Sci­en­tists warn Amer­i­cans are ex­pect­ing too much from a coro­n­avirus vac­cine

The White House and many Amer­i­cans have pinned their hopes for de­feat­ing the Covid-19 pan­dem­ic on a vac­cine be­ing de­vel­oped at “warp speed.” But some sci­en­tif­ic ex­perts warn they’re all ex­pect­ing too much, too soon.

“Every­one thinks COVID-19 will go away with a vac­cine,” said William Hasel­tine, chair and pres­i­dent of Ac­cess Health In­ter­na­tion­al, a foun­da­tion that ad­vo­cates for af­ford­able care.

On­go­ing clin­i­cal tri­als are pri­mar­i­ly de­signed to show whether Covid-19 vac­cines pre­vent any symp­toms of the dis­ease — which could be as mi­nor as a sore throat or cough. But the tri­als, which will study 30,000 to 60,000 vol­un­teers, will be too short in du­ra­tion and too small in size to prove that the vac­cines will pre­vent what peo­ple fear most — be­ing hos­pi­tal­ized or dy­ing — by the time the first vac­cine mak­ers file for emer­gency au­tho­riza­tion, ex­pect­ed to oc­cur lat­er this year, Hasel­tine said.

The Unit­ed States should hold out for an op­ti­mal vac­cine, with more proven ca­pa­bil­i­ties, Hasel­tine ar­gued. Oth­ers say the crush­ing toll of the pan­dem­ic — which has killed at least 225,000 Amer­i­cans — de­mands that the coun­try ac­cept the best vac­cine it can achieve with­in the next few months, even if sig­nif­i­cant ques­tions re­main af­ter its re­lease.

“There’s a ten­sion be­tween get­ting every piece of in­for­ma­tion and get­ting a vac­cine [out] in time to save lives,” said William Schaffn­er, a pro­fes­sor of pre­ven­tive med­i­cine and health pol­i­cy at the Van­der­bilt Uni­ver­si­ty Med­ical Can­cer.

“Would we like to know if the vac­cine re­duces ill­ness or mor­tal­i­ty? Of course,” said Pe­ter Lurie, a for­mer FDA of­fi­cial and the cur­rent pres­i­dent of the Cen­ter for Sci­ence in the Pub­lic In­ter­est. “But there is a re­al time pres­sure. This is a pan­dem­ic. It’s ex­plo­sive.”

Re­searchers de­bat­ed how rig­or­ous­ly to test COVID-19 vac­cines at a Thurs­day pub­lic meet­ing of the Food and Drug Ad­min­is­tra­tion ad­vi­so­ry com­mit­tee on vac­cines.

“Sim­ply pre­vent­ing mild cas­es is not enough and may not jus­ti­fy the risks as­so­ci­at­ed with vac­ci­na­tion,” said Pe­ter Doshi, an as­so­ciate pro­fes­sor at the Uni­ver­si­ty of Mary­land School of Phar­ma­cy who de­tailed his con­cerns in an ed­i­to­r­i­al in The BMJ.

But vac­cine ex­perts say there are good rea­sons to fo­cus on milder cas­es of Covid-19.

Vac­cines that pre­vent mild dis­ease typ­i­cal­ly pre­vent se­vere dis­ease, as well, said Arnold Mon­to, an epi­demi­ol­o­gist at the Uni­ver­si­ty of Michi­gan’s School of Pub­lic Health and tem­po­rary chair of the vac­cine com­mit­tee.

For ex­am­ple, the orig­i­nal stud­ies of the measles vac­cine showed on­ly that it pre­vent­ed measles, not hos­pi­tal­iza­tions or deaths, said Kath­leen Neuzil, di­rec­tor of the Uni­ver­si­ty of Mary­land’s Cen­ter for Vac­cine De­vel­op­ment and Glob­al Health.

Lat­er stud­ies found that measles vac­cines dra­mat­i­cal­ly re­duce mor­tal­i­ty. Ac­cord­ing to the World Health Or­ga­ni­za­tion, world­wide deaths from measles fell by 73% from 2000 to 2018 be­cause of vac­cines.

“There sim­ply does not ex­ist an ex­am­ple in vac­ci­nol­o­gy of vac­cines that are ef­fec­tive against mild dis­ease that are not more ef­fec­tive in se­vere dis­ease,” said Philip Krause, deputy di­rec­tor of the vac­cine of­fice at the FDA’s Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search, at Thurs­day’s hear­ing.

Paul Of­fit, who de­vel­oped the ro­tavirus vac­cine, com­pared pre­vent­ing the coro­n­avirus to fight­ing a fire.

“If you put out a small fire in the kitchen, you don’t have to wor­ry about the whole house catch­ing fire,” said Of­fit, a mem­ber of the FDA ad­vi­so­ry com­mit­tee on vac­cines.

