Long-term Follow-up After Critical COVID-19 (2024)

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Editorial

December 16, 2022

Michael L.Barnett,MD, MS1,2; Paul E.Sax,MD3

Author Affiliations Article Information

¹Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
²Division of General Internal Medicine and Primary Care, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
³Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

JAMA. 2023;329(1):25-27. doi:10.1001/jama.2022.23700

COVID-19 Resource Center

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Original Investigation Long-term Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial
Writing Committee for the REMAP-CAP Investigators; SiminFlorescu; DeliaStanciu; MihaelaZaharia; AlmaKosa; DanielCodreanu; AneelaKidwai; SobiaMasood; CallumKaye; AmandaCoutts; LynnMacKay; CharlotteSummers; PetraPolgarova; NedaFarahi; EleonoreFox; StephenMcWilliam; DanielHawcutt; LauraRad; LauraO’Malley; JenniferWhitbread; DawnJones; RachaelDore; PaulaSaunderson; OliviaKelsall; NicholasCowley; LauraWild; JessicaThrush; HannahWood; KarenAustin; JánosBélteczki; IstvánMagyar; ÁgnesFazekas; SándorKovács; ViktóriaSzőke; AdrianDonnelly; MartinKelly; NaoiseSmyth; SinéadO’Kane; DeclanMcClintock; MajellaWarnock; RyanCampbell; EdmundMcCallion; AmineAzaiz; CyrilCharron; MathieuGodement; GuillaumeGeri; AntoineVieillard-Baron; PaulJohnson; ShirleyMcKenna; JoanneHanley; AndrewCurrie; BarbaraAllen; ClareMcGoldrick; MoyraMcMaster; AshwinMani; MeghenaMathew; RevathiKandeepan; CVignesh; BharathTV; NRamakrishnan; AugustianJames; EvangelineElvira; DevachandranJayakumar; RamachandranPratheema; SureshBabu; REbenezer; SKrishnaoorthy; LakshmiRanganathan; ManishaGanesan; MadhuShree; EileenGuilder; MagdalenaButler; Keri-AnneCowdrey; MelissaRobertson; FarishaAli; EllieMcMahon; EamonDuffy; YanChen; CatherineSimmonds; RachaelMcConnochie; CarolineO’Connor; KhaledEl-Khawas; AngusRichardson; DianneHill; RobertCommons; HussamAbdelkharim; ManojSaxena; MargaretMuteithia; KelseyDobell-Brown; RajeevJha; MichaelKalogirou; ChristineEllis; VinodhKrishnamurthy; AibhilinO’Connor; SaranyaThurairatnam; DipakMukherjee; AgilanKaliappan; MarkVertue; AnneNicholson; JoanneRiches; GracieMaloney; LaurenKittridge; AmandaSolesbury; AngeloRamos; DanielCollins; KathyBrickell; LiadainReid; MichelleSmyth; PatrickBreen; SandraSpain; GerardCurley; NatalieMcEvoy; PierceGeoghegan; JenniferClarke; JonSilversides; PeterMcGuigan; KathrynWard; AislingO’Neill; StephanieFinn; ChrisWright; JackieGreen; ÉrinCollins; Cameron Knott; JulieSmith; CatherineBoschert; KittySlieker; EstherEwalds; ArnateSanders; WendyWittenberg; HeidiGeurts; Latesh Poojara; TreenaSara; KiranNand; BrendaReeve; WilliamDechert; BarbaraPhillips; LauraOritz-Ruiz deGordoa; JuliaAffleck; Arif Shaikh; AndrewMurray; MaheshRamanan; ThuyFrakking; JezPinnell; MattRobinson; LisaGledhill; TracyWood; RiteshSanghavi; DeepakBhonagiri; MeganFord; Harshel G.Parikh; BronwynAvard; MaryNourse; Bree