Yes, but for how long? The devil is in the details.

The consensus among those studying the immune response to SARS-CoV-2 infection is that antibodies do, in fact, equal immunity.

But the devil, as always, is in the details, according to Arturo Casadevall, MD, PhD, chair of the molecular microbiology and immunology department at Johns Hopkins University Bloomberg School of Public Health.

“We only have five months of experience with this organism,” Casadevall told BreakingMED, so it’s not surprising that a lot of questions remain open, including how long immunity might last.

And, he noted that an April 25 Twitter message from the World Health Organization, which suggested there is “currently no evidence” that antibodies in recovered patients equals immunity, was “inappropriate.”

WHO quickly stepped back from that position, saying that it accepts that most people who recover will have an antibody response that offers “some level of protection” to Covid-19, the disease caused by the novel coronavirus.

How Long Will Immunity Last?

But how much protection, and for how long, remain unknown, the agency said.

A central problem is that the immune response to human coronaviruses has historically not been well studied, Casadevall said. There are now seven such pathogens known — three that cause serious disease and four that are usually regarded as nuisances.

“Based on our experience with coronaviruses (and we don’t have that much — we have SARS, MERS, and the ones that cause runny noses) there will be some immunity to this one,” he said. After all, people do recover, he said, they clear the virus, and they produce neutralizing antibodies.

For most viral infections, that’s enough to make people immune, and there’s no reason to think infection with SARS-CoV-2 is any different. But the period of immunity can be lifelong — as with measles — or last mere months, as with norovirus, Casadevall said, and it’s simply too early to tell what will happen with SARS-CoV-2.

Sporadic reports of reinfection or relapse are not convincing. “I don’t see anything that’s well documented,” he said.

He noted that SARS-CoV-2 can be found in about a third of patients for up to two weeks after clinical recovery. If such a patient were to come down with a cold during that period, a re-test for Covid-19 might easily lead to the erroneous conclusion that reinfection had occurred.

Is Plasma from Recovered Patients the Answer?

The issue of antibodies has another aspect, he said, and that is the use of plasma from convalescent patients. The idea that the antibodies developed by recovered patients might help those in the throes of a disease is not new, but there is very limited data on how well it works.

A report from Chinese researchers on a small and uncontrolled study of five Covid-19 patients suggested the practice might have beneficial results. So far, there are “way over 1,000 cases” in which convalescent plasma has been administered, Casadevall said — perhaps enough to get a signal as to whether the practice is helpful.

But the proof will come from clinical trials, and those are actually hard to do, he said. The process is “relatively benign,” he said, so there’s no real downside to widespread compassionate use.

Except one — a very sick patient is likely to opt for compassionate use rather than take part in a placebo-controlled trial, Casadevall said.

To overcome that issue, Johns Hopkins is organizing two randomized, placebo-controlled trials in people who are less sick:

  • In one, investigators will enroll health-care workers who have had a “major exposure” to the virus and randomly assign them to get convalescent or non-convalescent plasma. The goal would be to see if there is a preventive effect.
  • In the other, researchers will enroll people with mild Covid-19 who are in home isolation and randomly give them convalescent or non-convalescent plasma. In the normal course of things, some of those people will develop more serious symptoms; a difference between the arms would indicate benefit.

The goal of the latter study is to see if convalescent plasma “can prevent people from crashing,” he said. If it can, he added, it would be an “enormous advance” in a field where treatment options are very limited.

But again, the lack of experience with SARS-CoV-2 comes into play.

Unlike drugs, human plasma is highly variable — it’s a natural product, after all. So, some people might have high levels of antibodies while others have lower titers and yet both recover. Is the plasma equivalent?

It’s also possible, Casadevall said, that the antibodies themselves might differ from person to person, targeting different parts of the virus. Again, does that matter?

“We don’t know,” he said.

Michael Smith, Contributing Writer, BreakingMED™

Cat ID: 125

Topic ID: 79,125,730,933,125,190,520,926,192,927,151,928