美国2020年年底推出的新冠病毒RNA疫苗,已经在数亿民众中使用。从各国的大数据看,其效果明显好过以前旧技术开发的病毒疫苗, 当然无论从抗体产生的水平和实际效果看, 也明显好过其它地区开发的减毒灭毒,载体病毒疫苗等。不可否认,所有的疫苗都有大小不等的毒副作用。历史上, 不乏疫苗造成弊大于利的例证, 但近代多种疫苗的出现, 大大改善了人类的生存和寿命的延长, 利远远大于弊。如果算上二,三期的临床测试, 加上近一年来在数亿民众间的广泛使用, RNA疫苗总体测试时间已经超过18个月。新冠RNA疫苗的安全性在绝大多数人身上,无可质疑。但目前大众关心的话题是, 新冠RNA疫苗的免疫保护力究竟能维持多久? 已有不少报道, 揭示在许多被注射疫苗的人身上, 免疫保护力持续地衰减,所以产生了不少疫苗效应被”突破”后而感染的病例。
换句话说, 疫苗保护的效率在几个月后,已经不是超过90%的有效性了。具体详情, 目前没有人能完全掌握。而据新加坡的报道, 新冠疫苗在不同年龄层的保护性差异极大。年轻人多数天然免疫力良好, 打不打疫苗, 死亡率差距不甚巨大;而超过80岁的人, 大多免疫力较差, 甚至各种疾病缠身, 疫苗的免疫保护力常常大打折扣。据未公开的大数据报道, 60-70岁阶层的疫苗大体保护力较其它年龄组为佳,施打疫苗与未注射者相比, 总体上,感染后病死率可降低大约50倍的机会。但落实到具体个人,身体情况可能有差异。有报道指出年长者,产生的抗体低而且衰减快, 癌症病人, 器官移植者, 免疫病患者等, 还有不确定的原因造成的免疫反应低下,均可能需要打第三针来加强免疫保护。
冬季已经到了, 天气渐凉。第二针的疫苗已注射超过半年, 我身体健康, 是否需要再打第三针呢?
除非利大于弊, 我不想盲目地注射异物在身上。在专家的指导下,本人半年前曾在第二针注射两周后, 测试了疫苗产生的对抗新冠病毒的抗体水平,自己也做了一些研究。目前官方尚未得出最后的结论, 即抗体水平高低与免疫力强弱间的直接关系。这个结论需要长时间, 大数据的观察, 和最后的多方的科学认定。现有的知识已经知道,在许多感染疾病中,抗体水平是产生免疫力保护的关键因素。此外,还有细胞免疫的抗病毒作用。但后者的测定和商业化运作,不如抗体测定的研究和发展。据资料显示, 至少已有四家公司的抗体检测, 已经获得FDA的紧急使用授权。当然,世界上已有无数的厂家和医疗机构开发了抗体检测服务。不同机构的结果报告,不可直接拿来对比;只能是测试结果与同时实验的"阴性"对照组比较。个人抗体水平变化的前后比较, 也应采用同厂商,同实验方法的测试标准。
半年前, 我的抗体水平为大众阴性"对照组”的三千倍以上。这个公司设置阴性标准为0.8, 阳性最高仅测到大过2500。再高的水平,则不报告了。据查证, 这个水平的人群比例仅占测试人群的大约6%, 而对疫苗没有反应的群体也大慨在6%左右。想像看打过疫苗的人, 仍然感染了病毒甚至病死, 因为可能开始即没有抗体,或者是抗体快速的衰退,存在这样的病例有何奇怪? 询问过专家, 发现与我同样开始有高抗体效价的人,在第二针注射后的第2,4,6个月后, 抗体下降可呈斜形直线,最后差异极大: 有人跌了十几倍, 也有人跌到所剩无几。后者, 可能真的需要第三个加强针了。
在专家朋友的催促下, 我终于完成了疫苗注射6个月后的第二次抗体检测。这个测试, 直接检测病毒的刺突蛋白抗体, 而公司为全美各地有连锁机构的S & P 上市公司, 信誉良好。结果出的极快, 似乎未到24小时, 已经收到了电邮的报告。我起初有点朦,抗体水平和第一次的检测竟然完全一样, 怎么可能呢? 专家给出了解读:
1, 第一次的抗体水平很高, 远高过2500, 第二次已经下降了, 但仍在2500以上, 但报告上反应不出来。
2, 最近接触过病毒, 身体立即反应, 马上反弹制造抗体, 并达到极高水平。
但我没有什么感染的感觉,为了排除体内仍有病毒的可能, 我被建议立即进行病毒核酸检测。但无论如何今年冬天, 我不需要打第三次新冠疫苗针了。
如果病毒检测阴性, 我可以撸起袖子, 迈开腿, 周游世界了。以上经验, 仅供参考,不应作为他人是否接种疫苗的指标或理由。好了, 我要开始预订感恩节和圣诞节的机票了。
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).
