Cytokine Levels and Pathological Characteristics of a Patient with Severe Coronavirus Disease 2019: A Case Report
The clinical spectrum of coronavirus disease 2019 (COVID-19) is wide, ranging from asymptomatic cases to severe progressive pneumonia with respiratory failure, multiorgan failure, and even death. This case report delves into the clinical and pathological characteristics of a patient who succumbed to severe COVID-19, providing insights into the pathogenesis and progression of the disease, which can help refine clinical strategies to combat it.
The patient, a 57-year-old man with no significant medical history, presented with fatigue and fever on January 23, 2020, after attending a family gathering two days prior. One of the attendees had traveled from Wuhan, the epicenter of the COVID-19 outbreak. Over the next nine days, the patient developed a worsening fever and cough, prompting a visit to the emergency department. A throat swab tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via real-time reverse-transcription polymerase chain reaction. He was admitted to a local hospital and received supportive therapies, including antiviral agents, atomized inhalation of interferon-g, and oxygen therapy.
Despite these interventions, the patient’s condition deteriorated. By February 8, he experienced worsening cough, fever, and dyspnea, necessitating non-invasive mechanical ventilation. On February 18, he was transferred to a superior hospital due to severe shortness of breath. His oxygenation index had dropped to 85.8 mmHg, prompting the initiation of invasive ventilation. Comprehensive treatment measures were employed, including antibiotics, sedatives, vasopressor support, and renal replacement therapy. The following day, his oxygenation index further decreased, leading to the initiation of extracorporeal membrane oxygenation (ECMO). After approximately two weeks of prone position ventilation with ECMO support, his vital signs remained unstable.
Severe COVID-19 in this patient was associated with leukocytosis and elevated inflammatory markers. Given the relationship between blood cells and immune function, cytokine levels were measured. Initial results showed interleukin (IL)-6 at 69.38 pg/mL and IL-10 at 32.13 pg/mL. On February 23, continuous renal replacement therapy was initiated to adsorb endotoxins and cytokines. Subsequent laboratory tests revealed a significant increase in IL-6 and IL-10 levels, reaching 345.51 pg/mL and 44.77 pg/mL, respectively. Additionally, the patient exhibited lymphopenia, with CD4+ T cell counts at 147 cells/mL and CD8+ T cell counts at 114 cells/mL. Lymphopenia is a critical factor associated with disease severity and mortality in COVID-19 patients.
On February 24, the patient experienced a sudden drop in blood pressure and blood oxygenation levels. Chest computed tomography revealed right hemopneumothorax. Thoracoscopy showed blood clots in the bleeding lobes. To investigate pulmonary inflammation, a right lung ultrasound-guided biopsy was performed on March 16. Histological examination revealed varied pathological changes in the lung tissue, including exudative inflammation, interstitial inflammation, and fibrosis in the alveoli, as well as focal hemorrhaging. The alveoli were damaged to varying degrees, with some filled with cellulose-like exudates and mucus-like substances. Type II alveolar epithelial cells had proliferated, with some shedding into the alveolar cavity. Mononuclear cells, macrophages, individual multinuclear giant cells, and atypical enlarged alveolar epithelial cells were observed in the alveolar cavity. These atypical cells exhibited large nuclei, prominent nucleoli, and eosinophilic changes around the nucleoli, indicative of viral cytopathic effects. No obvious intra-nuclear or cytoplasmic inclusion bodies were found.
The alveolar septum was widened, with inflammatory cell infiltration, proliferated and dilated blood vessels, and some thickened blood vessel walls. No clear thrombi were observed in the microvasculature. Areas of alveolar interstitial and perivascular fibrosis were also noted. Excessive mucus secretion with serous and fibrinous exudation likely contributed to ventilation dysfunction and hypoxemia. Immunohistochemical staining confirmed the expression of the 2019-novel coronavirus nucleoprotein in some alveolar epithelial cells. Thyroid transcription factor 1 was expressed in proliferative type II alveolar epithelium, and CD68-positive macrophages were found infiltrating the alveolar septum and alveoli. A small number of CD8-positive T cells and spot CD4-positive T cells were observed in the alveolar septum and pulmonary interstitium, but no CD20-positive B cells were detected.
The pathological findings in this patient align with those reported in the literature for severe COVID-19. The varied pathological changes in the lung tissue, including exudative inflammation, interstitial inflammation, fibrosis, and focal hemorrhaging, are typical manifestations of the disease. The alveoli were damaged to different degrees, with some filled with cellulose-like exudates and mucus-like substances. The proliferation and shedding of type II alveolar epithelial cells, along with the presence of mononuclear cells, macrophages, and atypical enlarged alveolar epithelial cells, highlight the severe inflammatory response and viral cytopathic effects. The widened alveolar septum, inflammatory cell infiltration, and vascular changes further underscore the extensive lung damage caused by SARS-CoV-2.
The excessive mucus secretion and fibrinous exudation likely exacerbated ventilation dysfunction, contributing to the patient’s hypoxemia. The immunohistochemical findings, including the expression of the 2019-novel coronavirus nucleoprotein in alveolar epithelial cells and the presence of CD68-positive macrophages, provide further evidence of the virus’s impact on lung tissue. The reduced counts of CD4+ and CD8+ T cells, despite an overall increase in white blood cell count, highlight the immune dysregulation characteristic of severe COVID-19.
COVID-19 shares certain pathological characteristics with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Infection with these viruses leads to pulmonary edema, consolidation, and hemorrhage. Microscopically, the lungs exhibit desquamation alveolitis, exudative lesions, extensive hyaline membrane formation, severe inflammatory reactions, and necrosis. In SARS patients, the alveoli contain many monocyte macrophages, while MERS patients develop diffuse exudative alveolar damage, alveolar septum destruction, and type II alveolar epithelial cell proliferation and exfoliation.
The clinical and pathological findings in this patient with severe COVID-19 provide valuable insights into the progression of SARS-CoV-2-related pneumonia. These findings can aid clinicians in developing targeted treatment strategies for severely ill patients, potentially reducing mortality. The case underscores the importance of monitoring cytokine levels and immune cell counts in managing severe COVID-19, as well as the need for further research into the immunopathology of the disease.
In conclusion, this case report highlights the severe immunopathological and histological changes associated with fatal COVID-19. The elevated levels of pro-inflammatory cytokines, such as IL-6 and IL-10, along with lymphopenia, reflect the maladjusted immune response that contributes to lung injury and poor outcomes. The pathological findings, including alveolar damage, inflammation, and fibrosis, provide a deeper understanding of the disease’s pathogenesis. These insights can inform the development of more effective treatment strategies for severe COVID-19, ultimately improving patient outcomes.
doi.org/10.1097/CM9.0000000000001540
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