Coronavirus vaccines may not work in some people. It’s because of their underlying conditions.

冠状病毒疫苗可能对某些人不起作用。因为他们有潜在的疾病。

Early research shows that 15 to 80 percent of people with certain medical conditions, such as specific blood cancers or organ transplants, are generating few antibodies after receiving coronavirus vaccines.

早期研究表明,15%到80%患有某些疾病的人,比如特定的血癌或器官移植,在接受冠状病毒疫苗后产生的抗体很少。

By Ariana Eunjung Cha
May 18, 2021 at 8:00 p.m. GMT+8
Maria Hoffman feels as though she has been left behind. Her adopted hometown of Charleston, S.C., is hopping — with restaurants and bars fully open, park concerts in full swing and maskless friends reuniting with hugs on streets.

玛丽亚·霍夫曼觉得自己好像被留下了。她定居的家乡南卡罗来纳州查尔斯顿(Charleston,S.C.)正在跳动——餐馆和酒吧已全面开放,公园音乐会如火如荼地举行,没戴口罩的朋友们在街上拥抱团聚。

Hoffman, 39, is fully vaccinated and eager to rejoin the world. But as a kidney transplant patient, she is hesitant to participate for fear of becoming infected. “Risk is very different for people in my situation,” she said. “I am 100 percent acting like I am not immunized.”

39岁的霍夫曼已经接种了疫苗,渴望重返世界。但作为一名肾移植患者,她不敢参与,因为害怕被感染。“对于我在这种情况下,风险是完全不同的,”她说我百分之百表现得好像我没有接种疫苗。”

The state worker is among millions of immunocompromised Americans, about 3 to 4 percent of the U.S. population, for whom the shots may not work fully, or at all, and who are unsure of their place in a country that is increasingly opening up. Emerging research shows that 15 to 80 percent of those with certain conditions, such as specific blood cancers or who have had organ transplants, are generating few antibodies.

这名国家工作人员是数百万免疫功能低下的美国人中的一员,约占美国人口的3%至4%,对他们来说,注射可能无法完全奏效,或者根本无法奏效,他们不确定自己在一个日益开放的国家中的位置。新的研究表明,15%到80%的患有某些疾病的人,比如特定的血癌或接受过器官移植的人,产生的抗体很少。

Federal health officials’ decision last week to rescind almost all masking and distancing recommendations for those who are fully vaccinated only added to the sense of fear, isolation and confusion for those with immune issues. On Twitter and other social media platforms, many such patients expressed frustration that the change might leave them with less — not more — freedom as their risk of infection grows as more of their neighbors and co-workers ditch their masks.

联邦卫生官员上周决定撤销针对那些完全接种疫苗的人的口罩和距离建议,这会增加那些有免疫问题的人的恐惧感、孤立感和困惑感。在Twitter和其他社交媒体平台上,许多这样的患者表示沮丧,因为随着越来越多的邻居和同事扔掉口罩,他们感染的风险越来越大,这种改变可能会让他们的自由更少,而不是更多。

Hoffman, who has been advised by her doctors to act as though she never got the shots, recounted how she visited a grocery store Thursday but became anxious and left after a maskless man struck up a conversation.

医生建议霍夫曼要像从来没有打过针似的生活。霍夫曼讲述了她星期四去一家杂货店,但在一个没戴口罩的男人搭话后,她感到焦虑,于是离开了。

“I wear my mask out of respect for others, and for those who are sick,” she said. “If you aren’t wearing a mask, we can’t make you now.”

她说:“我戴口罩是为了尊重别人,也为了那些生病的人。”如果你没有戴口罩,我们不能强迫你。”

Vaccine makers excluded immunocompromised people from their clinical trials in an understandable rush to develop a way to protect as many people as quickly as possible. As a result, there’s limited information about how this group is reacting to the shots, as well as to the loosening of Centers for Disease Control and Prevention restrictions.

