1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Medicine
  4. Volume 75, 2024
  5. Article

Annual Review of Medicine

Volume 75, 2024

Treatments for COVID-19

Abstract

The treatment for COVID-19 has evolved rapidly since the start of the pandemic and now consists mainly of antiviral and immunomodulatory agents. Antivirals, such as remdesivir and nirmatrelvir-ritonavir, have proved to be most useful earlier in illness (e.g., as outpatient therapy) and for less severe disease. Immunomodulatory therapies, such as dexamethasone and interleukin-6 or Janus kinase inhibitors, are most useful in severe disease or critical illness. The role of anti-SARS-CoV-2 monoclonal antibodies has diminished because of the emergence of viral variants that are not anticipated to be susceptible to these treatments, and there still is not a consensus on the use of convalescent plasma. COVID-19 has been associated with increased rates of venous thromboembolism, but the role of antithrombotic therapy is limited. Multiple investigational agents continue to be studied, which will alter current treatment paradigms as new data are released.

Keyword(s): antithrombotic therapy, antivirals, convalescent plasma, COVID-19, COVID-19 treatment, immunomodulators, neutralizing antibodies, SARS-CoV-2
Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-052422-020316
2024-01-29
2024-04-30
Loading full text...

Full text loading...

/deliver/fulltext/med/75/1/annurev-med-052422-020316.html?itemId=/content/journals/10.1146/annurev-med-052422-020316&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    WHO 2023. WHO coronavirus (COVID-19) dashboard World Health Organ https://covid19.who.int. Accessed May 15, 2023
  2. 2.
    CDC 2023. Coronavirus disease 2019 (COVID-19) Cent. Dis. Control Prev. https://www.cdc.gov/coronavirus/2019-ncov/your-health/about-covid-19.html. Accessed May 15, 2023
  3. 3.
    Tenforde MW, Kim SS, Lindsell CJ et al. 2020. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network—United States, March–June 2020. Morb. Mortal. Wkly. Rep. 69:30993–98
     [Google Scholar]
  4. 4.
    NIH 2023. Coronavirus disease 2019 (COVID-19) treatment guidelines Natl. Inst. Health http://www.covid19treatmentguidelines.nih.gov
  5. 5.
    Gandhi RT, Lynch JB, Del Rio C. 2020. Mild or moderate Covid-19. N. Engl. J. Med. 383:181757–66
     [Google Scholar]
  6. 6.
    Beigel JH, Tomashek KM, Dodd LE et al. 2020. Remdesivir for the treatment of Covid-19—final report. N. Engl. J. Med. 383:191813–26
     [Google Scholar]
  7. 7.
    Ali K, Azher T, Baqi M et al. 2022. Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial. CMAJ 194:7E242–51
     [Google Scholar]
  8. 8.
    WHO Solidarity Trial Consortium 2022. Remdesivir and three other drugs for hospitalized patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses. Lancet 399:103391941–53
     [Google Scholar]
  9. 9.
    Gottlieb RL, Vaca CE, Paredes R et al. 2022. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N. Engl. J. Med. 386:4305–15
     [Google Scholar]
  10. 10.
    Hammond J, Leister-Tebbe H, Gardner A et al. 2022. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N. Engl. J. Med. 386:151397–408
     [Google Scholar]
  11. 11.
    Pfizer 2022. Pfizer reports additional data on PAXLOVIDTM supporting upcoming new drug application submission to U.S. FDA Press Release June 14, Pfizer Inc. New York, NY: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-reports-additional-data-paxlovidtm-supporting
  12. 12.
    Arbel R, Wolff Sagy Y, Hoshen M et al. 2022. Nirmatrelvir use and severe Covid-19 outcomes during the omicron surge. N. Engl. J. Med. 387:9790–98
