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實施第三劑新冠疫苗,要先考慮好這些問題

Dana G. Smith
2021-09-13

通過加強劑的注射來提高群體免疫力似乎是一個簡單的解決方案,但現實要復雜得多。

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注射加強劑疫苗與否,這是美國公共衛生專家正在面臨的問題。今年8月,拜登政府宣布,所有美國民眾將在9月底之前獲得額外的新冠疫苗。但這一構想也只是初期階段,在聲明宣布之后,美國疾病控制中心(CDC)和美國食品與藥品管理局(FDA)也與白宮分道揚鑣,稱其需要更多的數據才能夠做出決定。但是,這兩個機構仍然建議免疫功能低下者注射加強針。

這個問題的出現有著廣泛的背景:越來越多的證據表明,疫苗的有效性會隨著時間的推移而減弱。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險增加呈現相關性。美國、英國和以色列的研究都顯示,接種疫苗后的時間越長,突破病例就越多。對抗體隱蔽性很強的德爾塔病毒變體,也在今年夏天讓已經接種完畢疫苗的人群中出現了不少突破性病例。

以色列是全球唯一一個為12歲以上的民眾推出大規模注射加強劑計劃的國家。最近兩篇尚未經過同行評審的預印本論文顯示,第三劑輝瑞(Pfizer)疫苗提高了抗體水平,也提高了對感染的保護能力。事實也可以支撐這些結論:以色列似乎已經在第三波疫情中轉危為安,過去兩周的新增病例比例已經下降。

隨著德爾塔變種毒株繼續在美國肆虐,通過加強劑的注射來提高群體免疫力似乎是一個簡單的解決方案。但其實,現實要復雜得多。

一方面,盡管疫苗對感染的保護能力隨著時間的推移而下降(據估計有效率最低只剩下50%),但對住院和死亡的保護仍然很強,僅從此前平均的95%略微下降到了85%。來自美國和以色列的醫院數據證實了這一點:這兩地的新冠肺炎住院病人大多數是尚未接種疫苗的人。

“有些人聽到免疫力下降的新聞時,他們會想:‘天哪,5、6個月后我就不再有任何免疫保護了,說明疫苗根本不起作用。’但事實上數據并非如此。”賓夕法尼亞大學(University of Pennsylvania)的生物統計學教授杰弗里·莫里斯說:“免疫保護的減弱,并不意味著消失。它尤其意味著對感染的抵抗力的減少。而至于重癥病例和住院病例,免疫保護并沒有真的減少多少。”

因此,有一個問題一直存在爭議:是每個人都應該注射第三劑,還是只應該注射那些風險最高的人群?有一種支持全面加強劑注射的觀點:免疫是一個數字游戲——盡管從統計上看,發展成重癥病例的可能性很小,但是,總體上感染的人數越多,住院和死亡的人數就會越多。通過在病例激增期間加強對感染的保護,就能夠阻止病毒的傳播,從而控制重癥病例的人數。

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了病例激增,醫院不堪重負。作為回應,以色列衛生部(Israeli Ministry of Health)強制幾乎所有符合條件的民眾注射了第三劑輝瑞疫苗。如果你沒有注射加強劑,你的疫苗護照(vaccine passport)將會過期。

“以色列陷入了病例負擔失控的危機之中,而這種情況現在才開始得到控制。所以他們竭盡了全力。”美國斯克里普斯轉化研究所(Scripps Research Translational Institute)的所長埃里克·托波爾稱,“我們知道,無論你多少歲,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。現在問題是,我們也這樣做的話,美國也會受益嗎?這仍然是一個未知數。”

托波爾建議,與其向所有美國民眾提供加強注射,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護人員。

“對60歲以上的人來說,提供加強劑的理由非常可靠……對衛生保健工作者也是,因為他們需要照顧病人。”他說,“而除此之外,我們還沒有真正的數據……很有可能的是,隨著年齡的下探,注射加強劑帶來的好處會更少。”

以色列醫生、新冠咨詢團隊前成員亞伊爾·劉易斯同意這個觀點。他認為,第三劑疫苗不應該針對每個人,而應該只提供給最脆弱的人。其余人群能夠通過非藥物干預措施得到保護,例如佩戴口罩、頻繁的核酸檢測,以及接觸病毒后的隔離。

“從以色列疫情激增的情況來看,對高危人群進行疫苗接種是非常重要的,這一點已經接近共識。”劉易斯說,“對這一點我舉雙手贊成。但接下來的問題是:‘剩下的所有人呢?’我可以代表我自己,我也能夠告訴你,其實很多和我交談過的同事都有類似的想法——一些非藥物干預可能會更明智。”

此外,限制加強劑注射還有一個道德考量:疫苗劑量應該留給接種率低得多的國家。另一個考量則是疫苗資源仍然應該集中于未接種疫苗人群的接種。賓夕法尼亞大學的生物統計學家莫里斯擔心,需要第三劑疫苗會讓猶豫不決的人放棄接種疫苗,因為他們會認為(第三劑疫苗的接種)意味著疫苗沒那么有效。

“在先前接種過疫苗的免疫保護基礎上,增加一點點,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為代價,那這或許就會變成完全消極的一件事情。”他說,“未接種疫苗的人即使只接種一劑疫苗,也比之前接種過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險。”(財富中文網)