疫苗生产商将免疫功能低下的人排除在临床试验之外,这是可以理解的,他们急于开发一种能够尽快保护尽可能多的人的方法。因此,关于这一群体对疫苗注射以及疾病控制和预防中心放宽限制的反应的信息有限。

The ability of such patients to fend off the novel coronavirus is not just a footnote in the pandemic involving one unlucky group — but potentially a critical part of the narrative about how new, more contagious variants are continuing to emerge worldwide.

这类患者抵御新型冠状病毒的能力不仅是涉及一个不幸群体的大流行中的一个注脚,而且可能是叙述新的、更具传染性的变种如何在世界范围内继续出现的一个关键部分。

The interaction between immunocompromised people and the virus is perhaps one of the pandemic’s most fraught questions. Case studies have detailed how some patients can have active infections for many months — resulting in questions about whether they can act as incubators for mutations that lead to new variants and underscoring the need for an effective vaccine strategy not just for their sake, but for the greater good.

免疫功能低下的人和病毒之间的相互作用可能是大流行中最令人担忧的问题之一。案例研究详细说明了一些患者如何在数月内发生活动性感染,由此产生了一个问题,即他们是否可以充当导致新变异的突变的孵化器,并强调需要一种有效的疫苗策略,不仅是为了他们,而且是为了更大的利益。

CDC Director Rochelle Walensky and White House adviser Anthony S. Fauci highlighted the challenges of such patients and the vaccines in a recent news briefing in which they acknowledged that the first documented case of the so-called New York variant, B. 1.526, was found in a patient with advanced AIDS.

疾病控制中心主任罗谢尔瓦伦斯基和白宫顾问安东尼S。Fauci在最近的一次新闻简报中强调了这类患者和疫苗面临的挑战,他们在简报中承认,第一例有记载的所谓纽约变种B。1.526,在一名晚期艾滋病患者中发现。

“Early studies actually show that these variants could emerge in a single host — in a single immunocompromised host,” Walensky said.

沃伦斯基说:“早期的研究实际上表明,这些变异可能出现在一个单一的宿主身上——在一个免疫功能低下的宿主身上。”。

But neither the federal government nor vaccine makers Pfizer-BioNTech and Moderna has stepped up to do a comprehensive study about whether the vaccines protect people with immune issues. As such, most of the research has been conducted piecemeal in academic centers — and many are reaching differing, sometimes conflicting, conclusions.

但无论是联邦政府还是疫苗制造商辉瑞生物科技公司(Pfizer BioNTech)和摩德纳公司(Moderna)都没有加紧对疫苗是否能保护有免疫问题的人进行全面研究。因此,大多数研究都是在学术中心零零碎碎地进行的——许多研究得出了不同的、有时相互矛盾的结论。

Early data suggests that the vaccines offer some protection, although perhaps to a lesser degree, for most patients with HIV and autoimmune conditions such as rheumatoid arthritis. But there’s worry about people with blood cancers and transplant recipients. Some of the weakened response appears to be related to certain immunosuppressive drugs, and potentially a commonly prescribed steroid.

早期的数据表明,疫苗对大多数艾滋病患者和类风湿性关节炎等自身免疫性疾病有一定的保护作用,尽管保护程度可能较低。但是有人担心血癌患者和移植受者。一些减弱的反应似乎与某些免疫抑制药物有关,也可能与常用的类固醇有关。

“The overwhelming majority of transplant patients, even after a second dose of the vaccine, appear to have suboptimal protection — if any protection — from the vaccine, which is frightening, disappointing and a bit surprising,” said Dorry Segev, a researcher at the Johns Hopkins University School of Medicine.

约翰·霍普金斯大学医学院研究员多里·塞格夫说:“绝大多数移植患者,即使接种了第二剂疫苗,对疫苗的保护(如果有保护的话)似乎也不理想,这是令人恐惧、失望和有点惊讶的。”。

For most of the pandemic, Segev said, it was rare to see transplant recipients get sick with covid-19, the disease caused by the coronavirus, because they had been so careful about staying at home. But that changed over the past two months, with newly infected patients now coming in at a pace of nearly one each day, he said.

