美國2020年年底推出的新冠病毒RNA疫苗,已經在數億民眾中使用。從各國的大數據看,其效果明顯好過以前舊技術開發的病毒疫苗, 當然無論從抗體產生的水平和實際效果看, 也明顯好過其它地區開發的減毒滅毒,載體病毒疫苗等。不可否認,所有的疫苗都有大小不等的毒副作用。曆史上, 不乏疫苗造成弊大於利的例證, 但近代多種疫苗的出現, 大大改善了人類的生存和壽命的延長, 利遠遠大於弊。如果算上二,三期的臨床測試, 加上近一年來在數億民眾間的廣泛使用, RNA疫苗總體測試時間已經超過18個月。新冠RNA疫苗的安全性在絕大多數人身上,無可質疑。但目前大眾關心的話題是, 新冠RNA疫苗的免疫保護力究竟能維持多久? 已有不少報道, 揭示在許多被注射疫苗的人身上, 免疫保護力持續地衰減,所以產生了不少疫苗效應被”突破”後而感染的病例。
換句話說, 疫苗保護的效率在幾個月後,已經不是超過90%的有效性了。具體詳情, 目前沒有人能完全掌握。而據新加坡的報道, 新冠疫苗在不同年齡層的保護性差異極大。年輕人多數天然免疫力良好, 打不打疫苗, 死亡率差距不甚巨大;而超過80歲的人, 大多免疫力較差, 甚至各種疾病纏身, 疫苗的免疫保護力常常大打折扣。據未公開的大數據報道, 60-70歲階層的疫苗大體保護力較其它年齡組為佳,施打疫苗與未注射者相比, 總體上,感染後病死率可降低大約50倍的機會。但落實到具體個人,身體情況可能有差異。有報道指出年長者,產生的抗體低而且衰減快, 癌症病人, 器官移植者, 免疫病患者等, 還有不確定的原因造成的免疫反應低下,均可能需要打第三針來加強免疫保護。
冬季已經到了, 天氣漸涼。第二針的疫苗已注射超過半年, 我身體健康, 是否需要再打第三針呢?
除非利大於弊, 我不想盲目地注射異物在身上。在專家的指導下,本人半年前曾在第二針注射兩周後, 測試了疫苗產生的對抗新冠病毒的抗體水平,自己也做了一些研究。目前官方尚未得出最後的結論, 即抗體水平高低與免疫力強弱間的直接關係。這個結論需要長時間, 大數據的觀察, 和最後的多方的科學認定。現有的知識已經知道,在許多感染疾病中,抗體水平是產生免疫力保護的關鍵因素。此外,還有細胞免疫的抗病毒作用。但後者的測定和商業化運作,不如抗體測定的研究和發展。據資料顯示, 至少已有四家公司的抗體檢測, 已經獲得FDA的緊急使用授權。當然,世界上已有無數的廠家和醫療機構開發了抗體檢測服務。不同機構的結果報告,不可直接拿來對比;隻能是測試結果與同時實驗的"陰性"對照組比較。個人抗體水平變化的前後比較, 也應采用同廠商,同實驗方法的測試標準。
半年前, 我的抗體水平為大眾陰性"對照組”的三千倍以上。這個公司設置陰性標準為0.8, 陽性最高僅測到大過2500。再高的水平,則不報告了。據查證, 這個水平的人群比例僅占測試人群的大約6%, 而對疫苗沒有反應的群體也大慨在6%左右。想像看打過疫苗的人, 仍然感染了病毒甚至病死, 因為可能開始即沒有抗體,或者是抗體快速的衰退,存在這樣的病例有何奇怪? 詢問過專家, 發現與我同樣開始有高抗體效價的人,在第二針注射後的第2,4,6個月後, 抗體下降可呈斜形直線,最後差異極大: 有人跌了十幾倍, 也有人跌到所剩無幾。後者, 可能真的需要第三個加強針了。
在專家朋友的催促下, 我終於完成了疫苗注射6個月後的第二次抗體檢測。這個測試, 直接檢測病毒的刺突蛋白抗體, 而公司為全美各地有連鎖機構的S & P 上市公司, 信譽良好。結果出的極快, 似乎未到24小時, 已經收到了電郵的報告。我起初有點朦,抗體水平和第一次的檢測竟然完全一樣, 怎麽可能呢? 專家給出了解讀:
1, 第一次的抗體水平很高, 遠高過2500, 第二次已經下降了, 但仍在2500以上, 但報告上反應不出來。
2, 最近接觸過病毒, 身體立即反應, 馬上反彈製造抗體, 並達到極高水平。
但我沒有什麽感染的感覺,為了排除體內仍有病毒的可能, 我被建議立即進行病毒核酸檢測。但無論如何今年冬天, 我不需要打第三次新冠疫苗針了。
如果病毒檢測陰性, 我可以擼起袖子, 邁開腿, 周遊世界了。以上經驗, 僅供參考,不應作為他人是否接種疫苗的指標或理由。好了, 我要開始預訂感恩節和聖誕節的機票了。
References:
1. https://www.medpagetoday.com/special-reports/exclusives/95156
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He has primarily worked with LabCorp, which reads out positive or negative for spike IgG antibodies (a test is negative if levels are below 0.8 units/mL; you can see a sample report here). The report also provides a numeric value, but only in a generic "units/mL."
Segev said he and his team do see some clear trends in the LabCorp data. They've confirmed that "antibody levels correlate with pseudoviral and live virus neutralization, and the curves are threshold linear."
