Abstract
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.
Highlights
Introduction conditions of the Creative CommonsMore than 4 million patients worldwide have already died due to the COVID-19 pandemic [1]
The development of lymphopenia in patients with COVID-19 could result from extrapulmonary dissemination and the direct effect of SARS-CoV-2 particles on the tissues of the mediastinal lymph nodes, which filter lymph flowing from the lung primary inflammatory focus, and spleen, as a significant human lymphoid organ [9,10,11,35]
The proposed SARS-COV-2 quantitation method based on serial dilutions of cloned calibrator templates is suitable for the relative SARS-COV-2 copy number estimation
Summary
Introduction conditions of the Creative CommonsMore than 4 million patients worldwide have already died due to the COVID-19 pandemic [1]. Lymphopenia was observed in 80% of patients with mild and 96% severe COVID-19 [5,6,7]. According to a meta-analysis of 3099 patients’ data, it was shown that lymphopenia with a level below 1000/μL was associated with a severe course of COVID-19 [8]. The pathogenesis of lymphopenia in COVID-19 may associate with more than 10 putative mechanisms [9,10,11]. One of the possible mechanisms of lymphopenia in patients with COVID19 is extrapulmonary dissemination and direct exposure of SARS-CoV-2 particles to the tissues of secondary lymphoid organs, such as spleen and mediastinal lymph nodes (LN) filtering the lymph from the lungs [11,12]
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