Table 4.

Neurohistopathological findings in patients infected with SARS-CoV-2 and their association with neurological manifestations.

Characteristics of the patients	Tissue and PMI	Histopathological findings	Neurological manifestations	References
Central nervous system
n = 18 age range: 53–75 years comorbidities: AF, ALL, BPH, CAD, CKD, COPD, DM, ESRD on HD, EtOH use disorder, HF, HTN, ILD, MGUS, NHL, OCD, OSA, PPV, PVD, RA-SLE.	Inferior-frontal lobe with olfactory tract/bulb, corpus callosum, hippocampus, occipital lobe, anterior basal ganglia, thalamus, cerebellum, midbrain, pons, and medulla. PMI: NS.	Acute hypoxic-ischemic injury with neuronal loss in the cerebral cortex, hippocampus, and cerebellar Purkinje cell layer. Arteriolosclerosis with perivascular rarefaction, a microglial nodule, and perivascular inflammation with scattered microglia were also detected.	It is associated with the confusional state, myalgia, headache or, hypogeusia.	(175)
n = 6 age range: 58–82 years comorbidities: EtOH use disorder, HTN, COPD, CKD, PHT, PVD, CAD, AF.	Hippocampus, neocortex, cerebellum, and brainstem nuclei. PMI: NS.	Lymphocytic panencephalitis and meningitis. Neuronal cell loss and axon degeneration in the dorsal motor nuclei of the CN X and V, NTS, dorsal raphe nuclei, and medial longitudinal fasciculus.	Associated with altered consciousness.	(176)
n = 1 age: 73 years commorbidities: DM and HTN.	Cortex, hippocampus, amygdala, striatum. PMI: NS.	Cerebellar hemorrhage, acute infarcts, global hypoxic changes with scattered hypereosinophilic shrunken neurons in the cerebral cortex, striatum, thalamus, amygdala, hippocampus, and the Purkinje cell layer.	Headache, nausea, vomiting, and loss of consciousness.	(177)
Cranial nerves and peripheric nervous system
n = 33 age range: 67–79 years commorbidities: DM, HTN, CVD, HLD, CKD, PS and dementia.	Olfactory mucosa, bulb and tuber, oral mucosa, trigeminal ganglion, medulla oblongata, and cerebellum. PMI: NS.	High levels of viral SARS-CoV-2 RNA (RT–qPCR) and protein within the olfactory mucosa. Lower levels were found in the cornea, conjunctiva, and oral mucosa; and in only a few COVID-19 autopsy cases, the cerebellum was positive for SARS-CoV-2.	Alterations of smell and taste perception, impaired consciousness, headache, and behavioral changes	(178)
n = 2 age: 51 and 94 years commorbidities: COPD, IHD and AML	Glossopharyngeal, vagal nerves and other brain areas. PMI: 3.3 days	SARS-CoV-2 viral proteins mapped to isolated cells.	Ageusia	(179)
n = 21 age range: 41–78 years commorbidities: DM, CVD, COPD, asthma, ASM and AHM.	Olfactory bulbs, NTS and other brain areas. PMI: NS.	Extensive inflammation and infiltrating immune cells.	Anosmia and dampening of the respiratory system.	(180)

AF, atrial fibrillation; AHM, active hematological malignancy; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; ASM, active solid malignancy; BPH, benign prostatic hyperplasia; CAD, coronary artery disease; CKD, chronic kidney disease; CN, cranial nerves; COPD, chronic obstructive lung disease; CVD, cardiovascular disease; DM, diabetes mellitus; ESRD on HD, end stage renal disease on dialysis; EtOH use disorder, alcohol use disorder; HF, heart failure; HLD, hyperlipidemia; HTN, hypertension; IHD, ischaemic heart disease; ILD, interstitial lung disease; MGUS, monoclonal gammopathy of undetermined significance; n, number of patients; NHL, non-Hodgkin lymphoma; NS, not specified; NTS, nucleus tractus solitarius; OCD, obsessive compulsive disorder; OSA, obstructive sleep apnea; PHT, pulmonary hypertension; PMI, postmortem interval; PS, prior stroke; PVD, peripheral vascular disease; RA-SLE, rheumatoid arthritis - systemic lupus erythematosus; RT-qPCR, reverse transcription-quantitative polymerase chain reaction.