2022.05.27 你会再一次得COVID...再一次...再一次

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You Are Going to Get COVID Again … And Again … And Again
Will the danger mount each time, or will it fade away?

By Katherine J. Wu
Collage with an image of a women blowing her nose, repeated 7 times
Jamie Hodgson / Getty; The Atlantic
MAY 27, 2022, 11:29 AM ET
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Two and a half years and billions of estimated infections into this pandemic, SARS-CoV-2’s visit has clearly turned into a permanent stay. Experts knew from early on that, for almost everyone, infection with this coronavirus would be inevitable. As James Hamblin memorably put it back in February 2020, “You’re Likely to Get the Coronavirus.” By this point, in fact, most Americans have. But now, as wave after wave continues to pummel the globe, a grimmer reality is playing out. You’re not just likely to get the coronavirus. You’re likely to get it again and again and again.

“I personally know several individuals who have had COVID in almost every wave,” says Salim Abdool Karim, a clinical infectious-diseases epidemiologist and the director of the Center for the AIDS Program of Research in South Africa, which has experienced five meticulously tracked surges, and where just one-third of the population is vaccinated. Experts doubt that clip of reinfection—several times a year—will continue over the long term, given the continued ratcheting up of immunity and potential slowdown of variant emergence. But a more sluggish rate would still lead to lots of comeback cases. Aubree Gordon, an epidemiologist at the University of Michigan, told me that her best guess for the future has the virus infiltrating each of us, on average, every three years or so. “Barring some intervention that really changes the landscape,” she said, “we will all get SARS-CoV-2 multiple times in our life.”

If Gordon is right about this thrice(ish)-per-decade pace, that would be on par with what we experience with flu viruses, which scientists estimate hit us about every two to five years, less often in adulthood. It also matches up well with the documented cadence of the four other coronaviruses that seasonally trouble humans, and cause common colds. Should SARS-CoV-2 joins this mix of microbes that irk us on an intermittent schedule, we might not have to worry much. The fact that colds, flus, and stomach bugs routinely reinfect hasn’t shredded the social fabric. “For large portions of the population, this is an inconvenience,” Paul Thomas, an immunologist at St. Jude Children’s Research Hospital, in Tennessee, told me. Perhaps, as several experts have posited since the pandemic’s early days, SARS-CoV-2 will just become the fifth cold-causing coronavirus.

Or maybe not. This virus seems capable of tangling into just about every tissue in the body, affecting organs such as the heart, brain, liver, kidneys, and gut; it has already claimed the lives of millions, while saddling countless others with symptoms that can linger for months or years. Experts think the typical SARS-CoV-2 infection is likely to get less dangerous, as population immunity builds and broadens. But considering our current baseline, “less dangerous” could still be terrible—and it’s not clear exactly where we’re headed. When it comes to reinfection, we “just don’t know enough,” says Emily Landon, an infectious-disease physician at the University of Chicago.

Read: Coronavirus reinfection will soon become our reality

For now, every infection, and every subsequent reinfection, remains a toss of the dice. “Really, it’s a gamble,” says Ziyad Al-Aly, a clinical epidemiologist and long-COVID researcher at Washington University in St. Louis. Vaccination and infection-induced immunity may load the dice against landing on severe disease, but that danger will never go away completely, and scientists don’t yet know what happens to people who contract “mild” COVID over and over again. Bouts of illness may well be tempered over time, but multiple exposures could still re-up some of the same risks as before—or even synergize to exact a cumulative toll.

“Will reinfection be really bad, or not a big deal? I think you could fall down on either side,” says Vineet Menachery, a coronavirologist at the University of Texas Medical Branch. “There’s still a lot of gray.”

The majority of infections we witnessed in the pandemic’s early chapters were, of course, first ones. The virus was hitting a brand-new species, which had few defenses to block it. But people have been racking up vaccine doses and infections for years now; immunity is growing on a population scale. Most of us are “no longer starting from scratch,” says Talia Swartz, an infectious-disease physician, virologist, and immunologist at Mount Sinai’s Icahn School of Medicine. Bodies, wised up to the virus’s quirks, can now react more quickly, clobbering it with sharper and speedier strikes.

