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Is antiviral treatment at the acute phase of COVID-19 effective for decreasing the risk of long-COVID? A systematic review

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A Correction to this article was published on 07 March 2024

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Abstract

Purpose

Preliminary evidence suggests a potential effect of antiviral medication used during the acute COVID-19 phase for preventing long-COVID. This review investigates if having received pharmacological treatment during acute SARS-CoV-2 infection may reduce the risk of long-COVID.

Methods

MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to July 15th, 2023. Articles comparing the presence of long-COVID symptoms between individuals who received or not a specific medication, particularly antivirals, during the acute phase of SARS-CoV-2 infection were included. Methodological quality was assessed using the Newcastle–Ottawa Scale or Cochrane’s Risk of Bias (RoB) tool.

Results

From 517 studies identified, 6 peer-reviewed studies and one preprint met all inclusion criteria. The sample included 2683 (n = 4) hospitalized COVID-19 survivors and 307,409 (n = 3) non-hospitalized patients. The methodological quality was high in 71% of studies (n = 5/7). Two studies investigating the effects of Nirmatrelvir/Ritonavir and three studies investigating the effect of Remdesivir reported conflicting results on effectiveness for preventing long-COVID. Three studies investigating the effects of other medication such as Dexamethasone (n = 2) or Metformin (n = 1) found positive results of these medications for preventing long-COVID.

Conclusion

Available evidence about the effect of medication treatment with antivirals during acute COVID-19 and reduced risk of developing long-COVID is conflicting. Heterogeneous evidence suggests that Remdesivir or Nirmatrelvir/Ritonavir could have a potential protective effect for long-COVID. A limited number of studies demonstrated a potential benefit of other medications such as Dexamethasone or Metformin, but more studies are needed.

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Data availability

All data derived from the study is presented in the current text.

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Funding

The project was supported by the LONG-COVID-EXP-CM, a grant associated to the Fondo Europeo De Desarrollo Regional—Recursos REACT-UE del Programa Operativo de Madrid 2014–2020, en la línea de actuación de proyectos de I + D + i en materia de respuesta a COVID 19. The sponsor had no role in the design, collection, management, analysis, or interpretation of the data, draft, review, or approval of the manuscript or its content. The authors were responsible for the decision to submit the manuscript for publication, and the sponsor did not participate in this decision.

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Authors and Affiliations

  1. Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos (URJC), Universidad Rey Juan Carlos, Avenida de Atenas S/N, 28922, Alcorcón, Madrid, Spain

    César Fernández-de-las-Peñas

  2. Department of Internal Medicine, Hospital Universitario Infanta Leonor-Virgen de La Torre, Madrid, Spain

    Juan Torres-Macho & Ana Franco-Moreno

  3. Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain

    Juan Torres-Macho

  4. Department of Medicine, Saint Peter’s University Hospital, New Brunswick, NJ, USA

    Jesus Alfonso Catahay & Mario Caldararo

  5. Department of Medicine, Monmouth Medical Center, Long Branch, NJ, USA

    Raymart Macasaet

  6. Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines

    Jacqueline Veronica Velasco

  7. Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, USA

    Sharina Macapagal

  8. Clinical Laboratory, Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Brandon Michael Henry

  9. Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy

    Giuseppe Lippi

  10. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Kin Israel Notarte

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  1. César Fernández-de-las-Peñas
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Contributions

All the authors cited in the manuscript had substantial contributions to the concept and design, the execution of the work, or the analysis and interpretation of data; drafting or revising the manuscript and have read and approved the final version of the paper. CF: conceptualization, visualization, methodology, validation, data curation, writing—original draft, writing—review and editing. JT-M: conceptualization, validation, data curation, writing—review and editing. JAC: methodology, validation, data curation, writing—original draft, writing—review and editing. RM: methodology, validation, data curation, writing—original draft, writing—review and editing. JVV: methodology, validation, data curation, writing—original draft, writing—review and editing. SM: methodology, validation, data curation, writing—original draft, writing—review and editing. MC: validation, writing—review and editing. BMH: validation, writing—review and editing. GL: review and editing. AF-M: methodology, validation, writing—review and editing. KIN: conceptualization, visualization, methodology, validation, data curation, writing—original draft, writing—review and editing.

Corresponding author

Correspondence to César Fernández-de-las-Peñas.

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Fernández-de-las-Peñas, C., Torres-Macho, J., Catahay, J.A. et al. Is antiviral treatment at the acute phase of COVID-19 effective for decreasing the risk of long-COVID? A systematic review. Infection 52, 43–58 (2024). https://doi.org/10.1007/s15010-023-02154-0

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