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實(shí)施第三劑新冠疫苗,要先考慮好這些問(wèn)題

Dana G. Smith
2021-09-13

通過(guò)加強(qiáng)劑的注射來(lái)提高群體免疫力似乎是一個(gè)簡(jiǎn)單的解決方案,但現(xiàn)實(shí)要復(fù)雜得多。

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注射加強(qiáng)劑疫苗與否,這是美國(guó)公共衛(wèi)生專(zhuān)家正在面臨的問(wèn)題。今年8月,拜登政府宣布,所有美國(guó)民眾將在9月底之前獲得額外的新冠疫苗。但這一構(gòu)想也只是初期階段,在聲明宣布之后,美國(guó)疾病控制中心(CDC)和美國(guó)食品與藥品管理局(FDA)也與白宮分道揚(yáng)鑣,稱其需要更多的數(shù)據(jù)才能夠做出決定。但是,這兩個(gè)機(jī)構(gòu)仍然建議免疫功能低下者注射加強(qiáng)針。

這個(gè)問(wèn)題的出現(xiàn)有著廣泛的背景:越來(lái)越多的證據(jù)表明,疫苗的有效性會(huì)隨著時(shí)間的推移而減弱。有研究表明,在完成疫苗接種之后,抗體水平逐漸下降,而這一降低與突破性感染風(fēng)險(xiǎn)增加呈現(xiàn)相關(guān)性。美國(guó)、英國(guó)和以色列的研究都顯示,接種疫苗后的時(shí)間越長(zhǎng),突破病例就越多。對(duì)抗體隱蔽性很強(qiáng)的德?tīng)査《咀凅w,也在今年夏天讓已經(jīng)接種完畢疫苗的人群中出現(xiàn)了不少突破性病例。

以色列是全球唯一一個(gè)為12歲以上的民眾推出大規(guī)模注射加強(qiáng)劑計(jì)劃的國(guó)家。最近兩篇尚未經(jīng)過(guò)同行評(píng)審的預(yù)印本論文顯示,第三劑輝瑞(Pfizer)疫苗提高了抗體水平,也提高了對(duì)感染的保護(hù)能力。事實(shí)也可以支撐這些結(jié)論:以色列似乎已經(jīng)在第三波疫情中轉(zhuǎn)危為安,過(guò)去兩周的新增病例比例已經(jīng)下降。

隨著德?tīng)査兎N毒株繼續(xù)在美國(guó)肆虐,通過(guò)加強(qiáng)劑的注射來(lái)提高群體免疫力似乎是一個(gè)簡(jiǎn)單的解決方案。但其實(shí),現(xiàn)實(shí)要復(fù)雜得多。

一方面,盡管疫苗對(duì)感染的保護(hù)能力隨著時(shí)間的推移而下降(據(jù)估計(jì)有效率最低只剩下50%),但對(duì)住院和死亡的保護(hù)仍然很強(qiáng),僅從此前平均的95%略微下降到了85%。來(lái)自美國(guó)和以色列的醫(yī)院數(shù)據(jù)證實(shí)了這一點(diǎn):這兩地的新冠肺炎住院病人大多數(shù)是尚未接種疫苗的人。

“有些人聽(tīng)到免疫力下降的新聞時(shí),他們會(huì)想:‘天哪,5、6個(gè)月后我就不再有任何免疫保護(hù)了,說(shuō)明疫苗根本不起作用。’但事實(shí)上數(shù)據(jù)并非如此?!辟e夕法尼亞大學(xué)(University of Pennsylvania)的生物統(tǒng)計(jì)學(xué)教授杰弗里·莫里斯說(shuō):“免疫保護(hù)的減弱,并不意味著消失。它尤其意味著對(duì)感染的抵抗力的減少。而至于重癥病例和住院病例,免疫保護(hù)并沒(méi)有真的減少多少?!?/p>

因此,有一個(gè)問(wèn)題一直存在爭(zhēng)議:是每個(gè)人都應(yīng)該注射第三劑,還是只應(yīng)該注射那些風(fēng)險(xiǎn)最高的人群?有一種支持全面加強(qiáng)劑注射的觀點(diǎn):免疫是一個(gè)數(shù)字游戲——盡管從統(tǒng)計(jì)上看,發(fā)展成重癥病例的可能性很小,但是,總體上感染的人數(shù)越多,住院和死亡的人數(shù)就會(huì)越多。通過(guò)在病例激增期間加強(qiáng)對(duì)感染的保護(hù),就能夠阻止病毒的傳播,從而控制重癥病例的人數(shù)。

