Shiv Gandhi

@gandhisk

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New Haven, CT
Joined December 2009
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  1. Retweeted
    Nov 10

    Highlights nicely why we need good clinical and virological longitudinal monitoring of severely immunosuppressed patients who have persistent SARS-CoV-2 infection and receive treatments that target the virus. Also need more research into combo vs. single agent treatment regimens.

    Our latest study is about an immunocompromised patient with persistent COVID ➡️ treated with remdesivir but developed resistant mutation ➡️ was then cured by monoclonal Ab cocktail. Study by et al. (1/)
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  2. Retweeted
    Nov 10

    Fascinating. I had wondered if the paucity of remdesivir resistance mutations was b/c of high barrier to resistance (good!) or low selective pressure (bad!). In this immunocompromised patient, they isolated an RDV resistant virus, effectively treated with mAbs (cas/imdev).

    Our latest study is about an immunocompromised patient with persistent COVID ➡️ treated with remdesivir but developed resistant mutation ➡️ was then cured by monoclonal Ab cocktail. Study by et al. (1/)
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  3. Nov 10

    Yes, and earlier consideration of mAb cocktails

    This is what worries me with Pfizer and Merck drugs being used in immunocompromised hosts long-term, allowing resistant mutations formed against "game-changer" drugs. Need vigilant "antibiotic stewardship" practiced particularly in immunocompromised hosts w/ COVID
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  4. Nov 10

    Much better tweetorial by the amazing !

    Our latest study is about an immunocompromised patient with persistent COVID ➡️ treated with remdesivir but developed resistant mutation ➡️ was then cured by monoclonal Ab cocktail. Study by et al. (1/)
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  5. Nov 9

    and and others who are not on twitter

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  6. Nov 9

    Thanks to all the co-authors! Study led by Dr. Albert Ko with contributions from and many others!

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  7. Nov 9

    Study highlights the need for surveillance of immunocompromised patients with COVID-19 as they can be a source of new variants, including those with drug resistance. Also suggests that these patients may respond to monoclonal antibody therapies

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  8. Nov 9

    and of neutropenia

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  9. Nov 9

    had resolution of infiltrates

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  10. Nov 9

    8g dose of the mAb resulted in a sustained, high-titer Ab level during follow-up

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  11. Nov 9

    patient eventually cleared virus after administration of casirivimab-imdevimab (blue shading)

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  12. Nov 9

    but it also resulted in a fitness cost on growth assay in absence of the drug

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  13. Nov 9

    when engineered into a laboratory strain, the mutation conferred a ~6-fold increase in IC50 to remdesivir compared to WT virus

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  14. Nov 9

    rebound coincided with the development of a mutation, E802D in the polymerase (nsp12)

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  15. Nov 9

    initially treated with a 10d course of remdesivir which was characterized by initial response in virological markers as well as resolution of fevers (above) but had virological rebound (grey shading RDV)

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  16. Nov 9

    had persistent infiltrates on CT chest

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  17. Nov 9

    also developed severe neutropenia requiring filgrastim

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  18. Nov 9

    Patient had ~150 days of symptoms after diagnosis with persistently low Ct values

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  19. Nov 9

    Just posted a preprint where we identify and validate a de novo remdesivir resistance mutation in the viral polymerase which emerged during treatment of an immunosuppressed patient with persistent SARS-CoV-2 infection

    De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: A case report
    4 replies 22 retweets 62 likes
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  20. Retweeted
    Nov 5

    Pfizer reports terrific data on a new mechanism to shut down the coronavirus. This has to be combined with molnupiravir at the very least, and it means that the fight against the pandemic has now truly changed:

    23 replies 301 retweets 790 likes
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