McDonald; NatashaEdmunds; OscarHoiting; MarcoPeters; ElsRengers; MirjamEvers; AntonPrinssen; MattMorgan; JadeCole; HelenHill; MichelleDavies; AngharadWilliams; EmmaThomas; RhysDavies; MattWise; PatrickGrimm; JensSoukup; RichardWetzold; MadlenLöbel; LisaStarke; FrancoisLellouche; PatriciaLizotte; PierreDeclerq; MarchalotAntoine; GelinotteStephanie; EraldiJean-Pierre; BourgerolFrançois; BeuzelinMarion; RigaudPhilippe; FranckPourcine; MehranMonchi; DavidLuis; RomainMercier; AnneSagnier; NathalieVerrier; CecileCaplin; JackRichecoeu; DanieleCombaux; ShidaspSiami; ChristelleAparicio; SarahVautier; AsmaJeblaoui; DelphineLemaire-Brunel; FrédérickD'Aragon; ElaineCarbonneau; JulieLeblond; GaetanPlantefeve; CécileLeparco; DamienContou; MurielFartoukh; LauraCourtin; VincentLabbe; GuillaumeVoiriot; SaraSalhi; MichaëlChassé; FrançoisCarrier; DouniaBoumahni; FatnaBenettaib; AliGhamraoui; Arnaudsem*nt; AlexandreGachet; AlexisHanisch; AbdelmagidHaffiane; Anne-HélèneBoivin; AmelieBarreau; ElodieGuerineau; SéverinePoupblanc; PierreEgreteau; MontaineLefevre; SimonBocher; GuillaumeLe Loup; LenaïgLe Guen; VanessaCarn; MelanieBertel; DavidAntcliffe; MaieTempleton; RoceldRojo; PhoebeCoghlan; JoannaSmee; GarethBarker; AndréFinn; GabrieleKreb; UweHoff; CarlHinrichs; JensNee; EuanMackay; JonCort; AmandaWhileman; ThomasSpencer; NickSpittle; SarahBeavis; AnandPadmakumar; KatieDale; JoanneHawes; EmmaMoakes; RachelGascoyne; KellyPritchard; LesleyStevenson; JustinCooke; KarolinaNemeth-Roszpopa; BasantaGauli; SirjanaBastola; GrégoireMuller; Mai-AnhNay; ToufikKamel; DalilaBenzekri; SophieJacquier; IsabelleRunge; ArmelleMathonnet; FrançoisBarbier; AnneBretagnol; JayCarter; KymbaleeVan Der Heyden; JanMehrtens; AnnaMorris; StaceyMorgan; TaraBurke; EmmanuelleMercier; DelphineChartier; CharlotteSalmon; Pierre-FrançoisDequin; DenisGarot; DavidBellemare; ÈveCloutier; RanaDaher; OlivierCosterousse; Marie-ClaudeBoulanger; ÉmilieCouillard-Chénard; François Lauzier; CharlesFrancoeur; BrunoFrancois; AlexandraGay; FedouAnne-Laure; MohamedRamali; OoiHC; AlisonGhosh; RawlingsOsagie; MalkaArachchige; MelissaHartley; WinstonCheung; HelenWong; PatrickSeigne; JoeEustace; Ann-MarieO'Callaghan; FionnualaO'Brien; PeterBamford; AndrewReid; KathrynCawley; MariaFaulkner; CharlottePickering; AshokRaj; GeorgiosTsinaslanidis; ReenaKhade; GloriaAgha; RoseSekiwala; TimSmith; ChrisBrewer; JaneGregory; JamesLimb; AmandaCowton; JulieO’Brien; KellyPostlethwaite; SalimMalakouti; EdvinMusic; DanRicketts; AndrewKing; GillesClermont; RobertBart; FlorianMayr; AndrewSchoenling; MarkAndreae; VarunShetty; EmilyBrant; BrianMalley; ChenellDonadee; RachelSackrowitz; AlexandraWeissman; DonaldYealy; DavidBarton; NadineTalia; NikitasNikitas; ColinWells; LianaLankester; HelenMcMillan; Huubvan den Oever; ArrietteKruisdijk-Gerritsen; GhadyHaidar; WilliamBain; IanBarbash; MeghanFitzpatrick; ChristopherFranz; GeorgiosKitsios; KavehMoghbeli; BrianRosborough; FaraazShah; TomekaSuber; MarkPulletz; PatriciaWilliams; JennyBirch; SophieWiseman; SarahHorton; AnaAlegria; SalahTurki; TarekElsefi; NikkiCrisp; LouiseAllen; NicholasTruman; MatthewSmith; SriChukkambotla; WendyGoddard; StephenDuberley; MeherunnisaKhan; AayeshaKazi; JoannaSimpson; GraemeDuke; PeterChan; BrittneyCarter; StephanieHunter; IngoVoigt; RobertSchueler; ElisabethBlank; VanessaHüning; MelanieSteffen; PatriciaGoralski; EdLitton; AdrianRegli; SusanPellicano; AnnamariaPalermo; EgeEroglu; ShaileshBihari; Russell D.Laver; XiaJin; JuliaBrown; Joanne