Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Apr 28;25(1):616.
doi: 10.1186/s12879-025-11012-3.

Early combined therapy for COVID-19 in immunocompromised patients: a promising approach against viral persistence and drug resistance

Salvatore Rotundo  1   2 , Francesca Serapide  3   4 , Lavinia Berardelli  3   5 , Sara Palma Gullì  3 , Simona Mongiardi  3 , Maria Teresa Tassone  3 , Enrico Maria Trecarichi #  3   6 , Alessandro Russo #  3   4
Affiliations
Review

Early combined therapy for COVID-19 in immunocompromised patients: a promising approach against viral persistence and drug resistance

Salvatore Rotundo et al. BMC Infect Dis. .

Abstract
in English, French

Immunocompromised (IC) patients face significant challenges in managing COVID-19 due to their heightened susceptibility to severe illness, persistent infections, and the potential development of drug resistance. Studies indicate that IC patients, particularly those with hematologic malignancies (HM), hematopoietic stem cell transplants (HSCTR), or solid organ transplants (SOTR), experience higher mortality rates and worse outcomes compared to the general population, even post-vaccination. The persistence of the virus in these patients, combined with its rapid mutation, further complicates treatment. Recent evidence supports the use of combined neutralizing monoclonal antibodies (mAbs) and direct-acting antivirals (DAAs) as a more effective approach to viral clearance, reducing mortality, and preventing relapses. However, the rise of resistant variants, especially to mAbs, and concerns about the safety of prolonged or intensive therapies pose ongoing challenges. Monotherapies often fail short to address these issues, highlighting the need for early combined therapy (ECT) with mAbs and DAAs. ECT has shown promise in managing COVID-19 in IC individuals by targeting multiple stages of the viral lifecycle, reducing viral load, and clearing infections at earlier stages, which helps mitigate the risks of severe disease and drug resistance. Continued research is essential to refine these treatment protocols, especially as the virus evolves. Although further studies are needed, current findings suggest that ECT may become the standard of care for managing COVID-19 in severely IC patients, offering better clinical outcomes and hindering viral persistence.

Not applicable.

Keywords: Antivirals; COVID-19; Combined therapy; Immunocompromised; Monoclonal antibodies.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Proposed management strategy for immunocompromised patients with COVID-19. DAAs: Direct Acting Antivirals; mAbs: monoclonal antibodies against SARS-CoV-2; ADRs: adverse drug reactions
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Antinori A, Bausch-Jurken M. The burden of COVID-19 in the immunocompromised patient: implications for vaccination and needs for the future. J Infect Dis. 2023;228(Suppl 1):S4–12. - PMC - PubMed
    1. Pagano L, Salmanton-Garcia J, Marchesi F, Busca A, Corradini P, Hoenigl M, Klimko N, Koehler P, Pagliuca A, Passamonti F, et al. COVID-19 infection in adult patients with hematological malignancies: a European hematology association survey (EPICOVIDEHA). J Hematol Oncol. 2021;14(1):168. - PMC - PubMed
    1. Pereira MR, Mohan S, Cohen DJ, Husain SA, Dube GK, Ratner LE, Arcasoy S, Aversa MM, Benvenuto LJ, Dadhania DM, et al. COVID-19 in solid organ transplant recipients: initial report from the US epicenter. Am J Transpl. 2020;20(7):1800–8. - PMC - PubMed
    1. Januel E, Hajage D, Labauge P, Maillart E, De Seze J, Zephir H, Pelletier J, Guilloton L, Bensa C, Heinzlef O, et al. Association between Anti-CD20 therapies and COVID-19 severity among patients with Relapsing-Remitting and progressive multiple sclerosis. JAMA Netw Open. 2023;6(6):e2319766. - PMC - PubMed
    1. Sun J, Zheng Q, Madhira V, Olex AL, Anzalone AJ, Vinson A, Singh JA, French E, Abraham AG, Mathew J, et al. Association between immune dysfunction and COVID-19 breakthrough infection after SARS-CoV-2 vaccination in the US. JAMA Intern Med. 2022;182(2):153–62. - PMC - PubMed

LinkOut - more resources