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1. Clinical characteristics and outcomes of critically ill mechanically ventilated COVID-19 patients receiving interleukin-6 receptor antagonists and corticosteroid therapy: a preliminary report from a multinational registry

Author

Marwa Amer, Ahmed M. Kamel, Mohammed Bawazeer, Khalid Maghrabi, Abid Butt, Talal Dahhan, Eiad Kseibi, Syed Moazzum Khurshid, Mohammed Abujazar, Razan Alghunaim, Muath Rabee, Maal Abualkhair, Ali Al-Janoubi, Abeer Turki AlFirm, Ognjen Gajic, Allan J. Walkey, Jarrod M. Mosier, Igor Borisovich Zabolotskikh, Oscar Y. Gavidia, Santiago Yus- Teruel, Michael A. Bernstein, Karen Boman, Vishakha K. Kumar, Vikas Bansal, Rahul Kashyap, and the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group

Subjects
Interleukin-6, Interleukin-6 receptor antagonist, Steroid, Critical care, Coronavirus disease 2019, Invasive mechanical ventilation, Medicine
Abstract

Abstract Background Interleukin-6 receptor antagonists (IL-6RAs) and steroids are emerging immunomodulatory therapies for severe and critical coronavirus disease (COVID-19). In this preliminary report, we aim to describe the epidemiology, clinical characteristics, and outcomes of adult critically ill COVID-19 patients, requiring invasive mechanical ventilation (iMV), and receiving IL-6RA and steroids therapy over the last 11 months. Materials and methods International, multicenter, cohort study derived from Viral Infection and Respiratory Illness University Study registry and conducted through Discovery Network, Society of Critical Care Medicine. Data were collected between March 01, 2020, and January 10, 2021. Results Of 860 patients who met eligibility criteria, 589 received steroids, 170 IL-6RAs, and 101 combinations. Patients who received IL-6RAs were younger (median age of 57.5 years vs. 61.1 and 61.8 years in the steroids and combination groups, respectively). The median C-reactive protein level was > 75 mg/L, indicating a hyperinflammatory phenotype. The median daily steroid dose was 7.5 mg dexamethasone or equivalent (interquartile range: 6–14 mg); 80.8% and 19.2% received low-dose and high-dose steroids, respectively. Of the patients who received IL-6RAs, the majority received one dose of tocilizumab and sarilumab (dose range of 600–800 mg for tocilizumab and 200–400 mg for sarilumab). Regarding the timing of administration, we observed that steroid and IL-6RA administration on day 0 of ICU admission was only 55.6% and 39.5%, respectively. By day 28, when compared with steroid use alone, IL-6RA use was associated with an adjusted incidence rate ratio (aIRR) of 1.12 (95% confidence interval [CI] 0.88, 1.4) for ventilator-free days, while combination therapy was associated with an aIRR of 0.83 (95% CI 0.6, 1.14). IL-6RA use was associated with an adjusted odds ratio (aOR) of 0.68 (95% CI 0.44, 1.07) for the 28-day mortality rate, while combination therapy was associated with an aOR of 1.07 (95% CI 0.67, 1.70). Liver dysfunction was higher in IL-6RA group (p = 0.04), while the bacteremia rate did not differ among groups. Conclusions Discordance was observed between the registry utilization patterns (i.e., timing of steroids and IL-6RA administration) and new evidence from the recent randomized controlled trials and guideline recommendations. These data will help us to identify areas of improvement in prescribing patterns and enhance our understanding of IL-6RA safety with different steroid regimens. Further studies are needed to evaluate the drivers of hospital-level variation and their impact on clinical outcomes. Trial registration ClinicalTrials.gov: NCT04486521. Registered on July 2020

Published
2021
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2. Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic

Author

Anna M. Cervantes-Arslanian, MD, Chakradhar Venkata, MD, Pria Anand, MD, Joseph D. Burns, MD, Charlene J. Ong, MD, Allison M. LeMahieu, MS, Phillip J. Schulte, PhD, Tarun D. Singh, MD, Alejandro A. Rabinstein, MD, Neha Deo, BS, Vikas Bansal, MBBS, MPH, Karen Boman, BS, Juan Pablo Domecq Garces, MD, Donna Lee Armaignac, PhD, APRN, Amy B. Christie, MD, Roman R. Melamed, MD, Yasir Tarabichi, MD, MSCR, Sreekanth R. Cheruku, MD, MPH, Ashish K. Khanna, MD, FCCP, FCCM, FASA, Joshua L. Denson, MD, MS, Valerie M. Banner-Goodspeed, MPH, Harry L. Anderson, III, MD, FACS, FICS, FCCM, FCCP, FAIM, Ognjen Gajic, MD, MS, Vishakha K. Kumar, MD, MBA, Allan Walkey, MD, Rahul Kashyap, MD, MBA, on behalf of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group, Jean-Baptiste Mesland, Pierre Henin, Hélène Petre, Isabelle Buelens, Anne-Catherine Gerard, Philippe Clevenbergh, Rolando Claure-Del Granado, Jose A. Mercado, Esdenka Vega-Terrazas, Maria F. Iturricha-Caceres, Ruben Garza, Eric Chu, Victoria Chan, Oscar Y Gavidia, Felipe Pachon, Yeimy A Sanchez, Danijel knežević, Mohamed El Kassas, Mohamed Badr, Ahmed Tawheed, Hend Yahia, Dimitrios Kantas, Vasileios Koulouras, Estela Pineda, Gabina María Reyes Guillen, Helin Archaga Soto, Ana Karen Vallecillo Lizardo, Csaba Kopitkó, Ágnes Bencze, István Méhész, Zsófia Gerendai,, Girish Vadgaonkar, Rekha Ediga, Shilpa Basety, Shwetha Dammareddy, Phani Sreeharsha Kasumalla, Smitha S. Segu, Tuhin Chakraborty, Epcebha Joyce, Sridhar Papani, Mahesh Kamuram, Mradul Kumar Daga, Munisha Agarwal, Ishan Rohtagi, Anusha Cherian, Sreejith Parameswaran, Magesh Parthiban, Phaneendra Doddaga, Neethi Chandra, Puneet Rijhwani, Ashish Jain, Aviral Gupta, Ram Mohan Jaiswal, Ambika Tyagi, Nimish Mathur, Madhav Prabhu, Vishal Jakati, Mukur Petrolwala, Bharat Ladva, Surapaneni Krishna Mohan, Ekambaram Jyothisree, Umamaheswara Raju, Janaki Manduva, Naresh Kolakani, Shreeja Sripathi, Sheetal Chaitanya, Kamlesh Kumar Agrawal, Vijendra Baghel, Kirti Kumar Patel, Nooshin Dalili, Mohsen Nafa, Wataru Matsuda, Reina Suzuki, Michihito Kyo, Shu Tahara, Mineji Hayakawa, Kunihiko Maekawa, Masamitsu Sanui, Sho Horikita, Yuki Itagaki, Akira Kodate, Yuki Takahashi, Koyo Moriki, Takuya Shiga, Yudai Iwasaki, Hidenobu Shigemitsu, Yuka Mishima, Nobuyuki Nosaka, Michio Nagashima, Abdulrahman Al-Fares, Rene Rodriguez-Gutierrez, Jose Gerardo Gonzalez-Gonzalez, Alejandro Salcido-Montenegro, Adrian Camacho-Ortiz, Mariana Janeth Hermosillo Ulloa, Fatimah Hassan-Hanga, Hadiza Galadanci, Abubakar Shehu Gezawa, Halima M. S. Kabara, Taiwo Gboluwaga Amole, Halima Kabir, Dalha Gwarzo Haliru, Abdullahi S Ibrahim, Muhammad Sohaib Asghar, Mashaal Syed, Syed Anosh Ali Naqvi, Igor Borisovich Zabolotskikh,, Konstantin Dmitrievich Zybin, Sergey Vasilevich Sinkov, Tatiana Sergeevna Musaeva, Razan K Alamoudi, Hassan M. AlSharif, Sarah A. Almazwaghi, Mohammed S Elsakran, Mohamed A Aid, Mouaz A Darwich, Omnia M Hagag, Salah A Ali, Alona rocacorba, Kathrine Supeña, Efren Ray Juane, Jenalyn Medina, Jowany Baduria, Marwa Ridha Amer, Mohammed Abdullah, Bawazeer, Talal I. Dahhan, Eiad Kseibi, Abid Shahzad Butt, Syed Moazzum Khurshid, Muath Rabee, Mohammed Abujazar, Razan Alghunaim, Maal Abualkhair, Abeer Turki AlFirm, Yaseen M Arabi, Sheryl Ann Abdukahil, Mohammed A Almazyad, Mohammed I Alarifi, Jara M Macarambon, Ahmad Abdullah Bukhari, Hussain A. Albahrani, Kazi N Asfina, Kaltham M Aldossary, Marija Zdravkovic, Zoran Todorovic, Viseslav Popadic, Slobodan Klasnja, Ana Andrijevic, Srdjan Gavrilovic, Vladimir Carapic, Bojan Kovacevic, Jovana Bojicic, Stevanovic Predrag, Dejan S Stojakov, Duska K Ignjatovic, Suzana C Bojic, Marina M Bobos, Irina B Nenadic, Milica S Zaric, Marko D Djuric, Vladimir R Djukic, Santiago Y. Teruel, Belen C. Martin, Uluhan Sili, Huseyin Bilgin, Pinar Ay, Varsha P Gharpure, Usman Raheemi, Kenneth W. Dodd, Nicholas Goodmanson, Kathleen Hesse, Paige Bird, Chauncey Weinert, Nathan Schoenrade, Abdulrahman Altaher, Esmael Mayar, Matthew Aronson, Tyler Cooper, Monica Logan, Brianna Miner, Gisele Papo, Eric M. Siegal, Phyllis Runningen, Suzanne Barry, Christopher Woll, Gregory Wu, Erin Carrole, Kathryn