Citations 2
Evaluation of Interventions for Cognitive Symptoms in Long COVID
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JAMA Neurology | November 10, 2025 | Volume: 83 | Issue: 1 | Pages: 49
Importance Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need. Objective To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID. Design, Setting, and Participants This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID. Interventions Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks. Main Outcomes and Measures Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days. Results A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, −0.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, −0.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions. Conclusions and Relevance This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID. Trial Registration ClinicalTrials.gov Identifier: NCT05965739 .
Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia: A Randomized Clinical Trial
Sise, Meghan E. , Santos, José Ramón, Goldman, Jason D. , Tuttle, Katherine R, Teixeira, J. Pedro , Seibert, A. F., Koullias, Yiannis , Llewellyn, Joe , Zhao, Yang , Hyland, Robert H. , Osinusi, Anu, Winter, Helen , Humeniuk, Rita , Hulter, Henry N., Gottlieb, Robert , Fusco, Dahlene N. , Birne, Rita , Small, Catherine B. , Plate, Markus, McPhail, Mark , Investigators, for the REDPINE, Ballesteros, Rosa , Malheiro, Luís , Silva, Gil, Correia, João Paulo , Vida, Ana Carlota, Silva, André, Carujo, Antonio, Fernandez, Jordi Carratala, Cruzado, Josep M. , Sandoval, Diego , Gimeno, Fransesc Puchades, Gómez‐Muñoz, Neus, Roma, María Martínez, Gallego, Juan Horcajada, Pablo, Castañeda, Silvia, Padilla Urrea, Sergio, Rial Crestelo, David, Santos Fernandez, Jose, Ramon, Benet, Susanna, Benítez, Rosa, Bracke, Carmen, Chamorro, Anna, Graterol, Fredzzia, Lladós, Gemma , Mateu, Lourdes , Rebollo, Boris, Romero, Alba , Soldevila, Laura , Abad, Elena, José, Alba San, Viladomiu, Alex Soriano, Abolnik, Igor Z., Acharya, Anjali , Allen, Leland, Bellovich, Keith, Burton, Mary Jane , Cameron, Miriam L., Criner, Gerard J., Criner, Lii-Yoong H, Lambert, Joseph, Rashid, Marium, Shore-Brown, Heidi, Diaz, George A., Dougherty, David W. , Erdmann, Nathaniel, Berrington, William R., Logar, Christine M., Vadivel, Nidyanandh, Everett, Allison, Lourdes, Gonzalez Suarez Maria, Berhe, Mezgebe , Colbert, Gates B. , Hebert, Christopher, Mehta, Ankit , Spak, Cedric W. , Estrada, Lorie, Vargas, Richard, Pham, Alex, Mason, Lynn, Tallmadge, Catherine, Braddom, Ariana, Nicholas, Melissa, Jamil, Aayla K. , McAllister, Ashley , Guerra, Christina, Sam, Teena , Solis, Edilia, Goyal, Munish, Laurence, Brett, Malhotra, Vinay , Manrique, Luis, McKinnell, James A., McMahon, Blaithin A. , Campbell, Ruth , Morse, Caryn G. , Navarro, Jesús, Ostrosky, Luis, Patel, Bela , Grimes, Carolyn Z. , Hernández, María , Mammadova, Mehriban, Nielsen, Laura, Umana, Virginia, Pusch, Tobias, Schrager, Harry, Mallada, Jason, Siegel, Marc , Slim, Jihad , Apodaca, Krystle D., Harkins, Michelle , Cunningham, Amy, Tuttle, Katherine R, Criner, Gerard J. , Tuttle, Katherine R. , Tuttle, Katherine R , Gottlieb, Robert L , Criner, Gerard , Teixeira, J Pedro , Tuttle, Katherine R, Regan, S. P. , Huang, Hailin , Stancampiano, Fernando F. , Libertin, Claudia R. , Investigators, for the REDPINE, Belhassen‐García, Moncef , Abelenda-Alonso, Gabriela , Rombauts, Alexander , Deltoro, Miguel García , España, Sergio, López, C. , Paredes, Roger , Viladomiu, Alex Soriano, Medjeral‐Thomas, Nicholas , Lobo, Suzana Margareth , Allen, Leland, Lambert, Joseph, Dougherty, David, Hebert, Christopher, Choe, Jennifer, McAllister, Ashley, Gotur, Deepa Bangalore , Koraishy, Farrukh M. , Malhotra, Vinay, Robinson, Philip Alan , Sanyal, Arun J. , Sriram, Peruvemba , Cunningham, Amy G, Tuttle, Katherine R
Clinical Infectious Diseases | June 24, 2024 | Volume: 79 | Issue: 5 | Pages: 1172-1181
Abstract Background Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment. Methods In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022). The primary efficacy end point was the composite of the all-cause mortality rate or invasive mechanical ventilation rate through day 29. Safety was evaluated through day 60. Results Although enrollment concluded early, 243 participants were enrolled and treated (remdesivir, n = 163; placebo, n = 80). At baseline, 90 participants (37.0%) had acute kidney injury (remdesivir, n = 60; placebo, n = 30), 64 (26.3%) had chronic kidney disease (remdesivir, n = 44; placebo, n = 20), and 89 (36.6%) had kidney failure (remdesivir, n = 59; placebo, n = 30); and 31 (12.8%) were vaccinated against COVID-19. Composite all-cause mortality or invasive mechanical ventilation rates through day 29 were 29.4% and 32.5% in the remdesivir and placebo group, respectively (P = .61). Treatment-emergent adverse events were reported in 80.4% for remdesivir versus 77.5% for placebo, and serious adverse events in 50.3% versus 50.0%, respectively. Pharmacokinetic plasma exposure to remdesivir was not affected by kidney function. Conclusions Although the study was underpowered, no significant difference in efficacy was observed between treatment groups. REDPINE demonstrated that remdesivir is safe in patients with COVID-19 and severe kidney impairment. Clinical Trials Registration EudraCT 2020-005416-22; Clinical Trials.gov NCT04745351.