That means, for LabCorp at least, "until you reach 250 units/mL, you have little evidence of neutralization," he added.
"When you get to 500 or 1,000, it rises in a linear fashion," Segev told MedPage Today. "So 2,000 gives you twice as much neutralizing capability as 1,000 on a LabCorp test."
Segev is confident enough in the data to interpret what it can mean, generally, for protection against COVID.
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2.
Whether you got vaccinated back in the spring, or you got COVID-19 a year ago — or both — are you protected from the virus? Should you get a booster? If so, when? If you are organizing an event that requires immunity, is confirming vaccination enough? Should you also confirm boosters for those who were vaccinated back in December 2020? Is it reasonable to include those with natural immunity who have not been vaccinated?
Thus far, there have been no good answers to any of these questions, which has caused significant confusion, frustration, risk and even animosity. Fortunately, antibody testing might be ready for primetime. Early tests only returned “positive” or “negative” and had questionable reliability, but now well-established, validated semi-quantitative tests can measure not just whether you have protective antibodies, but the level of those antibodies.
It was through semi-quantitative testing of thousands of patients that our research group at Johns Hopkins discovered that transplant patients and other immunocompromised individuals have poor immune responses to the vaccines and need additional doses. Semi-quantitative tests are now widely available and often don’t even require a doctor’s order.
We are also learning that antibody levels correlate with plasma neutralizing capability (your immune system’s ability to kill the virus in a test tube) and even with clinical protection (your ability to fight off a breakthrough infection). In a recent sub-study of the landmark Moderna trial, every 10-fold increase in antibodies meant an additional 34 percent lower risk of a clinical breakthrough infection. This means that across the “positive” range for antibody testing, some people have one-third the risk of a breakthrough infection compared to others.
Of course, antibodies are not the only component of the immune system. There are T-cells, memory B-cells and complex interactions between complex systems. However, antibodies are the mainstay of the immediate-early immune response, providing truly sterilizing immunity, so antibody levels determine how quickly you can react to the virus.
Antibody levels are critically important for two reasons: First, the faster you can react to the virus, the less time the virus has to replicate before your immune system kills it, so the less severe your infection will be. Second, and maybe even more important in the context of public health, the faster you can react to the virus, the less time you will be shedding virus asymptomatically and unknowingly putting others at risk. Imagine how many people you would unintentionally expose in a week of shedding the virus without symptoms. Keeping everyone’s antibody levels up could prevent future waves of this awful pandemic.
Boosters have started rolling out for individuals who were vaccinated early on, under the presumption that durability wanes with time. In other words, at the general population level, it seems that after six to nine months, antibody levels are much lower than they were after initial vaccination. We know that if antibody levels fall, protection falls, so boosters are needed. But when? At six months? At nine months? At 12 months? Is it different in older adults? Is it different in those who are immunocompromised in other ways?
Instead of just guessing, or assuming “one size fits all” (we saw what a disaster it caused when we assumed immunocompromised patients had the same response as everyone else), we can now test antibody levels and recommend boosters when levels fall below some threshold. We can even choose different thresholds for people of different risk profiles: If you have a higher risk of exposure to SARS-CoV-2 (or exposing others) because of your job, or if you have a higher risk of getting very sick with COVID-19 because of your comorbidity profile, you should get boosted at a higher antibody level. B if you have minimal exposure and are otherwise quite healthy, you could wait to reach a lower antibody level before boosting. This individualized approach would optimize protection while making the best use of available vaccine doses.
Antibody testing can also help us address the major controversy over natural immunity and “vaccine passports.” Many venues, including theaters and concerts and festivals, are starting to require proof of vaccination for entry. Unfortunately, this is quite a blunt instrument for determining how safe someone is to be around others, and it is becoming more and more unreliable as antibody levels from initial “full” vaccination are waning. Ideally, a space is safer if everyone in the space is immune: The risk of someone bringing the virus to the space is minimized, and the risk that the virus would impact the other immune folks in the space is also minimized.
So why have “immunity passports” devolved to “vaccine passports”? For a while, checking vaccination was much easier than somehow determining that someone had enough natural immunity to be safe: In the large clinical trials, nearly everyone mounted a strong antibody response to vaccination, so asking to see someone’s vaccine card was as close to a guarantee as we get these days that the person was immune. However, we are almost a year into vaccines, and antibody levels wane. Today, even vaccination does not necessarily mean strong immunity, and someone who had documented COVID-19 three months ago is likely more immune that someone who was vaccinated a year ago. The way to determine this is to check antibody levels: At a given antibody level, no matter how you got there (vaccines with or without boosters, natural infection with or without vaccines), it is safe for you to be around others.
This will take work. We have to choose the semi-quantitative antibody testing platforms that we trust. We have to choose an antibody level that is “safe enough.” And we have to figure out the logistics of how to check and confirm antibody levels. We could use a hybrid system of a vaccine dose within the last X months or an antibody level above a certain threshold within the last X months, or we can even get fancy with mathematical models of antibody waning. Whatever we do, it won’t be perfect. But it will be much better than what we’re actually doing right now, which is ignoring that vaccine immunity wanes, and ignoring that natural immunity can be just as powerful.
Dorry Segev, MD, Ph.D., is a professor of surgery at Johns Hopkins University School of Medicine and Professor of Epidemiology at Johns Hopkins Bloomberg School of Public Health. Segev has been leading an observational study of COVID-19 vaccine responses in immunosuppressed people since December 2020 and is the principal Investigator of the NIH/NIAID-funded interventional trial "COVID-19 Protection After Transplantation (CPAT).