Burke, Mustafa Mohammed, Roman R. Melamed, David M. Tierney, Love A. Patel, Vino S. Raj, Barite U. Dawud, Narayana Mazumder, Abbey Sidebottom, Alena M. Guenther, Benjamin D. Krehbiel, Nova J. Schmitz, Stacy L. Jepsen, Lynn Sipsey, Anna Schulte, Whitney Wunderlich, Cecely Hoyt, Abhijit A Raval, Andrea Franks, Katherine Irby, Ronald C. Sanders, Jr., Glenda Hefley, Jennifer M. Jarvis, Anmol Kharbanda, Sunil Jhajhria, Zachary Fyffe, Stephen Capizzi, Bethany Alicie, Martha Green, Lori Crockarell, Amelia Drennan, Kathleen Dubuque, Tonya Fambrough, Nikole Gasaway, Briana Krantz, Peiman Nebi, Jan Orga, Margaret Serfass, Alina Simion, Kimberly Warren, Cassie Wheeler, CJ Woolman, Amy B. Christie, Dennis W. Ashley, Rajani Adiga, Andrew S. Moyer, George M. Verghese, Andrea Sikora Newsome, Christy C. Forehand, Rebecca Bruning, Timothy W. Jones, Moldovan Sabov, Fatema Zaidi, Fiona Tissavirasingham, Dhatri Malipeddi, Jarrod M Mosier, Karen Lutrick, Beth Salvagio Campbell, Cathleen Wilson, Patrick Rivers, Jonathan Brinks, Mokenge Ndiva Mongoh, Boris Gilson, Donna Lee Armaignac, Don Parris, Maria Pilar Zuniga, Ilea Vargas, Viviana Boronat, Anneka Hutton, Navneet Kaur, Prashank Neupane, Nohemi Sadule-Rios, Lourdes M. Rojas, Aashish Neupane, Priscilla Rivera, Carlos Valle Carlos, Gregory Vincent, Mahesh Amin, Mary E Schelle, Amanda Steadham, Christopher M Howard, Cameron McBride, Jocelyn Abraham, Orlando Garner, Katherine Richards, Keegan Collins, Preethi Antony, Sindhu Mathew, Valerie C. Danesh, Gueorgui Dubrocq, Amber L. Davis, Marissa J Hammers, ill M. McGahey, Amanda C. Farris, Elisa Priest, Robyn Korsmo, Lorie Fares, Kathy Skiles, Susan M. Shor, Kenya Burns, Corrie A Dowell, Gabriela “Hope” Gonzales, Melody Flores, Lindsay Newman, Debora A Wilk, Jason Ettlinger, Jaccallene Bomar, Himani Darji, Alejandro Arroliga, Alejandro C Arroliga, Corrie A. Dowell, Gabriela Hope Conzales, Debora A. Wilk, Paras B. Khandhar, Elizabeth Kring, Valerie M. Banner-Goodspeed, Somnath Bose, Lauren E. Kelly, Melisa Joseph, Marie McGourty, Krystal Capers, Benjamin Hoenig, Maria C. Karamourtopoulos, Anica C. Law, Elias N. Baedorf Kassis, Allan J. Walkey, Sushrut S. Waikar, Michael A. Garcia, Mia Colona, Zoe Kibbelaar, Michael Leong, Daniel Wallman, Kanupriya Soni, Jennifer Maccarone, Joshua Gilman, Ycar Devis, Joseph Chung, Munizay Paracha, David N. Lumelsky, Madeline DiLorenzo, Najla Abdurrahman, Shelsey Johnson, Maj Andrew M. Hersh, CPT Stephanie L Wachs, Brittany S. Swigger, Stephanie L Wachs, Capt Lauren A. Sattler, Capt Michael N. Moulton, Kimberly Zammit, Patrick, J McGrath, William Loeffler, Maya, R. Chilbert, Aaron S. Miller, Edwin L. Anderson, Rosemary Nagy, Ravali R. Inja, Pooja A. Nawathe, Isabel Pedraza, Jennifer Tsing, Karen Carr, Anila Chaudhary, Kathleen Guglielmino, Raghavendra Tirupathi, Alymer Tang, Arshad Safi, Cindy Green, Jackie Newell, Rayan E. Ihle, Shelda A. Martin, Elaine A. Davis, Katja M. Gist, Imran A Sayed, John Brinton, Larisa Strom, Kathleen Chiotos, Allison M. Blatz, Giyoung Lee, Ryan H. Burnett, Guy I. Sydney, Danielle M. Traynor, Karissa Nauert, Annika Gonzalez, Mariel Bagley, Anita Santpurkar, Salim Surani, Joshua White, Aftab Khan, Rahul Dhahwal, Sreekanth Cheruku, Farzin Ahmed, Christopher Deonarine, Ashley Jones, Mohammad-Ali Shaikh, David Preston, Jeanette Chin, Vidula Vachharajani, Abhijit Duggal, Prabalini Rajendram, Omar Mehkri, Siddharth Dugar, Michelle Biehl, Gretchen Sacha, Stuart Houltham, Alexander King, Kiran Ashok, Bryan Poynter, Mary Beukemann, Richard Rice, Susan Gole, Valerie Shaner, Adarsh Conjeevaram, Michelle Ferrari, Narendrakumar Alappan, Steven Minear, Jaime Hernandez-Montfort, Syed Sohaib Nasim, Ravi Sunderkrishnan, Debasis Sahoo, Patrick S. Milligan, Sandeep K. Gupta, Joy M. Koglin, Regina Gibson, Lana Johnson, Felicia Preston, Crimson Scott, Bethany Nungester, Dana D Byrne, Christa A Schorr, Katie Grant, Katherine L Doktor, Maura C Porto, Olga Kaplan, James E. Siegler, III, Brian Schonewald, Ashley Woodford, Alan Tsai, Savina Reid, Kuntal Bhowmick, Saba Daneshpooy, Cyrus Mowdawalla, Trishna Akshay Dave, Wilhemina Kennedy, Connor Crudeli, Christopher Ferry, Long