以色列就是這么做的。盡管以色列的疫苗接種率很高,但是今年夏季仍然出現(xiàn)了病例激增,醫(yī)院不堪重負(fù)。作為回應(yīng),以色列衛(wèi)生部(Israeli Ministry of Health)強(qiáng)制幾乎所有符合條件的民眾注射了第三劑輝瑞疫苗。如果你沒(méi)有注射加強(qiáng)劑,你的疫苗護(hù)照(vaccine passport)將會(huì)過(guò)期。

“以色列陷入了病例負(fù)擔(dān)失控的危機(jī)之中,而這種情況現(xiàn)在才開(kāi)始得到控制。所以他們竭盡了全力?!泵绹?guó)斯克里普斯轉(zhuǎn)化研究所(Scripps Research Translational Institute)的所長(zhǎng)埃里克·托波爾稱,“我們知道,無(wú)論你多少歲,如果你接種了疫苗,而感染了突破病例,你仍然可以傳染給其他人。這種可能性比未接種疫苗要小得多,但為了打破這一傳染鏈,他們使出了渾身解數(shù)?,F(xiàn)在問(wèn)題是,我們也這樣做的話,美國(guó)也會(huì)受益嗎?這仍然是一個(gè)未知數(shù)?!?/p>

托波爾建議,與其向所有美國(guó)民眾提供加強(qiáng)注射,還不如先提供給那些受益最大的人——免疫功能低下者——60歲以上的老年人以及一線醫(yī)護(hù)人員。

“對(duì)60歲以上的人來(lái)說(shuō),提供加強(qiáng)劑的理由非常可靠……對(duì)衛(wèi)生保健工作者也是,因?yàn)樗麄冃枰疹櫜∪恕!彼f(shuō),“而除此之外,我們還沒(méi)有真正的數(shù)據(jù)……很有可能的是,隨著年齡的下探,注射加強(qiáng)劑帶來(lái)的好處會(huì)更少?!?/p>

以色列醫(yī)生、新冠咨詢團(tuán)隊(duì)前成員亞伊爾·劉易斯同意這個(gè)觀點(diǎn)。他認(rèn)為,第三劑疫苗不應(yīng)該針對(duì)每個(gè)人,而應(yīng)該只提供給最脆弱的人。其余人群能夠通過(guò)非藥物干預(yù)措施得到保護(hù),例如佩戴口罩、頻繁的核酸檢測(cè),以及接觸病毒后的隔離。

“從以色列疫情激增的情況來(lái)看,對(duì)高危人群進(jìn)行疫苗接種是非常重要的,這一點(diǎn)已經(jīng)接近共識(shí)。”劉易斯說(shuō),“對(duì)這一點(diǎn)我舉雙手贊成。但接下來(lái)的問(wèn)題是:‘剩下的所有人呢?’我可以代表我自己,我也能夠告訴你,其實(shí)很多和我交談過(guò)的同事都有類(lèi)似的想法——一些非藥物干預(yù)可能會(huì)更明智。”

此外,限制加強(qiáng)劑注射還有一個(gè)道德考量:疫苗劑量應(yīng)該留給接種率低得多的國(guó)家。另一個(gè)考量則是疫苗資源仍然應(yīng)該集中于未接種疫苗人群的接種。賓夕法尼亞大學(xué)的生物統(tǒng)計(jì)學(xué)家莫里斯擔(dān)心,需要第三劑疫苗會(huì)讓猶豫不決的人放棄接種疫苗,因?yàn)樗麄儠?huì)認(rèn)為(第三劑疫苗的接種)意味著疫苗沒(méi)那么有效。

“在先前接種過(guò)疫苗的免疫保護(hù)基礎(chǔ)上,增加一點(diǎn)點(diǎn),這很好。但如果這需要以不能使更多未接種疫苗的人得到保護(hù)為代價(jià),那這或許就會(huì)變成完全消極的一件事情?!彼f(shuō),“未接種疫苗的人即使只接種一劑疫苗,也比之前接種過(guò)疫苗的人接種第三劑疫苗,要更能減少傳播和重癥病例的風(fēng)險(xiǎn)?!保ㄘ?cái)富中文網(wǎng))

