Promising Covid-19 treatment using convalescent serum therapy fast-tracked
From episode 594 of <i>This Week in Virology</i>[1]:<p>Vincent Racaniello: <i>We have a bunch of emails and correspondence about the use of convalescent sera, and Frank, for example, who&#x27;s a professor at Misericordia University, said &quot;Why aren&#x27;t we using antisera from recovered patients to treat infected people?&quot; and we have some email from Ed Niles in a bit, but I want to just say that yesterday the FDA approved this kind of treatment for serious infections on an emergency basis.  So if you have a very serious or life-threatening infection you can apply to the FDA for what&#x27;s called emergency investigational drug application and you can get convalescent serum, which means serum from someone who&#x27;s recovered from the infection, is checked to make sure there&#x27;s nothing else -- no other viruses -- in it, and it can be given to you and we know from previous experience with other infections that this can work.</i><p>Rich Condit: <i>The idea here is that someone who has recovered from the disease has antibodies to the virus, in this particular case the SARS-CoV-2, and so if you give them intravenously this preparation that has these antibodies in it, presumably that can latch on to virus that&#x27;s infecting you and those pathogen antibody complexes will be disposed of appropriately in your body.  This what&#x27;s called, comes under the general umbrella of passive immunization, which you&#x27;re giving antibodies from some other source which will last you for some period of time and it can be up to weeks or months, actually (we&#x27;ve been through this before), as opposed to active immunization where you mount your own.</i><p>Racaniello: <i>Rich, you had some correspondence with Ed Niles.  Why don&#x27;t you...</i><p>Condit: <i>Yeah, he&#x27;s obsessed with this. [laughter] Ah.. let me see here, we haven&#x27;t highlighted this but I&#x27;ll clip through it.  This came to me, I forwarded it to everybody.  &quot;I listened to the first part of TWiV today, through the passive transfer comments,&quot; passive transfer being what we were just talking about, passive immunization, &quot;It was claimed that passive transfer was first used in Lhasa in 1968.  Smallpox docs shouldn&#x27;t be short-changed in this regard.  VIG, which is vaccinia immunoglobilin, was used a decade earlier.  I went to a meeting in 2009 where several smallpox docs talked about their experiences trying a host of putative anti-pox drugs and the impact on their patients.  One had tears recalling the impact treating sick patients with untested and unproven drugs.  I understand the urge to try something, but there are limits.&quot;</i><p>Condit:  <i>Ok.  So Ed, as background, worked for BARDA for a while.  I forget what the acronym stands for, but it&#x27;s a government agency that was born out of the...</i><p>Alan Dove:  <i>I think it was Biodefense Advanced Research and Development Agency, or something like that.</i><p>Condit: <i>There you go.  And, he, so he saw a lot of grants having to do with smallpox, anti-pox viral drugs and etc, so he&#x27;s pretty up on this, and the vaccinia immunoglobilin would be part of that.  He&#x27;s referring to the 60&#x27;s and before when the global smallpox eradication campaign went forward, and one of the things that was used was the vaccinia immunoglobilin.  VIG is, was, prepared by two companies under contract with the US government from pooled serum taken from vaccinies, mostly military at this point.  We have 100,000 doses in the stockpile.  However, 25 doses have been used in some cases to clear vaccination complications.  Provides a link to an article which provides some background for the practicalities of preparing and using coronavirus immunoglobilin if we get to that.  &quot;It helped remind me of what we were thinking about 15 years ago.  Seems like a lifetime.  On another note, pooled monoclonal antibodies have proven to be effective against pox viruses in animal models.  Unfortunately this is an expensive way to go,&quot; and suggest contacting our friend Mike Bershlinsky (sp?) for looking in more detail.  He attached an article from an old friend of ours, Rico Wittick (sp?), since deceased.  It summarizes the prep and use of vaccinia immunoglobilin over the decades.  Ok.  So this is like a review.  He correctly refers to a handful of reported anecdotal applications of vaccinia immunoglobilin against smallpox.  &quot;I don&#x27;t know that true controlled studies have been done at this point.  By 2011 there were none, even with the compassionate uses of vaccinia immunoglobilin ST-246,&quot; which is, was, an experimental anti-pox drug, now approved, &quot;and Senovavir.  It was never clear which, if any of them had a positive effect.  You need controlled trials.  In each case the patient cleared and survived.  Controlled studies are hard to come by.  So I&#x27;m not a big fan of VIG, vaccinia immunoglobilin, and if anyone wants an antibody approach to SARS-CoV-2 they may as well go directly to monoclonals and do the right set of studies.  Of course this will take time.  Alternatively, if you have other tools in the toolbox, maybe a convalescent serum study is warranted.  Any volunteers?  Keep the faith.&quot;</i><p>Racaniello: <i>Well, that&#x27;s exactly what the FDA is doing.  They are doing a convalescent antibody study in case, for prevention.  The emergency use is not for prevention, it&#x27;s for very sick people.</i><p>Dove: <i>Right.</i><p>Racaniello: <i>Because.. So, Brianne, what could go wrong if you gave someone anti... SARS-CoV-2 antibodies?</i><p>Brianne Barker: <i>Well, if we are imagining that there are no other viruses and nothing else there, there are some situations where antibodies and antigens can bind together and get sort of stuck in places, like in some cappilaries and some areas of the skin and kidney and lead to something that in class I call a type-3 hypersensitivity reaction, but really it&#x27;s something called serum sickness or it&#x27;s kind of similar to farmer&#x27;s lung that we see in a few different people.  So sometimes we can see some issues there where people will make a response to those antibodies that they&#x27;re getting from other people, because they are technically foreign proteins that you are injecting in to someone.</i><p>[1] - <a href="http:&#x2F;&#x2F;www.microbe.tv&#x2F;twiv&#x2F;twiv-594&#x2F;" rel="nofollow">http:&#x2F;&#x2F;www.microbe.tv&#x2F;twiv&#x2F;twiv-594&#x2F;</a> (about 23 minutes in to the program)