Nguyen, Sneha Modi, Niharika Padala, Pavan Jitendra Patel, Belle Lin, Lena Chatterjee, Jamie Qiuyun, Fan Mandi Liu, Rasagna Kota, Annesha Banerjee, Steven K. Daugherty, Sam Atkinson, Kelly Shrimpton, Sidney Ontai, Brian Contreras, Uzoma Obinwanko, Nneka Amamasi, Amir Sharafi, Sarah Lee, Zahia Esber, Chetna Jinjvadia, Raquel R Bartz, Vijay Krishnamoorthy, Bryan Kraft, Aaron Pulsipher, Eugene Friedman, Sachin Mehta, Margit Kaufman, Gregg Lobel, Nisha Gandhi, Amr Abdelaty, Elizabeth Shaji, Kiana Lim, Juan Marte, Dani Ashley Sosa, David P. Yamane, Ivy Benjenk, Nivedita Prasanna, Nicholas Perkins, Prera J. Roth, Banu Sivaraj, Haley Fulton, Madison G Herin, Marissa Crum, Morgan E. Fretwell, Emily-Rose Zhou, Christine Waller, Kara Kallies, Jonean Thorsen, Alec Fitzsimmons, Haley Olsen, Heda R. Dapul, Sourabh Verma, Alan Salas, Ariel Daube, Michelle Korn, Michelle Ramirez, Logi Rajagopalan, Laura Santos, Héctor Collazo Santiago, Ricardo Alan Hernandez, Norma Smalls, Asher G Bercow, Mark Shlomovich, Christine Crandall, Sasko Stojanovski, Kristin Johnson, Kelly Michienzi, Steven Q. Davis, Valentina Jovic, Max Masuda, Amanda Hayes, Katharine Nault, Michael Smith, William Snow, Riley Liptak, Hannah Durant, Valerie Pendleton, Alay Nanavati, Risa Mrozowsk, Namrata Nag, Jeff Brauer, Ashwin Dharmadhikari, Sahib Singh, Franco Laghi, Ghania Naeem, Andrew Wang, Kevin Bliden, Amit Rout, Jaime Barnes, Martin Gesheff, Asha Thomas, Melbin Thomas, Alicia R. Liendo, Jovan Milosavljevic, Kenan Abbasi, Nicholas B. Burley, Nicole Rapista, Samuel Amankwah, Sanjay K Poude, Saroj Timilsina, Sauradeep Sarkar, Oluwasayo Akinyosoye, Shashi K. Yalamanchili, Sheena Moorthy, Sonia Sugumar, Jonathan Ford, Martin C. Taylor, Charlotte Dunderdale, Alyssa Henshaw, Mary K. Brunk, Jessica Hagy, Shehryar Masood, Sushrutha Sridhar, Yuk Ming Liu, Sarah Zavala, Esther Shim, Ronald A. Reilkoff, Julia A. Heneghan, Sarah Eichen, Lexie Goertzen, Scott Rajala, Ghislaine Feussom, Ben Tang, Christine C. Junia, Robert Lichtenberg, Hasrat Sidhu, Diana Espinoza, Shelden Rodrigues, Maria Jose Zabala, Daniela Goyes, Ammu Susheela, Buddhi Hatharaliyadda, Naveen Rameshkumar, Amulya Kasireddy, Genessis Maldonado, Lisseth Beltran, Akshata Chaugule, Hassan Khan, Namrata Patil, Ruhi Patil, Rodrigo Cartin-Ceba, Ayan Sen, Fahimeh Talaei, Rahul Kashyap, Juan Pablo Domecq, Ognjen Gajic, Vikas Bansal, Aysun Tekin, Amos Lal, John C. O’Horo, Neha N. Deo, Mayank Sharma, Shahraz Qamar, Romil Singh, Diana J. Valencia Morales, Abigail T. La Nou, Marija Bogojevic, Simon Zec, Devang Sanghavi, Pramod Guru, Pablo Moreno Franco, Karthik Gnanapandithan, Hollie Saunders, Zachary Fleissner, Juan Garcia, Alejandra Yu Lee Mateus, Siva Naga Yarrarapu, Nirmaljot Kaur, Abhisekh Giri, Mohammed Mustafa Hasan, Ashrita Donepudi, Syed Anjum Khan, Nitesh Kumar Jain, Thoyaja Koritala, Alexander Bastidas, Gabriela Orellana, Adriana Briceno Bierwirth, Eliana Milazzo, Juan Guillermo Sierra, Thao Dang, Rahul S Nanchal, Paul A Bergl, Jennifer L Peterson, Jessica Timmer, Kimberly Welker, Travis Yamanaka, Nicholas A. Barreras, Michael Markos, Anita Fareeduddin, Rohan Mehta, Chakradhar Venkata, Miriam Engemann, Annamarie Mantese, Yasir Tarabichi, Adam Perzynski, Christine Wang, Dhatri Kotekal, Adriana C Briceno Bierwirth, Gabriela M Orellana, Gerardo Catalasan, Shohana Ahmed, Carlos F Matute, Ahmad Hamdan, Ivania Salinas, Genesis Del Nogal, Angel Tejada, Anna Eschler, Mary Hejna, Emily Lewandowski, Kristen Kusmierski, Clare Martin, Jen-Ting Chen, Aluko Hope, Zoe Tsagaris, Elise Ruen, Aram Hambardzumyan, Nasar A Siddiqi, Lesly Jurado, Lindsey Tincher, Carolyn Brown, Prithvi Sendi, Meghana Nadiger, Balagangadhar Totapally, Bhagat S. Aulakh, Sandeep Tripathi, Jennifer A. Bandy, Lisa M. Kreps, Dawn R. Bollinger, Neha Gupta, Brent R Brown, Tracy L Jones, Kassidy Malone, Lauren A Sinko, Amy B Harrell, Shonda C Ayers, Lisa M Settle, Taylor J Sears, Roger Scott Stienecker, Andre G. Melendez, Tressa A. Brunner, Sue M Budzon, Jessica L. Heffernan, Janelle M. Souder, Tracy L. Miller, Andrea G. Maisonneuve, Roberta E. Redfern, Jessica Shoemaker, Jennifer Micham, Lynn Kenney, Gabriel Naimy, Victoria