Thrombotic microvascular injury is not mediated by thrombotic microangiopathy despite systemic complement activation in Covid-19 patients

  1. Adrien De Voeght
  2. Doriane Calmes
  3. Floran Beck
  4. Jean-Baptiste Sylvestre
  5. Philippe Delvenne
  6. Pierre Peters
  7. Gaelle Vertenoeil
  8. Frédéric Baron
  9. Nathalie Layios
  10. Jean-Luc Canivet

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Abstract

Hypoxemia and coagulopathy are common in severe symptomatic patients of coronavirus disease 2019 (COVID-19). Histological evidence shows implication of complement activation and lung injury. We research sign of complement activation and presence of thrombotic microangiopathy in 8 severe patients. Six of them presented moderate elevation of final pathway of complement – sC5b-9 (median value : 350 ng/mL [IQR : 300,5 - 514,95 ng/mL]). Two patients have been autopsied and presence of thrombotic microvascular injury have been found. Interestingly, none the 8 patients had signs of mechanical hemolytic anemia (median value of hemoglobin : 10,5 gr/dL[IQR : 8,1 - 11,9], median value of haptoglobuline 4,49 [IQR 3,55-4,66], none of the patients has schistocyte) and thrombocytopenia (median value: 348000/mL [IQR : 266 000 - 401 000). Finally, all 8 patients had elevated d-dimer (median value : 2226 µgr/l [IQR : 1493 – 2362]) and soluble fibrin monomer complex (median value : 8.5 mg/mL, IQR[<6 – 10.6]). In summary, this study show moderate activation of complement and coagulation with presence of thrombotic microvascular injury in patients with severe COVID-19 without evidence of systemic thrombotic microangiopathy.

Key points

  • Severe covid-19 patients show moderate elevation of final activation of complement

  • No sign of Thrombotic microangiopathy is found in severe covid-19 patients

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      SciScore for 10.1101/2020.06.18.20115873: (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.

      Table 2: Resources

      No key resources detected.

      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 did not find any issues relating to the usage of bar graphs.

      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.

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    2. Version published to 10.1101/2020.06.18.20115873v1 on medRxiv