➥【接種mRNA疫苗可增加對抗新冠病毒原始武漢株及南非變異株的血清中和抗體】
■中文摘要
SARS-CoV-2利用棘(S)蛋白與宿主細胞結合。S蛋白由S1及S2組成,其中S1包含C端、N端及受體結合區域(receptor-binding domain; RBD),病毒利用RBD與宿主細胞表面的ACE2受體結合,進入宿主細胞。S2則是與病毒和宿主細胞間的融合有關。
迄今仍不清楚何者是評估免疫保護力(即免於SARS-CoV-2感染)的有效指標(correlate of protection),但目前認為中和抗體(neutralizing antibody)是對抗SARS-CoV-2的重要保護成分。研究顯示,SARS-CoV-2感染後,中和抗體會快速被誘導出且維持數月之久。而RBD是自然感染後產生的血清中和抗體最主要的標的,目前已有多種抗RBD的單株抗體被辨識出。
Pfizer/BioNTech BNT162b2和Moderna mRNA-1273兩種mRNA疫苗已在許多國家緊急授權使用。兩者都是以疫情早期的武漢病毒株(Wuhan-Hu-1)之S蛋白進行疫苗設計,兩疫苗保護力可達94%。
由於疫情仍嚴峻、病毒在社區持續傳播演化,病毒變異株陸續出現,如英國變異株(B.1.1.7)、南非變異株(B.1.351)及巴西變異株(P.1)。這些變異株的S蛋白出現變異,導致傳播能力增加。
以南非株為例,其蛋白的N端帶有D80A及D215G突變、RBD帶有K417N、E484K及N501Y 突變,S2則帶有D614G突變。三變異株在RBD都帶有N501Y突變,此突變會增加病毒與宿主ACE2受體結合的親和力。
D614則會增加S蛋白密度、感染力及傳播能力。另南非變異株及巴西變異株的RBD都帶有E484K突變。這些變異株對先前已感染過新冠肺炎的患者或已接種新冠疫苗的民眾所產生的中和抗體是否有抗性,令人關注。
為解答上述問題,美國及加拿大的研究團隊進行了病毒血清學研究。
■方法
分析染疫康復者及疫苗接種者在施打mRNA疫苗(任一品牌)前後的血清對早期武漢病毒株及新興南非變異株的病毒中和能力及相關抗體效價。
■受試者族群:包括以下3組
❶曾感染SARS-CoV-2、並已接種1或2劑mRNA疫苗(染疫/1劑疫苗或染疫/2劑疫苗)的受試者,共15位,取其疫苗接種前後的血清。
❷未曾感染SARS-CoV-2、已接種2劑mRNA疫苗(未染疫/2劑疫苗)的受試者,共13位,取其疫苗接種前後的血清。
❸疫情早期感染過SARS-CoV-2、但尚未接種疫苗的受試者之血清所分離出的單株抗體。
■病毒中和試驗:採用表現以下3種S蛋白全長的假病毒株(pseudovirus)進行試驗
❶武漢病毒株(Wuhan-Hu-1)。
❷南非變異株(B.1.351),帶有D80A、D215G、K417N、E484K、N501Y、D614G及A701V突變。
❸南非變異株(B.1.351Δ242-243),除上述B.1.351病毒株的變異外,也帶有Δ242-243缺失突變。
■結果
❶疫情早期感染過SARS-CoV-2、但尚未接種疫苗的受試者之血清所分離出的單株抗體對兩南非變異株的中和能力降低,表示南非變異株對早期染疫患者的血清有抗性。
❷若將染疫/1劑疫苗受試者及未染疫/2劑疫苗受試者血清中的抗RBD抗體去除,血清中和武漢病毒株的能力即會消失,顯示大部分被誘發的中和抗體的標的抗原是RBD。
❸疫苗接種前即有抗RBD IgG的染疫受試者在接種1劑疫苗後,其抗(武漢病毒株)RBD IgG效價增加為500倍,抗RBD IgA效價增加為200倍。染疫/1劑疫苗受試者和未染疫/2劑疫苗的受試者相比,前者抗RBD IgG及IgA的效價分別為後者的4.5倍及7.7倍。不論是否曾染疫,施打疫苗對抗RBD IgM效價影響不大,效價都偏低。
❹以武漢病毒株進行血清抗體中和試驗,若以可以中和50%病毒的抗體效價ID50而言,疫苗接種前即有抗RBD IgG的染疫受試者在接種1劑疫苗後,ID50效價上升至1000倍,追加第二劑疫苗效果則不顯著。未染疫/2劑疫苗受試者ID50較染疫/1-2劑疫苗受試者約低5-10倍。
❺在染疫康復者中,疫苗前血清對武漢病毒株的ID50明顯較兩南非變異株ID50高。約僅33%至46.7%的受試者疫苗前血清可部分中和兩南非變異株,且只有少數受試者血清ID50高於100。
施打1劑疫苗則可增加血清對武漢株及南非兩變異株的中和抗體效價,但和武漢病毒株ID50相比,血清對南非變異株B.1.351及B.1.351Δ242-243的ID50分別低了3倍及10倍。
染疫/1劑疫苗受試者血清對3種病毒株的中和效價,均較未染疫/2劑疫苗受試者高(7-30倍)。約61.5% (8/13)的未染疫/接受2劑受試者之血清可以達到抑制80%的南非變異株B.1.351-Δ242-243。
■總結
抗RBD抗體為血清中能中和病毒的主要成分。染疫康復者/疫苗前的血清可有效中和武漢病毒株,但只有部分的受試者血清可以中和南非變異株。
然而,施打一劑mRNA疫苗後,血清對武漢病毒株及兩南非變異株的中和抗體效價都會上升,部分可達1000倍之高,但施打第二劑並不會增加抗體效價。未曾染疫的受試者接種兩劑疫苗,也會產生對兩南非變異株的中和抗體,但效價都偏低。綜合而言,不論是否...完整轉譯文章,詳連結:http://forum.nhri.org.tw/covid19/virus/j_translate/j2597/ ( 財團法人國家衛生研究院 吳綺容醫師摘要整理)
📋 Science - 2021-03-25
mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection
■ Author:Leonidas Stamatatos, Julie Czartoski, Yu-Hsin Wan, et al.