McIntyre; CraigFrench; SamanthaBates; MiriamTowns; YangYang; ForbesMcGain; IainMcCullagh; TomCairns; HelenHanson; BijalPatel; IanClement; GeorgeEvetts; OmarTouma; SusanHolland; ChristopherHodge; HollyTaylor; MeeraAlderman; NickyBarnes; JoanaDaRocha; CatherineSmith; NicoleBrooks; ThanujaWeerasinghe; Julie-AnnSinclair; YousufAbusamra; RonanDoherty; JoannaCudlipp; RajeevSingh; HailiYu; AdmadDaebis; ChristopherNg; SaraKendrick; AnitaSaran; AhmedMakky; DanniGreener; LouiseRowe-Leete; AlexandraEdwards; YvonneBland; RozzieDolman; TracyFoster; JohnLaffey; BairbreMcNicholas; MichaelScully; SiobhanCasey; MaeveKernan; AoifeBrennan; RitikaRangan; RionaTully; SarahCorbett; AineMcCarthy; OscarDuffy; DavidBurke; VanessaLinnett; AmandaSanderson; JennyRitzema; HelenWild; RachaelLucas; YvonneMarriott; ZdravkoAndric; SabinaCviljevic; RenataBr; MarijaZapalac; GordanMirković; DivyaKhare; MeredithPinder; AmithaGopinath; ThogulavaKannan; StevenDean; PiyushVanmali; PieterDepuydt; JanDeWaele; LiesbetDe Bus; JanFierens; StephanieBracke; JorisVermassen; DaisyVermeiren; RichardPugh; RichardLean; XinyiQiu; JeremyScanlan; AndrewEvans; GwynethDavies; JoanneLewis; YvonnaPlesnikova; AhmedKhoud; SamanthaCoetzee; KathrynPuxty; SusanneCathcart; DominicRimmer; CatherineBagot; KathrynScott; LailaMartin; HakeemYusuff; GraziellaIsgro; ChrisBrightling; MichelleBourne; MichelleCraner; RebeccaBoyles; BrianAlexander; TraceyRoberts; ApoorvaNelli; RachelRosenstein-Sisson; RebeccaSpeyer; YadiraPech; JamesMcCullough; MandyTallott; GloriaVazquez-Grande; NicoleMarten; TheresaLiu; AtifSiddiqui; SushilKhanal; SameenaAmatya; TamasSzakmany; ShineyCherian; GemmaWilliams; ChristieJames; AbbyWaters; RachelProut; RogerStedman; LouisaDavies; SuzannahPegler; LynseyKyeremeh; LouiseMoorhouse; GillArbane; MarinaMarotti; AnetaBociek; SaraCampos; Keesvan Nieuwkoop; ThomasOttens; YorikVisser; Lettievan den Berg; Annemarievan der Kraan-Donker; StephenBrett; SoniaArias; RebeccaHall; HemPaneru; SabinKoirala; PratibhaPaudel; MaggieWilson; SuviVaara; LeenaPettilä; JonnaHeinonen; VillePettilä; SusanJain; AbhinavGupta; CatherineHolbrook; PierreAntoine; FerhatMeziani; HayatAllam; JessyCattelan; RaphaelClere-Jehl; JulieHelms; ChristineKummerlen; HamidMerdji; AlexandraMonnier; HasseneRahmani; AntoineStuder; FrancisSchneider; VincentCastelain; GuillaumeMorel; SylvieL’Hotellier; EvelinaOchin; ChristianVanjak; PatrickRouge; LyndaBendjemar; MartinAlbert; KarimSerri; AlexandrosCavayas; MathildeDuplaix; VirginieWilliams; Nuno José Teodoro Amaro dos SantosCatorze; Tiago Nuno Alfaro LimaPereira; Ricardo Manuel CastroFerreira; Joana Margarida Pereira SousaBastos; Teresa Margarida OliveiraBatista; JulioBadie; FernandoBerdaguer; SylvainMalfroy; ChaoukiMezher; CharlotteBourgoin; GuyMoneger; ElodieBouvier; RosanaMuñoz-Bermúdez; JudithMarin-Corral; AnnaDegracia; FranciscoGómez; MariaLópez; RominaAceto; AlessioAghemo; SalvatoreBadalamenti; EnricoBrunetta; MaurizioCecconi; MicheleCiccarelli; ElenaConstantini; MassimilianoGreco; MarcoFolci; CarloSelmi; AntonioVoza; JeremyHenning; StephenBonner; KeithHugill; EmanuelCirstea; DeanWilkinson; JessicaJones; MohammedAltomy; MichalKarlikowski; HelenSutherland; ElvaWilhelmsen; JaneWoods; JulieNorth; MathiasPletz; StefanHagel; JulianeAnkert; SteffiKolanos; FrankBloos; KoenSimons; Tamaravan