Thread by @tmhohl71

With #Omicron rapidly spreading nationwide, I am concerned about all the members of our communities with damage and injury in the immune system, particularly to cell-mediated injury (to T cells and Ab-producing cells). In neutralization studies, most monoclonal Abs used to date

2/ have lost activity to #Omicron and are no longer useful in areas with high attack rates (pretty much everywhere in US right now). There are two possible exceptions. The first is #sotrovimab which was originally isolated from an individual with

3/ #SARSCoV1 (not a typo) back in 2003. The Ab recognizes a conserved glycan motif at the base of the Spike protein (away from the ACE-2 receptor-binding domain). Extremely limited supplies and fairly narrow emergency use authorization, as follows:

4/ Limitations of Authorized Use.
• Sotrovimab is not authorized for use in patients:
o who are hospitalized due to COVID-19, OR
o who require oxygen therapy due to COVID-19, OR
o who require an increase in baseline oxygen flow rate due to COVID-19 (in those on chronic oxygen

5/ therapy due to underlying non-COVID-19 related comorbidity).
• Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID-19. (Copied from the EUA)

6/ The second mAb which may retain activity against #OmicronVariant is Tixagevimab/cilgavimab (Evusheld). The EUA stipulates use only for prophylaxis, but NOT for post-exposure prophylaxis, as follows, in the follwoing patients > 12 yo:

7/ • Who are NOT currently infected with SARS-CoV-2 and who have not had a known recent exposure to an individual infected with SARS-CoV-2 and
• Who have moderate to severe immune compromise due to a medical condition or receipt of immunosuppressive medications or treatments

8/ and may not mount an adequate immune response
to COVID-19 vaccination or
• For whom vaccination with any available COVID-19 vaccine, according to the approved or authorized schedule, is not recommended due to a history of severe adverse reaction

9/ There is a clear gap between these different EUAs. There is no coverage for post-exposure prophylaxis with either agent. In addition, neither agent is indicated for patients in hospital with #COVID19. The situation may change rapidly. In the meantime, dexamethasone and

10/ remdesivir remain treatment options. In addition, we are eagerly awaiting news on paxlovid (which is Spike protein/variant agnostic based on mechanism on action). The goal is to limit morbidity among vulnerable patients @sloan_kettering and around the world. You can do your

11/ part by getting vaccinated, boosted, wearing a mask, and sending kind words to your exhausted health care provider doing their best to everyone safe, well, and alive. #GetVaccinatedNow #GetBoostedNow #Sotrovimab #monoclonalAb #COVID19

12/ Re: #Evusheld - it would be highly informative to see the primary data from @AstraZeneca that supports the statement on the retention of activity against #OmicronVariant - astrazeneca.com/media-centre/p…
@LionakisLab astutely points to the following data:

13/ Source: biorxiv.org/content/10.110…

The question is how this observation translates to a real-world prophylaxis setting - given the increase in IC50, will the duration of protection (6 months) be negatively impacted? Important questions as prepare to administer to vulnerable

14/ groups @sloan_kettering and elsewhere. Great to have in arsenal but needs further study. #TxID #IDTwitter