Schauf, Sara Utley, Holly Balcer, Kerry P. J. Pulver, Jennifer Yehle, Alicia Weeks, Terra Inman, Majdi Hamarshi, Jeannette Ploetz, Nick Bennett, Kyle Klindworth, Moustafa Younis, Adham Mohamed, Brian L. Delmonaco, Anthony Franklin, Mitchell Heath, Diane Barkas, Antonia L. Vilella, Sara B. Kutner, Kacie Clark, Danielle Moore, Shina Menon, John K McGuire, Deana Rich, Harry L. Anderson, III, Dixy Rajkumar, Ali Abunayla, Jerrilyn Heiter, Howard A. Zaren, Stephanie J. Smith, Grant C. Lewis, Lauren Seames, Cheryl Farlow, Judy Miller, Gloria Broadstreet, John Lin, Cindy Terrill, Brock Montgomery, Sydney Reyes, Summer Reyes, Alex Plattner, Anthony Martinez, Micheal Allison, Aniket Mittal, Rafael Ruiz, Aleta Skaanland, Robert Ross, Umang Patel, Jordesha Hodge, Krunal Kumar Patel, Shivani Dalal, Himanshu Kavani, Sam Joseph, Michael A. Bernstein, Ian K. Goff, Matthew Naftilan, Amal Mathew, Deborah Williams, Sue Murdock, Maryanne Ducey, Kerianne Nelson, Jason Block, James Mitchel, Connor G O’Brien, Sylvan Cox, William Marx, Ioana Amzuta, Asad J. Choudhry, Mohammad T. Azam, Kristina L Carter, Michael A Olmos, Brittany M Parker, Julio Quintanilla, Tara A Craig, Brendon J Clough, Jeffrey T Jameson, Utpal S. Bhalala, Joshua Kuehne, Melinda Garcia, Morgan Beebe, Heather Herrera, Chris Fiack, Stephanie Guo, May Vawer, Beth Blackburn, Caleb Darby, Kristy Page, Amanda Brown, Jessie McAbee, Katherine A. Belden, Michael Baram, Devin M. Weber, Rosalie DePaola, Yuwei Xia, Hudson Carter, Aaron Tolley, Mary Barletta, Mark Steele, Laurie Kemble, Joshua L. Denson, A. Scott Gillet, Margo Brown, Rachael Stevens, Andrew Wetherbie, Kevin Tea, Mathew Moore, Abdurrahman Husain, Atul Malhotra, Qais Zawaydeh, Benjamin J Sines, Thomas J Bice, Emily A. Vail, Susannah Nicholson, Rachelle B. Jonas, AnnaRose E. Dement, William Tang, Mark DeRosa, Robert E. Villarreal, Rajany V. Dy, Alfredo Iardino, Jill Sharma, Richard Czieki, Julia Christopher, Ryan Lacey, Marwan Mashina, Kushal Patel, Erica C. Bjornstad, Nancy M. Tofil, Scott House, Isabella Aldana, Nikhil K. Meena, Jose D. Caceres, Nikhil K Meena, Sarenthia M. Epps, Harmeen Goraya, Kelsey R. Besett, Ryan James, Lana Y. Abusalem, Akash K. Patel, Lana S Hasan, Dina Gomaa, Michael Goodman, Devin Wakefield, Anthony Spuzzillo, John O. Shinn II, Robert MacLaren, Azra Bihorac, Tezcan Ozrazgat Baslanti, George Omalay, Haleh Hashemighouchani, Julie S. Cupka, Matthew M Ruppert, Patrick W. McGonagill, Colette Galet, Janice Hubbard, David Wang, Lauren Allan, Aditya Badheka, Madhuradhar Chegondi, Usman Nazir, Garrett Rampon, Jake Riggle, Nathan Dismang, Vicki Montgomery, Janice Sullivan, Sarah Morris, Jennifer Nason, Ozan Akca, Rainer Lenhardt, Rodrigo S. Cavallazzi, Ann Jerde, Alexa Black, Allison Polidori, Haily Griffey, Justin Winkler, Thomas Brenzel, Roger A. Alvarez, Amarilys Alarcon-Calderon, Marie Anne Sosa, Sunita K. Mahabir, Mausam J. Patel, Pauline Park, Andrew Admon, Sinan Hanna, Rishi Chanderraj, Maria Pliakas, Ann Wolski, Jennifer Cirino, Dima Dandachi, Hariharan Regunath, Maraya N. Camazine, Grant. E. Geiger, Abdoulie O. Njai, Baraa M. Saad, Faraaz Ali Shah, Byron Chuan, Sagar L. Rawal, Manal Piracha, Joseph E. Tonna, Nicholas M. Levin, Kayte Suslavich, Rachel Tsolinas, Zachary T. Fica, Chloe R. Skidmore, Renee D. Stapleton, Anne E. Dixon, Olivia Johnson, Sara S. Ardren, Stephanie Burns, Anna Raymond, Erika Gonyaw, Kevin Hodgdon, Chloe Housenger, Benjamin Lin, Karen McQuesten, Heidi Pecott-Grimm, Julie Sweet, Sebastian Ventrone, Nita Khandelwal, T. Eoin West, Ellen S. Caldwell, Lara Lovelace-Macon, Navya Garimella, Denisse B. Dow, Sreekanth R. Cheruku, Catherine Chen, Murtaza Akhter, Rania Abdul Rahman, Mary Mulrow, Erin M. Wilfong, Kelsi Vela, Ashish K. Khanna, Lynne Harris, Bruce Cusson, Jacob Fowler, David Vaneenenaam, Glen McKinney, Imoh Udoh, Kathleen Johnson, Patrick G. Lyons, Andrew P Michelson, Sara S. Haluf, Lauren M. Lynch, Nguyet M. Nguyen, Aaron Steinberg, Nicholas Braus, Vishwanath Pattan, Jessica Papke, Ismail Jimada, Nida Mhid, Samuel Chakola, Kevin Sheth, Abdalla Ammar, Mahmoud Ammar, Victor Torres Lopez, Charles Dela Cruz,, Akhil Khosla, and Samir Gautam

