Колку брзо вакцините против Ковид-19 ќе го вратат животот во нормала?

До крајот на јануари, скоро 100 милиони луѓе ширум светот примиле вакцини против КОВИД-19, а повеќе од 1 милион добивале снимки секој ден во САД и Кина. Напорот заостануваше во Европа и остануваат зачудувачки глобални нееднаквости. Светската здравствена организација забележа на 5 февруари дека 75% од вакцинациите се случиле во 10 земји. Околу 130 земји допрва треба да инјектираат некому со вакцина КОВИД-19. Сепак, вакцините, прикажани во клиничките испитувања, имаат ефикасност до 95% против симптоматска болест, конечно му дадоа на светот можност за бегство од долгата опсада на КОВИД-19. „Има толку многу надеж“, вели Абелес.

Сега, како што кампањите за вакцинација добиваат брзина, се појавија огромни прашања: Дали вакцинирањето значи дека нема да го ширите вирусот? Кога кампањите ќе започнат да ја зауздуваат пандемијата и да дозволат секојдневниот живот да се врати во нормала? И, што значат новите варијанти на САРС-CoV-2, кои можат побрзо да се шират или да избегнат имунолошки одговори, за ветувањето за вакцини? „Реалноста е дека овој вирус се развива“, вели Лоренс Кори, вирусолог од Универзитетот во Вашингтон, Сиетл, кој е ко-предводник на мрежата поддржана од владата на САД, која тестира вакцини КОВИД-19.

Сепак, се појавуваат одговори.

Колку наскоро ќе има влијание?
Еден месец по кампањата за вакцинација во САД, Абелес смета дека веќе го видела нејзиниот ефект. Почнувајќи од средината на декември 2020 година, околу 11.000 вработени во Сан Диего Здравје започнаа да примаат вакцина Pfizer-BioNTech или Moderna, и двете содржат гласник РНК (mRNA) што ги насочува клетките на телото да создадат површински протеини од SARS-CoV-2 , скок, да предизвика имунолошки одговор. И покрај извештаите за здравствени работници кои се двоумат дали да ги направат вакцините, 96% од колегите на Абелес ги прифатиле снимките. Секоја недела, овие вработени се тестираат за САРС-CoV-2, кој експлодира во округот Сан Диего, почнувајќи од декември, дури и ако се чувствуваат здрави.

На врвот, Здружението за здравствени установи во Сан Диего откриваше 20-30 инфекции секој ден кај вработените, многумина беа асимптоматски. До третата недела во јануари, бројот падна на само неколку. Абелес нагласува дека доказите се далеку од убедливи, но вели дека „ние сме крајно надежни“ дека врската помеѓу падот и масовната вакцинација е вистинска.

Поубедливи, ако сеуште прелиминарни, докази доаѓаат од Израел, дом на досега најагресивната и најдобро проучена кампања за имунизација во светот. Земја со 9 милиони жители, Израел има универзална здравствена заштита обезбедена главно преку четири системи-организации-мрежи кои менаџираат достапност на стандардни здравствени услуги – health maintenance organization (HMO) со одлични електронски медицински досиеја. Израелската влада преговараше со Pfizer за брзо објавување на снимките од mRNA во замена за споделување податоци за нивното влијание со компанијата. Помеѓу 19 декември и 4 февруари, 39% од Израелците примиле барем една доза на вакцина. По глава на жител, тоа е далеку поголема покриеност отколку во која било друга земја освен слично малите Обединети Арапски Емирати (36%).

Izraelska vlada pregovarala je s Pfizerom o brzom iznošenju svojih mRNA snimaka u zamjenu za razmjenu podataka o njihovom utjecaju s tvrtkom. Između 19. prosinca i 4. veljače 39% Izraelaca primilo je barem jednu dozu cjepiva. To je daleko veće pokrivenost po glavi stanovnika nego u bilo kojoj zemlji osim u sličnim malim Ujedinjenim Arapskim Emiratima (36%).

