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Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology.
Singh, Amit Kumar; Kasarpalkar, Nandini; Bhowmick, Shilpa; Paradkar, Gaurav; Talreja, Mayur; Shah, Karan; Tiwari, Abhishek; Palav, Harsha; Kaginkar, Snehal; Kulkarni, Rajiv; Patil, Ashwini; Kalsurkar, Varsha; Agrawal, Sachee; Shastri, Jayanthi; Dere, Rajesh; Bharmal, Ramesh; Mahale, Smita D; Bhor, Vikrant M; Patel, Vainav.
  • Singh AK; Department of Biochemistry & Virology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Kasarpalkar N; Department of Biochemistry & Virology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Bhowmick S; Department of Molecular Immunology & Microbiology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Paradkar G; Department of Biochemistry & Virology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Talreja M; Department of Molecular Immunology & Microbiology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Shah K; Department of Molecular Immunology & Microbiology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Tiwari A; Department of Molecular Immunology & Microbiology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Palav H; Department of Biochemistry & Virology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Kaginkar S; Department of Biochemistry & Virology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Kulkarni R; Department of Biochemistry & Virology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Patil A; Department of Molecular Immunology & Microbiology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Kalsurkar V; Department of Molecular Immunology & Microbiology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Agrawal S; Department of Molecular Immunology & Microbiology, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Shastri J; Department of Microbiology, BYL Nair Hospital, Mumbai, Maharashtra, India.
  • Dere R; Department of Microbiology, BYL Nair Hospital, Mumbai, Maharashtra, India.
  • Bharmal R; BKC COVID Jumbo Facility, Municipal Corporation of Greater Mumbai, Maharashtra, India.
  • Mahale SD; Office of the Dean, TN Medical College & BYL Nair Hospital, Mumbai, Maharashtra, India.
  • Bhor VM; Emeritus Scientist, ICMR-NIRRH, Mumbai, Maharashtra, India.
  • Patel V; Department of Molecular Immunology & Microbiology, ICMR-NIRRH, Mumbai, Maharashtra, India.
J Leukoc Biol ; 111(6): 1287-1295, 2022 06.
Article in English | MEDLINE | ID: covidwho-1650087
ABSTRACT
Immune cell dysregulation and lymphopenia characterize COVID-19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study, we evaluated the association of circulating IL-6, soluble mucosal addressin cell adhesion molecule (sMAdCAM), and IL-15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19. A cohort of SARS-CoV-2 infected individuals (n = 130) at various stages of disease progression together with healthy controls (n = 16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 levels. sMAdCAM, IL-15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells, were observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL-6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, plasma IL-15 levels negatively correlated with T, B, and NK count suggesting a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL-15 and IL-6, but not sMAdCAM, were associated with a longer duration of hospitalization.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interleukin-15 / COVID-19 / Lymphopenia Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Topics: Long Covid Limits: Humans Language: English Journal: J Leukoc Biol Year: 2022 Document Type: Article Affiliation country: JLB.3COVBCR0621-300R

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interleukin-15 / COVID-19 / Lymphopenia Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Topics: Long Covid Limits: Humans Language: English Journal: J Leukoc Biol Year: 2022 Document Type: Article Affiliation country: JLB.3COVBCR0621-300R