Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The Conceptual Framework for SARS-CoV-2 Related Lymphopenia

Version 1 : Received: 5 April 2020 / Approved: 6 April 2020 / Online: 6 April 2020 (09:28:00 CEST)

How to cite: Rahimmanesh, I.; Kouhpayeh, S.; Khanahmad, H. The Conceptual Framework for SARS-CoV-2 Related Lymphopenia. Preprints 2020, 2020040045 (doi: 10.20944/preprints202004.0045.v1). Rahimmanesh, I.; Kouhpayeh, S.; Khanahmad, H. The Conceptual Framework for SARS-CoV-2 Related Lymphopenia. Preprints 2020, 2020040045 (doi: 10.20944/preprints202004.0045.v1).

Abstract

The emerging of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is associated with high morbidity and mortality rates globally. One of the most prominent characteristics of coronavirus disease-19 (COVID-19) is lymphopenia which is in contrast to other viral infections. This controversy might be explained by the evaluation of impaired innate and adaptive immune responses during the SARS-CoV-2 infection. During the innate immune response, poly-ADP-ribose polymerase (PARP) hyperactivated due to virus entry and extensive DNA damage sequentially leading to NAD+ depletion, ATP depletion and finally cell death. In contrast to the immune response against viral infections, cytotoxic T lymphocytes decline sharply in SARS-CoV-2 infection which might be due to infiltration and trapping in the lower respiratory tract. In addition, there are more factors proposed to involve in lymphopenia in COVID-19 infection like the role of CD38 which functions as NADase and intensifies NAD depletion which in turn affects NAD+ dependent Sirtuin proteins, as the regulators of cell death and viability. Lung tissue sequestration following cytokine storm supposed to be another reason for lymphopenia in COVID-19 patients. Protein 7a as one of the virus-encoded proteins induces apoptosis in various organ-derived cell lines. These mechanisms proposed to induce lymphopenia, although there are still more studies needed to clarify the underlying mechanisms for lymphopenia in COVID-19 patients.

Subject Areas

SARS-CoV-2; lymphopenia; NAD+ depletion; CD38

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