下一个Covid-19战斗将是关于疫苗的孩子

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星期一,田纳西州卫生署米歇尔比派出了顶级疫苗官员。她的违法:在5月,她向国家寄出了一份备忘录,在州的药房和医生中发了一份备忘录,转发了田纳西州最高法院的决定,允许青少年寻求医疗保健,包括疫苗接种,没有父母的同意。当时,食品和药物管理局刚刚授权12至17岁的辉瑞疫苗,即将举行一个用于现代疫苗。“不仅仅是青少年的Covid-19疫苗外徒,而且围绕任何类型的疫苗沟通,”她写道。

星期一,田纳西州卫生署米歇尔比派出了顶级疫苗官员。她的违法:在5月,她向国家寄出了一份备忘录,在州的药房和医生中发了一份备忘录,转发了田纳西州最高法院的决定,允许青少年寻求医疗保健,包括疫苗接种,没有父母的同意。当时,食品和药物管理局刚刚授权12至17岁的辉瑞疫苗,即将举行一个用于现代疫苗。

FISCUS的备忘录由州长员工批准,而且没有政策变动。它讨论的法律裁决于1987年被交给。但是,国家立法者指责她“刺激”儿童寻求疫苗。她被召唤到了两个听证会;一方面,一名立法者提议将整个国家卫生部门的报复溶解。

在一份声明周一晚上给了Tennessean,Fiscus表示,为了保护自己,该部门已经关闭了所有关于疫苗接种的沟通活动。 “不仅仅是青少年的Covid-19疫苗外徒,而且围绕任何类型的疫苗沟通,”她写道。 “由于大流行,没有向30,000多名父母到达30,000多名父母的父母疫苗。在国家的人乳头瘤病毒疫苗周围没有消息传递,该国的最高HPV癌症率之一。“ (周二,田纳西州确认疫苗促销和在学校举行的疫苗接种诊所已被关闭。)

在达拉斯的保守政治行动会议上的一群人群中,FISCUS'射击来了两天欢呼宣布,拜登政府在7月4日之前没有达到一剂疫苗的疫苗。它还来到疾病控制和预防中心的三天后放宽了该机构以前关于戴着面具内部建筑物的指导方针。将这些活动放在一起,他们是一个暴风雨警报器,为下一个Covid战斗,这次过度接种的孩子 - 这将随着病毒的三角洲变异的进步和学年即将开始。

目前正进行的临床试验正对11岁至6个月的儿童进行mRNA疫苗的安全性、有效性、剂量和接种时机的测试;大约4500名儿童辉瑞的试验中,大约7000名儿童摩德纳的试验中。辉瑞的一位官员6月份表示,第一份紧急授权申请应该9月或10月提交给FDA(强生公司;约翰逊现才开始青少年中进行试验,还没有包括更小的孩子。)

这些试验在美国和几个欧洲国家的医疗中心散落于更多的欧洲国家 - 根据几个主要调查人员,更多的网站,因为这些公司认为,这些公司觉得迫切需要收集数据并尽可能迅速地走向批准。那是因为,现在成年人可以接种疫苗,孩子占从科迪德生病的更大比例。

据美国儿科院统计,7月份7月份占美国美国所有案件的14.2%,占2月20日的2%。就在美国,超过400万个孩子从科迪德堕落。虽然大多数体验只有轻微的疾病,但截至7月8日,16,623人已经住院,344人死亡。截至6月底,4,196名儿童和青少年已经开发了MIS-C,令人困惑的,有时致命的炎症,在Covid感染后发生,影响心脏,肺,肾脏和脑。

“Covid是儿童的风险,”UC圣地亚哥医学院儿科教授和FDA疫苗和相关生物制品咨询委员会(VRBPAC)临时投票成员(VRBPAC)的临时投票成员,审查了代表提交的证据covid疫苗。 “报告的死亡至少与儿科死亡人数中最糟糕的流感季节一样糟糕,并且可能比这更糟糕。这甚至没有让我们进入可能发生的长期后果,无论是来自MIS-C还是所谓的长途科科德。这甚至没有触及公共卫生论证,这是我们需要儿童不要将Covid带给他们的祖父母和那些处于极高风险的人。“