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN:. Prospective observational study. SETTING:. One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS:. Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS:. None. RESULTS:. Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0–81.0 yr) versus 61 years (48.0–72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, –0.84, –1.34, and –0.84; p < 0.001). CONCLUSIONS:. Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

Published
2022
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3. Risk Factors for Critical Coronavirus Disease 2019 and Mortality in Hospitalized Young Adults: An Analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Coronavirus Disease 2019 Registry

Author

Sandeep Tripathi, MD, MS, Imran A. Sayed, MD, Heda Dapul, MD, Jeremy S. McGarvey, MS, Jennifer A. Bandy, RN, Karen Boman, BS, Vishakha K. Kumar, MD, MBA, Vikas Bansal, MBBS, MPH, Lynn Retford, CAE, Sreekanth Cheruku, MD, MPH, Margit Kaufman, MD, FASA, Smith F. Heavner, MS, RN, Valerie C. Danesh, PhD, RN, Catherine A. St. Hill, DVM, PhD, Ashish K. Khanna, MD, Utpal Bhalala, MD, Rahul Kashyap, MBBS, MBA, Ognjen Gajic, MD, MS, Allan J. Walkey, MD, MS, Katja M. Gist, DO, MSc, for The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group, Jean-Baptiste Mesland, Pierre Henin, Hélène Petre, Isabelle Buelens, Anne-Catherine Gerard, Philippe Clevenbergh, Rolando Claure-Del Granado, Jose A. Mercado, Esdenka Vega-Terrazas, Maria F. Iturricha-Caceres, Ruben Garza, Eric Chu, Victoria Chan, Oscar Y Gavidia, Felipe Pachon, Yeimy A Sanchez, Mohamed El Kassas, Mohamed Badr, Ahmed Tawheed, Hend Yahia, Sierra-Hoffman, Fernando Valerio, Oscar Diaz, Jose Luis Ramos Coello, Guillermo Perez, Ana Karen Vallecillo Lizardo, Gabina María Reyes Guillen, Helin Archaga Soto, Mradul Kumar Daga, Munisha Agarwal, Ishan Rohtagi, Anusha Cherian, Sreejith Parameswaran, Magesh Parthiban, Menu Priya A., Girish Vadgaonkar, Rekha Ediga, Shilpa Basety, Shwetha Dammareddy, Phani Sreeharsha Kasumalla, Sridhar Papani, Mahesh Kamuram, Smitha S. 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Garcia, Mia Colona, Zoe Kibbelaar, Michael Leong, Daniel Wallman, Kanupriya Soni, Jennifer Maccarone, Joshua Gilman, Ycar Devis, Joseph Chung, Munizay Paracha, David N. Lumelsky, Madeline DiLorenzo, Najla Abdurrahman, Shelsey Johnson, Andrew M. Hersh, Stephanie L Wachs, Brittany S. Swigger, Lauren A. Sattler, Michael N. Moulton, Kimberly Zammit, J Patrick, William McGrath, Maya Loeffler, R Chilbert, Aaron S. Miller, Edwin L. Anderson, Rosemary Nagy, Ravali R. Inja, Raghavendra Tirupathi, Alymer Tang, Arshad Safi, Cindy Green, Jackie Newell, Rayan E. Ihle, Shelda A. Martin, Elaine A. Davis, Katja M. Gist, Imran A Sayed, John Brinton, Larisa Strom, Kathleen Chiotos, Allison M. Blatz, Giyoung Lee, Ryan H. Burnett, Guy I. Sydney, Danielle M. 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Maguire, Jessica Timmer, Raquel R Bartz, Vijay Krishnamoorthy, Bryan Kraft, Aaron Pulsipher, Eugene Friedman, Sachin Mehta, Margit Kaufman, Gregg Lobel, Nisha Gandhi, Amr Abdelaty, Elizabeth Shaji, Kiana Lim, Juan Marte, Dani Ashley Sosa, David P. Yamane, Ivy Benjenk, Nivedita Prasanna, Smith F. Heavner-Sullivan, Prera J. Roth, Banu Sivaraj, Haley Fulton, Madison G Herin, Marissa Crum, Morgan E. Fretwell, Emily-Rose Zhou, Christine Waller, Kara Kallies, Jonean Thorsen, Alec Fitzsimmons, Haley Olsen, Heda R. Dapul, Sourabh Verma, Alan Salas, Ariel Daube, Michelle Korn, Michelle Ramirez, Logi Rajagopalan, Laura Santos, Orma Smalls, Atul Malhotra, Abdurrahman Husain, Qais Zawaydeh, J.H. Steuernagle, Steven Q. Davis, Valentina Jovic, Max Masuda, Amanda Hayes, Katharine Nault, Michael Smith, William Snow, Riley Liptak, Hannah Durant, Valerie Pendleton, Alay Nanavati, Risa Mrozowsk, LiManoj K Gupta, Franscene E. Oulds, Akshay Nandavar, Yuk Ming Liu, Sarah Zavala, Esther Shim, Ronald A. Reilkoff, Julia A. Heneghan, Sarah Eichen, Lexie Goertzen, Scott Rajala, Ghislaine Feussom, Ben Tang, Christine C. Junia, Robert Lichtenberg, Hasrat Sidhu, Diana Espinoza, Shelden Rodrigues, Maria Jose Zabala, Daniela Goyes, Ammu Susheela, Buddhi Hatharaliyadda, Naveen Rameshkumar, Amulya Kasireddy, Genessis Maldonado, Lisseth Beltran, Akshata Chaugule, Hassan Khan, Namrata Patil, Ruhi Patil, Rodrigo Cartin-Ceba, Ayan Sen, Amanda Palacios, Giyth M. Mahdi, Rahul Kashyap, Ognjen Gajic, Vikas Bansal, Aysun Tekin, Amos Lal, John C. O’Horo, Neha N. Deo, Mayank Sharma, Shahraz Qamar, Cory J. Kudrna, Juan Pablo Domecq Garces, Abigail T. La Nou, Marija Bogojevic, Devang Sanghavi, Pramod Guru, Karthik Gnanapandithan, Hollie Saunders, Zachary Fleissner, Juan Garcia, Alejandra Yu Lee Mateus, Siva Naga Yarrarapu, Syed Anjum Khan, Juan Pablo Domecq, Nitesh Kumar Jain, Thoyaja Koritala, Alexander Bastidas, Gabriela