Olfactory Bulb and Amygdala Gene Expression Changes in Subjects Dying with COVID-19

Abstract

In this study we conducted RNA sequencing on two brain regions (olfactory bulb and amygdala) from subjects who died from COVID-19 or who died of other causes. We found several-fold more transcriptional changes in the olfactory bulb than in the amygdala, consistent with our own work and that of others indicating that the olfactory bulb may be the initial and most common brain region infected. To some extent our results converge with pseudotime analysis towards common processes shared between the brain regions, possibly induced by the systemic immune reaction following SARS-CoV-2 infection. Changes in amygdala emphasized upregulation of interferon-related neuroinflammation genes, as well as downregulation of synaptic and other neuronal genes, and may represent the substrate of reported acute and subacute COVID-19 neurological effects. Additionally, and only in olfactory bulb, we observed an increase in angiogenesis and platelet activation genes, possibly associated with microvascular damages induced by neuroinflammation. Through coexpression analysis we identified two key genes (CAMK2B for the synaptic neuronal network and COL1A2 for the angiogenesis/platelet network) that might be interesting potential targets to reverse the effects induced by SARS-CoV-2 infection. Finally, in olfactory bulb we detected an upregulation of olfactory and taste genes, possibly as a compensatory response to functional deafferentation caused by viral entry into primary olfactory sensory neurons. In conclusion, we were able to identify transcriptional profiles and key genes involved in neuroinflammation, neuronal reaction and olfaction induced by direct CNS infection and/or the systemic immune response to SARS-CoV-2 infection.

Metabolic dyshomeostasis induced by SARS-CoV-2 structural proteins reveals immunological insights into viral olfactory interactions

“…However, only 3% of the proteome modulated by the S protein was shared across studies, indicating that a great proportion of proteostatic events intercepted by structural SARS-CoV-2 proteins are cell-dependent. In addition, part of the altered molecular routes identified in our in-vitro system have been recently detected in the OB from COVID-19 subjects (Piras et al, 2021) ( Supplementary Figure 3 ), pointing out specific pathways directly targeted by SARS-CoV-2 structural proteins beyond the CNS affectation and/or the systemic immune response to SARS-CoV-2 infection.…”

SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19

“…Results have previously been partially presented in preprint form ( 155 ). After removing low-quality RNA samples, the final AMY sample size was 36, of which 18 were from COVID-19 cases and 18 were from controls.…”

Repeated ethanol exposure and withdrawal alters ACE2 expression in discrete brain regions: Implications for SARS-CoV-2 infection

“…Moreover, RNA-sequencing analysis of amygdala tissue of COVID-19 patients displays upregulation of interferon-related neuroinflammation genes as well as downregulation of synaptic and other neuronal genes (Piras et al, 2021). Based on the COVID-19 reports and the significance of amygdalar circuits in alcohol dependence, we next measured ACE2 levels in the amygdala of CIE mice and found that they were decreased after exposure.…”

“…Besides the brainstem and hypothalamus, ACE2 was also highly expressed in the amygdala (Lukiw et al, 2022;Piras et al, 2021), a brain region implicated in anxiety, stress-related disorders, and the reinforcing effects of alcohol and other drugs of abuse (Roberto et al, 2021).…”

“…Besides the brainstem and hypothalamus, ACE2 was also highly expressed in the amygdala (Lukiw et al, 2022; Piras et al, 2021), a brain region implicated in anxiety, stress-related disorders, and the reinforcing effects of alcohol and other drugs of abuse (Roberto et al, 2021). Moreover, RNA-sequencing analysis of amygdala tissue of COVID-19 patients displays upregulation of interferon-related neuroinflammation genes as well as downregulation of synaptic and other neuronal genes (Piras et al, 2021). Based on the COVID-19 reports and the significance of amygdalar circuits in alcohol dependence, we next measured ACE2 levels in the amygdala of CIE mice and found that they were decreased after exposure.…”