Can COVID-19 coronavirus “invade” human brain tissue? (Quick answer: evidence so far is mixed)

Brain scans show low­er part of a COVID-19 patient’s brain stem, post­mortem. Arrows point to light and dark spots sug­gest­ing blood ves­sel dam­age, with­out signs of infec­tion by the coro­n­avirus that caus­es COVID-19. Cred­it: Nation­al Insti­tute of Neu­ro­log­i­cal Dis­or­ders and Stroke, NIH

Tak­ing a Clos­er Look at COVID-19’s Effects on the Brain (NIH Direc­tor’s blog):

While pri­mar­i­ly a res­pi­ra­to­ry dis­ease, COVID-19 can also lead to neu­ro­log­i­cal prob­lems. The first of these symp­toms might be the loss of smell and taste, while some peo­ple also may lat­er bat­tle headaches, debil­i­tat­ing fatigue, and trou­ble think­ing clear­ly, some­times referred to as “brain fog.” All of these symp­toms have researchers won­der­ing how exact­ly the coro­n­avirus that caus­es COVID-19, SARS-CoV­‑2, affects the human brain.

In search of clues, researchers at NIH’s Nation­al Insti­tute of Neu­ro­log­i­cal Dis­or­ders and Stroke (NINDS) have now con­duct­ed the first in-depth exam­i­na­tions of human brain tis­sue sam­ples from peo­ple who died after con­tract­ing COVID-19. Their find­ings, pub­lished in the New Eng­land Jour­nal of Med­i­cine, sug­gest that COVID-19’s many neu­ro­log­i­cal symp­toms are like­ly explained by the body’s wide­spread inflam­ma­to­ry response to infec­tion and asso­ci­at­ed blood ves­sel injury—not by infec­tion of the brain tis­sue itself … The team focused on the brain’s olfac­to­ry bulb that con­trols our abil­i­ty to smell and the brain­stem, which reg­u­lates breath­ing and heart rate. Based on ear­li­er evi­dence, both areas are thought to be high­ly sus­cep­ti­ble to COVID-19.

Indeed, the MRI images revealed in both regions an unusu­al num­ber of bright spots, a sign of inflam­ma­tion … per­haps equal­ly note­wor­thy is what Nath and col­leagues didn’t see in those sam­ples. They could find no evi­dence in the brain tis­sue sam­ples that SARS-CoV­‑2 had invad­ed the brain tis­sue. In fact, sev­er­al meth­ods to detect genet­ic mate­r­i­al or pro­teins from the virus all turned up empty.

The find­ings are espe­cial­ly intrigu­ing because there has been some sug­ges­tion based on stud­ies in mice that SARS-CoV­‑2 might cross the blood-brain bar­ri­er and invade the brain…Another recent report in the Jour­nal of Exper­i­men­tal Med­i­cine, which used mouse and human brain tis­sue, sug­gests that SARS-CoV­‑2 may indeed direct­ly infect the cen­tral ner­vous sys­tem, includ­ing the brain.

The Studies:

• Microvas­cu­lar Injury in the Brains of Patients with Covid-19 (New Eng­land Jour­nal of Medicine)
• Neu­roin­va­sion of SARS-CoV­‑2 in human and mouse brain (Jour­nal of Exper­i­men­tal Med­i­cine). Abstract: Although COVID-19 is con­sid­ered to be pri­mar­i­ly a res­pi­ra­to­ry dis­ease, SARS-CoV­‑2 affects mul­ti­ple organ sys­tems includ­ing the cen­tral ner­vous sys­tem (CNS). Yet, there is no con­sen­sus on the con­se­quences of CNS infec­tions. Here, we used three inde­pen­dent approach­es to probe the capac­i­ty of SARS-CoV­‑2 to infect the brain. First, using human brain organoids, we observed clear evi­dence of infec­tion with accom­pa­ny­ing meta­bol­ic changes in infect­ed and neigh­bor­ing neu­rons. How­ev­er, no evi­dence for type I inter­fer­on respons­es was detect­ed. We demon­strate that neu­ronal infec­tion can be pre­vent­ed by block­ing ACE2 with anti­bod­ies or by admin­is­ter­ing cere­brospinal flu­id from a COVID-19 patient. Sec­ond, using mice over­ex­press­ing human ACE2, we demon­strate SARS-CoV­‑2 neu­roin­va­sion in vivo. Final­ly, in autop­sies from patients who died of COVID-19, we detect SARS-CoV­‑2 in cor­ti­cal neu­rons and note patho­log­i­cal fea­tures asso­ci­at­ed with infec­tion with min­i­mal immune cell infil­trates. These results pro­vide evi­dence for the neu­roin­va­sive capac­i­ty of SARS-CoV­‑2 and an unex­pect­ed con­se­quence of direct infec­tion of neu­rons by SARS-CoV­‑2.

Studies in Context:

• NIH Strate­gic Response to COVID-19
• Sur­vey finds ischaemic stroke and altered men­tal sta­tus as most com­mon neu­ro­log­i­cal com­pli­ca­tions in severe COVID-19 cases
• Neu­ro­log­i­cal Impli­ca­tions of COVID-19 Infections
• Three ways to pro­tect your men­tal health dur­ing –and after– COVID-19
• Explor­ing the human brain and how it responds to stress (1/3)