a Neumann, Henry |e investigator |4 oth | |
| 700 | 1 | |a Viswanathan, Anand |e investigator |4 oth | |
| 700 | 1 | |a Hochman, Sarah |e investigator |4 oth | |
| 700 | 1 | |a Mulligan, Mark |e investigator |4 oth | |
| 700 | 1 | |a Eckhardt, Benjamin |e investigator |4 oth | |
| 700 | 1 | |a Carmody, Ellie |e investigator |4 oth | |
| 700 | 1 | |a Ahuja, Neera |e investigator |4 oth | |
| 700 | 1 | |a Nadeau, Kari |e investigator |4 oth | |
| 700 | 1 | |a Svec, David |e investigator |4 oth | |
| 700 | 1 | |a Macaraeg, Jeffrey C |e investigator |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t The Lancet. Respiratory medicine |d 2013 |g 10(2022), 9 vom: 15. Sept., Seite 888-899 |w (DE-627)NLM232005109 |x 2213-2619 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2022 |g number:9 |g day:15 |g month:09 |g pages:888-899 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/S2213-2600(22)00088-1 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2022 |e 9 |b 15 |c 09 |h 888-899 | ||