Thread by @white_bite

An interesting study that takes a look into the early host response during SARS2 infection. Some takeaways from the study. (1/n)
science.org/doi/10.1126/sc…

The study made use of hamsters that were infected through the nose with SARS2 in order to assess immune response via the respiratory route. (2/n)

An immune response was noted due to upregulation of genes related to interferon production in different organs of the body. Noted too was the presence of viruses capable of replication in some organs like the heart and nose, although most were concentrated in the lungs.(3/n)

Expression of genes related to interferon signaling outside the lungs were most noted in the kidneys. (4/n)

Interferon is a protein that is necessary in the initial stages of the immune response since these help in preventing the virus from replicating in the body. (5/n)

The study notes the immediate expression of Ifnl, -- interferon usually associated to the immune response in lung tissue underscoring the immediate onset of the immune response in the lungs. Expression in the blood is seen only after immunity is activated in the lungs. (6/n)

To further test the importance of the immune response in the lungs, the hamsters were given dexamethasone, a corticosteroid that dampens the immune response.
The study notes that in a normal immune response, viral clearance is achieved in 5 days from infection in hamsters (7/n)

Noted too is a marked decrease in T-cells after SARS2 infection, as compared to B-Cells. This was regardless of whether or not there was a dampening of the immune response from dexamethasone. (8/n)

The study showed how a dampened immune response led to prolonged viral replication in the lungs and delayed clearance. (increase noted through day 5 post infection) (9/n)

Noted too were the lessened presence of antigen presenting cells, such as macrophages and dendritic cells, during a dampened immune response. (10/n)

It was also shown how the delay/dampened immune response in the lungs led to infection in other organs.(11/n)

To further test this result, the authors infected the hamsters intravenously in order to bypass the respiratory route. Viral replication was more noticeable in hamsters who were directly infected through the blood, compared to these who were infected through the nose.(12/n)

Also seen was the need for organs to be primed through innate immunity, stressing the importance of a well-functioning immune system needed to protect against SARS2. (13/n)

Personal takeaways:
The study shows how viral persistence may indeed be happening in people with long COVID since the study shows prolonged replication and delayed clearance can happen.
This also shows the importance of the quick immune response in the lungs in order to (14/n)

prevent the onset of long COVID. BUT, given other variants which do not exhibit fusogenicity to the lower RT, other avenues wrt long COVID mechanisms should be explored.
Do take note that there are still those who develop long COVID in the absence of lower RT symptoms and (15/n)

clinical manifestations.
The study again notes how T-cells are affected by SARS2.
What also comes to mind is how the immune response will be affected, especially with newer variants that attempt to downregulate interferon expression.
Finally, the study doesn't address (16/n)

what may happen upon repeat exposure to SARS2. The study already shows immune dysfunction during infection. What happens then when people are repeatedly infected w/o much time for recovery? (end) @DavidJoffe64 @HarrySpoelstra @ejustin46 @elisaperego78 @RadCentrism @crwequine

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