Viral Load and Patterns of SARS-CoV-2 Dissemination to the Lungs, Mediastinal Lymph Nodes, and Spleen of Patients with COVID-19 Associated Lymphopenia

Viruses. 2021 Jul 20;13(7):1410. doi: 10.3390/v13071410.


Lymphopenia is a frequent hematological manifestation, associated with a severe course of COVID-19, with an insufficiently understood pathogenesis. We present molecular genetic immunohistochemical, 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.

Keywords: COVID-19; SARS-CoV-2; lymphopenia; multiplex real-time polymerase chain reaction; viral load.

MeSH terms

  • Aged
  • Aged, 80 and over
  • COVID-19 / virology*
  • COVID-19 Testing
  • Female
  • Humans
  • Immunohistochemistry
  • Lung / pathology
  • Lung / virology*
  • Lymph Nodes / virology*
  • Lymphopenia / immunology
  • Lymphopenia / virology*
  • Male
  • Mediastinum / virology*
  • Middle Aged
  • Multiplex Polymerase Chain Reaction
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / isolation & purification*
  • Spike Glycoprotein, Coronavirus / genetics
  • Spleen / virology*
  • Viral Load


  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2