塞格夫说,在大流行的大部分时间里,很少看到移植受者感染冠状病毒引起的covid-19,因为他们一直非常小心地呆在家里。但在过去的两个月里,情况发生了变化,新感染的病人现在几乎每天都有一个。
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Many tell the same story: After being fully vaccinated, they had finally ventured out for a meal, reunited with family members or otherwise relaxed their social distancing precautions.

许多人讲述了同样的故事:在接种完疫苗后,他们终于冒险出去吃饭,与家人团聚,或者以其他方式放松社交距离的预防措施。
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“We expected a slightly blunted effect,” Segev said, “not something this stark.”

“我们预计会有一点减弱的影响,”塞格夫说,“不会有这么明显的影响。”

The good news, he and other researchers say, is that scientists are prepared with some potential solutions, such as boosters or high-dose shots. They just need to scramble to study them so they can offer them as soon as possible.

他和其他研究人员说,好消息是,科学家们已经准备好了一些可能的解决方案,比如助推器或高剂量注射。他们只需要迅速地研究它们,以便尽快提供它们。

Immune mystery

免疫之谜

The body’s immune system can be a capricious thing.

人体的免疫系统可能是一个反复无常的东西。

It can serve as a defensive shield one minute, and then shift into overdrive the next and attack itself. Many scientists believe that figuring out the puzzle of how the different components work together and how to control them is one of the holy grails of medicine that could lead to cures for many of the ills that plague humanity.

它可以在前一分钟充当防御盾牌,然后在下一分钟转换到超速档并攻击自己。许多科学家认为,找出不同成分如何协同工作以及如何控制它们的谜团,是能够治愈许多困扰人类的疾病的医学圣杯之一。

But compared with, say, the heart, researchers’ understanding of the immune system is still limited. They’ve long known, for example, that vaccines work better in some people than others but they are still trying to figure out why.

但与心脏相比,研究人员对免疫系统的了解仍然有限。例如,他们早就知道疫苗在某些人身上比在其他人身上效果更好,但他们仍在试图找出原因。
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From studying other vaccines, for instance, they know that age and underlying conditions can be factors. People older than 65 have been shown to produce 50 to 75 percent fewer antibodies in response to flu shots than their younger counterparts, which is why manufacturers produce a high-dose version for them. HIV patients often receive three hepatitis B shots, instead of two.

例如,通过对其他疫苗的研究,他们知道年龄和潜在条件可能是一个因素。研究表明,65岁以上的人注射流感疫苗后产生的抗体比年轻人少50%到75%,这就是为什么制造商为他们生产高剂量疫苗的原因。艾滋病患者通常接受三次乙肝疫苗注射,而不是两次。

Given this knowledge, some differences in the coronavirus vaccine response of immunocompromised people were expected.

鉴于这一知识,免疫功能低下人群的冠状病毒疫苗反应可能存在一些差异。

Most of the work has looked at only one facet of the immune response — the creation of antibodies, which are simple to measure with a blood test. Studies have mostly focused on the mRNA vaccines made by Pfizer-BioNTech and Moderna because they are most widely used.

大部分工作只关注了免疫反应的一个方面——抗体的产生,这很容易用血液测试来衡量。研究主要集中在辉瑞生物科技公司(Pfizer BioNTech)和Moderna公司生产的mRNA疫苗上,因为它们的应用最为广泛。

At the University of California at San Francisco, Monica Gandhi and her colleagues found that HIV patients seem to produce fewer antibodies on average, but she is optimistic that the amount is sufficient to protect most people.

在加州大学旧金山分校,莫妮卡·甘地和她的同事发现,艾滋病患者平均产生的抗体似乎较少,但她乐观地认为,这一数量足以保护大多数人。

She said one recent study showed that another arm of the immune system — T cells, or the white blood cells that fight infection — appear to respond to the vaccines similarly in both HIV patients and those without the disease.

她说,最近的一项研究表明,免疫系统的另一个分支——T细胞,或抗感染的白细胞——对艾滋病患者和无艾滋病患者的疫苗反应相似。

“With the antibody response being blunted, but the T-cell response not, it may mean more susceptibility to mild infection, but not likely severe disease,” she said.

