COVID-19 pathology: comparison between lung, kidney, heart and brain

This article describes and compares pathological features of COVID-19 across some of the main organs of the human body. The organs considered were: lungs, kidneys, heart and brain. Many assume the presence of active viral replication not only in the lung but also in other organs but, probably, each tissue has a different relationship with the virus and comparative studies between the various organs are lacking, so we wanted to better define the interaction of the disease with such organs. The aims of this work are: 1) to compare the pathological findings of lungs, massively affected by SARS-CoV-2 invasion, with the alterations of heart and brain tissues that are not a direct target for the virus; 2) to better clarify to what extent these organs are involved and how the virus spreads and persists throughout the organism; 3) to emphasize the most interesting clinical-pathological correlations. Considering the 15 autopsies of COVID-19 subjects performed during the study period (spring 2020), 9 were selected, in which it was obtained a brain of adequate quality for neuropathology. A comparison is underway between lung, heart and brain considering morphology (Hematoxylin-Eosin, Luox Fast Blue), and immunohistochemical characteristics by using the following antibodies: CD3 (T-lymphocytes), CD20 (B-lymphocytes), CD68 (monocytes-macrophages-microglia), CD42b (activated platelets) and anti-SARS-CoV-2 nucleocapsid. Furthermore, PCR techniques are used to verify the presence of viral RNA in tissues. Ten matched SARS-CoV-2 negative controls are also examined (4 for lung and 6 for brain). The 9 COVID-19 subjects (4 females, 5 males) who were selected died 0 to 32 days after the diagnosis (mean: 10 days). The mean post-mortem delay is 7 days (range: 3-13). The mean age is 79 (range: 29-94). Except for one case, all subjects had several comorbidities of varying severity, including pulmonary diseases, hypertension, diabetes, obesity and cancer. What has been observed in the brain constitutes the neuropathological basis of the COVID-19 encephalopathic syndrome in the elderly, which seems more linked to microglial hyperactivation than to the presence of the virus. In the lung, the main SARS-CoV-2 replication site, the virus persists longer with a significant T-lymphocyte recruitment. In the kidneys there's proof that replication also happens, with related cytotoxic and inflammatory damage. On the contrary, in the heart and brain there is a boosting of the innate immunity and a concurrent dampening of the adaptive immune system. This is demonstrated by the large number of macrophages in the heart and of microglial amoeboid cells in the brain, with a very small number of T-lymphocytes. In these tow organs traces of viral antigenicity are very low suggesting an impersistent or absent viral replication. Particularly, our data suggest that SARS-CoV-2 slightly penetrates the brain but does not actively replicate within it. The detection of viral proteins is very rare and limited to the lower brainstem, probably coming from the respiratory and pharyngeal mucosa through the lower cranial nerves. From these observations it is inferred that SARS-CoV-2 is not a neurotropic virus and, importantly, there is no evidence proving its persistence within the brain after the acute infection. Actually, the available data suggest that SARS-CoV-2 causes an acute infection with progressive "cleaning" of the virus from the affected organs. Instead, a significant inflammatory state may persist for months after the infection healing, generating the so-called long-COVID.