The Israeli government negotiated with Pfizer to rapidly roll out its mRNA shots in exchange for sharing data about their impact with the company. Between 19 December and 4 February, 39% of Israelis had received at least one dose of the vaccine. Per capita, that is far higher coverage than in any country other than the similarly small United Arab Emirates (36%).

На национално ниво, случаите на КОВИД-19 и хоспитализациите се чини дека опаѓаат побрзо кај луѓето од 60 години или постари, први што примиле вакцини отколку кај сегментот стари 40-60 години. И во соопштението за печатот од 1 февруари, Центарот за истражување и иновации во Макаби – еден од четирите HMO – истакна дека следел 132.015 свои членови постари од 60 години, кои примиле доза на вакцина во првите 9 дена од кампањата за имунизација. Дијагностицираните инфекции со САРС-CoV-2 во таа група достигнаа врв околу 10 дена по почетокот на имунизациите. До 28 ден, кога повеќето луѓе ја примија втората, засилувачка доза, дијагнозите паднаа за две третини, а хоспитализацијата поврзана со КОВИД-19 се намали од дневно високо ниво од седум лица на една. Кај општата популација, забележува тимот, пријавените случаи паднале многу побавно.

Dijagnosticirane infekcije SARS-CoV-2 u toj su skupini dosegle vrhunac oko 10 dana nakon početka imunizacije. Do 28. dana, kada je većina ljudi primila drugu, obnovljivu dozu, dijagnoze su pale za dvije trećine, a hospitalizacija u vezi s COVID-19 pala je s dnevnog maksimuma od sedam ljudi na jednog. U općoj populaciji, primjećuje tim, prijavljeni slučajevi padali su mnogo sporije.

Diagnosed SARS-CoV-2 infections in that group peaked about 10 days after immunizations began. By day 28, when most people had received their second, booster dose, diagnoses had fallen by two-thirds, and COVID-19–related hospitalization had dropped from a daily high of seven people to one. In the general population, the team notes, reported cases dropped much more slowly.

Тоа откритие претставува „убедлив доказ за реалната корист од вакцинацијата, особено затоа што претходните ограничувања во однесувањето во Израел изгледаше дека не ги заштитуваа селективно оние над 60 години“, вели Роби Батачарија, специјалист за заразни болести во Општата болница во Масачусетс.

To otkriće predstavlja “uvjerljiv dokaz stvarne koristi od cijepljenja, pogotovo jer se činilo da prethodna ograničenja u ponašanju u Izraelu nisu selektivno zaštitila starije od 60 godina”, kaže Roby Bhattacharyya, specijalist za zarazne bolesti u općoj bolnici Massachusetts.

That finding constitutes “persuasive evidence of real-world benefit of vaccination, especially since prior behavioral restrictions in Israel did not seem to selectively protect those over 60,” says Roby Bhattacharyya, an infectious disease specialist at Massachusetts General Hospital.

Во Соединетите држави, луѓето што живеат во установи за долготрајна грижа, повеќето од нив постари лица, и вработените во установите беа ставени на предната линија на вакцините. Оние жители сочинуваат околу 40% од смртните случаи во земјата КОВИД-19, така што влијанието на вакцинациите врз нивната хоспитализација и морталитет веројатно ќе се види „сигурно за еден месец или два“, вели Ира Лонгини, биостатистичар на Универзитетот во Флорида

Ефектот можеби веќе стана видлив. Случаите со КОВИД-19 опаѓаат на национално ниво од декември, вклучително и во домови за стари лица. Интервенциите, освен вакцините, објаснуваат дел од падот. Но, споредбата на ниво на округ на објекти кои ги добија своите први снимки од 18 до 27 декември и оние што не покажаа пад на дневните случаи беше повеќе од двојно поголема во претходните вакцинирани установи (пад од 48% наспроти 21%) .