随着多年来,许多研究人员指出,孩子不仅仅是小成年人。经过青少年的几年,成年人大多数达到了脂肪和肌肉的最终高度和大小禁止的大增长或损失 - 以及与世界的沉降的免疫平衡。但孩子们一直在改变,而不仅仅是大小和肌肉质量,而且在他们的免疫系统如何捍卫世界。

“多年来,免疫反应变化的频谱和强度”,“耶鲁医学院的儿科医学院和全球健康的疫苗学家和全球健康副教授告诉我们通过电子邮件连接。 “例如,健康13个月的孩子通常具有较高数量的淋巴细胞,这是免疫系统的许多组成部分之一,与健康的15岁儿童相比,我们如何回应疫苗。青少年。”

尽管我们有关于成年人如何应对Covid疫苗的数据 ​​- 从获得疫苗的临床试验,但疫苗的应急授权,以及来自现实世界的观察 - 我们不能认为孩子的反应是一样的。奇怪地,他们可能会更好。例如,在引入HPV疫苗(可防止子宫颈,颈部和喉咙的癌症)后,联邦当局决定只需两种剂量,而不是三个时代,而不是三个,而不是三个人,因为年轻的孩子对疫苗的反应是如此强烈。

但由于Covid仍然是一个新的和研究疾病,我们必须做临床试验来探索这些反应的可能性。随着世界卫生组织在5月的会议中强调的,我们仍然没有确定定义免疫力的“保护”相关性。那些将在免疫反应的指标上达成一致 - 例如,最小数量的抗体或T细胞存在的测量 - 当已经接受疫苗的人受到保护免受感染时。如果我们能够定义这些相关性,我们可以跳过针对头脑研究的安慰剂对照试验比较不同的疫苗,甚至使用血液测试。由于我们没有,在成年人中,孩子们的完全试验是必要的。

沃尔特说:“我们不应该简单地向儿童推荐疫苗,因为它适用于年龄较大的人群。”。奥伦斯坦是埃默里大学疫苗政策与发展的主任和主任,他曾比尔和普林斯领导过免疫计划。梅林达盖茨基金会和疾病预防控制中心。我们需要确定什么是最佳剂量,看看什么是安全系数,这样FDA就有了一个合理的数据集来做出判断。”

一些安全问题出现了。 6月,疾病疾病委员会披露了226名以下30人,其中包括79名16-岁和17岁的人,在收到疫苗后,在他们的心中发芽了炎症。原子能机构及其顾问在免疫惯例咨询委员会会议上审查了问题,但不支持青少年疫苗建议的任何变化。

尽管科迪德疫苗受到政治化争议,但年轻儿童的试验并没有任何困难招聘孩子。 “我们拥有比我们有空间的兴趣更远的人,”Johns Hopkins Bloomberg公共卫生学院的国际健康医师和副教授Kawsar Rasmy Talaat说,在那里她导致辉瑞疫苗的疫苗疫苗12岁及以下。 “在我们甚至知道我们是一个网站之前,我们有一个名单上的名字,父母说,”如果你这样做,我希望我的孩子在学习中 - 数百和数百个名字。“

(Talaat和其他主要调查人员表示,招募孩子的许多父母都竟然是从医学院和进行审判的大学的其他地区,他们恰好是因为他们的工作提前了解试验。这可能是一个问题,因为它可能已经意外地创建了几样的审判人群 - 不一定是种族或国家起源,而是经济地位和生活条件,这两者都受到了在科米德的第一波期间受到伤害的影响。)