     [Google Scholar]
  13. 13.
    Dryden-Peterson S, Kim A, Kim AY et al. 2023. Nirmatrelvir plus ritonavir for early COVID-19 in a large U.S. health system: a population-based cohort study. Ann. Intern. Med. 176:177–84
     [Google Scholar]
  14. 14.
    Ganatra S, Dani SS, Ahmad J et al. 2023. Oral nirmatrelvir and ritonavir in nonhospitalized vaccinated patients with coronavirus disease 2019. Clin. Infect. Dis. 76:4563–72
     [Google Scholar]
  15. 15.
    FDA 2023. Antimicrobial Drugs Advisory Committee meeting announcement https://www.fda.gov/advisory-committees/advisory-committee-calendar/updated-information-march-16-2023-antimicrobial-drugs-advisory-committee-meeting-announcement
  16. 16.
    Deo R, Choudhary MC, Moser C et al. 2023. Symptom and viral rebound in untreated SARS-CoV-2 infection. Ann. Intern. Med. 176:3348–54
     [Google Scholar]
  17. 17.
    Jayk Bernal A, Gomes da Silva MM, Musungaie DB et al. 2022. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N. Engl. J. Med. 386:6509–20
     [Google Scholar]
  18. 18.
    Butler CC, Hobbs FDR, Gbinigie OA et al. 2023. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet 401:10373281–93
     [Google Scholar]
  19. 19.
    Reis G, Moreira Silva EAS, Medeiros Silva DC et al. 2023. Early treatment with pegylated interferon lambda for Covid-19. N. Engl. J. Med. 388:6518–28
     [Google Scholar]
  20. 20.
    Uehara T. 2023. Ensitrelvir for mild-to-moderate COVID-19: phase 3 part of phase 2/3 study Paper presented at Conf. Retrovir. Opportunistic Infect. Seattle, WA: Feb. 19–22
  21. 21.
    Cao Z, Gao W, Bao H et al. 2023. VV116 versus nirmatrelvir-ritonavir for oral treatment of Covid-19. N. Engl. J. Med. 388:5406–17
     [Google Scholar]
  22. 22.
    RECOVERY Collab. Group 2021. Dexamethasone in hospitalized patients with Covid-19. N. Engl. J. Med. 384:8693–704
     [Google Scholar]
  23. 23.
    Abani O, Abbas A, Abbas F et al. 2023. Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 401:103871499–507
     [Google Scholar]
  24. 24.
    Chauvet P, Mallat J, Arumadura C et al. 2020. Risk factors for invasive pulmonary aspergillosis in critically ill patients with coronavirus disease 2019-induced acute respiratory distress syndrome. Crit Care Explor. 2:11e0244
     [Google Scholar]
  25. 25.
    De Wilton A, Nabarro LE, Godbole GS et al. 2021. Risk of Strongyloides Hyperinfection Syndrome when prescribing dexamethasone in severe COVID-19. Travel Med. Infect. Dis. 40:101981
     [Google Scholar]
  26. 26.
    Liu J, Wang T, Cai Q et al. 2020. Longitudinal changes of liver function and hepatitis B reactivation in COVID-19 patients with pre-existing chronic hepatitis B virus infection. Hepatol. Res. 50:111211–21
     [Google Scholar]
  27. 27.
    RECOVERY Collab. Group 2021. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 397:102851637–45
     [Google Scholar]
  28. 28.
    REMAP-CAP Investig 2021. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N. Engl. J. Med. 384:161491–502
     [Google Scholar]
  29. 29.
    Marconi VC, Ramanan AV, de Bono S et al. 2021. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir. Med. 9:121407–18
     [Google Scholar]
  30. 30.
    RECOVERY Collab. Group 2022. Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis. Lancet 400:10349359–68
     [Google Scholar]
  31. 31.
    2022. Tixagevimab and cilgavimab (Evusheld) for pre-exposure prophylaxis of COVID-19. JAMA 327:4384–85
     [Google Scholar]
  32. 32.