The effect may have already become visible. COVID-19 cases have been dropping nationwide since December, including at nursing homes. Interventions other than vaccines explain some of the fall. But a county-level comparison of facilities that got their first shots from 18 to 27 December and those that didn’t showed the drop in daily cases was more than twice as large in the earlier vaccinated facilities (a 48% decline versus 21%).

Затапувањето на случаи КОВИД-19 на национално ниво е долга игра, сепак, особено во земја како што се Соединетите Држави, каде ширењето на вакцините не било толку брзо или униформно како во Израел. „Имаме голема земја. Имаме многу пренос “, вели Лонгини. „Не мислам дека ќе видиме големо влијание врз бројот на случаи“ од вакцините до летото.

Ometanje slučajeva COVID-19 širom zemlje duga je igra, međutim, posebno u zemlji kao što su Sjedinjene Države, gdje uvođenje cjepiva nije bilo tako brzo niti jednoliko kao u Izraelu. “Imamo veliku zemlju. Imamo puno prijenosa ”, kaže Longini. “Mislim da do ljeta nećemo imati velikog utjecaja na broj slučajeva” od cjepiva.

Blunting COVID-19 cases nationwide is a long game, however, especially in a country such as the United States, where the vaccine rollout has not been as fast or uniform as in Israel. “We have a big country. We have a lot of transmission,” Longini says. “I don’t think we’ll see a big impact on numbers of cases” from vaccines until the summer.

Дали вакцинацијата ќе ве спречи да го ширите вирусот?
Ако вакцините создадоа позната како стерилизирачки имунитет цело време, ниту едно вакцинирано лице не би го пренело вирусот. Вакцинирани баби и дедовци можеле безбедно да си играат со нивните неимунизирани внуци. Земјите можеа да ги пречекаат посетителите кои имаа доказ за вакцинација со мал страв од воведување нови вирусни варијанти или повторно разгорување на епидемиите.

Тоа ниво на сигурност е висока наредба. Неколку вакцини, за какви било заразни болести, создаваат стерилизирачки имунитет – дури и најефикасните. Инактивираната вакцина против полиовирус развиена од Jonонас Салк не направи многу за да ја блокира инфекцијата или пренесувањето на вирусот, но сепак моќно го спречи паралитичкото детска парализа. До 1961 година, 6 години откако беше лиценцирана, само 54% ​​од населението во САД ја прими вакцината, но сепак, паралитичните случаи со детска парализа се намалија за повеќе од 90%.

For practical reasons, the recent COVID-19 vaccine efficacy trials evaluated mainly the frequency of symptomatic disease, typically detected after participants feel sick and get a virus test. It’s tougher to identify all SARS-CoV-2 infections, which remain invisible if they don’t cause symptoms. Yet models suggest asymptomatic cases account for about half of transmission, so tracking them among vaccine recipients is key. “There are easy ways to look at transmission and hard ways,” says Ruth Karron, who runs the Johns Hopkins University Center for Immunization Research.

One approach, says John Mascola, who heads the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID), is to ask: “If you’re vaccinated, could you have the virus in your nose and shed it?” That’s how researchers studying the AstraZeneca–University of Oxford vaccine recently tried to get at transmission. In a U.K. efficacy trial of that vaccine, participants did weekly nasal swabs at home. Results showed vaccination reduced asymptomatic infections by 49.3%. The data suggest, but do not prove, that the vaccine stymies viral spread; misleading news coverage claimed the vaccine had cut transmission by two-thirds. Moderna has also reported a similar decline in asymptomatic infections after just one dose of its mRNA vaccine in a subset of its large efficacy trial, which found overall that the vaccine had 94% efficacy against mild disease.

Several COVID-19 vaccine studies have opted for a simpler, if less precise, look at the issue. They took repeated blood samples from people in both the placebo and vaccinated groups at different time points. The trials tested for antibodies against the viral N protein, which are triggered by infection but not by most vaccines. If the placebo group has more positive N antibody tests than the vaccinated group, that would suggest the vaccine had cut asymptomatic infections—and therefore transmission. No group has yet reported results from those “serosurveys.”

