COVID-19 Alaska Clinical Update, July 6
Alaska DOH sent this bulletin at 07/06/2020 07:33 PM AKDT
Monday, July 6, 2020
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Current state of evidence for the use of convalescent plasma
Convalescent plasma (CP) has been proposed as a treatment for severe COVID-19, based at least in part on sparse evidence that found some benefit in SARS and H1N1. Reviewing the evidence so far, there is reasonable preliminary safety data and not yet much evidence for efficacy. Convalescent plasma is currently recommended only in the context of a clinical trial.
A large safety study of CP is ongoing at Mayo. The FDA website on CP, where clinicians can enroll patients into a CP clinical trial, discusses that preliminary results from 20,000 patients found very few severe adverse events in relation to CP, particularly a <1% rate of major transfusion reaction. This study is not designed to assess efficacy and has no control group, so conclusions about efficacy should not be drawn from these data. The outcomes of the first 5k patients were previously published and also showed very low rates of serious adverse reactions (of 5000 patients, 7 had TACO, 11 had TRALI, 3 had a severe allergic reaction, and there were15 deaths within 4 hours of CP, 4 of which were judged to be possibly or probably related to the infusion).
FDA guidelines for CP require a patient to have severe or life-threatening COVID-19. They do not specify how many days the patient should be since symptom onset, but a Seattle study found that most patients were getting admitted 7 +/-4 days after symptom onset, so it would be reasonable to think that most patients who currently qualify for CP would be relatively late in the course of their illness.
In terms of efficacy data, one RCT in preprint was stopped early because they found that by the time patients had respiratory failure or other signs of critical illness [enrolled at mean 10 days of symptoms, IQR 6-15], patients already had high concentrations of circulating antibodies. Another, which began towards the end of the epidemic in Wuhan, was stopped early because they ran out of patients with severe COVID-19 to enroll. No mortality benefit was seen in the enrolled cohort who received CP. Of note, they started plasma a median of 30 days after symptom onset.
A 10-patient safety study showed viremia resolved in 7 patients at 7 days after the plasma was given. The plasma was given an average of about 17 days after symptom onset. However, even severe COVID tends not to be viremic for more than 2-3 weeks and many people have undetectable viral loads after 6-11 days. Another pilot study of five patients with COVID-19 and ARDS requiring mechanical ventilation found that 3 patients were able to wean from the ventilator and 2 remained on the ventilator but ‘stable’; however, there was no control group and the patients were also given antivirals. While both studies did not see major adverse effects of CP, neither are designed to provide evidence for its use.
While evidence for or against convalescent plasma in COVID-19 remains lean, there are several larger randomized controlled trials ongoing nationally and internationally. As several of the studies in SARS showed efficacy in patients who were viremic but had not yet developed antibodies, as trials expand and patients are put on CP earlier, we may uncover a greater detectable efficacy if started earlier in the course of illness; however, currently the use of CP in many centers is restricted to patients who already have severe illness and are typically in the second or third week, by which time they may have already developed a significant concentration of circulating antibodies as seen in the more recent RCT.
Testing for COVID-19 at home
There are now three at-home tests that have received an FDA emergency use authorization to test for COVID-19. These all use PCR and should be comparable in accuracy to other molecular tests in terms of laboratory accuracy, although the same caveats about adequate sample collection and timing apply. Specifically, if you recommend these to a patient, it may be worth stressing that the nasopharyngeal swab must be peformed quite deeply, and that the test will be most accurate if performed within 3-5 days of symptom onset since many people, particularly those with only mild symptoms, may no longer have detectable viral load by 6-11 days after symptom onset.
Some insurance companies may cover these tests (in full or part) in certain circumstances, so patients should be encouraged to check with their insurance to see if the test will be covered.
At-home tests advertise a goal of 48-72 hour turnaround, including same-day or overnight shipping to and from the patient.
Everlywell: https://www.everlywell.com/products/covid-19-test/
Pixel LabCorps: https://www.pixel.labcorp.com/covid-19
Picture Genetics: https://picturegenetics.com/covid19
Links are provided as a convenience and do not reflect an endorsement or recommendation of any particular company.
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