編譯:楊二一

注射加強(qiáng)劑疫苗與否,這是美國(guó)公共衛(wèi)生專(zhuān)家正在面臨的問(wèn)題。今年8月,拜登政府宣布,所有美國(guó)民眾將在9月底之前獲得額外的新冠疫苗。但這一構(gòu)想也只是初期階段,在聲明宣布之后,美國(guó)疾病控制中心(CDC)和美國(guó)食品與藥品管理局(FDA)也與白宮分道揚(yáng)鑣,稱其需要更多的數(shù)據(jù)才能夠做出決定。但是,這兩個(gè)機(jī)構(gòu)仍然建議免疫功能低下者注射加強(qiáng)針。

這個(gè)問(wèn)題的出現(xiàn)有著廣泛的背景:越來(lái)越多的證據(jù)表明,疫苗的有效性會(huì)隨著時(shí)間的推移而減弱。有研究表明,在完成疫苗接種之后,抗體水平逐漸下降,而這一降低與突破性感染風(fēng)險(xiǎn)增加呈現(xiàn)相關(guān)性。美國(guó)、英國(guó)和以色列的研究都顯示,接種疫苗后的時(shí)間越長(zhǎng),突破病例就越多。對(duì)抗體隱蔽性很強(qiáng)的德?tīng)査《咀凅w,也在今年夏天讓已經(jīng)接種完畢疫苗的人群中出現(xiàn)了不少突破性病例。

以色列是全球唯一一個(gè)為12歲以上的民眾推出大規(guī)模注射加強(qiáng)劑計(jì)劃的國(guó)家。最近兩篇尚未經(jīng)過(guò)同行評(píng)審的預(yù)印本論文顯示,第三劑輝瑞(Pfizer)疫苗提高了抗體水平,也提高了對(duì)感染的保護(hù)能力。事實(shí)也可以支撐這些結(jié)論:以色列似乎已經(jīng)在第三波疫情中轉(zhuǎn)危為安,過(guò)去兩周的新增病例比例已經(jīng)下降。

隨著德?tīng)査兎N毒株繼續(xù)在美國(guó)肆虐,通過(guò)加強(qiáng)劑的注射來(lái)提高群體免疫力似乎是一個(gè)簡(jiǎn)單的解決方案。但其實(shí),現(xiàn)實(shí)要復(fù)雜得多。

一方面,盡管疫苗對(duì)感染的保護(hù)能力隨著時(shí)間的推移而下降(據(jù)估計(jì)有效率最低只剩下50%),但對(duì)住院和死亡的保護(hù)仍然很強(qiáng),僅從此前平均的95%略微下降到了85%。來(lái)自美國(guó)和以色列的醫(yī)院數(shù)據(jù)證實(shí)了這一點(diǎn):這兩地的新冠肺炎住院病人大多數(shù)是尚未接種疫苗的人。

“有些人聽(tīng)到免疫力下降的新聞時(shí),他們會(huì)想:‘天哪,5、6個(gè)月后我就不再有任何免疫保護(hù)了,說(shuō)明疫苗根本不起作用?!聦?shí)上數(shù)據(jù)并非如此?!辟e夕法尼亞大學(xué)(University of Pennsylvania)的生物統(tǒng)計(jì)學(xué)教授杰弗里·莫里斯說(shuō):“免疫保護(hù)的減弱,并不意味著消失。它尤其意味著對(duì)感染的抵抗力的減少。而至于重癥病例和住院病例,免疫保護(hù)并沒(méi)有真的減少多少?!?/p>

因此,有一個(gè)問(wèn)題一直存在爭(zhēng)議:是每個(gè)人都應(yīng)該注射第三劑,還是只應(yīng)該注射那些風(fēng)險(xiǎn)最高的人群?有一種支持全面加強(qiáng)劑注射的觀點(diǎn):免疫是一個(gè)數(shù)字游戲——盡管從統(tǒng)計(jì)上看,發(fā)展成重癥病例的可能性很小,但是,總體上感染的人數(shù)越多,住院和死亡的人數(shù)就會(huì)越多。通過(guò)在病例激增期間加強(qiáng)對(duì)感染的保護(hù),就能夠阻止病毒的傳播,從而控制重癥病例的人數(shù)。

以色列就是這么做的。盡管以色列的疫苗接種率很高,但是今年夏季仍然出現(xiàn)了病例激增,醫(yī)院不堪重負(fù)。作為回應(yīng),以色列衛(wèi)生部(Israeli Ministry of Health)強(qiáng)制幾乎所有符合條件的民眾注射了第三劑輝瑞疫苗。如果你沒(méi)有注射加強(qiáng)劑,你的疫苗護(hù)照(vaccine passport)將會(huì)過(guò)期。

