Β-Amyloid Deposits in Young COVID Patients

A 58-year-old woman who died of COVID infection was included as a control subject in an ongoing autopsy study of the neuropathology of military traumatic brain injury (TBI). An immunohistochemical stain for β-amyloid done only because that stain is performed on all the cases in the TBI study resulted in the serendipitous observation of numerous focal β-amyloid deposits in the neocortex of this relatively young woman with no significant neurologic history. The immunohistochemical study was replicated in a second laboratory using a different anti-amyloid monoclonal antibody with the same result. The deposits failed to stain with thioflavin-S. We subsequently found identical findings in 10 out of 10 additional autopsies of severely ill, hospitalized COVID patients younger than 60 years.These patients were all severely ill COVID patients who died of their disease and they are probably not representative of the typical COVID patient who often has a relatively mild clinical course and no need for hospitalization. From this perspective we also report the only other COVID patient in our ongoing autopsy study of the neuropathology of military TBI. This 39-year-old-man was self-isolating at home when he became acutely short of breath and died the same day in spite of advanced cardiac life support efforts. We interpret this case as an example of a typical mild COVID infection which was probably complicated by a COVID-associated pulmonary embolus. At autopsy this patient had only extremely rare focal β-amyloid deposits. The focal β-amyloid deposits described here are not unique to COVID patients. Examination of patients who died in the pre-COVID era with adult respiratory distress syndrome also revealed these amyloid deposits, suggesting a link to hypoxia. COVID encephalopathy and/or the persistent cognitive impairment in COVID survivors is well documented and becoming a serious public health concern. We speculate that the β-amyloid deposits described here may play a role in the pathophysiology of that syndrome. If that is true, COVID encephalopathy may respond to treatment with anti-amyloid therapeutics.Funding Information: None to declare. Declaration of Interests: None to declare. Ethics Approval Statement: The brain tissues used have undergone procedures for donation of the tissue, its storage, and use of available clinical information that have been approved by the USU Institutional Review Board (IRB) prior to the initiation of the study. All studies were performed in accordance with current federal, state, Department of Defense, and NIH guidelines and regulations for post-mortem analysis. The autopsy study for patients at Columbia University Irving Medical Center (CUIMC) and Mount Sinai Hospital was approved by the Institutional Review Board and is in line with the Declaration of Helsinki. The requirement for written informed consent for chart review was waived as the study design was deemed to cause no more than minimal risk. Consent for autopsy was obtained from patient surrogates through standardized consenting procedures via telephone or by direct signatures of consent forms.