她说:“抗体反应减弱,但T细胞反应没有减弱,这可能意味着更容易受到轻度感染,但不太可能是严重疾病。”。

Gandhi said that although more research is needed, the strong T-cell response may reflect how many people with HIV in the United States are quite healthy because they are treated with retroviral drugs. She said the situation may be different in Africa and other parts of the world for those not on treatment. She said she gave one of her vaccinated patients who had zero antibody response an extra dose of the Johnson & Johnson coronavirus vaccine.

甘地说,尽管还需要更多的研究,但强大的T细胞反应可能反映出美国有多少艾滋病毒感染者相当健康,因为他们接受了逆转录病毒药物治疗。她说,对于那些没有接受治疗的人来说,非洲和世界其他地区的情况可能不同。她说,她给一个抗体反应为零的接种过疫苗的病人额外注射了强生冠状病毒疫苗。

For most of her patients, however, she said she has “no concerns yet.”

然而,对于她的大多数病人,她说她“还没有担心”

“We are a very tightknit HIV community. We all talk, and would know if we were seeing a lot of breakthrough infections,” she said. “But fortunately we are not.”

“我们是一个非常紧密的艾滋病社区。她说:“我们都在交谈,如果有很多爆发性的感染,我们会知道。”但幸运的是我们没有。”

‘Disheartening’

'令人沮丧'
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The results have been more disappointing for some other types of immunocompromised patients.

对于其他类型的免疫功能低下患者来说,结果更令人失望。

Mounzer Agha, a hematologist at the University of Pittsburgh Medical Center and lead author of a study on blood cancers and the vaccines posted online before peer review, described how crushed he felt when he saw the low antibody results for nearly half of the 67 patients his group tracked.

匹兹堡大学医学中心的血液学专家、同行评议前在网上发布的一项关于血癌和疫苗的研究的主要作者Mounzer Agha描述了当他看到他的小组跟踪的67名患者中近一半的抗体水平低下时,他是多么的沮丧。

Patients on treatments that impact B-cell function appeared to have the weakest results. That made sense to him because B cells produce antibodies.

接受影响B细胞功能治疗的患者似乎效果最差。这对他来说是有意义的,因为B细胞产生抗体。

But the data also contained what he called an “unwelcome surprise”: Patients with a condition known as chronic lymphocytic leukemia had a very weak response even if they were not undergoing treatment. The condition, which affects the blood and bone marrow, can sometimes be asymptomatic.

但这些数据也包含了他所谓的“不受欢迎的惊喜”:患有慢性淋巴细胞白血病的患者即使没有接受治疗,反应也非常微弱。这种影响血液和骨髓的疾病有时是无症状的。
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“When I found patients who had never received therapy still did not respond to the vaccine, that was very disheartening,” he said. “Now what are you going to do for these individuals?”

他说:“当我发现从未接受过治疗的病人仍然对疫苗没有反应时,这是非常令人沮丧的。”现在你要为这些人做些什么?”

Agha said his clinic has been scrambling to reassess care plans in the context of the pandemic. Some patients who are more stable are taking cancer treatment “holidays” while they get the vaccine; others have opted to forgo the shots.

阿加说,他的诊所一直在迅速地重新评估大流行背景下的护理计划。一些病情较稳定的患者在接种疫苗的同时正在“休假”接受癌症治疗;其他人则选择放弃注射。

“The information has come out so recently that there are no clinical guidelines, and decisions have to be made on a case-by-case basis on the fly,” he said.

他说:“这些信息是最近才出来的,因此没有临床指南,必须在工作中根据具体情况作出决定。”。

Agha said he fears that for some patients, the vaccines may never work even at higher doses, and that they will have to rely on the inoculation of those around them for their safety.

阿加说,他担心,对一些病人来说,疫苗可能永远不会起作用,甚至在更高的剂量,他们将不得不依靠接种周围的人,他们的安全。

“Everyone should get the vaccine for the sake of their loved ones,” he urged. “Everyone knows someone who has cancer. And if you care about that person, you should get the vaccine and tell your friends to get it.”