Zuylen; AngelaBouman; NikhilKumar; Raksh*tPanwar; Amber-LouisePoulter; KrishnaSunkara; GáborSzigligeti; JánosLeszkoven; BramRochwerg; TimKarachi; SimonOczkowski; JohnCentofanti; TinaMillen; DhineshSundaran; LaszloHollos; AnnaWilliams; MargaretTurns; JoanneWalsh; EmanAlQasim; LolowaAlswaidan; MohamedHegazy; HatimArishi; AliAlAmri; SamahAlQahtani; BrinthaNaidu; HaythamTlayjeh; SajidHussain; FarhanAl Enezi; Sheryl AnnAbdukahil; PhilHopkins; JohnSmith; HarrietNoble; KevinO’Reilly; ReenaMehta; OnyeeWong; EstherMakanju; DeepakRao; NymaSikondari; SianSaha; EleCorcoran; EvitaPappa; Maeveco*ckrell; ClareDonegan; MortezaBalaie; DanielaNickoleit-Bitzenberger; BernhardSchaaf; WernerMeermeier; KatharinaPrebeg; HarunAzzaui; MartinHower; Klaus-GerdBrieger; CorinnaElender; TimoSabelhaus; AnsgarRiepe; CerenAkamp; JuliusKremling; DanielaKlein; ElkeLandsiedel-Mechenbier; ShondiponLaha; MarkVerlander; AlexandraWilliams; AvinashJha; BrunoMegarbane; SebastianVoicu; NicolasDeye; IsabelleMalissin; LaetitiaSutterlin; AymenMrad; AdrienLehalleur; GiuliaNaim; PhilippeNguyen; Jean-MichelEkhérian; YvonnickBoué; GeorgiosSidéris; DominiqueVodovar; EmmanuelleGuérin; CarolineGrant; MatthewBrain; SarahMineall; ElankumaranParamasivam; ElizabethWilby; BethanOgg; ClareHowcroft; AngeliqueAspinwall; SamCharlton; RichardGould; DeenaMistry; SidraAwan; CarolineBedford; JoanneCarr-Wilkinson; AndrewHall; JillCooke; CarolineGardiner-Hill; CarolynMaloney; NigelBrunskill; OliviaWatchorn; ChloeHardy; HafizQureshi; NeilFlint; SarahNicholson; SaraSouthin; AndrewNicholson; AmardeepGhattaoraya; DanielHarding; SineadO’Halloran; AmyCollins; EmmaSmith; EstefaniaTrues; BarbaraBorgatta; IanTurner-Bone; AmieReddy; LauraWilding; CraigWilson; ZuhraSurti; Anders Aneman; JenneneMiller; HaydenWhite; KristenEstensen; LynetteMorrison; JoanneSutton; MelanieCooper; LokuWarnapura; RonanAgno; PrasannakumariSathianathan; DeborahShaw; NaziaIjaz; AdamSpong; SuganyaSabaretnam; DeanBurns; EvaLang; MargaretTate; RoyFischer; VishwanathBiradar; 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FarahAl-Beidh,PhD; DjillaliAnnane,MD, PhD; Yaseen M.Arabi,MD; AbiBeane,PhD; Wilmavan Bentum-Puijk,MSc; ZahraBhimani,MPH; Marc J. M.Bonten,MD, PhD; Charlotte A.Bradbury,MD, PhD; Frank M.Brunkhorst,MD, PhD; AidenBurrell,MBBS, PhD; AdrianBuzgau,MSc; MeredithBuxton; Walton N.Charles,MBBS; MatthewCove,MBBS; Michelle A.Detry,PhD; Lise J.Estcourt,MBBCh, PhD; Elizabeth O.fa*gbodun,MSc; MarkFitzgerald,PhD; Timothy D.Girard,MD, MSCI; Ewan C.Goligher,MD, PhD; HermanGoossens,PhD; RashanHaniffa,PhD; ThomasHills,MBBS, PhD; Christopher M.Horvat,MD; David T.Huang,MD, MPH; NaoIchihara,MD, MPH, PhD; FrancoisLamontagne,MD; John C.Marshall,MD; Daniel F.McAuley,MD; AnnaMcGlothlin,PhD; Shay P.McGuinness,MD; Bryan J.McVerry,MD; Matthew D.Neal,MD; Alistair D.Nichol,MD, PhD; Rachael L.Parke,PhD; Jane C.Parker,BN; KarenParry-Billings,MSc; Sam E. C.Peters,BArch; Luis F.Reyes,MD, PhD; Kathryn M.Rowan,PhD; HirokiSaito,MD, MPH; Marlene S.Santos,MD, MSHS; Christina T.Saunders,PhD; ArySerpa-Neto,PhD, MSc, MD; Christopher W.Seymour,MD, MSc; ManuShankar-Hari,MD, PhD; Lucy M.Stronach,BSc; Alexis F.Turgeon,MD, MSc; Anne M.Turner,MPH; Frank L.van de Veerdonk,MD, PhD; RyanZarychanski,MD, MSc; CameronGreen,MSc; Roger J.Lewis,MD, PhD; Derek C.Angus,MD, MPH; Colin J.McArthur,MD; ScottBerry,PhD; Lennie P. G.Derde,MD, PhD; Anthony C.Gordon,MBBS, MD; Steve A.Webb,MD, PhD; Patrick R.Lawler,MD, MPH