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Future versions of SARS-CoV-2 could continue to shape-shift out of existing antibodies’ reach, as coronaviruses often do. But the body is flush with other fighters that are much tougher to bamboozle—among them, B cells and T cells that can quash a growing infection before it spirals out of control. Those protections tend to build iteratively, as people see pathogens or vaccines more often. People vaccinated three times over, for instance, seem especially well equipped to duke it out with all sorts of SARS-CoV-2 variants, including Omicron and its offshoots.

Gordon, who is tracking large groups of people to study the risk of reinfection, is already starting to document promising patterns: Second infections and post-vaccination infections “are significantly less severe,” she told me, sometimes to the point where people don’t notice them at all. A third or fourth bout might be more muted still; the burden of individual diseases may be headed toward an asymptote of mildness that holds for many years. Gordon and Swartz are both hopeful that the slow accumulation of immunity will also slash people’s chances of developing long COVID. An initial round of vaccine doses seems to at least modestly trim the likelihood of coming down with the condition, and the risk may dwindle further as defenses continue to amass. (“We do need more data on that,” Gordon said.)

Read: The pandemic after the pandemic

Immunity, though, is neither binary nor permanent. Even if SARS-CoV-2’s assaults are blunted over time, there are no guarantees about the degree to which that happens, or how long it lasts. Maybe most future tussles with COVID will feel like nothing more than a shrimpy common cold. Or maybe they’ll end up like brutal flus. Wherever the average COVID case of the future lands, no two people’s experience of reinfection will be the same. Some may end up never getting sick again, at least not noticeably; others might find themselves falling ill much more frequently. A slew of factors could end up weighting the dice toward severe disease—among them, a person’s genetics, age, underlying medical conditions, health-care access, and frequency or magnitude of exposure to the virus. COVID redux could pose an especially big threat to people who are immunocompromised. And for everyone else, no amount of viral dampening can totally eliminate the chance, however small it may be, of getting very sick.

Long COVID, too, might remain a possibility with every discrete bout of illness. Or maybe the effects of a slow-but-steady trickle of minor, fast-resolving infections would sum together, and bring about the condition. Every time the body’s defenses are engaged, it “takes a lot of energy, and causes tissue damage,” Thomas told me. Should that become a near-constant barrage, “that’s probably not great for you.” But Swartz said she worries far more about that happening with viruses that chronically infect people, such as HIV. Bodies are resilient, especially when they’re offered time to rest, and she doubts that reinfection with a typically ephemeral virus such as SARS-CoV-2 would cause mounting damage. “The cumulative effect is more likely to be protective than detrimental,” she said, because of the immunity that’s laid down each time.


Al-Aly sees cause for worry either way. He is now running studies to track the long-term consequences of repeat encounters with the virus, and although the data are still emerging, he thinks that people who have caught the virus twice or thrice may be more likely to become long-haulers than those who have had it just once.

There’s still a lot about SARS-CoV-2, and the body’s response to it, that researchers don’t fully understand. Some other microbes, when they reinvade us, can fire up the immune system in unhelpful ways, driving bad bouts of inflammation that burn through the body, or duping certain defensive molecules into aiding, rather than blocking, the virus’s siege. Researchers don’t think SARS-CoV-2 will do the same. But this pathogen is “much more formidable than even someone working on coronaviruses would have expected,” Menachery told me. It could still reveal some new, insidious qualities down the line.

Studying reinfection isn’t easy: To home in on the phenomenon and its consequences, scientists have to monitor large groups of people over long periods of time, trying to catch as many viral invasions as possible, including asymptomatic ones that might not be picked up without very frequent testing. Seasonal encounters with pathogens other than SARS-CoV-2 don’t often worry us—but perhaps that’s because we’re still working to understand their toll. “Have we been underestimating long-term consequences from other repeat infections?” Thomas said. “The answer is probably, almost certainly, yes.”


Of the experts I spoke with for this story, several told me they hadn’t yet been knowingly infected by SARS-CoV-2; of those who had, none were eager for the sequel. Menachery is in the latter group. He was one of the first people in his community to catch the virus, back in March of 2020, when his entire family fell ill. That November, he discovered that he had lost most of his kidney function, a rapid deterioration that he and his doctors suspect, but cannot prove, was exacerbated by COVID. Menachery received a transplant three months ago, and has been taking immunosuppressive medications since—a major shift to his risk status, and his outlook on reinfection writ large. “So I wear my mask everywhere,” he told me, as do his wife and their three young kids. Should the virus return for him, it’s not totally clear what might happen next. “I’m nervous about reinfection,” he said. “I have reason to be.”

