What do we know about covid in immunocompromised people? – The BMJ

Oral versions of currently intravenous-only drugs such as remdesivir are in development, which would make them easier to access. Longer duration treatments are also needed, which could help reduce toxicity and lower the likelihood of drug resistance developing. Trials are already under way to study longer duration courses of nirmatrelvir-ritonavircomparing the current five day course with 10 and 15 daysin immunocompromised adults.13

But as drug resistance is an ever growing worry, combination treatments seem a likely avenue for immediate exploration.14 One small scale trial has found that a combination of remdesivir and nirmatrelvir-ritonavir with monoclonal antibodies induced a good clinical response in immunocompromised patients with prolonged or relapsed covid-19. Other trials suggest that combinations of convalescent plasma with different antivirals may be effective.15

Alternatives are needed, however, particularly where contraindications have severely limited the use of existing drugs. The ritonavir part of Paxlovid, for instance, works by preventing the liver from breaking down certain compounds, but this could be a major problem with other drugs a patient might need, as these also wont be broken down so might build to harmful levels.

Stephen Griffin, virologist at the University of Leeds, UK, says that ritonavir was part of the reason Paxlovid isnt licensed for under 18s. He explains, Theres such a huge raft of interactions between ritonavir and other drugs, because it acts on the liver to stop it degrading things. That is a real concern going forward for many clinically vulnerable people.

For clinically vulnerable people on multiple medications, its a bit of a minefield. Referring that out to GPs to manage may be a little difficult. Theyve got to work out, How does this interact with the meds my patient is on?

Yes, but it faces questions over how effective it is and whether its cost effective and practical as a standard treatment.

Originally developed to fight Ebola virus, the antiviral remdesivir was tested against SARS-CoV-2 at the height of the covid pandemic and was found to be effective as a covid treatment.

The catch is that remdesivir is administered intravenously. The major issue is logistical, says Arturo Casadevall of Johns Hopkins University. You need three infusions in three sequential days, and that can be very difficult for some patients, depending on their resources.

More commonly, doctors give it to hospital inpatients as a five or 10 day course. In non-ventilated patients with covid-19, remdesivir may shorten the time to recovery and reduce mortality.16

However, Alex Richter of the University of Birmingham highlights problems with availability. In the UK, she tells The BMJ, access to remdesivir is very patchy and depends on individual hospital trusts and how they have chosen to interpret current NICE and government commissioning guidelines in the context of clinical unmet need. She adds that theres an urgent need to clarify current treatment options so that all clinically vulnerable patients can get access to treatments and clinical advice from clinicians with experience of treating covid infection in immune vulnerable people.

In immunocompromised patients remdesivir can suppress, but not always eradicate, SARS-CoV-2 when used over a longer period.17 However, the problem with repeated or prolonged treatment with remdesivir is the possibility of viral resistancesomething that concerns Stephen Griffin, a virologist at Leeds University. The consequences of a pandemic virus becoming resistant, particularly for vulnerable people, could be really bad. Theres no rescue therapy there, he tells The BMJ.

Recent studies have also questioned the efficacy of remdesivir. One test of hospital inpatients18 showed no evidence that it cleared the virus more quickly than if the drug hadnt been taken; another showed no benefit in patients severely ill with covid-19.19 The suspicion is that the antiviral effects of remdesivir shown in the laboratory may not be replicated in patients.

Despite this, remdesivir does have advantages over some other covid treatments. Unlike Paxlovid, it can be used in under 18s, and few side effects or drug interactions have currently been reported. Oral versions of remdesivir are under investigation.20

Another major factor is cost. In the US remdesivir cost $520 (397; 465) per 100 mg vial at the time of writing.21 First treatment is two vials, then one vial daily until the end of the course, so a three day course totals over $2000, and the minimum hospital course of five days costs more than $3000. Added to the questions over its efficacy, this has led some experts to say that theres little justification for its use in hospital inpatients.

In the UK the latest recommendations from NICE state22: Compared with standard care, remdesivir reduces death at day 28 in hospitalised people who require no or low-flow oxygen. However, there is no evidence that remdesivir is more effective than placebo or standard care in treating hospitalised patients with covid-19 who require high-flow oxygen supplementation, non-invasive ventilation or invasive ventilation compared to standard care.

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What do we know about covid in immunocompromised people? - The BMJ