Immune Alterations in a Patient with SARS-CoV-2-Related Acute Respiratory Distress Syndrome
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Abstract
We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19 in Europe. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2–3-fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in γδ T cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a pro-inflammatory cytokine storm, Th1 and Th2 activation, and markers of T cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response. The investigation was conducted as part of an overall French clinical cohort assessing patients with COVID-19 and registered in clinicaltrials.gov under the following number: NCT04262921.
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SciScore for 10.1101/2020.05.01.20087239: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: It was approved by the French Ethics Committee and written informed consent was obtained from each patient involved.
Consent: It was approved by the French Ethics Committee and written informed consent was obtained from each patient involved.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources γδ T cells were identified using an anti-TCR γδ antibody. anti-TCRsuggested: NoneSoftware and Algorithms Sentences Resources Immune cell phenotyping was performed with an LSRII Fortessa 4-laser (488, 640, 561, and 405 nm) flow cytometer (BD Biosciences), and FlowJo … SciScore for 10.1101/2020.05.01.20087239: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: It was approved by the French Ethics Committee and written informed consent was obtained from each patient involved.
Consent: It was approved by the French Ethics Committee and written informed consent was obtained from each patient involved.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources γδ T cells were identified using an anti-TCR γδ antibody. anti-TCRsuggested: NoneSoftware and Algorithms Sentences Resources Immune cell phenotyping was performed with an LSRII Fortessa 4-laser (488, 640, 561, and 405 nm) flow cytometer (BD Biosciences), and FlowJo software version 9.9.6 FlowJosuggested: (FlowJo, RRID:SCR_008520)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: We detected the following sentences addressing limitations in the study:Our observations suffered from several serious limitations. First, we did not sample the patient at the very early phase of the disease. In addition, we only explored peripheral blood. Immune abnormalities of the other organs of the lymphoid compartments require further study. Nevertheless, we believe that this case report supports the worldwide effort to repurpose several marketed drugs and immunomodulators to reduce the inflammatory reaction and pathophysiology caused by the virus30. First, it clearly shows that the immune alterations are dynamic. In the first phase, the innate immune system, driven by monocytes, macrophages, and Tγδ lymphocytes, is activated and leads to T-lymphocyte exhaustion. The activation of B lymphocytes then contributes to a substantial humoral response. Finally, we observed endothelial activation. Overall, this individual case also underscores the need to combine two complementary approaches to limit the severity of the disease: to control viral replication with an antiviral, with the aim to limit the source of hyperinflammation, and to potentiate this effect using a specific immune modulator that targets the cytokine storm as a trigger of the pathophysiological response. These interventions should be evaluated in well-designed studies. This longitudinal analysis may help to determine the timing of such interventions and provide tools for the clinical follow-up of patients.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04262921 Recruiting French COVID Cohort Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 21, 22, 24, 25, 26 and 27. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
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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