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New research shows Tau is a possible cause of long COVID “brain fog.” Another study suggests specific genes passed on from Neanderthals confer extra risk of severe COVID-19 symptoms.

Studies have shown that contracting COVID-19 can worsen Alzheimer’s disease in patients. The infection may also make people more prone to develop Alzheimer’s disease than people who did not catch the disease.

The Italian Institute of Neuroscience’s Cristina Di Primio and colleagues investigated the ability of SARS-CoV-2 infection to induce Tau, which is thought to be one of the root causes of Alzheimer’s disease, in human neuroblastoma cell cultures as well as in mice. Their work was published this week in PNAS nexus.

The team found that when the SARS-CoV-2 virus infects cultured neuronal cells or the mouse brain, the virus interacts with Tau, a microtubule-associated protein that is known to tangle and clump in neurons in people with Alzheimer’s disease. Specifically, upon infection by the virus, Tau undergoes hyperphosphorylation at pathological epitopes—binding locations for antibodies—in a similar fashion as the protein does in Alzheimer’s patients.

This hyperphosphorylation makes Tau more likely to form aggregates. The authors also detected a significant increase of Tau in the insoluble fraction of infected cells, a sign of pathological alterations to the protein. It is still not clear whether these changes are directly caused by the virus or are part of a cellular defense response that functions to keep the virus out of the cellular areas where the virus could replicate.

In other research, a group of scientists led by Giuseppe Remuzi recently found genes passed down from Neanderthals may confer higher risk from COVID-19. Remuzi is with Mario Negri Institute for Pharmacological Research in Milan. This research was done on behalf of WHO’s ORIGIN study group. Their work was published in eScience.

They conducted a GWAS of COVID-19 outcomes among inhabitants of the Bergamo province in Italy, which they say in spring 2020 was the epicenter of the SARS-Cov-2 pandemic in Europe.

As they write, “In the province of Bergamo, the first official case was reported on 23 February, 2020 in Nembro, a small village with ∼11,000 inhabitants, which in March 2020 recorded an 850 percent increase in the number of deaths. Soon, Nembro, nearby towns, and the entire province, became known to the world as the pandemic’s epicenter [in Europe].” A notable feature of Bergamo, is that its population is relatively homogeneous.

The researchers point out that during the outbreak in Bergamo, “We saw young, healthy women grow critically ill, and conversely, elderly men with multiple diseases did not develop any symptoms despite significant exposure. The high variability observed in infection outcomes suggested the involvement of host genetics.”

The team genotyped 1195 individuals and replicated the association at the 3p21.31 locus with severity, but with a stronger effect size that further increased in gravely ill patients. A transcriptome-wide association study highlighted eQTLs for LZTFL1 and CCR9. The team also identified 17 loci not previously reported, suggestive for an association with either COVID-19 severity or susceptibility. Three of those genes were variations in DNA thought to be inherited from Neanderthals.

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