Cellular and Molecular Effects of SARS-CoV-2 Linking Lung Infection to the Brain

Abstract

In December 2019, a new viral disease emerged and quickly spread all around the world. In March 2020, the COVID-19 outbreak was classified as a global pandemic and by June 2021, the number of infected people grew to over 170 million. Along with the patients’ mild-to-severe respiratory symptoms, reports on probable central nervous system (CNS) effects appeared shortly, raising concerns about the possible long-term detrimental effects on human cognition. It remains unresolved whether the neurological symptoms are caused directly by the SARS-CoV-2 infiltration in the brain, indirectly by secondary immune effects of a cytokine storm and antibody overproduction, or as a consequence of systemic hypoxia-mediated microglia activation. In severe COVID-19 cases with impaired lung capacity, hypoxia is an anticipated subsidiary event that can cause progressive and irreversible damage to neurons. To resolve this problem, intensive research is currently ongoing, which seeks to evaluate the SARS-CoV-2 virus’ neuroinvasive potential and the examination of the antibody and autoantibody generation upon infection, as well as the effects of prolonged systemic hypoxia on the CNS. In this review, we summarize the current research on the possible interplay of the SARS-CoV-2 effects on the lung, especially on alveolar macrophages and direct and indirect effects on the brain, with special emphasis on microglia, as a possible culprit of neurological manifestation during COVID-19.

Subtle vascular and astrocytic changes in the brain of coronavirus disease 2019 (COVID‐19) patients

“…A myriad of complex intricate factors alters smooth muscle tonus and vessel diameter in COVID‐19 patients. Direct hypoxaemia and cytokine release in the CNS after a systemic immune response can already lead to the loss of tonicity in larger vessels with thick smooth muscle layers [ 43 , 44 , 45 , 46 , 47 , 48 ]. Previous studies have shown that SARS‐CoV‐2 can directly infect the smooth muscle cells within the blood vessel wall in different organs including the brain, heart, liver, kidney and pancreas [ 49 ].…”

How COVID-19 shaped mental health: from infection to pandemic effects

“…As studies generally lack control patients with other severe illnesses, the specificity of such findings to SARS-CoV-2 also remains unclear. Systemic inflammatory processes, including cytokine release, have been linked to glial activation with expression of chemoattractants that recruit immune cells, leading to neuroinflammation and injury 85 . Cerebrospinal fluid concentrations of neurofilament light, a biomarker of neuronal damage, were reportedly elevated in patients hospitalized with COVID-19 regardless of whether they exhibited neurologic diseases 86 .…”

Mechanisms of coronavirus infectious disease 2019-related neurologic diseases

“…Systemic cytokines can also cause glial activation leading to increased CNS levels of chemoattractants for peripheral immune cells, promoting inflammation [74]. Studies of postmortem specimens from patients who succumbed to acute COVID-19 reveal hypoxic damage, microglial activation, astrogliosis, leukocytic infiltration, and microhemorrhages [29,75 ▪▪ ,76 ▪▪ ].…”