Orellana, Adriana Briceno Bierwirth, Eliana Milazzo, Juan Guillermo Sierra, Thao Dang, Amy B. Christie, Dennis W. Ashley, Rajani Adiga, Rahul S Nanchal, Paul A Bergl, Jennifer L Peterson, Travis Yamanaka, Nicholas A. Barreras, Michael Markos, Anita Fareeduddin, Rohan Mehta, Chakradhar Venkata, Miriam Engemann, Annamarie Mantese, Yasir Tarabichi, Adam Perzynski, Christine Wang, Dhatri Kotekal, Adriana C Briceno Bierwirth, Gabriela M Orellana, Gerardo Catalasan, Shohana Ahmed, Carlos F Matute, Ahmad Hamdan, Ivania Salinas, Genesis Del Nogal, Angel Tejada, Anna Eschler, Mary Hejna, Emily Lewandowski, Kristen Kusmierski, Clare Martin, Jen-Ting Chen, Aluko Hope, Zoe Tsagaris, Elise Ruen, Aram Hambardzumyan, Prithvi Sendi, Meghana Nadiger, Balagangadhar Totapally, Bhagat S. Aulakh, Jennifer A. Bandy, Lisa M. Kreps, Dawn R. Bollinger, Roger Scott Stienecker, Andre G. Melendez, Tressa A. Brunner, Sue M Budzon, Jessica L. Heffernan, Janelle M. Souder, Tracy L. Miller, Andrea G. Maisonneuve, Roberta E. Redfern, Jessica Shoemaker, Jennifer Micham, Lynn Kenney, Gabriel Naimy, Sara Utley, Holly Balcer, Kerry P. J. Pulver, Jennifer Yehle, Alicia Weeks, Terra Inman, Brian L. Delmonaco, Anthony Franklin, Mitchell Heath, Antonia L. Vilella, Sara B. Kutner, Kacie Clark, Danielle Moore, Shina Menon, John K McGuire, Deana Rich, Harry L. Anderson, III, Dixy Rajkumar, Ali Abunayla, Jerrilyn Heiter, Howard A. Zaren, Stephanie J. Smith, Grant C. Lewis, Lauren Seames, Cheryl Farlow, Judy Miller, Gloria Broadstreet, John Lin, Cindy Terrill, Brock Montgomery, Sydney Reyes, Summer Reyes, Alex Plattner, Anthony Martinez, Micheal Allison, Aniket Mittal, Rafael Ruiz, Aleta Skaanland, Robert Ross, Umang Patel, Jordesha Hodge, KrunalKumar Patel, Shivani Dalal, Himanshu Kavani, Sam Joseph, Michael A. Bernstein, Ian K. Goff, Matthew Naftilan, Amal Mathew, Deborah Williams, Sue Murdock, Maryanne Ducey, Kerianne Nelson, Paul K Mohabir, Connor G O’Brien, Komal Dasani, William Marx, Ioana Amzuta, Asad J. Choudhry, Mohammad T. Azam, Kristina L Carter, Michael A Olmos, Brittany M Parker, Julio Quintanilla, Tara A Craig, Brendon J Clough, Jeffrey T Jameson, Neha Gupta, Tracy L Jones, Shonda C Ayers, Amy B Harrell, Dr.Brent R Brown, Utpal S. Bhalala, Joshua Kuehne, Melinda Garcia, Morgan Beebe, Heather Herrera, Chris Fiack, Stephanie Guo, May Vawer, Beth Blackburn, Megan Edwards, Caleb Darby, Kristy Page, Amanda Brown, Jessie McAbee, Katherine A. Belden, Michael Baram, Devin M. Weber, Rosalie DePaola, Yuwei Xia, Hudson Carter, Aaron Tolley, Mark Steele, Laurie Kemble, Joshua L. Denson, A. Scott Gillet, Margo Brown, Rachael Stevens, Andrew Wetherbie, Kevin Tea, Mathew Moore, Benjamin J Sines, Thomas J Bice, Emily A. Vail, Susannah Nicholson, Rachelle B. Jonas, AnnaRose E. Dement, William Tang, Mark DeRosa, Robert E. Villarreal, Rajany V. Dy, Alfredo Iardino, Jill Sharma, Richard Czieki, Julia Christopher, Ryan Lacey, Marwan Mashina, Kushal Patel, Erica C. Bjornstad, Nancy M. Tofil, Scott House, Isabella Aldana, Nikhil K. Meena, Jose D. Caceres, Nikhil K Meena, Sarenthia M. Epps, Harmeen Goraya, Kelsey R. Besett, Ryan James, Lana Y. Abusalem, Akash K. Patel, Lana S Hasan, Dina Gomaa, Michael Goodman, Devin Wakefield, Anthony Spuzzillo, John O. Shinn, II, Azra Bihorac, Tezcan Ozrazgat Baslanti, George Omalay, Haleh Hashemighouchani, Julie S. Cupka, Matthew M Ruppert, Patrick W. McGonagill, Colette Galet, Janice Hubbard, David Wang, Lauren Allan, Aditya Badheka, Madhuradhar Chegondi, Usman Nazir, Garrett Rampon, Jake Riggle, Nathan Dismang, Vicki Montgomery, Janice Sullivan, Sarah Morris, Jennifer Nason, Roger A. Alvarez, Amarilys Alarcon-Calderon, Marie Anne Sosa, Sunita K. Mahabir, Mausam J. Patel, Pauline Park, Andrew Admon, Sinan Hanna, Rishi Chanderraj, Maria Pliakas, Ann Wolski, Jennifer Cirino, Dima Dandachi, Hariharan Regunath, Maraya N. Camazine, Grant. E. Geiger, Abdoulie O. Njai, Baraa M. Saad, Faraaz Ali Shah, Byron Chuan, Sagar L. Rawal, Manal Piracha, Joseph E. Tonna, Nicholas M. Levin, Kayte Suslavich, Rachel Tsolinas, Zachary T. Fica, Chloe R. Skidmore, Renee D. Stapleton, Anne E. Dixon, Olivia Johnson, Sara S. Ardren, Stephanie Burns, Anna Raymond, Erika Gonyaw, Kevin Hodgdon, Chloe Housenger, Benjamin Lin, Karen McQuesten, Heidi Pecott-Grimm, Julie Sweet, Sebastian Ventrone, Nita Khandelwal, T. Eoin West, Ellen S. Caldwell, Lara Lovelace-Macon, Navya Garimella, Denisse B. Dow, Murtaza Akhter, Rania Abdul Rahman, Mary Mulrow, Erin M. Wilfong, Kelsi Vela, Ashish K. Khanna, Lynne Harris, Bruce Cusson, Jacob Fowler, David Vaneenenaam, Glen McKinney, Imoh Udoh, Kathleen Johnson, Patrick G. Lyons, Andrew P Michelson, Sara S. Haluf, Lauren M. Lynch, Nguyet M. Nguyen, Aaron Steinberg, Nicholas Braus, Vishwanath Pattan, Jessica Papke, Ismail Jimada, Nida Mhid, and Samuel Chakola

