Long-time readers know that I’ve been banging the drum for convalescent plasma therapy since early March. My initial enthusiasm—and I was very enthusiastic as we had virtually no treatment options—slowly waned.

This was due less to the logistical issues—the Red Cross and others did incredible work surmounting these—as much as it was that we didn’t have any good studies proving efficacy. Collectively the medical establishment used it enough that we knew it to be relatively safe (though certainly not universally so), but we had little more than anecdotal evidence (really, this should be “evidence”) and a long history of similar attempts with other viruses.

Eventually, I ended up in a place no one wants to be: Might as well try it, probably won’t hurt, might help. Given the choice, I’d take it.

Well, I’m not in that position any longer. The results are in: Convalescent plasma therapy doesn’t work against COVID-19.

Released today, November 24, in The New England Journal of Medicine is a multicenter randomized, double-blind, placebo-controlled clinical (RCT) of 228 patients hospitalized with severe covid-19 who received either standard-of-care and convalescent plasma therapy or standard-of-care plus placebo. The primary outcome the researchers tracked was “clinical status” during follow-up at day 30.

The average age of participants was 62 years, and the majority were identified as male. Over one-fourth of patients were in intensive care units. Importantly, 93 percent of patients were on steroids, such as dexamethasone—meaning that they were already receiving the one treatment that has been shown to improve mortality rates in covid-19 patients with severe illness.

Interestingly, 68.6 percent and 61.8 percent of patients given placebo and convalescent plasma, respectively, were discharged home in good condition, though that difference was not statistically significant. Unfortunately, by day 30 there were no significant differences noted between the convalescent plasma group and the placebo group with regard to clinical outcomes or mortality. Adverse events were similar in both groups. Previous retrospective studies have found that convalescent plasma can cause serious harms, despite the general talking point that “plasma is safe.” But in a trial with just 228 patients, it is unlikely that many adverse events would occur.

This is disappointing in that we are left with only steroids in the arsenal against Covid. But wishing something would work does not make it so, and I’m convinced now that convalescent plasma therapy is ineffective. I am curious if this also means that we’ll find monoclonal antibodies to be similarly useless, as that’s sort of the same underlying idea for attacking the virus—just with better quality control and manufacturing.

It may be that antibodies are not the key in combatting the virus once acquired. If that’s true, it might explain the failure of CP and monoclonal antibodies. If the latter does work, then it would be interesting to know what the specific differences between the two therapies are that lead to different outcomes. 

We continue to need a treatment. 

Fortunately, the vaccines in the pipeline that prevent the spread of the coronavirus work by priming the body to block the spike protein that the virus uses to attach to the ACE2 receptor. That will keep people from getting or transmitting the virus, which means not getting the virus until a vaccine is available remains crucial. Once you have the virus, there remains not a lot we can do to make you better. But at least we know now one more thing that does not work.