What does this say? In this study immunosuppressed people including those taking B cell depleting therapies, were given an anti-viral therapy following infection with SARS-CoV-2. Most people recovered from their infections, which is what the anti-viral antibody therapy was supposed to do. However afew people did not clear the virus quickly and in these people they found mutations in the surviving SARS-CoV-2 that was poorly controlled by the immune system. This is a case which has been reported previously in that immune escape variants can occur in immunosupressed people. So it may be interesting to know how long you make virus for. I was about 11 days. The chemical antivirals are perhaps less likely to make Spike mutants as there are not directed to Spike, but could virus escape these chemicals.
High incidence of sotrovimab resistance and viral persistence after treatment of immunocompromised patients infected with the SARS-CoV-2 Omicron variant Huygens, S., Oude Munnink, B., Gharbharan, A., Koopmans, M., Rijnders, B.10.1101/2022.04.06.22273503
Background Sotrovimab is a monoclonal antibody that neutralizes SARS-CoV-2 by binding to a highly conserved epitope in the receptor binding domain. It retains activity against the Omicron BA.1 variant and is used to treat immunocompromised patients as they are at increased risk for a severe outcome of COVID-19.
Methods We studied viral evolution in 47 immunocompromised patients infected with Omicron BA.1 or 2 and treated with sotrovimab. SARS-CoV-2 PCR was performed at baseline and weekly thereafter. All RNA samples were sequenced to determine the variant and occurrence of mutations, in particular in the Spike protein, after treatment.
Results Twenty-four (51%) of the 47 patients were male and their median age was 63 years. Thirty-one (66%) had undergone a solid organ transplantation and 13 (28%) had received prior B-cell depleting therapy. Despite a history of vaccination, 24 of 30 patients with available data on anti-SARS-CoV-2 IgG Spike antibodies prior to treatment with sotrovimab had very low or no antibodies. Median time to viral clearance (Ct-value ≥ 30) after treatment was 15 days (IQR 7-22). However, viral RNA……was continuously detected for at least 28 days after treatment in four patients infected with BA.1. Mutations in the Spike protein at position 337 or 340 were observed in all four patients. Similar mutations were also found after treatment of two patients with a BA.2 infection but both cleared the virus within two weeks. Thus following treatment with sotrovimab, spike mutations associated with reduced in vitro susceptibility were detected in 6 of 47 (13%) patients.
Conclusion Viral evolution towards resistance against sotrovimab can explain treatment failure in most immunocompromised patients and these patients can remain infectious after treatment. Therefore, documenting viral clearance after treatment is recommended to avoid that these patients unintentionally become a source of new, sotrovimab resistant, variants. Research on direct acting antivirals and possibly combination therapy for the treatment of COVID-19 in immunocompromised patients is needed.
You may want to read this article:
Molnupiravir’s authorisation was premature. BMJ 2022; 376 doi: https://doi.org/10.1136/bmj.o443
In summary, the current evidence base for molnupiravir raises more questions than answers. It is not clear whether regulatory authorities have been granted access to patient-level databases from the Indian trials of molnupiravir. It would make sense to wait for results from the Oxford PANORAMIC trial before decisions on the wider use of molnupiravir are taken.
Post script Currently over 20,000 people have been recruited (actually 25,000) which is double the planned original target (10,000), they have now moved on to Paxlovid. So if you are over 50 over 18 with co-morbidity you can volunteer. As a volunteer, it seems that they must be picking and chosing who gets enrolled as both I and Mrs Mouse tried to enroll on the same day. (maybe only one enrollment per address)…only I got the call back….If they had used her it would have been more beneficial as I dont add to the usefulness because by the time I was randomised the COVID was been dealt with and the process didnt work over a weekend and so I had infected every body but the time of randomisation. I was randomised to standard of care with means nothing and so there is no blinding. However such data is important as we need real word data to confirm or refute the trial data
CoI: Non relevant
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