JAMA

The year 2020 was a grim and uncertain time for any clinician caring for inpatients with COVID-19, especially those with critical illness. In an era of modern medicine in which the range of options for many conditions can seem limitless, this novel viral threat was a reminder of the historical norm in medicine—a struggle to find the best available treatment.

As a stark example of ambiguities and resulting divergent practices during the dark days of early 2020, one of us was an infectious diseases consultant to medical teams caring exclusively for inpatients with COVID-19.¹ On one of the teams, all of their patients received adjunctive hydroxychloroquine as part of their admission medications. A second team, doing their daily rounds on the same floor of the hospital, chose the opposite approach—none of their patients received it. Members of both teams could mobilize logical arguments in favor of their practice, while simultaneously acknowledging that they were doing so without high-quality data from randomized clinical trials.

Now, more than 3 years since the first cases of COVID-19, multiple well-conducted studies have served to greatly expand treatment options. Importantly, clinical research has also crossed many ineffective treatments off the list of potential options, including, for the record, hydroxychloroquine.² Research has breathing room to evolve beyond the “triage” mindset of the early years of the pandemic toward refining treatment approaches and studying more than just mortality and hospitalization. Currently, 2 evidence gaps are particularly large: understanding treatment outcomes beyond a few weeks and measuring not just survival, but also quality of life.

In this issue of JAMA,³ investigators from the international Randomized Embedded Multifactorial Adaptive Platform for Community Acquired Pneumonia (REMAP-CAP) consortium make a substantial step toward closing these evidence gaps through a prespecified secondary analysis of their previously published randomized clinical trials. Using an adaptive study design,⁴ the REMAP-CAP trial evaluated 6 treatment classes for 4689 patients admitted to the intensive care unit with COVID-19 from March 2020 through June 2021. Most notable among their initial trial findings was a substantial clinical benefit, including short-term 21-day survival, of the IL-6 receptor antagonists tocilizumab and sarilumab.⁵ These results contributed to the inclusion of this strategy in treatment guidelines for COVID-19 among critically ill patients.⁶ Anticoagulation with heparin in noncritical disease of moderate severity (but not in critical disease) also improved outcomes,⁷ but none of the other tested therapies yielded favorable results.

