Johns Hop­kins re­searchers pub­lish a how-to guide­book on Covid-19 plas­ma trans­fu­sions

The nov­el coro­n­avirus’ rapid spread, far out­strip­ping even the ac­cel­er­at­ed time­lines set for new drugs and vac­cines, has sent doc­tors turn­ing to a ther­a­py re­searchers say is promis­ing but which hasn’t been wide­ly used in the US in decades: blood plas­ma do­na­tions from re­cov­er­ing pa­tients.

Yet the nov­el­ty of the pro­ce­dure has left hos­pi­tals fac­ing many ques­tions, rang­ing from how ef­fec­tive the treat­ment is to the ba­sic lo­gis­tics of how to go about get­ting the plas­ma from the arm of a now-healthy per­son and in­to the arm of a still-sick one.

To fill that knowl­edge gap, a team of ex­perts at Johns Hop­kins Med­i­cine has pub­lished a guide­book for con­va­les­cent plas­ma in the Jour­nal of Clin­i­cal On­col­o­gy. Con­tain­ing both step-by-step in­struc­tions for how to han­dle in­fu­sions and an overview of the ev­i­dence sup­port­ing its use, the ar­ti­cle func­tions as both a man­u­al and one of the most sys­tem­at­ic and care­ful Eng­lish lan­guage en­dorse­ments for the use of plas­ma do­na­tions in Covid-19 pa­tients since the out­break be­gan.

Evan Bloch

“We’ve re­ceived many in­quiries from health care providers look­ing to ramp up their abil­i­ty to de­liv­er this ther­a­py,” Evan Bloch, an in­fec­tious dis­ease pro­fes­sor at Hop­kins and lead au­thor, said in a state­ment. “There is his­tor­i­cal prece­dent for its use to pre­vent and treat vi­ral ill­ness. How­ev­er, dur­ing the chaos of an epi­dem­ic, the ther­a­py is of­ten de­ployed with­out rig­or­ous­ly study­ing its ef­fects. Care­ful­ly con­duct­ed stud­ies are crit­i­cal­ly need­ed to un­der­stand which peo­ple are most like­ly to ben­e­fit from this ther­a­py and how best to ap­ply it to op­ti­mize that ben­e­fit.”

The guide­book – which al­so drew from ex­perts at Stan­ford, Co­lum­bia and Wash­ing­ton Uni­ver­si­ty in St. Louis, among oth­ers – ex­plained that al­though da­ta from clin­i­cal tri­als are still need­ed, con­va­les­cent plas­ma has been used as ther­a­py and post-ex­po­sure pro­phy­lax­is for past in­fec­tious dis­eases, in­clud­ing the dead­ly coro­n­avirus­es SARS and MERS, and was used in a lim­it­ed num­ber of Covid-19 cas­es in Chi­na. The ther­a­py works by tak­ing the pas­sive an­ti­bod­ies a pa­tient nat­u­ral­ly gen­er­at­ed in re­sponse to the virus and trans­fer­ring to a new pa­tient, where (hope­ful­ly) it binds to the virus, halt­ing in­fec­tion.

The plas­ma ap­pears to be ef­fec­tive at mul­ti­ple stages but works bet­ter the ear­li­er it is giv­en, the au­thors wrote. They cit­ed a Hong Kong study from the SARS out­break, in which pa­tients giv­en plas­ma in the first 14 days re­cov­ered faster than those giv­en lat­er. Still, a re­port of five crit­i­cal­ly ill Covid-19 pa­tients in Chi­na found that all 5 im­proved af­ter trans­fu­sion, ev­i­dence that “con­va­les­cent plas­ma is safe, re­duces vi­ral load and may im­prove clin­i­cal out­comes.”

“Im­por­tant­ly, pas­sive an­ti­body ad­min­is­tra­tion of­fers the on­ly short-term strat­e­gy to con­fer im­me­di­ate im­mu­ni­ty to sus­cep­ti­ble in­di­vid­u­als,” they wrote. “This is par­tic­u­lar­ly the case in the set­ting of a nov­el, emerg­ing in­fec­tious dis­ease such as SARS- CoV-2/COVID-19.”

By their count, five tri­als have been pro­posed to test the ther­a­py: As post-ex­po­sure pro­phy­lax­is, in mild cas­es, in mod­er­ate cas­es, in chil­dren and as a “res­cue in­ter­ven­tion” for those se­vere­ly ill. The post-ex­po­sure tri­al — a Phase II be­ing run but the Mayo Clin­ic — could give “di­rect clin­i­cal ben­e­fit” for pa­tients while al­so of­fer­ing “wide-rang­ing” so­cial ben­e­fits such as pro­tect­ing health­care work­ers on the front­line. Treat­ing mod­er­ate­ly ill pa­tients might help stave off ven­ti­la­tion and pre­serve the short sup­ply of equip­ment. Crit­i­cal­ly ill pa­tients may be helped by plas­ma, but tri­als on those pa­tients may of­fer lit­tle con­clu­sive da­ta be­cause of “con­found­ing vari­ables,” in­clud­ing oth­er ex­per­i­men­tal ther­a­pies, the au­thors con­clud­ed.

There’s still much we don’t know about plas­ma trans­fu­sions and an­ti­bod­ies to Covid-19, they ac­knowl­edged. That in­cludes which of the an­ti­bod­ies the body makes best to neu­tral­ize the virus, and though you can screen blood for dif­fer­ent an­ti­bod­ies, it takes time. Their re­view of the lab da­ta in­di­cat­ed most pa­tients would have enough an­ti­bod­ies for do­na­tion 14 days af­ter their symp­toms end­ed.

For eq­ui­table ac­cess to plas­ma, they rec­om­mend­ed donors be screened in a clin­ic for both the virus and its an­ti­bod­ies. If the for­mer’s neg­a­tive and the lat­ter pos­i­tive, they are then di­rect­ed to do­nate at a blood cen­ter, which then shares it with hos­pi­tals, who dis­trib­ute it ac­cord­ing to those in clin­i­cal tri­als or with emer­gency use au­tho­riza­tions. They ar­gued risks — ei­ther from con­tract­ing an in­fec­tion from the donor or from a phe­nom­e­na called an­ti­body-de­pen­dent en­hance­ment, where mon­o­clon­al an­ti­bod­ies can wors­en the dis­ease — were low, but cau­tioned time and da­ta were need­ed.

“The risks of COVID-19 in­fec­tion are pro­found,” they con­clud­ed. “Hu­man plas­ma from re­cov­ered COVID-19 pa­tients is pro­ject­ed to be a safe and po­ten­tial­ly ef­fec­tive ther­a­py for treat­ment and post-ex­po­sure pro­phy­lax­is alike. Sub­stan­tial ev­i­dence of ben­e­fit with pri­or use for vi­ral in­fec­tions of­fers strong prece­dent for such an ap­proach. How­ev­er, it is crit­i­cal­ly im­por­tant to per­form well con­trolled clin­i­cal tri­als to con­firm ef­fi­ca­cy, there­by in­form­ing ra­tio­nal ev­i­dence-based de­ci­sion-mak­ing.”

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