Clinical diagnosis
Case 252
【Discussion】
What happened in the lung of this patient ? Lymphocyte count decreased and neutrophil count increased in laboratory test and bronchoalveolar lavage (BAL) fluid. Chest CT showed the worsening of pulmonary opacity from mild ground glass opacity to thick ground glass with crazy paving appearance and finally to consolidation. All kinds of antibiotics were given but in vain, ineffective.
Lymphocyte count decreased less than 1000/mm3, terming lymphocytopenia (1). The count of lymphocyte of this patient had been low less than 1000/mm3 since the first admission to our hospital. It indicates the less production of antibody from acquired immunity. The increase of KL6 and LDH implies the damage of alveolar cell type II and type I (2). Although autopsy was not conducted on our patient, literatures says that microscopic examination from surgically resected lung and autopsied lung revealed protein with lymphocyte infiltration to alveolar space and diffuse alveolar damages, respectively (3, 4). This indicates the process or battle of virus invasion versus immunity resistance. Namely, macrophages and lymphocytes accumulate to alveolus to phagocyte virus and produce antibody against virus. When immunity surpass virus pathogenicity, it is cured. Conversely, virus pathogenicity can overcome immunity. COVID-19 virus can replicate in the cell with receptor ACE2 (angiotensin converting enzyme). Alveolar cell type II owns ACE2, indicating one of the target cells for the virus. Meanwhile, alveolar cell type II secretes surfactant to block virus and lymphocytes produce antibody. Microscopic findings in specimen obtained from surgically resected lung reflect the battle scene; protein, lymphocyte infiltration, type II alveolar cell hyperplasia (3). When virus pathogenicity gets passed surfactant, antibody and phagocyte, virus infect to surrounding cells: type II alveolar cell, type I alveolar cell, fibroblast and finally lymphocyte. Microscopic findings in specimen obtained from autopsied lung reflect this cruel scene: diffuse alveolar damage with neutrophils infiltration (4). Virus is known to infect to lymphocyte but not to neutrophils and macrophages with ability to phagocyte virus.
When virus infects lymphocyte, virus cannot replicate in immune cells and they simultaneously die (5). The more infected cells and their fragments increase indicate the increase work of disposal of those. Macrophages are working for process but the process speed is very slow, 5 to 6 hours, while neutrophils process work is more speedy (6, 7). Then, in cytokine storm secreting from infected cells beckon infiltration of neutrophils. Neutrophils work to increase permeability of capillaries as well as phagocyte infected cells. Edematous fluids flow in alveolar space, inducing hypoxemia and acute respiratory distress syndrome.
In our case, laboratory test four days after the onset revealed lymphocytopenia, indicating the shortage of antibody production. As days progressed, lymphocyte count decreased to less than 500/mm3. It might imply virus infect to lymphocyte as well as alveolar cells inducing to migrate neurocytes for processing the infected cells and enhance the permeability of capillaries, leading to ARDS.
【Summary】
We presented a seventy seven-year-old male with COVID-19 whose prognosis was fetal. Laboratory data and bronchoalveolar lavage revealed KL 6 elevation lymphopenia and neutrophilic leukocytosis. It was borne in mind that virus infects to lymphocyte that induces simultaneous death of both infected lymphocytes and virus, and induces infiltration of neutrocytes for phagocyting virus, disposing of infected cells and their fragments. Neutrophil works permeability of capillaries, inducing to inflow edematous fluid into alveolar space, leading ARDS.
【References】
1."Lymphocytopenia". National Heart, Lung and Blood Institute. NIH. Retrieved 10 February 2020.
2.Nakamura H, et al. Serum KL-6 can distinguish between different phenotypes of severe COVID-19. J Med Virol. 2021 Jan;93(1):158-160
3.Sambit K Mohanty, et al. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19) - anatomic pathology perspective on current knowledge. Diagn Pathol 2020 Aug 14;15(1):103
4.Konopka KE, et al. Diffuse alveolar damage (DAD) resulting from coronavirus disease 2019 Infection is Morphologically Indistinguishable from Other Causes of DAD. Histopathology 2020, 77, 570–578
5.Ho DD, et al. Idiopathic CD4+ T-Lymphocytopenia -- Immunodeficiency without Evidence of HIV infection. N Engl J Med 1993; 328:380-385
6.Eum SY, et al. Neutrophils Are the Predominant Infected Phagocytic Cells in the Airways of Patients With Active Pulmonary TB. Chest 2010; 137: 122-128
7.Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19. Front. Immunol., 18 August 2020 https://doi.org/10.3389/fimmu.2020.02063
2021.12.10