Early data from Israel indicate vaccinated people who nevertheless became infected with SARS-CoV-2 have reduced levels of virus, which may make them less contagious. A research team from the Maccabi group and the Israel Institute of Technology measured viral loads in nasal samples taken from more than 1000 people who became infected between 12 to 28 days after their first dose, the period in which immunity begins to build. The amount of virus found was significantly less than in a similar group of unvaccinated, infected Israelis, the group reported on 8 February in a preprint on bioRxiv.

Myron Cohen, an infectious disease clinician at the University of North Carolina, Chapel Hill, and colleagues at the COVID-19 Prevention Network have a proposal at NIAID to study the question in college students. One group would receive the vaccine immediately and a control population would get it weeks later. Both groups of students would swab their noses daily to assess whether there are differences in the rate of asymptomatic SARS-CoV-2 infections and levels of the virus. Withholding vaccine would be ethically dodgy if doses were plentiful, but most college students are still not eligible for vaccination, and they are less likely to develop serious COVID-19 than older adults. Cohen is confident the trial will receive the necessary ethical approvals.

Knowing whether vaccines stop transmission may not matter to government officials. “In the next 6 months, we’re probably going to have a menu of vaccines and each is going to have characteristics related to the cold chain, number of doses required, reactogenicity, and efficacy,” Karron notes. “We’re going to make policy decisions about use based on all of those characteristics. I don’t think that some superimprecise measure of transmission is going to be one of the things that goes into our calculus.”

But Cohen contends that the difficult studies to evaluate whether immunized people spread the virus are worth doing. “Unless we answer this question, we are a masked society. We need to address this to become maskless.”

When will we get back to normal?

That depends on the definition of normal. To many people now, it means herd immunity, in which a high percentage of a population has either been vaccinated or naturally infected, leaving too few susceptible hosts for a virus to continue to spread. “It’s such a clean, beautiful concept, the tipping point idea, that if we can just get there, the virus will go away, and then we can just go about our business as if it’s gone,” Longini says. “It’s kind of a pie-in-the-sky concept that’s very, very attractive.”

The idea of herd immunity, a term imported from livestock veterinarians, has become more beguiling as huge swaths of populations in parts of the world recover from SARS-CoV-2 infections, leaving them with some degree of immunity. In India, for example, serosurveys have found antibodies to the virus in about half of people in the city of Delhi and the entire state of Karnataka. And though no one is claiming this meets the herd immunity threshold, new cases have recently dropped precipitously.

Still unclear is what percentage of a population needs to be vaccinated or recovered from COVID-19 before herd immunity kicks in. Early predictions were between 60% and 70% and then rose as high as 90%—but that’s all based on modeling or even guesswork. Anthony Fauci, who heads NIAID, has been taken to task for changing his own estimates. Recently on CNN, Fauci acknowledged that: “I think we all have to be honest and humble. Nobody really knows for sure.”

Recent developments have been sobering. The COVID-19 vaccines rolling out are highly effective against hospitalization and death, but their success against mild and moderate symptoms plummets when faced with viral variants that can evade vaccine-triggered antibodies. And herd immunity, even if it emerged, could easily fade as immunity waned or new variants arose.

Yet there is growing recognition that even if widespread vaccination can’t halt the spread of the virus, it promises a major step back toward normal. Preventing severe disease and death in the elderly and people with comorbidities such as obesity and hypertension—the most vulnerable—is still a resounding victory over the virus, many epidemiologists say.

Large swaths of the population might still become infected and develop minor disease or asymptomatic infections. That prospect worries some scientists and clinicians, who note that even mild cases can lead to the “long COVID” phenomenon of lingering symptoms. Hospitals, though, will not become overwhelmed with emergency cases and deaths will become increasingly rare.

To Corey, those metrics are the most relevant. “When will the ICU use and all of this decant so that we’re at the point where, yes, we can sort of tolerate this?” he asks.