Almost no one can expect to avoid the virus altogether, but that doesn’t mean we can’t limit our exposures. It’s true that the body’s bulwarks against infection tend to erode rather rapidly; it’s true that this virus is very good at splintering into variants and subvariants that can hop over many of the antibodies we make. But the rhythm of reinfection isn’t just about the durability of immunity or the pace of viral evolution. It’s also about our actions and policies, and whether they allow the pathogen to transmit and evolve. Strategies to avoid infection—to make it as infrequent as possible, for as many people as possible—remain options, in the form of vaccination, masking, ventilation, paid sick leave, and more. “There are still very good reasons” to keep exposures few and far between, Landon, of the University of Chicago, told me. Putting off reinfection creates fewer opportunities for harm: The dice are less likely to land on severe disease (or chronic illness) when they’re rolled less often overall. It also buys us time to enhance our understanding of the virus, and improve our tools to fight it. “The more we know about COVID when we get COVID,” the better off we’ll be, she said.


Read: The coronavirus’s next move

SARS-CoV-2 may yet become another common-cold coronavirus, no more likely to screw with its hosts the fifth time it infects them than the first. But that’s no guarantee. The outlooks of the experts I spoke with spanned the range from optimism to pessimism, though all agreed that uncertainty loomed. Until we know more, none were keen to gamble with the virus—or with their own health. Any reinfection will likely still pose a threat, “even if it’s not the worst-case scenario,” Abdool Karim told me. “I wouldn’t want to put myself in that position.”

Katherine J. Wu is a staff writer at The Atlantic.




你会再一次得到COVID...再一次...再一次
每次的危险都会增加，还是会逐渐消失？

作者：Katherine J. Wu
一个女人擤鼻涕的图像拼贴画，重复了7次
Jamie Hodgson / Getty; The Atlantic
2022年5月27日，美国东部时间上午11:29

在这场大流行的两年半时间里，估计有数十亿的感染者，SARS-CoV-2的访问显然已经变成了永久性的停留。专家们很早就知道，对几乎所有人来说，感染这种冠状病毒将是不可避免的。正如詹姆斯-汉布林在2020年2月令人难忘地指出，"你很可能会感染冠状病毒"。到这时，事实上，大多数美国人都已经感染了。但是现在，随着一波又一波的浪潮继续冲击着全球，一个更严峻的现实正在上演。你不仅有可能感染冠状病毒。你很可能会一次又一次地感染它。

"萨利姆-阿卜杜勒-卡里姆（Salim Abdool Karim）说，他是一名临床传染病流行病学家，也是南非艾滋病研究项目中心的主任，南非已经经历了五次精心追踪的疫情，而那里只有三分之一的人口接种了疫苗。专家们怀疑，鉴于免疫力的持续增强和变异体出现的潜在放缓，一年几次的再感染片段将长期持续。但是，更缓慢的速度仍然会导致大量的复发病例。密歇根大学的流行病学家奥布里-戈登（Aubree Gordon）告诉我，她对未来的最佳猜测是，这种病毒平均每三年左右渗透到我们每个人身上。"她说："除非有某种干预措施真正改变了局面，否则我们都会在一生中多次感染SARS-CoV-2。"

如果戈登关于每十年三次的速度是正确的，这将与我们经历的流感病毒相提并论，科学家估计流感病毒大约每两到五年袭击我们一次，在成年后不那么频繁。这也与其他四种冠状病毒的记录节奏相吻合，这些冠状病毒季节性地困扰人类，并导致普通感冒。如果SARS-CoV-2加入到这种间歇性地困扰我们的微生物组合中，我们可能不必太担心。感冒、流行性感冒和胃病经常再感染的事实并没有破坏社会结构。"田纳西州圣裘德儿童研究医院的免疫学家保罗-托马斯告诉我，"对于大部分人来说，这只是一种不便。也许，正如几位专家从大流行的早期就提出的那样，SARS-CoV-2将只是成为第五种导致感冒的冠状病毒。

