Viral load and patterns of sars-cov-2 dissemination to the lungs, mediastinal lymph nodes, and spleen of patients with covid-19 associated lymphopenia

Lymphopenia is a frequent hematological manifestation, associated with a severe course of COVID-19, with an insufficiently understood pathogenesis. We present molecular genetic im-munohistochemical, and electron microscopic data on SARS-CoV-2 dissemination and viral load (VL) in lungs, mediastinum lymph nodes, and the spleen of 36 patients who died from COVID-19. Lymphopenia <1 × 109/L was observed in 23 of 36 (63.8%) patients. In 12 of 36 cases (33%) SARS-CoV-2 was found in lung tissues only with a median VL of 239 copies (range 18–1952) SARS-CoV-2 cDNA per 100 copies of ABL1. Histomorphological changes corresponding to bronchopneumonia and the proliferative phase of DAD were observed in these cases. SARS-CoV-2 dissemination into the lungs, lymph nodes, and spleen was detected in 23 of 36 patients (58.4%) and was associated with the exudative phase of DAD in most of these cases. The median VL in the lungs was 12,116 copies (range 810–250281), lymph nodes—832 copies (range 96–11586), and spleen—71.5 copies (range 0–2899). SARS-CoV-2 in all cases belonged to the 19A strain. A immunohistochemical study revealed SARS-CoV-2 proteins in pneumocytes, alveolar macrophages, and bronchiolar epithelial cells in lung tissue, sinus histiocytes of lymph nodes, as well as cells of the Billroth pulp cords and spleen capsule. SARS-CoV-2 particles were detected by transmission electron microscopy in the cytoplasm of the endothelial cell, macrophages, and lymphocytes. The infection of lymphocytes with SARS-CoV-2 that we discovered for the first time may indicate a possible link between lymphopenia and SARS-CoV-2-mediated cytotoxic effect. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Abdullaev A.1 , Odilov A. 2 , Ershler M.3 , Volkov A. 2, 4 , Lipina T.5 , Gasanova T.6 , Lebedin Y.7 , Babichenko I. 2 , Sudarikov A.1
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  • 1 National Research Center for Hematology, Laboratory of Molecular Hematology, Novy Zykovski Lane 4a, Moscow, 125167, Russian Federation
  • 2 Department of Pathological Anatomy, Peoples’ Friendship, University of Russia, (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation
  • 3 National Research Center for Hematology, Hematopoiesis Physiology Laboratory, Novy Zykovski Lane 4a, Moscow, 125167, Russian Federation
  • 4 Department of Pathological Anatomy, Municipal Clinical Hospital Named after E.O. Mukhin, 17 Federativny Prospect, Moscow, 111399, Russian Federation
  • 5 Department of Cell biology and Histology, Faculty of Biology, Lomonosov Moscow State University, Leninskie Gori, 1, 12, Moscow, 119234, Russian Federation
  • 6 Department of Virology, Lomonosov Moscow State University, Leninskie Gori, 1, 40, Moscow, 119234, Russian Federation
  • 7 XEMA Company Limited, 9th Parkovaya St., 48, Moscow, 105043, Russian Federation
Ключевые слова
COVID-19; Lymphopenia; Multiplex real-time polymerase chain reaction; SARS-CoV-2; Viral load
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