“为了亲人,每个人都应该接种疫苗,”他敦促道每个人都知道有人得了癌症。如果你关心那个人,你应该接种疫苗,并告诉你的朋友接种。”

As for transplant patients, the early data are also concerning: A May 5 study published in JAMA found that 46 percent of 658 transplant patients did not mount an antibody response after two doses of the Pfizer-BioNTech or Moderna vaccines.

至于移植患者,早期的数据也涉及到:5月5日发表在JAMA的一项研究发现,658名移植患者中,46%的患者在两剂辉瑞BioNTech或Moderna疫苗后没有产生抗体反应。

“Although this study demonstrates an improvement in … antibody responses in transplant recipients after dose two … these data suggest that a substantial proportion of transplant recipients likely remain at risk for covid-19 after 2 doses of mRNA vaccine,” the researchers wrote. They think this lack of reaction is probably a result of the immunosuppressive drugs they take.

研究人员写道:“尽管这项研究表明,第二剂后,移植受者的抗体反应有所改善……但这些数据表明,相当一部分移植受者可能在第二剂mRNA疫苗后仍有感染covid-19的风险。”。他们认为这种缺乏反应可能是他们服用免疫抑制药物的结果。

Segev, a co-author, said that although antibody reaction is only part of the picture, “knowing what we know about immunosuppression, I would be surprised if transplant patients who had no antibody response had a robust T-cell response.”

合著者塞格夫说,虽然抗体反应只是其中的一部分,“了解我们对免疫抑制的了解,如果没有抗体反应的移植患者有强大的T细胞反应,我会感到惊讶。”
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“The irony of it all is transplant patients were being very, very careful,” he said, adding: “It’s a very scary problem.”

“讽刺的是,移植病人要非常非常小心,”他说,“这是一个非常可怕的问题。”

In St. Louis, Washington University’s Alfred Kim said that although the majority of patients with autoimmune conditions who were studied are mounting a healthy antibody response, about 15 percent had very blunted or undetectable antibody responses. The participants in the study had a wide range of illnesses, including inflammatory bowel disease, systemic lupus and rheumatoid arthritis.

在圣路易斯,华盛顿大学的Alfred Kim说,尽管被研究的大多数患有自身免疫疾病的患者都出现了健康的抗体反应,但大约15%的患者的抗体反应非常迟钝或无法检测到。参与研究的人患有多种疾病,包括炎症性肠病、系统性狼疮和类风湿性关节炎。

The original study, which has not yet been peer reviewed, was based on 133 people, but it has now grown to more than 300, with similar results.

最初的研究还没有经过同行评审,是以133人为研究对象的,但现在已经发展到300多人,结果相似。

As with the blood cancer study, many of those most severely affected were on B-cell-depleting medications, such as rituximab, used to treat certain autoimmune diseases and cancer, or ocrelizumab, a newer drug for multiple sclerosis.

与血癌研究一样,许多受影响最严重的患者服用了B细胞消耗药物,如用于治疗某些自身免疫性疾病和癌症的利妥昔单抗,或用于治疗多发性硬化症的新型药物奥列珠单抗。

Patients taking drugs for rheumatoid arthritis were likely to have a moderately reduced response.

服用类风湿性关节炎药物的患者可能会有中度的缓解。
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Kim, an assistant professor in the division of rheumatology, said one perplexing finding is that steroid use also appeared to diminish the vaccine response. Although he cautioned that only a small number of patients were involved, he said prednisone, which is used to treat such conditions as arthritis in adults and breathing difficulties in children, appeared to result in a tenfold reduction in antibody production, regardless of the dose given if administered around the time of the vaccine.

风湿病学系的助理教授Kim说,一个令人困惑的发现是类固醇的使用似乎也减少了疫苗的反应。尽管他提醒说,只有少数患者参与,但他说,用于治疗成人关节炎和儿童呼吸困难等疾病的强的松似乎会导致抗体产生量减少10倍,而不管疫苗接种前后给药的剂量是多少。

“Right now, we’re telling them to pretend they weren’t vaccinated,” Kim said. “That is the easiest solution but it’s only a short-term one. The step beyond is: What do we do to mitigate this?”

