Sustained expression of inflammatory monocytes and activated T cells in COVID‐19 patients and recovered convalescent plasma donors

  1. Ravinder Singh
  2. Hamed Hemati
  3. Meenu Bajpai
  4. Pushpa Yadav
  5. Ashish Maheshwari
  6. Suresh Kumar
  7. Sonal Agrawal
  8. Jayesh Kumar Sevak
  9. Mojahidul Islam
  10. Jaswinder Singh Mars
  11. Shiv K Sarin
  12. Nirupama Trehanpati

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Abstract

Introduction

Intense monocyte activation and infiltration into the target tissues are the main mechanisms of lung injury in severe acute respiratory syndrome coronavirus 2 infection. A reduction in the degree and nature of such cellular responses is expected following recovery. We aimed to investigate the immune responses in moderate coronavirus disease 2019 (COVID‐19) patients and recovered patients.

Methods

Moderate COVID‐19 patients ( n  = 34) at Lok Nayak Hospital, New Delhi, and COVID‐19 recovered patients ( n  = 15) from the mild disease who were considered for convalescent plasma (COPLA) donation at the Institute of Liver and Biliary Sciences, New Delhi and healthy individuals ( n  = 10), were recruited. We have assessed 21 plasma cytokines using cytokine bead array, performed proteomics on serum proteins, and analyzed immune cells using a detailed multicolor flow cytometry.

Results

A significant increase in inflammatory markers such as macrophage inflammatory protein (MIP)1‐α, monocyte chemotactic protein‐1, macrophage migration inhibitory factor, vascular endothelial growth factor‐A, and Leptin was observed in the moderate patients. Nonsurvivors additionally showed increased interleukin (IL)‐6 levels. Consistently, the proteomics analysis showed the signatures of cytokine production and interferon‐γ response, and increased level of acute‐phase protein SAA1 in the serum of COVID‐19 patients. Despite the sustained expression of MIPs, the recovered COPLA donors showed a surge in MCSF and IL‐18 levels. Both the groups had increased CCR2, CX3CR1 positive monocytes, low CD8 + T cells, A proliferation‐inducing ligand, and B‐cell activating factor receptor + B cells compared with healthy subjects.

Conclusions

Patients who have recovered and considered for COPLA donations still have compromised immunity with sustained expression of inflammatory monocytes and activated T cells.

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  1. Version published to 10.1002/iid3.476
  2. ScreenIT

    SciScore for 10.1101/2020.11.17.20233668: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Patients less than 18 years or more than 65 years of age, those with co-morbid conditions(cardiopulmonary disease, structural or valvular heart disease, coronary artery disease, COPD, chronic liver disease, chronic kidney disease), patients presenting with multi-organ failure, pregnant females, individuals with HIV, viral hepatitis, cancer, morbid obesity with a BMI>35 kg/m2, extremely moribund patients with an expected life expectancy of <24 hours, or failure to obtain informed consent were excluded from this study.
    IACUC: The study was performed in accordance with Institutional Ethical Committee approval (No.F.37/(1)/9/ILBS/DOA/2020/20217/260).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablePatients less than 18 years or more than 65 years of age, those with co-morbid conditions(cardiopulmonary disease, structural or valvular heart disease, coronary artery disease, COPD, chronic liver disease, chronic kidney disease), patients presenting with multi-organ failure, pregnant females, individuals with HIV, viral hepatitis, cancer, morbid obesity with a BMI>35 kg/m2, extremely moribund patients with an expected life expectancy of <24 hours, or failure to obtain informed consent were excluded from this study.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibodies were labelled with different flouorochromes and used for B Cells; anti-CD3, CD14, CD56, CD19, CD27, CD21, IgD, CD40, CD38, CD274, CD185
    anti-CD3
    suggested: (BioLegend Cat# 348805, RRID:AB_2889063)
    CD14
    suggested: (BioLegend Cat# 348805, RRID:AB_2889063)
    CD56
    suggested: (RayBiotech Cat# CS-11-0123, RRID:AB_1228026)
    CD19
    suggested: (Agilent Cat# TC67401, RRID:AB_579635)
    CD27
    suggested: (Thermo Fisher Scientific Cat# EPX140-15803-901, RRID:AB_2576106)
    CD21
    suggested: None
    CD40
    suggested: None
    CD38
    suggested: None
    CD274
    suggested: None
    Software and Algorithms
    SentencesResources
    Data was analyzed using FlowJo software version 10.
    FlowJo
    suggested: (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: 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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.11.17.20233668 on medRxiv