“We’re not going to shut down this virus and end transmission,” agrees Nicole Lurie, an adviser to the Coalition for Epidemic Preparedness Innovations. “We have to make a decision as a society about how much of this we can and want to live with.” Society lives with influenza, after all, which remains endemic despite a vaccine. But Lurie stresses that flu is not an appealing model. It kills up to 60,000 people per year in the United States alone—a toll she would not want to accept from COVID-19.

Still, immunologist Brigitte Autran, a member of France’s Scientific Committee on COVID-19 Vaccines, says herd immunity isn’t needed to bring back normalcy. “The first goal is to have individual protection, and by summing the individual protections, to have a protection of the society that will allow countries to come back to almost real, true lives.”

How much of a threat do viral mutants pose to immunity?

That concern quickly moved from the theoretical to the real world when multicountry studies recently revealed several vaccines were least effective against symptomatic COVID-19 in South Africa. That’s where 95% of infections now stem from a viral variant that in test tube studies could dodge antibodies against the viral spike protein. Novavax’s protein-based vaccine went from 89.3% protection in the United Kingdom, where the variant is rare, to 49.4% in South Africa. And South Africa even halted its planned rollout of the AstraZeneca-Oxford vaccine, which consists of a harmless viral “vector” carrying the gene for the spike protein, after a small trial there indicated the vaccine had 22% efficacy.

Still, the vaccine-triggered immune responses may retain plenty of muscle, enough to prevent serious symptoms. A third vaccine, from Johnson & Johnson, also fell short against mild disease in South Africa, but it prevented almost all severe disease—with no hospitalizations or deaths. (The AstraZeneca-Oxford and Novavax studies were too small to address impact on severe disease.)

One explanation could be that the level of key spike antibodies, those capable of “neutralizing” SARS-CoV-2’s infectivity, jumped so high after vaccination that there was a cushion: Even though several labs reported that the variant in South Africa reduced the impact of the vaccine-induced antibodies by up to ninefold, if those immune fighters rise to high enough levels they may still pack enough punch to thwart serious disease.

Other arms of the immune system less affected by the mutations in the variant likely contribute to protection. Pfizer and BioNTech have shown their mRNA vaccine triggers a steep increase in key T cells. One set, which carries the CD8 receptor, targets and destroys cells that SARS-CoV-2 manages to infect. Underscoring the importance of those cells, Pfizer and BioNTech found that even though neutralizing antibody levels triggered by their vaccine were minimal in the 21 days between the first and second doses, it still gave 52.4% protection against disease during that period. “Vaccine-induced T cell responses are important for COVID-19 vaccines, particularly for resistant variants that might partially evade neutralizing antibodies,” suggests Dan Barouch of Harvard Medical School, whose lab has documented the importance of CD8+ cells for protecting monkeys from coronavirus reinfection.

Mixing and matching COVID-19 vaccines may also boost both antibody and T cell responses to higher levels, creating bigger cushions. Studies of various combinations have begun.

Will the variants change the course of the pandemic?

That’s the realm of modelers like Longini. Often, they restrict their analyses to tight geographical areas, which makes it easier to amass high-quality data and to account for variables that can alter outcomes. So Longini and Thomas Hladish, also at UF, created a model for their home state that extrapolates from actual case numbers for COVID-19 and assumes a rapid rollout, starting with people older than 65, of vaccines that are 60% effective at preventing infection. Assuming the virus doesn’t change, they found that a vaccination campaign reaching half the population would slash symptomatic disease and death by 30% by August.

Surprisingly, their Florida model shows COVID-19 cases would steadily decline even without vaccination. That’s because the state’s reproductive number for SARS-CoV-2—how many other people each COVID-19 case infects—has dropped below 1. “It’s mostly masking, social distancing, and the slow buildup of natural immunity in the population,” Longini says. Indeed, as in many U.S. states, Florida’s cases began to drop steeply in January.