“以色列陷入了病例負(fù)擔(dān)失控的危機(jī)之中,而這種情況現(xiàn)在才開(kāi)始得到控制。所以他們竭盡了全力?!泵绹?guó)斯克里普斯轉(zhuǎn)化研究所(Scripps Research Translational Institute)的所長(zhǎng)埃里克·托波爾稱,“我們知道,無(wú)論你多少歲,如果你接種了疫苗,而感染了突破病例,你仍然可以傳染給其他人。這種可能性比未接種疫苗要小得多,但為了打破這一傳染鏈,他們使出了渾身解數(shù)。現(xiàn)在問(wèn)題是,我們也這樣做的話,美國(guó)也會(huì)受益嗎?這仍然是一個(gè)未知數(shù)?!?/p>

托波爾建議,與其向所有美國(guó)民眾提供加強(qiáng)注射,還不如先提供給那些受益最大的人——免疫功能低下者——60歲以上的老年人以及一線醫(yī)護(hù)人員。

“對(duì)60歲以上的人來(lái)說(shuō),提供加強(qiáng)劑的理由非??煽俊瓕?duì)衛(wèi)生保健工作者也是,因?yàn)樗麄冃枰疹櫜∪??!彼f(shuō),“而除此之外,我們還沒(méi)有真正的數(shù)據(jù)……很有可能的是,隨著年齡的下探,注射加強(qiáng)劑帶來(lái)的好處會(huì)更少?!?/p>

以色列醫(yī)生、新冠咨詢團(tuán)隊(duì)前成員亞伊爾·劉易斯同意這個(gè)觀點(diǎn)。他認(rèn)為,第三劑疫苗不應(yīng)該針對(duì)每個(gè)人,而應(yīng)該只提供給最脆弱的人。其余人群能夠通過(guò)非藥物干預(yù)措施得到保護(hù),例如佩戴口罩、頻繁的核酸檢測(cè),以及接觸病毒后的隔離。

“從以色列疫情激增的情況來(lái)看,對(duì)高危人群進(jìn)行疫苗接種是非常重要的,這一點(diǎn)已經(jīng)接近共識(shí)。”劉易斯說(shuō),“對(duì)這一點(diǎn)我舉雙手贊成。但接下來(lái)的問(wèn)題是:‘剩下的所有人呢?’我可以代表我自己,我也能夠告訴你,其實(shí)很多和我交談過(guò)的同事都有類(lèi)似的想法——一些非藥物干預(yù)可能會(huì)更明智。”

此外,限制加強(qiáng)劑注射還有一個(gè)道德考量:疫苗劑量應(yīng)該留給接種率低得多的國(guó)家。另一個(gè)考量則是疫苗資源仍然應(yīng)該集中于未接種疫苗人群的接種。賓夕法尼亞大學(xué)的生物統(tǒng)計(jì)學(xué)家莫里斯擔(dān)心,需要第三劑疫苗會(huì)讓猶豫不決的人放棄接種疫苗,因?yàn)樗麄儠?huì)認(rèn)為(第三劑疫苗的接種)意味著疫苗沒(méi)那么有效。

“在先前接種過(guò)疫苗的免疫保護(hù)基礎(chǔ)上,增加一點(diǎn)點(diǎn),這很好。但如果這需要以不能使更多未接種疫苗的人得到保護(hù)為代價(jià),那這或許就會(huì)變成完全消極的一件事情。”他說(shuō),“未接種疫苗的人即使只接種一劑疫苗,也比之前接種過(guò)疫苗的人接種第三劑疫苗,要更能減少傳播和重癥病例的風(fēng)險(xiǎn)?!保ㄘ?cái)富中文網(wǎng))

編譯:楊二一

To booster or not to booster, that is the question facing U.S. public health experts. In August, the Biden administration announced that all Americans would have access to an additional vaccine dose for COVID-19 by the end of September. But the declaration was premature, and the CDC and FDA have since split with the White House, saying they need more data before making the decision. (Both agencies still recommend that people who are immunocompromised get a booster shot.)