或者也许不是。这种病毒似乎能够与身体的每一个组织纠缠在一起，影响心脏、大脑、肝脏、肾脏和肠道等器官；它已经夺走了数百万人的生命，同时使无数人的症状持续数月或数年。专家们认为，随着人口免疫力的建立和扩大，典型的SARS-CoV-2感染可能会越来越不危险。但是考虑到我们目前的基线，"不那么危险 "仍然可能是可怕的--而且不清楚我们究竟要去哪里。当涉及到再感染时，我们 "知道的还不够多"，芝加哥大学的传染病医生Emily Landon说。

阅读。冠状病毒再感染将很快成为我们的现实

目前，每一次感染，以及随后的每一次再感染，仍然是一次掷骰子的过程。"圣路易斯华盛顿大学的临床流行病学家和长期从事COVID研究的Ziyad Al-Aly说："真的，这是一场赌博。疫苗接种和感染诱导的免疫力可能会使骰子不至于落在严重的疾病上，但这种危险永远不会完全消失，而且科学家们还不知道那些反复感染 "温和 "COVID的人会发生什么。随着时间的推移，疾病的发作可能会有所缓和，但多次接触仍可能重新增加一些与以前相同的风险，或者甚至协同作用，造成累积的损失。

"再感染是非常糟糕，还是没什么大不了的？我认为你可能会在任何一边倒下，"德克萨斯大学医学部的冠状动脉学专家Vineet Menachery说。"仍然有很多灰色"。

当然，我们在大流行的早期章节中看到的大多数感染是第一次感染。病毒袭击的是一个全新的物种，它没有什么防御措施来阻挡它。但是，人们已经累积了多年的疫苗剂量和感染；免疫力正在以人口规模增长。西奈山伊坎医学院的传染病医生、病毒学家和免疫学家塔利亚-斯瓦茨说，我们大多数人 "不再是从零开始"。对病毒的怪癖有所了解的身体，现在可以更迅速地做出反应，以更犀利、更快速的打击来打击它。

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未来版本的SARS-CoV-2可能会像冠状病毒经常做的那样，继续在现有抗体的范围外变形。但是身体里有其他更难对付的战士--其中包括B细胞和T细胞，它们可以在感染失控之前平息它的增长。这些保护措施往往是反复建立的，因为人们更经常地看到病原体或疫苗。例如，接种过三次疫苗的人似乎特别有能力与各种SARS-CoV-2变种，包括Omicron及其分支进行决斗。

戈登正在追踪大群人以研究再感染的风险，他已经开始记录有希望的模式。她告诉我，第二次感染和疫苗接种后的感染 "明显不那么严重"，有时人们根本注意不到它们。第三次或第四次感染可能会更加温和；个别疾病的负担可能会朝着温和的渐近点发展，并保持多年。戈登和斯沃茨都希望，免疫力的缓慢积累也将减少人们患上长期COVID的几率。最初一轮的疫苗剂量似乎至少可以适度降低患这种疾病的可能性，而且随着防御系统的不断积累，风险可能会进一步降低。("我们确实需要更多这方面的数据，"戈登说。)

阅读。大流行之后的大流行

不过，免疫力既不是二元的，也不是永久的。即使SARS-CoV-2的攻击随着时间的推移被削弱，也不能保证其发生的程度，或持续的时间。也许未来大多数与COVID的搏斗会感觉像一个小规模的普通感冒。也可能它们最终会像残酷的流感一样。无论未来COVID的平均病例落在哪里，没有两个人的再感染经历会是一样的。有些人可能最终不再生病，至少不会明显地生病；其他人可能发现自己生病的频率更高。一系列的因素最终可能使骰子向严重疾病倾斜--其中包括一个人的遗传学、年龄、潜在的医疗条件、卫生保健机会以及接触病毒的频率或程度。COVID复发可能对免疫力低下的人构成特别大的威胁。而对于其他人来说，无论多少病毒抑制措施都不能完全消除患重病的机会，无论这种机会有多小。