The present analysis extends the 21-day primary outcome horizon of the previous trials to evaluate 180-day mortality (the primary outcome), 180-day quality of life measured through the 5-level EuroQol-5 Dimension (EQ-5D-5L) score, and 180-day disability using the 12-item World Health Organization Disability Assessment Schedule. The 6 pragmatic trials had varying treatment and control groups. The randomized groupings were a fixed 7-day course of intravenous hydrocortisone, a shock-dependent course, or no steroids; 1 of 2 IL-6 receptor antagonists, interferon beta-1a, or no immune modulator; lopinavir-ritonavir, hydroxychloroquine, a combination of the 2, or no proposed antiviral treatment; convalescent plasma treatment, delayed treatment, or no plasma; therapeutic-dose or thromboprophylaxis-dose heparin; and aspirin, a P2Y12 inhibitor (eg, clopidogrel), or no antiplatelet agent. Notably absent from this list of interventions is remdesivir, the only antiviral that is approved by the US Food and Drug Administration for inpatient treatment of COVID-19 to date. Such an exclusion is unlikely to invalidate these results because there is limited evidence for benefit of this drug in critical illness,⁸ which contrasts with clear efficacy when given earlier and in milder stages of the disease.⁹

Several unique aspects of this analysis deserve emphasis as one considers the results. The REMAP-CAP trial was an ambitious and forward-looking “perpetual platform trial,” initially organized in 2016 with an explicit purpose to provide rapid evidence in a pandemic.¹⁰ In the earliest days of the COVID-19 pandemic, the collaboration sprang into action and expanded to 197 international sites using this adaptable research platform. Another distinctive quality of the REMAP-CAP studies was their focus on pragmatic interventions, whose goal was to “replace random variation in treatment with randomized variation in treatment,” thereby embedding trials into routine care delivery. This was coupled with a sophisticated statistical framework using bayesian methods particularly well suited to deliver meaningful, time-sensitive evidence. Finally, the authors had the foresight to prespecify quality of life outcomes in their adaptive platform, enabling the important secondary outcomes in this study. The investigators deserve the highest praise for executing an expansive, forward-thinking initiative that has produced a wealth of evidence under intense pressure.

One of the main findings is unlikely to surprise readers aware of the short-term results of the REMAP-CAP trial and the current treatment guidelines for COVID-19. For the primary outcome of 180-day mortality, IL-6 receptor antagonists (tocilizumab or sarilumab) again demonstrated a very high probability of superiority (adjusted hazard ratio, 0.74 [95% credible interval {CrI}, 0.61-0.90]; >99.9% probability of superiority vs placebo). This 180-day outcome provides reassurance that early mortality benefit from IL-6 receptor antagonists did not result in longer-term adverse outcomes, such as susceptibility to late-onset opportunistic or other infections, that would offset short-term benefits.

Somewhat surprisingly given the negative results from the 21-day analysis,¹¹ antiplatelet agents (aspirin or P2Y12 inhibitors) also demonstrated a high likelihood of improving 180-day mortality (adjusted hazard ratio, 0.85 [95% CrI, 0.71-1.03]; 95.0% probability of superiority). Unlike the IL-6 receptor antagonists, these agents are not currently standard of care for management of critical COVID-19. Although it may seem contradictory that the corticosteroid domain did not show improved mortality rates, this component of the trial was importantly halted sooner than planned due to early evidence of benefit from the RECOVERY trial,¹² so it was underpowered to provide additional insight. As previously shown, therapeutic anticoagulation (in severe disease), lopinavir-ritonavir, hydroxychloroquine, and convalescent plasma had minimal benefit or even possible harm. Hydroxychloroquine treatment was associated with a concerning increase in mortality (adjusted hazard ratio, 1.51 [95% CrI, 0.98-2.29]). This is a reminder of the caution that clinicians should exercise in using unproven treatments and the importance of changing practice as evidence evolves.

