Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension

  1. Lei-Ke Zhang
  2. Yuan Sun
  3. Haolong Zeng
  4. Qingxing Wang
  5. Xiaming Jiang
  6. Wei-Juan Shang
  7. Yan Wu
  8. Shufen Li
  9. Yu-Lan Zhang
  10. Zhao-Nian Hao
  11. Hongbo Chen
  12. Runming Jin
  13. Wei Liu
  14. Hao Li
  15. Ke Peng
  16. Gengfu Xiao

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Abstract

The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to >200 countries posing a global public health concern. Patients with comorbidity, such as hypertension suffer more severe infection with elevated mortality. The development of effective antiviral drugs is in urgent need to treat COVID-19 patients. Here, we report that calcium channel blockers (CCBs), a type of antihypertensive drug that is widely used in clinics, inhibited the post-entry replication events of SARS-CoV-2 in vitro, while no in vitro anti-SARS-CoV-2 effect was observed for the two other major types of antihypertensive drugs, namely, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. CCB combined with chloroquine showed a significantly enhanced anti-SARS-CoV-2 efficacy. A retrospective clinical investigation on hospitalized COVID-19 patients with hypertension as the only comorbidity revealed that the CCB amlodipine besylate therapy was associated with a decreased case fatality rate. The results from this study suggest that CCB administration to COVID-19 patients with hypertension as the comorbidity might improve the disease outcome.

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  1. Version published to 10.1038/s41421-020-00235-0
  2. ScreenIT

    SciScore for 10.1101/2020.04.08.20047134: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Then they were incubated for 2 hours with the anti-sera (1:1000 dilution) against the NP of a bat SARS-related CoV as the primary antibody, followed by incubation with Alexa 488-labeled goat anti-rabbit IgG (Abcam, ab150077; 1:500 dilution).
    anti-sera
    suggested: (Equitech-Bio Cat# GAHAFC-1000, RRID:AB_781182)
    anti-rabbit IgG
    suggested: (Abcam Cat# ab150077, RRID:AB_2630356)
    Experimental Models: Cell Lines
    SentencesResources
    Cells, virus and reagents: Vero E6 cell line was obtained from American Type Culture Collection (ATCC) and maintained in minimum Eagle’s medium (MEM; Gibco Invitrogen) supplemented with 10% fetal bovine serum (FBS; Gibco Invitrogen), 1% antibiotic/antimycotic (Gibco Invitrogen), at 37 °C in a humidified 5% CO2 incubator.
    Vero E6
    suggested: None
    Huh7 cell line was cultured in Dulbecco’s modified Eagle’s medium (DMEM; Gibco Invitrogen) supplemented with 10% FBS, 1% antibiotic/antimycotic (Gibco Invitrogen), at 37 °C in a humidified 5% CO2 incubator.
    Huh7
    suggested: None
    Software and Algorithms
    SentencesResources
    All statistical analyses were performed using SPSS software, version 19.0.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2020.04.08.20047134v1 on medRxiv