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Letter to the editor| Volume 96, ISSUE 6, P1672, June 2021

COVID-19: Precision Medicine and Vascular Endothelium

      To The Editor:
      We read with care and interest the original article from Pereira et al on the development of a precision medicine approach to the COVID-19 pandemic.
      • Pereira N.L.
      • Ahmad F.
      • Byku M.
      • et al.
      COVID-19: understanding inter-individual variability and implications for precision medicine.
      We appreciate very much the specialist explanation about the demographic (such as age, race, ethnicity, sex) and biological variables (such as angiotensin converting enzyme 2 expression, immune regulation, body mass index, and genetics) that may characterize the high-risk patient and can serve for optimizing hospitalization, vaccination and targeted drug therapy.
      However, “predictive algorithms may help in individualizing targeted therapy including hospitalization and assist in the logistics of vaccine administration” only if all key factors are included. In our opinion, it is of paramount importance to introduce the vascular endothelium into the discussion.
      • Tricarico G.
      • Zavan B.
      • Travagli V.
      Clinical evidence and therapeutic treatments at the time of the coronaviruses responsible for SARS: a perspective and points of view with a focus on vascular endothelium.
      In fact, endothelial damage to various organs was highlighted by autopsy outcomes,
      • Maccio U.
      • Zinkernagel A.S.
      • Shambat S.M.
      • et al.
      SARS-CoV-2 leads to a small vessel endotheliitis in the heart.
      and severe SARS-CoV-2 infection could have a more complete and significant interpretation evaluating integrity of endothelial glycocalyx.
      • Yamaoka-Tojo M.
      Vascular endothelial glycocalyx damage in COVID-19.
      In conclusion, the recognition of the whole COVID-19 host/genetic factors that contribute to COVID-19 susceptibility and subsequent pathogenesis advocates the use of precision medicine in better designing clinical trials and in treatment of the disease.
      • Thierry A.R.
      Host/genetic factors associated with COVID-19 call for precision medicine.

      References

        • Pereira N.L.
        • Ahmad F.
        • Byku M.
        • et al.
        COVID-19: understanding inter-individual variability and implications for precision medicine.
        Mayo Clin Proc. 2021; 96: 446-463
        • Tricarico G.
        • Zavan B.
        • Travagli V.
        Clinical evidence and therapeutic treatments at the time of the coronaviruses responsible for SARS: a perspective and points of view with a focus on vascular endothelium.
        Coronaviruses. 2021; 2: 1
        • Maccio U.
        • Zinkernagel A.S.
        • Shambat S.M.
        • et al.
        SARS-CoV-2 leads to a small vessel endotheliitis in the heart.
        EBioMedicine. 2021; 63: 103182
        • Yamaoka-Tojo M.
        Vascular endothelial glycocalyx damage in COVID-19.
        Int J Mol Sci. 2020; 21: 9712
        • Thierry A.R.
        Host/genetic factors associated with COVID-19 call for precision medicine.
        Precis Clin Med. 2020; 3: 228-234

      Linked Article

      • COVID-19: Understanding Inter-Individual Variability and Implications for Precision Medicine
        Mayo Clinic ProceedingsVol. 96Issue 2
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          Coronavirus disease 2019 (COVID-19) is characterized by heterogeneity in susceptibility to the disease and severity of illness. Understanding inter-individual variation has important implications for not only allocation of resources but also targeting patients for escalation of care, inclusion in clinical trials, and individualized medical therapy including vaccination. In addition to geographic location and social vulnerability, there are clear biological differences such as age, sex, race, presence of comorbidities, underlying genetic variation, and differential immune response that contribute to variability in disease manifestation.
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      • In reply—COVID-19: Precision Medicine and Vascular Endothelium
        Mayo Clinic ProceedingsVol. 96Issue 6
        • Preview
          We appreciate the kind comments provided by Travagli et al regarding our article on interindividual variability1 and fully agree with their statement that recognition of coronavirus disease 2019 (COVID-19) host/genetic factors should inform the design of precision clinical trials in this disease. We also acknowledge that inflammatory changes in the vascular endothelium are an important component of the response to COVID-19 infection. However, the studies cited by the authors do not provide evidence of interindividual variability in these processes (small vessel endotheliitis, vascular endothelial glycocalyx levels, or neutrophil extracellular trap formation and/or dysregulation) that could contribute to the variability observed in COVID-19 susceptibility, severity, and outcome.
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