編譯:楊二一

注射加強劑疫苗與否,這是美國公共衛生專家正在面臨的問題。今年8月,拜登政府宣布,所有美國民眾將在9月底之前獲得額外的新冠疫苗。但這一構想也只是初期階段,在聲明宣布之后,美國疾病控制中心(CDC)和美國食品與藥品管理局(FDA)也與白宮分道揚鑣,稱其需要更多的數據才能夠做出決定。但是,這兩個機構仍然建議免疫功能低下者注射加強針。

這個問題的出現有著廣泛的背景:越來越多的證據表明,疫苗的有效性會隨著時間的推移而減弱。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險增加呈現相關性。美國、英國和以色列的研究都顯示,接種疫苗后的時間越長,突破病例就越多。對抗體隱蔽性很強的德爾塔病毒變體,也在今年夏天讓已經接種完畢疫苗的人群中出現了不少突破性病例。

以色列是全球唯一一個為12歲以上的民眾推出大規模注射加強劑計劃的國家。最近兩篇尚未經過同行評審的預印本論文顯示,第三劑輝瑞(Pfizer)疫苗提高了抗體水平,也提高了對感染的保護能力。事實也可以支撐這些結論:以色列似乎已經在第三波疫情中轉危為安,過去兩周的新增病例比例已經下降。

隨著德爾塔變種毒株繼續在美國肆虐,通過加強劑的注射來提高群體免疫力似乎是一個簡單的解決方案。但其實,現實要復雜得多。

一方面,盡管疫苗對感染的保護能力隨著時間的推移而下降(據估計有效率最低只剩下50%),但對住院和死亡的保護仍然很強,僅從此前平均的95%略微下降到了85%。來自美國和以色列的醫院數據證實了這一點:這兩地的新冠肺炎住院病人大多數是尚未接種疫苗的人。

“有些人聽到免疫力下降的新聞時,他們會想:‘天哪,5、6個月后我就不再有任何免疫保護了,說明疫苗根本不起作用。’但事實上數據并非如此。”賓夕法尼亞大學(University of Pennsylvania)的生物統計學教授杰弗里·莫里斯說:“免疫保護的減弱,并不意味著消失。它尤其意味著對感染的抵抗力的減少。而至于重癥病例和住院病例,免疫保護并沒有真的減少多少。”

因此,有一個問題一直存在爭議:是每個人都應該注射第三劑,還是只應該注射那些風險最高的人群?有一種支持全面加強劑注射的觀點:免疫是一個數字游戲——盡管從統計上看,發展成重癥病例的可能性很小,但是,總體上感染的人數越多,住院和死亡的人數就會越多。通過在病例激增期間加強對感染的保護,就能夠阻止病毒的傳播,從而控制重癥病例的人數。

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了病例激增,醫院不堪重負。作為回應,以色列衛生部(Israeli Ministry of Health)強制幾乎所有符合條件的民眾注射了第三劑輝瑞疫苗。如果你沒有注射加強劑,你的疫苗護照(vaccine passport)將會過期。

“以色列陷入了病例負擔失控的危機之中,而這種情況現在才開始得到控制。所以他們竭盡了全力。”美國斯克里普斯轉化研究所(Scripps Research Translational Institute)的所長埃里克·托波爾稱,“我們知道,無論你多少歲,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。現在問題是,我們也這樣做的話,美國也會受益嗎?這仍然是一個未知數。”

托波爾建議,與其向所有美國民眾提供加強注射,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護人員。

“對60歲以上的人來說,提供加強劑的理由非常可靠……對衛生保健工作者也是,因為他們需要照顧病人。”他說,“而除此之外,我們還沒有真正的數據……很有可能的是,隨著年齡的下探,注射加強劑帶來的好處會更少。”

以色列醫生、新冠咨詢團隊前成員亞伊爾·劉易斯同意這個觀點。他認為,第三劑疫苗不應該針對每個人,而應該只提供給最脆弱的人。其余人群能夠通過非藥物干預措施得到保護,例如佩戴口罩、頻繁的核酸檢測,以及接觸病毒后的隔離。

“從以色列疫情激增的情況來看,對高危人群進行疫苗接種是非常重要的,這一點已經接近共識。”劉易斯說,“對這一點我舉雙手贊成。但接下來的問題是:‘剩下的所有人呢?’我可以代表我自己,我也能夠告訴你,其實很多和我交談過的同事都有類似的想法——一些非藥物干預可能會更明智。”

此外,限制加強劑注射還有一個道德考量:疫苗劑量應該留給接種率低得多的國家。另一個考量則是疫苗資源仍然應該集中于未接種疫苗人群的接種。賓夕法尼亞大學的生物統計學家莫里斯擔心,需要第三劑疫苗會讓猶豫不決的人放棄接種疫苗,因為他們會認為(第三劑疫苗的接種)意味著疫苗沒那么有效。

“在先前接種過疫苗的免疫保護基礎上,增加一點點,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為代價,那這或許就會變成完全消極的一件事情。”他說,“未接種疫苗的人即使只接種一劑疫苗,也比之前接種過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險。”(財富中文網)

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.”

財富中文網所刊載內容之知識產權為財富媒體知識產權有限公司及/或相關權利人專屬所有或持有。未經許可,禁止進行轉載、摘編、復制及建立鏡像等任何使用。
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