But that decline could quickly reverse if a mutant strain takes off that’s 50% more infectious, such as the B.1.1.7 variant strain that exploded first in the United Kingdom and has come to the United States, including Florida. “We will have a much bigger epidemic that starts happening now,” Longini says. But with more viral spread, the impact of vaccination would be bigger, averting twice as many symptomatic cases and deaths.

Vaccines versus variant

Models suggest the impact of COVID-19 vaccinations in San Diego will be blunted by the fast-spreading B.1.1.7 variant, which already accounts for 5% of SARS-CoV-2 infections there. If other prevention efforts are relaxed, a surge of cases will swamp the gains from vaccination.

Swipe or click the arrows to view modeling of other vaccination and behavior scenarios.Daily COVID-19 cases (per 100,000)Current protective behavior, no vaccinationCurrent behavior, fast vaccine rollout**Fast vaccine rollout, relaxation of protectionStandard SARS-CoV-2B.1.1.7 variant*010203040507 February18 AprilProtective behavior relaxed

Modeler Natasha Martin and her team at the University of California, San Diego, have looked at the interplay of variants and vaccines in an even smaller area: their home county. Sequencing of COVID-19 cases in San Diego county has shown the highly transmissible B.1.1.7 variant has a 5% prevalence so far—10 times higher than recently estimated for the nation. Martin’s model shows that if the variant takes over, as many researchers expect, aggressive vaccination campaigns over the next 3 months will still cut case numbers in half. But if the county drops its guard and people become lax about prevention efforts, COVID-19 cases will triple even with rapid vaccination. “We are at a critical moment in the epidemic, where our progress in terms of declining cases could quickly be reversed as the B.1.1.7 strain expands,” Martin says. “We have the tools we need to fight the spread of this virus: masking, social distancing, vaccination. Now is the time to vaccinate as many people as fast as we can, and double down on masking and distancing.”

How quickly can we tailor vaccines to the new variants?

Vaccine developers proved in 2020 that they can move from concept to candidate vaccine, ready to test in people, in as little as 2 months. Changing the genetic code used in an mRNA or vector-based vaccine, or making a new inactivated-virus preparation, should be at least as fast. (A genetically engineered protein, such as the Novavax vaccine, takes longer.)

But by far the biggest time sink and expense for getting COVID-19 vaccines into use were the large-scale efficacy trials, which took about 4 months. Would those need to be repeated for each updated vaccine? No, says Peter Marks, who heads the vaccine division at the U.S. Food and Drug Administration. All the agency would likely require, he says, is a “modest size” study in humans showing the immune responses elicited by the new vaccine resemble those triggered by the original and are likely to be protective.

Flu vaccines, after all, are updated yearly to keep up with the ever-morphing influenza virus and are quickly approved. Makers can pop out components from the old vaccine and replace them with new ones. Regulators require minimal evidence about the revised product—often just animal studies showing it performs as well as last year’s model.

But with COVID-19 vaccines, no one knows which immune responses correlate with protection. Many vaccine experts assume neutralizing antibodies to the spike protein are the most important driver of protection. To prove that, however, researchers need to compare immune responses between vaccinated people infected by viruses that “broke through” their protection and vaccinated people who did not become infected. A more in-depth “sieve” analysis of breakthrough cases refines the correlates of protection by looking at the genetics of the variants that break through. Those studies are underway, but the Moderna and Pfizer-BioNTech vaccines, the first approved, worked so well that it was difficult to figure out the protective immune responses. “There weren’t that many vaccinated, infected people,” explains Mascola, who is helping coordinate the analyses.

Still, Marks says he anticipates that by the time makers of vaccines formulate new preparations to combat variants and test them in small human studies, the key immune responses will have become clear. “We may well have the correlate confirmed by March when it is really needed,” he says. That could open the way for rapid approval and rollout of boosters designed to keep up with the evolving virus—and ensure that any hard-won progress against the pandemic isn’t undone. Posted in: 

  • Science Health Coronavirus By Jon CohenFeb. 16, 2021 , 5:45 PM doi:10.1126/science.abh0618