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Review
. 2022 Feb 28:11:16.
doi: 10.4103/abr.abr_303_20. eCollection 2022.

Conceptual Framework for SARS-CoV-2-Related Lymphopenia

Ilnaz Rahimmanesh  1 , Shirin Kouhpayeh  2 , Yadollah Azizi  3 , Hossein Khanahmad  3   4
Affiliations
Review

Conceptual Framework for SARS-CoV-2-Related Lymphopenia

Ilnaz Rahimmanesh et al. Adv Biomed Res. .

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 hyperactivated due to virus entry and extensive DNA damage sequentially, leading to nicotinamide adenine dinucleotide (NAD)+ depletion, adenosine triphosphate 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 such as 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.

Keywords: ADP-ribosyl cyclase 1; NAD; SARS-CoV-2; lymphopenia.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Possible mechanisms involved within the reduction of peripheral lymphocyte subsets in patients with severe acute respiratory syndrome coronavirus 2. The nicotinamide adenine dinucleotide + depletion subsequent to poly-ADP-ribose polymerase 1 hyperactivation and CD38 overexpression leads to cell death and T cell depletion. Further, the negative effect of cytokines on T cells and virus-induced apoptosis could also be involved in severe acute respiratory syndrome coronavirus 2-related lymphopenia
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