在试验中,儿童进入者将分层分成组 - 根据年龄范围。例如,斯坦福大学医学院加入了婴儿和幼儿的辉瑞阶段I安全审判,他们被分为6个月和2年之间的孩子群,然后至少比2年龄较小的孩子斯坦福现在是托管阶段II阶段阶段的课程阶段阶段的疗效试验之一,而且还运行了5岁至11岁儿童的第二阶段和III次试验。 (III期试验也测试疗效,但在更大的群体中,因为只有在添加更多参与者时才能观察到一些罕见的效果。)

根据斯坦福州的流行病学和人口健康教授和斯坦福州的健康教授和斯坦福州的卫生和校长教授的说法,辉瑞试验这些研究是已经返回的信息,表明疫苗疫苗的信息表明疫苗可能在儿童中造成更强的疫苗,而不是成年人。 “将提交给FDA的五月的第一个数据表明,辉瑞疫苗在儿童中引发了比成人在成年人中的更高抗体滴度,”马尔多纳多说。在最终授权中,这些发现可以很好地呈现给含有比成人疫苗中存在的更小剂量的活性成分的疫苗。

总的来说,似乎没有重大挫折。但是接近艰难的挑战。一旦试验数据确定儿童剂量和拍摄时间表通过FDA - 作为紧急使用授权或全新的药物批准 - 分配镜头的活动将由个人国家运行,以同性疫苗的方式运行。这个春天,这是混乱的。

什么可能拯救儿童疫苗,脆弱的老人和免疫中心的健康与儿童接触的人,是系统分配镜头的系统不必从头开始构建。美国公共卫生机构已经建议孩子和青少年在18岁的麻疹,腮腺炎,风疹,白喉,百日咳,两种类型的肝炎,轮状病毒,鸡痘,流感等时接受16种不同的疫苗这些疫苗需要多剂量。大规模的基础设施提供,追踪和支付这些镜头:医师实践,商业药房,卫生部诊所和县健康展览会;卫生部注册机构和国家学校入学标准;私人保险公司和一系列联邦购买计划。 (在美国境外,资金组合来自各国政府和国际慈善事务,该疫苗机可能是医生办公室,公共卫生诊所或志愿者运行的网站。)将Covid疫苗添加到该分布不会是微不足道的,但它不应该是不可能的。

“如果你想让疫苗出来人口,那么通过儿科免疫,最实用的方式是通过儿科免疫,”征收儿科传染病临床医生和波士顿儿童医院精密疫苗计划主任,也是临时的VRBPAC的投票成员。 “世界上大部分地区提供疫苗的基础设施是针对儿童的,而疫苗接种给全球儿童的人口渗透率为80%至90%。”


英文译文:

On Monday, the Tennessee Department of Health fired its top vaccine official, Michelle Fiscus. Her transgression: In May, she had sent a memo to pharmacies and physicians in the state, relaying a Tennessee Supreme Court decision that allows teens to seek medical care, including vaccinations, without their parents’ consent. At the time, the Food and Drug Administration had just authorized the Pfizer vaccine for 12- to 17-year-olds, and one for the Moderna vaccine was soon to follow.

Fiscus’ memo was approved by the governor’s staff, and it contained no policy changes. The legal ruling it discussed was handed down in 1987. State legislators, though, accused her of “prodding” children to seek the vaccine. She was summoned to two hearings; at one, a legislator proposed dissolving the entire state health department in retaliation.

In a statement she gave to The Tennessean Monday evening, Fiscus said that, to protect itself, the department has shut down all its communication campaigns about vaccination. “Not just Covid-19 vaccine outreach for teens, but ALL communications around vaccines of any kind,” she wrote. “No back-to-school messaging to the more than 30,000 parents who did not get their children measles vaccines last year due to the pandemic. No messaging around human papillomavirus vaccine to the residents of the state with one of the highest HPV cancer rates in the country.” (On Tuesday, The Tennessean confirmed that vaccine promotion, and vaccination clinics held at schools, had been shut down.)