■ Link:https://science.sciencemag.org/content/early/2021/03/24/science.abg9175
〈 國家衛生研究院-論壇 〉
➥ COVID-19學術資源-轉譯文章 - 2021/04/19
衛生福利部
疾病管制署 - 1922防疫達人
疾病管制署
covid-19 infection中文 在 Roger Chung 鍾一諾 Facebook 的最佳解答
今早為Asian Medical Students Association Hong Kong (AMSAHK)的新一屆執行委員會就職典禮作致詞分享嘉賓,題目為「疫情中的健康不公平」。
感謝他們的熱情款待以及為整段致詞拍了影片。以下我附上致詞的英文原稿:
It's been my honor to be invited to give the closing remarks for the Inauguration Ceremony for the incoming executive committee of the Asian Medical Students' Association Hong Kong (AMSAHK) this morning. A video has been taken for the remarks I made regarding health inequalities during the COVID-19 pandemic (big thanks to the student who withstood the soreness of her arm for holding the camera up for 15 minutes straight), and here's the transcript of the main body of the speech that goes with this video:
//The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, continues to be rampant around the world since early 2020, resulting in more than 55 million cases and 1.3 million deaths worldwide as of today. (So no! It’s not a hoax for those conspiracy theorists out there!) A higher rate of incidence and deaths, as well as worse health-related quality of life have been widely observed in the socially disadvantaged groups, including people of lower socioeconomic position, older persons, migrants, ethnic minority and communities of color, etc. While epidemiologists and scientists around the world are dedicated in gathering scientific evidence on the specific causes and determinants of the health inequalities observed in different countries and regions, we can apply the Social Determinants of Health Conceptual Framework developed by the World Health Organization team led by the eminent Prof Sir Michael Marmot, world’s leading social epidemiologist, to understand and delineate these social determinants of health inequalities related to the COVID-19 pandemic.
According to this framework, social determinants of health can be largely categorized into two types – 1) the lower stream, intermediary determinants, and 2) the upper stream, structural and macro-environmental determinants. For the COVID-19 pandemic, we realized that the lower stream factors may include material circumstances, such as people’s living and working conditions. For instance, the nature of the occupations of these people of lower socioeconomic position tends to require them to travel outside to work, i.e., they cannot work from home, which is a luxury for people who can afford to do it. This lack of choice in the location of occupation may expose them to greater risk of infection through more transportation and interactions with strangers. We have also seen infection clusters among crowded places like elderly homes, public housing estates, and boarding houses for foreign domestic helpers. Moreover, these socially disadvantaged people tend to have lower financial and social capital – it can be observed that they were more likely to be deprived of personal protective equipment like face masks and hand sanitizers, especially during the earlier days of the pandemic. On the other hand, the upper stream, structural determinants of health may include policies related to public health, education, macroeconomics, social protection and welfare, as well as our governance… and last, but not least, our culture and values. If the socioeconomic and political contexts are not favorable to the socially disadvantaged, their health and well-being will be disproportionately affected by the pandemic. Therefore, if we, as a society, espouse to address and reduce the problem of health inequalities, social determinants of health cannot be overlooked in devising and designing any public health-related strategies, measures and policies.
