Patterns of Inflammatory Cell Infiltration in the Lungs of Patients with COVID-19, An Autopsy Study

ABSTRACT

Background: SARS-CoV-2 causes diffuse alveolar damage, lymphocyte infiltration in the lungs and a cytokine storm. In this study we examined inflammatory cell infiltrates in the lungs of patients with COVID-19. Design: Eighteen COVID-19 autopsy cases (COVID group), 9 non-COVID cases with diffuse alveolar damage (DAD, non-COVID group), and eleven controls without lung diseases were included. Immunostainings for CD3, CD4, CD8, CD68 and broad-spectrum keratins were performed. Results: The average age of COVID-19 patients was 64.4±2.1 years. The most common co-morbidities were hypertension (12/17, 70.6%), diabetes mellitus (9/17, 52.9%) and chronic kidney disease (3/17, 17.6%). The survival duration of 17 patients with available clinical information was 21.2 ± 3.4 days (range 7-53 days) after onset of symptoms. Patients younger than 67 years old (namely young patients thereafter, N=9) survived 26.4 ± 5.9 days after onset of symptoms, which was significantly longer than those greater than 67 years old (namely older patients thereafter, 15.2 ± 1.4 days, N=8, P<0.05). The younger patients had significantly lower platelet counts (107.7 ± 33.2 x 109/L, N=8) than the older ones (224.6 ± 42.4 x 109/L, N=8, P<0.05). Conversely, the younger patients had much higher absolute lymphocyte counts (1.5 ± 0.4 x 109/L, N=7) than the older ones (0.7 ± 0.1 x 109/L, N=8, P<0.05). Interestingly, the patients with low platelet counts (<100 x 109/L) survived longer than those with higher platelet counts (P<0.05). Patients with high troponin levels (>0.2 ng/ml) had shorter survival duration after onset of symptoms (16.8 ± 1.9 days) than those with low troponin levels (30.8 ± 8.0 days, P<0.05). Patients with macrophages >130/HPF, CD3+ T cells >145/HPF, CD8+ T cells <30/HPF and CD8+/CD4+ ratio<1 had a shorter survival time compared to those with macrophages <130/HPF, CD3+ T cells <145/HPF, CD8+ T cells >30/HPF and CD8+/CD4+ ratio>1, respectively. Conclusions: Patients' age > 67 years, blood troponin levels >0.2 ng/ml, platelet count >100 x 109/L, lung macrophages >130/HPF, CD3+ T cells >145/HPF, CD8+ T cells <30/HPF, and CD8/CD4 ratio <1 were associated with shorter survival duration after onset of symptoms.