Results examining the secondary outcomes of quality of life and disability are both more unexpected and more nuanced. There is further reassurance that the IL-6 receptor antagonists did not lead to worse quality of life or greater disability, and likely even improved these outcomes at 180 days. The benefits were even more certain for the antiplatelet agents, with a substantial gain of 0.08 in health-related quality of life over a baseline of 0.63 in the control group (adjusted mean difference, 0.08 [95% CrI, 0.02-0.13]). This result, combined with the 180-day mortality results also suggesting benefit, constitutes some of the most favorable evidence to date for these agents,¹³ especially in light of the initial trial from the REMAP-CAP group showing a 95.7% probability of futility.¹¹

Conflicting results and a higher bleeding risk with antiplatelet therapy for COVID-19 in critical illness¹³ means that this new evidence is not yet enough to motivate changed practice or alter consensus guidelines. Additionally, it is important to note that quality of life and disability outcome data were missing for more than 60% of the study sample, with differences between the populations with and without missing data. Regardless, antiplatelet agents deserve further study in other trials with extended data available. Ongoing study could be particularly valuable given that one proposed explanation for long-term symptoms from COVID-19 is microvascular clotting, a plausible pathophysiologic mechanism that antiplatelet agents would target.¹⁴

One unavoidable limitation of the present study and its applicability to current practice is that COVID-19 as a disease has changed. Although infection with SARS-CoV-2 is still very much with us, preexisting population-level immunity, from vaccination, prior infection, or both, has made severe disease progressively less common.¹⁵ There is also laboratory evidence that the widely circulating Omicron variant exhibits decreased lung infectivity,¹⁶ making pneumonia—the clinical entity most commonly leading to intensive care unit admission—a less likely manifestation of disease. The evidence in this study remains valuable given that COVID-19 will continue to be a common cause of critical illness globally. However, the most effective strategy to reduce mortality and critical illness will be prevention through a global effort to expand COVID-19 vaccination.

Article Information

Corresponding Author: Michael L. Barnett, MD, MS, Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Kresge 411, Boston, MA 02115 (mbarnett@hsph.harvard.edu).

Published Online: December 16, 2022. doi:10.1001/jama.2022.23700

Conflict of Interest Disclosures: Dr Barnett reported receiving personal fees from Greylock McKinnon Associates outside the submitted work and being retained as an expert witness in government litigation against opioid manufacturers and distributors. No other disclosures were reported.

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Barnett ML, Sax PE. Long-term Follow-up After Critical COVID-19: REMAP-CAP Revisited. JAMA. 2023;329(1):25–27. doi:10.1001/jama.2022.23700

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Long-term Follow-up After Critical COVID-19 (2024)

FAQs

What is long COVID post ICU syndrome? ›

Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others, which generally have an impact on everyday function. Symptoms may be new onset, following initial recovery from an acute COVID-19 episode, or persist from the initial illness.

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What is the recovery time for critical COVID-19? ›

Most people with COVID-19 will recover completely within a few weeks. However, some may keep experiencing symptoms for weeks or months after their diagnosis. This is called 'long COVID', 'post-acute sequelae of SARS-CoV-2' or 'post COVID-19 condition'.

Discover More Details ›

What are some potential lingering symptoms after COVID-19? ›

However, there are lots of symptoms you can have after a COVID-19 infection, including:

loss of smell.
chest pain or tightness.
difficulty sleeping (insomnia)
pins and needles.
depression and anxiety.
tinnitus, earaches.
feeling sick, diarrhoea, stomach aches, loss of appetite.

More items...

Know More ›

What are three long term complications of COVID-19? ›

The most commonly reported symptoms of post- COVID-19 syndrome include:

Fatigue.
Symptoms that get worse after physical or mental effort.
Fever.
Lung (respiratory) symptoms, including difficulty breathing or shortness of breath and cough.

Get More Info ›

What are complications of COVID-19 ICU? ›

Other Complications Related to Intensive Care Units

Patients who are critically ill with COVID-19 are at risk for nosocomial infections, such as ventilator-associated pneumonia, hospital-acquired pneumonia, and catheter-related bloodstream infections, and for other complications of critical illness care.

Read The Full Story ›

What is the long vax syndrome? ›

However, instances of long-lasting frosted branch angiitis, or 'Long Vax' syndrome, characterized by prolonged ocular inflammation after mRNA COVID-19 vaccination, were previously unknown and highlight a new area of interest in vaccine-related adverse effects.