Although a higher rate of incidence and deaths have been widely observed in the socially disadvantaged groups, especially in countries with severe COVID-19 outbreaks, this phenomenon seems to be less discussed and less covered by media in Hong Kong, where the disease incidence is relatively low when compared with other countries around the world. Before the resurgence of local cases in early July, local spread of COVID-19 was sporadic and most cases were imported. In the earlier days of the pandemic, most cases were primarily imported by travelers and return-students studying overseas, leading to a minor surge between mid-March and mid-April of 874 new cases. Most of these cases during Spring were people who could afford to travel and study abroad, and thus tended to be more well-off. Therefore, some would say the expected social gradient in health impact did not seem to exist in Hong Kong, but may I remind you that, it is only the case when we focus on COVID-19-specific incidence and mortality alone. But can we really deduce from this that COVID-19-related health inequality does not exist in Hong Kong? According to the Social Determinants of Health Framework mentioned earlier, the obvious answer is “No, of course not.” And here’s why…
In addition to the direct disease burden, the COVID-19 outbreak and its associated containment measures (such as economic lockdown, mandatory social distancing, and change of work arrangements) could have unequal wider socioeconomic impacts on the general population, especially in regions with pervasive existing social inequalities. Given the limited resources and capacity of the socioeconomically disadvantaged to respond to emergency and adverse events, their general health and well-being are likely to be unduly and inordinately affected by the abrupt changes in their daily economic and social conditions, like job loss and insecurity, brought about by the COVID-19 outbreak and the corresponding containment and mitigation measures of which the main purpose was supposedly disease prevention and health protection at the first place. As such, focusing only on COVID-19 incidence or mortality as the outcomes of concern to address health inequalities may leave out important aspects of life that contributes significantly to people’s health. Recently, my research team and I collaborated with Sir Michael Marmot in a Hong Kong study, and found that the poor people in Hong Kong fared worse in every aspects of life than their richer counterparts in terms of economic activity, personal protective equipment, personal hygiene practice, as well as well-being and health after the COVID-19 outbreak. We also found that part of the observed health inequality can be attributed to the pandemic and its related containment measures via people’s concerns over their own and their families’ livelihood and economic activity. In other words, health inequalities were contributed by the pandemic even in a city where incidence is relatively low through other social determinants of health that directly concerned the livelihood and economic activity of the people. So in this study, we confirmed that focusing only on the incident and death cases as the outcomes of concern to address health inequalities is like a story half-told, and would severely truncate and distort the reality.
Truth be told, health inequality does not only appear after the pandemic outbreak of COVID-19, it is a pre-existing condition in countries and regions around the world, including Hong Kong. My research over the years have consistently shown that people in lower socioeconomic position tend to have worse physical and mental health status. Nevertheless, precisely because health inequality is nothing new, there are always voices in our society trying to dismiss the problem, arguing that it is only natural to have wealth inequality in any capitalistic society. However, in reckoning with health inequalities, we need to go beyond just figuring out the disparities or differences in health status between the poor and the rich, and we need to raise an ethically relevant question: are these inequalities, disparities and differences remediable? Can they be fixed? Can we do something about them? If they are remediable, and we can do something about them but we haven’t, then we’d say these inequalities are ultimately unjust and unfair. In other words, a society that prides itself in pursuing justice must, and I say must, strive to address and reduce these unfair health inequalities. Borrowing the words from famed sociologist Judith Butler, “the virus alone does not discriminate,” but “social and economic inequality will make sure that it does.” With COVID-19, we learn that it is not only the individuals who are sick, but our society. And it’s time we do something about it.
Thank you very much!//
Please join me in congratulating the incoming executive committee of AMSAHK and giving them the best wishes for their future endeavor!
Roger Chung, PhD
Assistant Professor, CUHK JC School of Public Health and Primary Care, @CUHK Medicine, The Chinese University of Hong Kong 香港中文大學 - CUHK
Associate Director, CUHK Institute of Health Equity
covid-19 infection中文 在 國家衛生研究院-論壇 Facebook 的精選貼文
➥目前新冠肺炎臨床症狀資料大多來自成人個案,兒童被視為感染新冠肺炎的低危險族群,因此,兒童方面的臨床症狀資料十分缺乏。
Shekerdemian博士和其研究團隊的觀察性研究結果指出,於48位因新冠肺炎而住院的兒童病患中,年紀大多落在4到17歲之間,25位(52%)為男生,8位(17%)無慢性病史,其中16位(33%)為重症,21位(44%)使用羥氯喹(hydroxychloroquine)治療,8位(17%)使用瑞德西韋或其他抗病毒藥物治療,13位(28%)使用兩種以上藥物治療,2位(4%)因病死亡,到研究截止時,15位(32%)仍住院治療。
本研究為少數報告北美地區在兒童加護病房治療新冠肺炎病童臨床結果,未來需更多結果來支持。(「財團法人國家衛生研究院」蔡慧如博士 摘要整理 ➥http://forum.nhri.org.tw/covid19/virus/j_translate/j966/ )
📋 Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units (2020/05/11)+中文摘要轉譯
■ Author:
Lara S. Shekerdemian, Nabihah R. Mahmood, Katie K. Wolfe, et al.
■ Link:
(JAMA) https://jamanetwork.com/journals/jamapediatrics/fullarticle/2766037?resultClick=1
🔔豐富的學術文獻資料都在【論壇COVID-19學術專區】
■ http://forum.nhri.org.tw/covid19/
#2019COVID19Academic
衛生福利部
疾病管制署 - 1922防疫達人
疾病管制署
國家衛生研究院-論壇
covid-19 infection中文 在 COVID-19病毒是如何传播的?我们如何自我防范? - YouTube 的推薦與評價
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