长时间的COVID，也可能在每一次不连续的疾病中保持一种可能性。或者，也许缓慢但稳定的小规模、快速解决的感染的影响会加在一起，并带来这种情况。托马斯告诉我，每次身体的防御系统被激活时，都会 "耗费大量的能量，并导致组织损伤。如果这成为一种近乎持续的攻击，"这对你来说可能不是好事"。但斯沃茨说，她更担心这种情况发生在长期感染人的病毒上，如艾滋病毒。身体是有弹性的，特别是当它们有时间休息的时候，她怀疑再次感染典型的短暂性病毒，如SARS-CoV-2，会造成越来越大的损害。她说："累积效应更有可能是保护性的，而不是破坏性的，"因为每次都会有免疫力。


Al-Aly认为无论如何都有理由担心。他现在正在进行研究，跟踪重复遭遇该病毒的长期后果，尽管数据仍在不断涌现，但他认为两次或三次感染该病毒的人可能比只感染过一次的人更有可能成为长途旅行者。

关于SARS-CoV-2，以及身体对它的反应，研究人员仍然有很多东西没有完全理解。一些其他的微生物，当它们重新侵入我们的时候，会以无益的方式激发免疫系统，推动炎症的恶性发作，烧毁整个身体，或者诱使某些防御分子协助而不是阻止病毒的围攻。研究人员不认为SARS-CoV-2会做同样的事情。但是这种病原体 "甚至比从事冠状病毒研究的人预期的要可怕得多"，Menachery告诉我。它仍然可能揭示出一些新的、阴险的特性。

研究再感染并不容易：为了掌握这一现象及其后果，科学家们必须长期监测大群人，试图捕捉尽可能多的病毒入侵，包括无症状的病毒，如果不进行非常频繁的测试，可能不会被发现。季节性遇到SARS-CoV-2以外的病原体并不经常让我们担心--但也许这是因为我们仍在努力了解其损失。"我们是否低估了其他重复感染的长期后果？" 托马斯说。"答案可能是，几乎肯定是，是的。"


在我为这个故事采访的专家中，有几个人告诉我他们还没有被SARS-CoV-2感染过；在那些已经感染过的人中，没有人渴望续集。梅纳切里属于后一类人。他是他所在社区最早感染病毒的人之一，早在2020年3月，他的全家人都病倒了。那年11月，他发现自己失去了大部分的肾脏功能，他和他的医生怀疑，但无法证明，这种迅速的恶化是由COVID加剧的。三个月前，Menachery接受了移植手术，此后一直在服用免疫抑制药物--这对他的风险状况以及他对再感染的前景来说是一个重大转变。"他告诉我："所以我在任何地方都戴着口罩，他的妻子和他们的三个孩子也一样。如果病毒重新回到他身上，还不完全清楚接下来会发生什么。"他说："我对重新感染感到紧张。"我有理由这么做。"

几乎没有人能够指望完全避免病毒，但这并不意味着我们不能限制我们的接触。诚然，身体抵抗感染的堡垒往往会迅速被侵蚀；诚然，这种病毒非常善于分裂成变体和亚变体，可以跳过我们制造的许多抗体。但是再感染的节奏不仅仅是关于免疫力的持久性或病毒进化的速度。它还关系到我们的行动和政策，以及它们是否允许病原体传播和进化。避免感染的策略--让尽可能多的人不被感染--仍然是选项，其形式包括疫苗接种、掩蔽、通风、带薪病假等等。芝加哥大学的兰登告诉我，"仍然有非常好的理由 "来保持很少和很远的接触。推迟再感染创造了更少的伤害机会。当骰子总体上被掷出的次数较少时，就不太可能落在严重的疾病（或慢性病）上。这也为我们赢得了时间，以加强我们对病毒的了解，并改进我们的工具来对抗它。她说："当我们得到COVID时，我们对COVID的了解越多，"我们就会越顺利。


阅读。冠状病毒的下一步行动

SARS-CoV-2可能还会成为另一种普通的感冒冠状病毒，在它第五次感染宿主时不会比第一次感染时更有可能破坏它们。但这并不能保证。与我交谈的专家们的前景从乐观到悲观不等，尽管他们都认为不确定性迫在眉睫。在我们了解更多情况之前，没有人热衷于拿病毒或自己的健康做赌注。任何再感染都可能构成威胁，"即使它不是最坏的情况，"阿卜杜勒-卡里姆告诉我。"我不想把自己放在那个位置上。"

凯瑟琳-J-吴是《大西洋》杂志的一名工作人员。