Prov­ing that a vac­cine pre­vents se­vere ill­ness and death is hard­er than show­ing it pro­tects against mild ill­ness be­cause hos­pi­tal­iza­tions and deaths are much rar­er. That’s es­pe­cial­ly true among the type of health-con­scious peo­ple who vol­un­teer for vac­cine tri­als, who are prob­a­bly more like­ly than oth­ers to wear masks and so­cial­ly dis­tance, Schaffn­er said.

“When we looked at hos­pi­tal­iza­tions in old­er adults with in­fluen­za, those were two-year tri­als,” Neuzil said. In an on­go­ing study, in which “we’re look­ing at ty­phoid vac­cines in near­ly 30,000 chil­dren, it’s a two-year tri­al.”

The Covid-19 pan­dem­ic has of­fi­cial­ly in­fect­ed about 8.7 mil­lion Amer­i­cans. Con­sid­er­ing that the true num­ber of Amer­i­cans in­fect­ed is es­ti­mat­ed to be six to 10 times high­er than re­port­ed, the mor­tal­i­ty rate is about 0.6%, said Amesh Adal­ja, a se­nior schol­ar at the Johns Hop­kins Uni­ver­si­ty Cen­ter for Health Se­cu­ri­ty.

Sci­en­tists agree that the ide­al vac­cine would pro­vide “ster­il­iz­ing im­mu­ni­ty” — which means pre­vent­ing not on­ly dis­ease symp­toms but any in­fec­tion with the virus, said Corey Casper, a vac­ci­nol­o­gist with the Fred Hutchin­son Can­cer Re­search Cen­ter and chief ex­ec­u­tive of­fi­cer at the In­fec­tious Dis­ease Re­search In­sti­tute in Seat­tle.

For ex­am­ple, two dos­es of measles vac­cines pre­vent 97% of peo­ple from even be­com­ing in­fect­ed with that virus.

Few ex­pect Covid-19 vac­cines to be that ef­fec­tive. “We’re try­ing to low­er that bar and de­ter­mine how much low­er is ac­cept­able,” Casper said.

Pre­vent­ing mild dis­ease could curb dis­ease and pre­vent ill­ness, Casper said.

“We’re prob­a­bly not go­ing to have the per­fect vac­cine,” he said. “But I do think we’re like­ly to have vac­cines that, if we can show they’re safe, can put an in­flec­tion point on this pan­dem­ic. … I think it’s still im­por­tant to have a vac­cine that has some ef­fect even on mild ill­ness.”

Flu shots aren’t su­per ef­fec­tive — with ef­fec­tive­ness each year rang­ing from 19% to 70% — but they’re still ex­treme­ly use­ful, Casper said.

Dur­ing the 2018-19 U.S flu sea­son, vac­ci­na­tion pre­vent­ed an es­ti­mat­ed 4.4 mil­lion in­fluen­za ill­ness­es, 2.3 mil­lion med­ical vis­its, 58,000 hos­pi­tal­iza­tions and 3,500 in­fluen­za-as­so­ci­at­ed deaths, ac­cord­ing to the Cen­ters for Dis­ease Con­trol and Pre­ven­tion.

A tri­al of 30,000 to 60,000 peo­ple is al­ready fair­ly large by his­tor­i­cal stan­dards. Dra­mat­i­cal­ly ex­pand­ing the size be­yond that isn’t prac­ti­cal in a com­pressed time frame, Krause said.

“If the end­point of the tri­al is se­vere dis­ease, the tri­als may need to be al­most 10 times as big,” he said at the meet­ing. “And those tri­als would be in­fea­si­ble and we would nev­er get a vac­cine.”

On the oth­er hand, “if there is a vac­cine that ap­pears to have high ef­fi­ca­cy or ap­pears to be ca­pa­ble of sav­ing lives, one doesn’t want to stop that vac­cine if there is a sig­nif­i­cant chance that it will save lives,” Krause said.

Al­though the coro­n­avirus vac­cine tri­als are mea­sur­ing se­vere dis­ease or death, these are “sec­ondary end­points,” mean­ing the cur­rent size of the study isn’t large enough to pro­duce a sta­tis­ti­cal­ly sig­nif­i­cant an­swer, Neuzil said.

Whether vac­cines re­duce se­vere dis­ease and death will be­come clear in lat­er stud­ies, af­ter vac­cines are dis­trib­uted, Neuzil said.

Of­fit said the de­bate re­volves around one ques­tion: “How much un­cer­tain­ty are we will­ing to live with, know­ing that we’re fac­ing a virus that has brought us to our knees?”

By Liz Sz­abo and JoNel Alec­cia

First pub­lished at KHN (Kaiser Health News) — a non­prof­it news ser­vice cov­er­ing health is­sues. It is an ed­i­to­ri­al­ly in­de­pen­dent pro­gram of KFF (Kaiser Fam­i­ly Foun­da­tion), which is not af­fil­i­at­ed with Kaiser Per­ma­nente.

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