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

IMPORTANCE:. Even with its proclivity for older age, coronavirus disease 2019 has been shown to affect all age groups. However, there remains a lack of research focused primarily on the young adult population. OBJECTIVES:. To describe the epidemiology and outcomes of coronavirus disease 2019 and identify the risk factors associated with critical illness and mortality in hospitalized young adults. DESIGN, SETTINGS, AND PARTICIPANTS:. A retrospective cohort study of the Society of Critical Care Medicine’s Viral Infection and Respiratory Illness Universal Study registry. Patients 18–40 years old, hospitalized from coronavirus disease 2019 from March 2020 to April 2021, were included in the analysis. MAIN OUTCOMES AND MEASURES:. Critical illness was defined as a composite of mortality and 21 predefined interventions and complications. Multivariable logistic regression was used to assess associations with critical illness and mortality. RESULTS:. Data from 4,005 patients (152 centers, 19 countries, 18.6% non-U.S. patients) were analyzed. The median age was 32 years (interquartile range, 27–37 yr); 51% were female, 29.4% Hispanic, and 42.9% had obesity. Most patients (63.2%) had comorbidities, the most common being hypertension (14.5%) and diabetes (13.7%). Hospital and ICU mortality were 3.2% (129/4,005) and 8.3% (109/1,313), respectively. Critical illness occurred in 25% (n = 996), and 34.3% (n = 1,376) were admitted to the ICU. Older age (p = 0.03), male sex (adjusted odds ratio, 1.83 [95% CI, 1.2–2.6]), and obesity (adjusted odds ratio, 1.6 [95% CI, 1.1–2.4]) were associated with hospital mortality. In addition to the above factors, the presence of any comorbidity was associated with critical illness from coronavirus disease 2019. Multiple sensitivity analyses, including analysis with U.S. patients only and patients admitted to high-volume sites, showed similar risk factors. CONCLUSIONS:. Among hospitalized young adults, obese males with comorbidities are at higher risk of developing critical illness or dying from coronavirus disease 2019.

Published
2021
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4. Clinical Characteristics and Outcomes of Critically ill Mechanically Ventilated COVID-19 Patients Receiving interleukin-6 Receptor Antagonists and/or Corticosteroid Therapy, the INTERACT study: A Multicenter International Observational Study

Author

Oscar Y. Gavidia, Marwa Amer, Talal Dahhan, Abeer Turki AlFirm, Rahul Kashyap, Ognjen Gajic, I.B. Zabolotskikh, Maal Abualkhair, Allan J. Walkey, Muath Rabee, Syed Moazzum Khurshid, Ahmed Mohamed Kamal, Razan Alghunaim, Eiad Kseibi, Ali Al-Janoubi, Michael A. Bernstein, Jarrod Mosier, Mohammed Abujazar, Vishakha K. Kumar, Karen Boman, Abid Butt, Khalid Maghrabi, Mohammed Bawazeer, Vikas Bansal, and Santiago Yus Teruel

Subjects
Mechanical ventilation, medicine.medical_specialty, Combination therapy, business.industry, medicine.medical_treatment, Antagonist, Odds ratio, Rate ratio, medicine.disease, Internal medicine, Bacteremia, Cohort, Medicine, business, Dexamethasone, medicine.drug
Abstract

ObjectivesTo compare the clinical characteristics and outcomes of critically ill coronavirus disease (COVID-19) patients requiring mechanical ventilation (MV), receiving interleukin-6 receptor (IL-6R) antagonists, steroids, or a combination of both.DesignAn international, multicenter, observational study derived from the COVID-2019 Viral Infection and Respiratory Illness University Study (VIRUS) registry and conducted through the Discovery Network, the Society of Critical Care Medicine. Marginal structural modeling was used to adjust for time-dependent confounders, and observations were weighted using the inverse probability of treatment weight. Sensitivity analysis was conducted to emulate a target trial design.Setting168 hospitals in 16 countries.Patientsadult ICU patients (≥ 18 years) requiring MV for COVID-19 between March 01, 2020, and January 10, 2021.InterventionNone.Measurements and Main ResultsA total of 860 patients met eligibility criteria: 589 received steroids, 170 IL-6R antagonists, and 101 combination therapy, and the groups were balanced after adjustment. The median daily steroid dose was 7.5 mg dexamethasone or equivalent (IQR: 6–14 mg); 80.8% received low-dose and 19.2% high-dose steroids (> 15 mg/day of dexamethasone or equivalent). The median C-reactive protein level was > 75 mg/L in majority of our cohort. The use of IL-6R antagonists alone or in combination was not associated with a significant difference in ventilator-free days (VFD) compared to steroids alone (adjusted incidence rate ratio [95% CI]): IL-6R antagonists (1.12 [0.88,1.4]), combination (0.83 [0.6,1.14]). Patients treated with low or high-dose steroids had non-significant differences in VFD compared to IL-6R antagonists (ß= 0.62, 95% CI −1.54, 2.78 for low-dose steroid; ß= −1.19, 95% CI −3.85, 1.47 for high-dose steroid). The use of IL-6R antagonists alone or in combination was not associated with a significant difference in 28-day mortality compared to steroids alone (adjusted odds ratio [95% CI]): IL-6R antagonists alone (0.68 [0.44,1.07]), combination (1.07 [0.67,1.7]). There was no difference in hospital mortality compared to steroids alone (aOR 0.68, 95% CI 0.43,1.09 for IL6-R antagonist, aOR 1.23, 95 % CI 0.72,2.11 for combination). The findings of sensitivity analysis were consistent with the primary analysis. The rate of liver dysfunction was higher in the IL-6R antagonist (p=0.038), while the rate of bacteremia did not differ among the three groups.ConclusionsWe observed no difference in outcomes between mechanically ventilated adult ICU patients who received IL-6R antagonists, steroids, or combination therapy and those who received IL-6R antagonists or low- or high-dose steroids. Further trials are needed to evaluate high-dose steroids as substitutes for IL-6R antagonists in resource-limited settings.

Published
2021

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