    FDA 2022. Bamlanivimab and etesevimab EUA letter of authorization, Jan. 24, 2022 https://www.fda.gov/media/145801/download
  33. 33.
    FDA 2021. Fact sheet for health care providers: emergency use authorization (EUA) of REGEN-COV® (casirivimab and imdevimab) https://www.fda.gov/media/145611/download
  34. 34.
    FDA 2021. Fact sheet for healthcare providers: emergency use authorization for sotrovimab https://www.fda.gov/media/149534/download
  35. 35.
    FDA 2022. Bebtelovimab EUA letter of authorization, Oct. 27, 2022 https://www.fda.gov/media/156151/download
  36. 36.
    CDC 2023. COVID data tracker Cent. Dis. Control. Prev. https://covid.cdc.gov. Accessed June 15, 2023
  37. 37.
    Wang Q, Iketani S, Li Z et al. 2023. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell 186:2279–86.e8
     [Google Scholar]
  38. 38.
    Casadevall A, Pirofski L-A. 2020. The convalescent sera option for containing COVID-19. J. Clin. Investig. 130:41545–48
     [Google Scholar]
  39. 39.
    Simonovich VA, Burgos Pratx LD, Scibona P et al. 2021. A randomized trial of convalescent plasma in Covid-19 severe pneumonia. N. Engl. J. Med. 384:7619–29
     [Google Scholar]
  40. 40.
    RECOVERY Collab. Group 2021. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 397:102892049–59
     [Google Scholar]
  41. 41.
    Sullivan DJ, Gebo KA, Shoham S et al. 2022. Early outpatient treatment for Covid-19 with convalescent plasma. N. Engl. J. Med. 386:181700–11
     [Google Scholar]
  42. 42.
    Libster R, Pérez Marc G, Wappner D et al. 2021. Early high-titer plasma therapy to prevent severe Covid-19 in older adults. N. Engl. J. Med. 384:7610–18
     [Google Scholar]
  43. 43.
    Levine AC, Fukuta Y, Huaman MA et al. 2023. COVID-19 convalescent plasma outpatient therapy to prevent outpatient hospitalization: a meta-analysis of individual participant data from five randomized trials. Clin. Infect. Dis. 76:122077–86
     [Google Scholar]
  44. 44.
    Lu LL, Suscovich TJ, Fortune SM et al. 2018. Beyond binding: antibody effector functions in infectious diseases. Nat. Rev. Immunol. 18:146–61
     [Google Scholar]
  45. 45.
    Khoury DS, Cromer D, Reynaldi A et al. 2021. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 27:71205–11
     [Google Scholar]
  46. 46.
    Goldblatt D, Alter G, Crotty S et al. 2022. Correlates of protection against SARS-CoV-2 infection and COVID-19 disease. Immunol. Rev. 310:16–26
     [Google Scholar]
  47. 47.
    McMahan K, Yu J, Mercado NB et al. 2021. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature 590:7847630–34
     [Google Scholar]
  48. 48.
    Addetia A, Crawford KHD, Dingens A et al. 2020. Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with a high attack rate. J. Clin. Microbiol. 58:11e02107-20
     [Google Scholar]
  49. 49.
    Yamin R, Jones AT, Hoffmann H-H et al. 2021. Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy. Nature 599:7885465–70
     [Google Scholar]
  50. 50.
    Winkler ES, Gilchuk P, Yu J et al. 2021. Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection. Cell 184:71804–20.e16
     [Google Scholar]
  51. 51.
    Ullah I, Prévost J, Ladinsky MS et al. 2021. Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy. Immunity 54:92143–58.e15
     [Google Scholar]
  52. 52.
    Liu L, Wei Q, Lin Q et al. 2019. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight 4:4e123158
     [Google Scholar]
  53. 53.
    Park H-S, Barranta C, Yin A et al. 2023. Antibody correlates of protection for COVID-19 convalescent plasma associated with reduced outpatient hospitalizations. medRxiv 2023.04.13.23288353
  54. 54.