“现在,我们告诉他们要假装没有接种疫苗,”金说这是最简单的解决办法,但只是短期的。接下来的步骤是:我们该怎么做来缓解这种情况?”
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Boosting immunity

增强免疫力

Numerous potential solutions for the immunocompromised are being debated. One simple idea is to provide one or more booster shots for those with weak responses. So an immunocompromised person might get three doses of the Pfizer-BioNTech or Moderna vaccine, instead of two.

免疫功能低下的许多潜在解决方案正在辩论中。一个简单的想法是为那些反应较弱的人提供一个或多个助推器注射。所以一个免疫功能低下的人可能会得到三剂辉瑞生物技术或摩德纳疫苗,而不是两剂。

Another possibility is to try preventive doses of lab-produced antibody proteins known as monoclonal antibodies that until now have been mostly used as treatments for those who are infected with the coronavirus.

另一种可能性是尝试预防剂量的实验室产生的抗体蛋白,称为单克隆抗体,迄今为止,这些抗体主要用于治疗那些感染冠状病毒的人。

One thing doctors don’t recommend is for vaccinated people to get antibody tests. First of all, no one knows what levels of antibodies are effective against the virus. Moreover, Kim emphasized that antibodies are only one part of the immune system and that it’s possible that the vaccines have activated other, more difficult-to-measure components.

医生不推荐的一件事是让接种疫苗的人接受抗体检测。首先,没有人知道抗体的水平对病毒有效。此外,金先生强调,抗体只是免疫系统的一部分,疫苗可能激活了其他更难测量的成分。

“It’s not something that we can act on,” he said of such information. “All it can do is mount worries for the patient.”

“我们无法采取行动,”他谈到这些信息时说它所能做的就是为病人增加忧虑。”

Many physicians urge immunocompromised patients to continue to practice social distancing and take other precautions.

许多医生敦促免疫受损的患者继续进行社会隔离,并采取其他预防措施。

Seville Christian, 60, an HIV-positive substance abuse counselor in San Francisco, has been working in person through the pandemic and said she plans to continue to do so.

60岁的塞维利亚·克里斯蒂安是旧金山的艾滋病毒阳性药物滥用顾问,在这场流行病期间她一个人工作,她说她计划继续这样做。

But she said optional social outings will remain off the table. Even though she planned to get her second shot May 12, she will go to restaurants only for takeout, meet friends virtually and minimize her time in stores until the science is clearer.

但她说,社交活动会继续停止。尽管她计划5月12日打第二针疫苗,但她还是会去餐馆买外卖,尽量减少和朋友见面以及呆在商店里的时间,直到研究更清楚为止。

She’s still weighing whether return to her to church, fully masked, when it reopens.

她也考虑是否回到教堂,戴着口罩,当它重新开放的时候。

“I wish I could go back to normal, but there are still a lot of questions I have,” Christian said.

“我希望我能回到正常的状态,但我还有很多问题,”Christian说。

Hoffman, too, is struggling to navigate the new normal in Charleston. After having a kidney transplant at age 9 and spending most of her childhood in hospitals, she is acutely aware of her mortality. So she said she tries to find the right balance between living her life and staying safe.

霍夫曼也在努力适应在查尔斯顿的新常态。在9岁接受肾脏移植,并将大部分童年都花在医院后,她敏锐地意识到自己的死亡命运。所以她说她试图在生活和安全之间找到正确的平衡。

When a friend gets married in Ohio in a few weeks, she hopes to go and participate in the outdoor events. She is also talking to friends about reserving a socially distant spot for an outdoor band performance. But otherwise, she’s continuing to keep her distance from others.

当一个朋友会在俄亥俄州数周后结婚,她希望出去并参加这个户外活动。她还和朋友们谈论,为了看户外乐队表演预留一个社交距离较远的地点。否则,她将继续保持与他人的距离。

“I just love talking to people and meeting people,” she said. “It has been crazy and lonely.”

“我只是喜欢与人交谈以及认识别人。”她说,“这是疯狂和孤独。”