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Coronavirus Update

Towards Solving the Long Covid Puzzle

A big week of new data and enhanced understanding


FEB 22


In recent days, there were several important new reports that help explain the pathophysiology of Long Covid. By coincidence, we published a Perspective in Science today to summarize the progress that has been made and the vital work that lies ahead.

The Figure that accompanied our Science paper

Here we’ll summarize the new findings:

The Leaky Blood-Brain Barrier

A systematic study of people with Long Covid and controls, using MRI, brain-specific S100β protein, RNA-seq of white blood cells, endothelial cell response in culture provided new insights about the disrupted blood-brain barrier (BBB) in individuals with Long Covid and symptoms of brain fog . They are well summarized by Prof Katerina Akassoglou from the Gladstone Institute who was not involved in the study and is a highly regarded scientist in the field of neurovascular inflammation: “This study is the first report of BBB disruption correlating with brain fog in patients with long COVID by dynamic contrast enhanced MRI. The MRI findings are in line with neuropathology reporting blood protein accumulation in brains from patients with COVID-19, and I expect that it will be the foundation for future studies at the blood–brain and immune interface for the discovery of mechanisms, biomarkers and therapies for neurological manifestations in long COVID.”

The numbers of participants in each group was small but the phenotyping was extraordinarily deep. Beyond the BBB, the notable findings were dysregulation of the clotting system and pro-inflammatory effects of endothelial cells.

Persistent Infections of SARS-CoV-2 as a Risk Factor

From a large community surveillance project in the UK , 381 participants were found to have evidence of persistent infections of SARS-CoV-2 for 30 days or more. That was considerably higher than anticipated.

1 to 3% had persistent infections for more than 30 days

0.1 to 0.5% had persistent infections for more than 60 days

Serial assessment of viral loads indicated many of the people had rebounding high levels, indicating there was likely actively replicating virus

The risk of Long Covid was 55% increased in people with 12 weeks or more of persistent infection, 24% increased in those with 26 weeks or more (adjusted odds ratio, Table below) 

Interferon-Gamma As a Possible Biomarker for Diagnosis and Treatment

A new report assayed interferon-gamma, part of the first line of defense of innate immunity to a SARS-CoV-2 infection. Individuals with Long Covid had persistent elevation after the acute phase, and during follow-up serial assessment of this biomarker showed resolution among the participants with symptom resolution. This will need further assessment, but if replicated and extended, it might fulfill a major unmet need for both confirmation of diagnosis and a surrogate measure for treatments that are being assessed in prospective clinical trials, no less an objective metric for correlation with symptoms.

Two New Reports of Vaccination Protection Vs Long Covid

From a study in the Annals of Epidemiology, Michiganders derived an important protective benefit against Long Covid: Long COVID prevalence was 40-60% lower among adults vaccinated (vs. unvaccinated) prior to their COVID-19. This level of protection is consistent with many recent reports and has not been emphasized enough regarding an added benefit of booster shots. The data were previously reviewed on Ground Truths here.

And a new preprint report on protection in children and adolescents which looked at different variants (Delta and Omicron) and cause and effect relationship for direct benefit of vaccination, summarized in the Table below. More protection was found in teens than children with the range of 60 to 75%.