    Herman JD, Wang C, Loos C et al. 2021. Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response. Nat. Commun. 12:16853
     [Google Scholar]
  55. 55.
    Ullah I, Beaudoin-Bussières G, Symmes K et al. 2023. The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice. Cell Rep. Med. 4:1100893
     [Google Scholar]
  56. 56.
    Yang X-L, Hu B, Wang B et al. 2015. Isolation and characterization of a novel bat coronavirus closely related to the direct progenitor of severe acute respiratory syndrome coronavirus. J. Virol. 90:63253–56
     [Google Scholar]
  57. 57.
    Piepenbrink MS, Park J-G, Deshpande A et al. 2022. Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody. PLOS Pathog. 18:7e1010691
     [Google Scholar]
  58. 58.
    Aridis Pharmaceuticals, Inc 2022. Aridis’ pan-coronavirus, inhaled monoclonal antibody cocktail AR-701 is protective in non-human primates PR Newswire https://www.prnewswire.com/news-releases/aridis-pan-coronavirus-inhaled-monoclonal-antibody-cocktail-ar-701-is-protective-in-non-human-primates-301603355.html
  59. 59.
    López-Muñoz AD, Kosik I, Holly J et al. 2022. Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity. Sci. Adv. 8:31eabp9770
     [Google Scholar]
  60. 60.
    Ali YM, Ferrari M, Lynch NJ et al. 2021. Lectin pathway mediates complement activation by SARS-CoV-2 proteins. Front. Immunol. 12:714511
     [Google Scholar]
  61. 61.
    Herman JD, Wang C, Burke JS et al. 2022. Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy. Cell Rep. Med. 3:11100811
     [Google Scholar]
  62. 62.
    Dangi T, Sanchez S, Class J et al. 2022. Improved control of SARS-CoV-2 by treatment with a nucleocapsid-specific monoclonal antibody. J. Clin. Investig. 132:23e162282
     [Google Scholar]
  63. 63.
    Connors JM, Iba T, Gandhi RT. 2021. Thrombosis and coronavirus disease 2019: controversies and (tentative) conclusions. Clin. Infect. Dis. 73:122294–97
     [Google Scholar]
  64. 64.
    Spyropoulos AC, Bonaca MP. 2022. Studying the coagulopathy of COVID-19. Lancet 399:10320118–19
     [Google Scholar]
  65. 65.
    Barco S, Voci D, Held U et al. 2022. Enoxaparin for primary thromboprophylaxis in symptomatic outpatients with COVID-19 (OVID): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet Haematol. 9:8e585–93
     [Google Scholar]
  66. 66.
    Cools F, Virdone S, Sawhney J et al. 2022. Thromboprophylactic low-molecular-weight heparin versus standard of care in unvaccinated, at-risk outpatients with COVID-19 (ETHIC): an open-label, multicentre, randomised, controlled, phase 3b trial. Lancet Haematol. 9:8e594–604
     [Google Scholar]
  67. 67.
    ATTACC Investig., ACTIV-4a Investig., REMAP-CAP Investig., et al. 2021. Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19. N. Engl. J. Med. 385:9790–802
     [Google Scholar]
  68. 68.
    REMAP-CAP Investig., ACTIV-4a Investig., ATTACC Investig., et al. 2021. Therapeutic anticoagulation with heparin in critically ill patients with Covid-19. N. Engl. J. Med. 385:9777–89
     [Google Scholar]
  69. 69.
    ACTIV-3/TICO Study Group 2022. The association of baseline plasma SARS-CoV-2 nucleocapsid antigen level and outcomes in patients hospitalized with COVID-19. Ann. Intern. Med. 175:101401–10
     [Google Scholar]
/content/journals/10.1146/annurev-med-052422-020316
Loading
Treatments for COVID-19
Annual Review of Medicine 75, 145 (2024); https://doi.org/10.1146/annurev-med-052422-020316
/content/journals/10.1146/annurev-med-052422-020316
/content/journals/10.1146/annurev-med-052422-020316
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error