Tell Me More ›

What is the critical stage of COVID-19? ›

Severe COVID-19 means that the lungs don't work correctly, and the person needs oxygen and other medical help in the hospital. Critical COVID-19 illness means the lung and breathing system, called the respiratory system, has failed and there is damage throughout the body.

Read The Full Story ›

What does COVID feel like in 2024? ›

Other typical symptoms include chills, fever, body aches, fatigue, chest pain, changes in smell, or confusion (especially in elderly patients). Diarrhea, vomiting and other stomach issues are more common with current variants than they were early in the pandemic.

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How long does it take to get your energy back after COVID? ›

How long does fatigue last after COVID-19? Your recovery from COVID-related fatigue will likely depend on how severe your illness was. After a mild case of COVID-19 your fatigue may clear up after about 2-3 weeks. But if you had a severe case, it's possible to feel sluggish and tired for months.

Learn More ›

How to get rid of lingering COVID congestion? ›

Deep breathing technique

Sit in a comfortable position.
Put one hand on your tummy just below your ribs and the other hand on your chest.
Take a deep breath through your nose and let your tummy push your hand out. ...
Breathe out through pursed lips like you are whistling. ...
Do this breathing 3 to 5 times.

How to tell if you have Long COVID? ›

Symptoms of Long COVID may include:

Fatigue, feeling tired.
Weakness.
Brain fog (problems concentrating or thinking)
Headaches.
Tremor.
Rapid or pounding heartbeat, feeling of skipped heartbeats (palpitations)
Dizziness upon standing.

More items...

Get More Info Here ›

What is the best treatment for Long COVID? ›

Pulmonary rehabilitation: Our respiratory therapists use the most advanced techniques to restore lung function and strengthen the muscles that help you breathe. Your treatment may include a combination of customized respiratory therapy, breathing exercises and medications.

Learn More Now ›

What organs does COVID affect long-term? ›

However, most experts agree that the long-term effects of COVID-19 are associated with the coronavirus' ability to trigger a massive inflammatory response in some individuals. “This inflammation, which results in blood clotting in blood vessels in the lungs, heart, brain, kidneys, and even legs,” said Dr. Connors.

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Does long-term COVID affect the brain? ›

Estimates vary as to exactly how many of those people struggle with cognitive function, but in one study of people with Long COVID, close to half reported having poor memory or brain fog. For most people, Long COVID brain fog eventually goes away, but it still can have a life-altering impact.

See Details ›

What are the long symptoms of COVID-19 that won't go away? ›

Long COVID is a collection of symptoms that last three months or longer after your first COVID symptoms. It can steal your energy, your ability to think clearly, and your sense of smell or taste. You might feel anxious or depressed, get frequent headaches, be short of breath or have heart palpitations.

What are the symptoms of post vac syndrome? ›

The most common symptoms were exercise intolerance reported by 170 (71%) participants, excessive fatigue by 167 (69%), numbness by 153 (63%), brain fog by 151 (63%), neuropathy by 151 (63%), insomnia by 148 (61%), palpitations by 145 (60%), myalgia by 132 (55%), tinnitus or humming in ears by 131 (54%), headache by 128 ...

Keep Reading ›

What is post intensive care syndrome in COVID-19 patients discharged from the intensive care unit? ›

Patients with Covid-19, after discharge from the intensive care unit (ICU), experience some psychological, physical, and cognitive disorders, which is known as the post–intensive care syndrome and has adverse effects on patients and their families.

Tell Me More ›

Is post acute COVID syndrome the same as long COVID? ›

Overview. Long COVID, also known as Post-COVID Conditions (PCC), refers to the wide range of symptoms and conditions that some people experience four or more weeks after an initial infection by SARS-CoV-2, the virus that causes COVID-19.

Find Out More ›

What factors are associated with post-Covid syndrome? ›

Based on the previous studies, the following variables were selected as the risk factors potentially associated with long COVID syndrome: sex (men and women), age (mean±SD), length of hospital stay (mean±SD), respiratory problems at the onset, neurological problems at the onset, gastrointestinal problems at the onset, ...