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Sunday, December 6, 2020

Vaccines and the Renal patient- COVID19

As vaccines are arriving at a rapid rate (historic) for SARs-COv2, most of the United States is still dealing with a larger more deadlier wave of infections. Hospitals at most of the US are again at a standstill with what we had seen in March, April in NY. 

mRNA vaccine.. we are not used to that technology in the medical world. While reading more on this topic, I found this simplified version by Dr Daniel Goldstein, CT surgeon at Montefiore and a well known voice of COVID care on Linkedin. I have made some changes and additions to his thoughts. 

mRNA Vaccines: A primer
The process, simplified:

1. Use DNA, enzymes to create the mRNA sequence that codes for part of SARSCoV2 spike protein
2. Attach 5’cap, poly-A tail and UTRs for stability and better translation
3. Purify and get rid of reagents, enzymes other additives
4. Encapsulate in lipid nanoparticle (phospholipids, PEG, cholesterol) to protect and facilitate delivery into cells.
5. Store in cold (or extremely cold) until use
6. Inject intramuscularly (2 shots, 3-4 wks apart)
7. Encapsulated mRNA taken up by muscles cells.
8. mRNA released into cytoplasm where protein building machinery (ribosomes) will bind to it sequentially and produce many spike proteins. Average 20 sec - couple of mins to make one protein
9. mRNA has half-life about 10 hrs. Sufficient to make lots of protein. Eventually broken down by RNAses.
10. Protein is bound to cell surface where it is recognized as foreign by immune system
11. Ab production, and Ag specific memory B cells and T follicular helper cells are produced
12. More robust response of the above with 2nd injection as body has been “primed”

Advantages of mRNA vaccine:
1. Non-infectious
2. Doesn’t insert into DNA (nucleus).
3. Half life, immunogenicity and delivery can be regulated
4. Quick to make

Disadvantages to me: Seem none, except it's a new technology. 

Well we are in a pandemic with a new deadly virus- I would roll those shirts and get the vaccine. What is the data on our renal patients.- Essentially none. 

ESKD patients:

To my knowledge, ESKD patients were not in the large vaccine trials but these are vulnerable populations. The UK released a statement of the patients who are most vulnerable in nephrology. 

Renal Transplant patients:

Although initial clinical trials of COVID-19 vaccines did not include immunosuppressed patients, we would expect the vaccines to offer protection against COVID-19 infection in these extremely vulnerable patients. An effective COVID-19 vaccine should reduce staff and patient infection resulting in lower rates of serious illness and death. What is interesting as few studies done during the pandemic showed that the renal transplant patients do have a good immune response to the virus( not a lowered one).  Studies from Germany and the US showed decent antibody converting. This suggests that vaccines would work in the organ transplant patients and provide amazing protection.

CKD and patients with autoimmune glomerular diseases: No data exists but vaccines would be helpful here as well.

Nephrology community awaits the arrival of the vaccines...


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