Fiscus’ firing came two days after a crowd at the Conservative Political Action Conference in Dallas cheered an announcement that the Biden administration hasn’t achieved its goal of getting one dose of vaccine into 70 percent of Americans by July 4th. It also came three days after the Centers for Disease Control and Prevention relaxed the agency’s previous guidelines about wearing masks inside school buildings. Add those events together, and they’re a storm siren for the next Covid battle, this time over vaccinating children—which will arrive as the virus’s Delta variant advances and the school year is about to begin.

Clinical trials underway now are testing the safety, efficacy, dosing, and timing of mRNA vaccines for kids between the ages of 11 years and 6 months; about 4,500 children are in Pfizer’s trial, and about 7,000 in Moderna’s. A Pfizer official said in June that the first request for emergency authorization should be sent to the FDA in September or October. (Johnson & Johnson is only now beginning trials in teens and has not yet included younger kids.)

Those trials are scattered across medical centers in the US and several European countries—more sites than were initially planned for, according to several principal investigators, because the companies feel it’s urgent to gather data and move toward approval as rapidly as possible. That's because, now that adults can get vaccinated, children make up a larger proportion of those getting sick from Covid.

Kids represented 14.2 percent of all US cases in July, compared to 2 percent in April 2020, according to the American Academy of Pediatrics. Just in the US, more than 4 million children have fallen ill from Covid. And though most experience only mild illness, 16,623 had been hospitalized as of July 8, and 344 had died. As of the end of June, 4,196 children and teens had developed MIS-C, the perplexing and sometimes fatal inflammation that occurs after Covid infection and affects the heart, lungs, kidneys, and brain.

“Covid is a risk for children,” says Mark Sawyer, a professor of pediatrics at the UC San Diego School of Medicine and temporary voting member of the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), which reviewed evidence submitted on behalf of the Covid vaccines. “The reported deaths are at least as bad as the worst influenza season in terms of pediatric deaths, and probably a little worse than that. That doesn't even get us into what long-term consequences could occur, either from MIS-C or so-called long-haul Covid. And that doesn't even touch the public health argument, which is that we need children not to be bringing Covid to their grandparents and others who are at extremely high risk.”

As many researchers have pointed out over the years, children aren’t just small adults. Once past the teen years, adults have mostly achieved their final height and size—barring big gains or losses in fat and muscle—and, crucially, a settled immune balance with the world. But children are changing all the time, not just in size and muscle mass, but in how their immune systems defend them against the world.

“The spectrum and the strength of the immune response changes over years,” Inci Yildirim, a vaccinologist and associate professor of pediatrics and global health at the Yale School of Medicine, told WIRED by email. “For example, a healthy 13-month-old child usually has a higher number of lymphocytes, which is one of many components of the immune system playing a role in how we respond to the vaccines, compared with a healthy 15-year-old teenager.”

Even though we have data on how adults respond to the Covid vaccines—from the clinical trials that got the vaccines their emergency authorizations, and also from real-world observations—we can’t assume that children’s reactions will be the same. Weirdly, they might be better. For instance, after the introduction of the HPV vaccine (which prevents cancers of the cervix, neck, and throat), federal authorities decided that 9- to 14-year-olds need only two doses, not three as older teens and adults do, because the younger kids’ response to the vaccine was so strong.

But because Covid is still a new and under-researched disease, we have to do clinical trials to explore what those reactions might be. As the World Health Organization highlighted in a meeting in May, we still have not identified the “correlates of protection” that define immunity. Those would be agreed-upon metrics for immune response—a minimum number of antibodies, for instance, or measurements of the presence of T cells— that would indicate when someone who has received a vaccine is protected against infection. If we could define those correlates, we could skip placebo-controlled trials for head-to-head studies comparing different vaccines, or even use blood tests. Since we don’t, full trials in kids, patterned on the adult ones, are necessary.

“We should not simply recommend the vaccine for children because it's available for older age groups,” says Walter A. Orenstein, a physician and director of vaccine policy and development at Emory University, who previously led immunization programs at the Bill & Melinda Gates Foundation and the CDC. “We need to determine what the optimal doses are and look at what the safety factors are, so that the FDA has a reasonable data set upon which to make a judgment.”