The question comes as evidence mounts that vaccine effectiveness does wane over time. Studies have shown that antibody levels gradually decline after vaccination, and lower antibody levels are associated with a higher risk of breakthrough infection. Research from the U.S., the U.K., and Israel all show an increase in breakthroughs the more time has passed since vaccination—although the Delta variant, which is more likely to evade antibodies, also played a role in the rise in cases among vaccinated people this summer.

In Israel, the only country to roll out a mass booster initiative for everyone over the age of 12, two recent preprint papers—which have not yet been peer reviewed—show that a third dose of the Pfizer vaccine raises antibody levels and improves protection against infection. Backing up the research, the country appears to have turned the corner on its third wave, and case rates have dropped for the past two weeks.

As Delta continues to wreak havoc in the U.S., boosting people’s immunity with a third shot seems like an easy solution. But the reality is more complicated.

For one thing, while vaccine protection against infection declines over time, by some estimates bottoming out around 50%, protection against hospitalization and death remains high, dipping only slightly from an average of 95% to 85%. Hospital data from the U.S. and Israel bear this out, where the vast majority of beds are taken up by people who are still unvaccinated.

“I think some people, when they hear waning immunity, they think, ‘Oh no, after five or six months, I no longer have any immune protection. The vaccine doesn't work at all.’ But the data doesn’t say that,” says Jeffrey Morris, a professor of biostatistics at the University of Pennsylvania. “The waning immune protection doesn’t mean it’s gone, it just means that it’s decreased, especially against infection. And when we look against severe disease and hospitalization, we don’t really see much waning there at all.”

As a result, one ongoing debate is whether everyone should get a third dose or only the groups that have the highest risk. An argument in favor of booster shots for all is that, in many ways, immunity is a numbers game. Even if the statistical likelihood of developing severe disease is small, the more people who are infected overall, the more hospitalizations and deaths there will be. By increasing protection against infection during a surge, you will stop the spread of the virus, and in turn limit the number of people with serious illness.

That was the rationale in Israel, where a surge in cases this summer overwhelmed hospitals despite a high vaccination rate. In response, the Israeli Ministry of Health all but mandated a third dose of the Pfizer vaccine for everyone who was eligible—if you didn’t get your booster shot, your vaccine passport expired.

“Israel has been kind of in a crisis with a runaway case burden, which is only now starting to get under control, so they pulled out all the stops,” says Eric Topol, director of the Scripps Research Translational Institute. “We know that if you’re at any age, if you’re vaccinated and you get a breakthrough, you still can transmit to others. The chances are much less than if you were unvaccinated, but to break the chain, they pulled out all the stops. The question is, would we benefit in the U.S. by doing that? And that’s an unknown.”

Instead of offering booster shots to all Americans, Topol suggests limiting eligibility to those who would benefit the most: people who are immunocompromised, over the age of 60, or frontline health care workers.

“I think the booster case is very solid now for people over age 60…and you can also make a pretty strong case for health care workers because they need to be taking care of the sick,” he says. “After that, we don’t really have data yet…but there’s going to be a lesser net benefit of the boosters, most likely, as we go down in age.”

Yair Lewis, an Israeli physician and former member of the country’s COVID-19 advisory team, agrees. Instead of boosting everybody’s antibody levels, he says a third dose should only be offered to the most vulnerable. The rest of the population should be protected through nonpharmaceutical interventions, such as masking, frequent testing, and quarantining after exposure to the virus.

“I think there was close to a consensus that from the way the surge was going on in Israel, it was really important to vaccinate the high-risk populations,” Lewis says. “I definitely supported that. Then there came the issue. ‘Okay, so are we going to boost the entire population?’ And I can speak for myself—I can also tell you that a lot of the colleagues I’ve spoken with think something similar—is that it probably would have been wiser to enforce some sort of light NPI, some nonpharmaceutical interventions.”

One reason for restricting booster shots is the ethical argument that the doses should be saved for countries where vaccination rates are much lower. Another is that resources should still be focused on improving uptake among those who remain unvaccinated. Morris, the UPenn biostatistician, worries that requiring a third dose will dissuade people who are on the fence from getting a vaccine because they’ll interpret it as meaning the vaccines aren’t very effective.

“To get some benefit from just supercharging a little bit of the immune protection that the previously vaccinated already has is nice, but if it comes at the cost of not being able to get more of the unvaccinated to be protected, it could be a net negative,” he says. “Getting even one dose in an unvaccinated person will reduce transmission and risk of serious disease way more than getting a third dose in a previously [vaccinated] person.”

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