And some safety issues have shown up. In June, the CDC disclosed that 226 people under 30, including 79 16- and 17-year-olds, had developed inflammation in or around their hearts after receiving the vaccine. The agency and its advisers examined the problem in a meeting of the Advisory Committee on Immunization Practices, but did not support any change in vaccine recommendations for teens.

Despite Covid vaccines being subjected to politicized controversy, the trials in younger children haven’t had any difficulty recruiting kids. “We had far more people interested than we have spaces,” says Kawsar Rasmy Talaat, a physician and associate professor of international health at the Johns Hopkins Bloomberg School of Public Health, where she leads a trial of the Pfizer vaccine for kids 12 and under. “Before we even knew we were a site, we had names on a list, parents who said, ‘If you do this, I want my kid to be in the study’—hundreds and hundreds of names.”

(Talaat and other principal investigators said many of the parents enrolling their kids turned out to be faculty from medical schools and other parts of universities conducting the trials, who happened to hear about the trials early because of their jobs. That could turn out to be a problem, because it may have accidentally created trial populations that are low on diversity—not necessarily of race or national origin, but of economic status and living conditions, both of which affected who was vulnerable during Covid’s first wave.)

Within the trials, child entrants are stratified—separated into groups—according to age ranges. The Stanford University School of Medicine, for instance, joined the Pfizer Phase I safety trial for infants and toddlers, who were divided into groups of kids between the ages of 6 months and 2 years, and then kids who were at least 2 but younger than 5. Stanford now is one of the sites hosting Phase II efficacy trials for the under-5 group, and also is running part of the Phase II and III trials for the 5- to 11-year-olds. (A Phase III trial also tests efficacy, but in a larger group, because some rare effects are only observable when more participants are added.)

The Pfizer trial those studies are part of is already returning information showing that the vaccines may create stronger immunity in kids than in adults, according to Yvonne Maldonado, a pediatrician and professor of epidemiology and population health and principal investigator of the Stanford trial site. “The first data that was put out in May, that was submitted to FDA, showed that the Pfizer vaccine had elicited much higher antibody titers in children than it did in adults,” Maldonado says. Those findings could well lead, in the final authorizations, to vaccines containing much smaller doses of active ingredients than are present in the adult vaccines.

Overall, it seems there have been no major setbacks. But there’s a difficult challenge approaching. Once trial data determining children’s doses and shot schedule passes the FDA—as either an emergency use authorization or a full new drug approval—the campaigns that distribute the shots will be run by the individual states, in the same way that the adult vaccines were. This spring, that was chaotic.

What might save the child vaccine, and the health of vulnerable elderly and immunocompromised people in contact with children, is that the system to distribute the shots won’t have to be built from scratch. American public health agencies already recommend that children and teens receive 16 different vaccines by the time they turn 18—against measles, mumps, rubella, diphtheria, pertussis, two types of hepatitis, rotavirus, chicken pox, flu, and so on—and many of those vaccines require multiple doses. A massive infrastructure delivers, tracks, and pays for those shots: physician practices, commercial pharmacies, health department clinics, and county health fairs; health department registries and state school-entry standards; private insurers and an array of federal buying programs. (Outside the US, the mix of funding comes from national governments and international philanthropies, and the vaccinators may be doctors’ offices, public health clinics, or volunteer-run sites.) Adding a Covid vaccine into that distribution would not be trivial, but it should not be impossibly hard.

“If you want to get vaccines out to a population, the most practical way to do that is through pediatric immunization,” says Ofer Levy, a pediatric infectious diseases clinician and director of the precision vaccines program at Boston Children’s Hospital, and also a temporary voting member of VRBPAC. “The majority of the world’s infrastructure for delivering vaccines is directed at children, and vaccines that are given to children around the globe get a population penetration of 80 percent to 90 percent.”


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