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CoVID-19 Antibody Tests of Archived Blood Samples in the US and China - a Compar

热度 1已有 507 次阅读2021-5-29 11:12 |个人分类:科普|系统分类:科技

Disclaimer: This article is an analysis and summary of scientific literature, and does not make political speculations


In December 2019, Chinese health researchers first discovered cases of what now kown as COVID-19 in Wuhan, and identified the novel coronavirus that caused COVID-19. After that, countries around the world faced an epidemic spreading on a large scale. Around the world, various preventive measures and treatment methods had been implemented, yet COVID-19 has so far caused 4,600 deaths in China, among a population of 1.4 billion, and 593,000 deaths in the United States, among a population of 300 million (May 27, 2021-Google data). Since the epidemic was first discovered in Wuhan, due to preconceived cognitive biases, relevant early studies focused on China. The in-depth understanding of COVID and the development of related detection methods have enabled scientists to test archived samples. In November last year, researchers from the US CDC (Centers for Disease Control and Prevention) published a peer-reviewed paper in "Clinical Infectious Diseases" with the title "Serologic Testing of US Blood Donations to Identify Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)–Reactive Antibodies: December 2019–January 2020" (Ref. 1 ). Coincidentally, at the beginning of this year, Chinese researchers published a paper entitled "The prevalence of antibodies to SARS-CoV-2 among blood donors in China" in "Nature Communications"(Ref. 2) , the serum samples covered in this paper dated from January to April 2020. As the titles suggest, the two studies in China and the United States both investigated the initial spread of the novel coronavirus by testing the blood donors' serum for antibodies to the virus. Due to the large number of donated blood samples, relevant analysis provides a solid objective basis and scientific foundation for the research on the origin and spread of the virus.

Before comparing the key data of the two papers, let me briefly introduce the relevant background knowledge. After being invaded by a virus, the human immune system will produce corresponding antibody protein molecules. A protein molecule is a long string of different amino acids connected in sequence, and then folded into various shapes. A targeting hook on one end of the antibody can bind to certain target, and the other end of the antibody can hook on white blood cells, so that the latter can eliminate the target hooked by the antibody. Antibodies are specific, otherwise it will cause problems by hooking to things that shouldn't be targeted. For different viruses (or other toxins) and different parts of the same virus, the immune system produces different Ig antibody proteins. Ig is the abbreviation of immunoglobulin. As the name globulin implies, it is a protein that folds into a ball shape. There are many types and subtypes of Ig, such as IgA, IgG, IgM and so on. The IgM is large and the production cost is high. IgM has multiple "hooks" and has stronger capture power. It is produced at the beginning of the immune response and will disappear after a few days. It is replaced by a relatively small IgG. IgG can exist in the body for several months or even longer, which belongs to the body's immune memory. Studies have shown that about 5 days after a person is infected with the novel coronavirus, the immune system will generate the corresponding IgM antibodies. IgM then disappears, and the human body produces IgG antibodies within one to two weeks. It should be emphasized that there can be different IgG antibodies for the same virus. The novel coronavirus has a spherical shape with spike proteins on the surface, and genetic material and nucleoprotein within. There may be different Ig antibodies for different parts of the spike protein. There can also be Ig antibodies against the nucleoprotein of the novel coronavirus.

Studies have found that IgG antibodies for the novel coronavirus can be maintained for at least 4 months in the human bodyBased on this background knowledge, we can infer that if IgM antibodies are found in human serum (assuming a normal immune system), it means that the person has just contracted the virus. If IgG antibodies are found in the serum but no IgM antibodies, it means that the person had been infected with the novel coronavirus two weeks ago or earlier.

Blood donors in China and the United States undergo basic physical examinations to ensure the health of their plasma. Blood donors must meet some basic health standards, such as not being sick a few weeks before donating, having normal body temperature and showing no signs of infections when donating blood, etc. The antibody test methods of the two papers are similar. Both of them use a full-spectrum COVID-19 antibody test assay for the first round of serum testing, and the positive samples of the first round will be confirmed in subsequent detailed tests. In the US research, after the pan Ig antibody test was used to detect seropositivity, specific IgG and IgM antibody tests were performed for the second round of antibody testing, and then neutralization test was performed with live novel coronavirus, which is to use diluted serum to see if it can kill the virus. The order of tests in the Chinese test is slightly different. After the initial selection of positive samples with a total antibody test, a pseudo SARS-COV-2 virus (created by attaching the spike protein of SARS-COV-2 on another virus) was used for a neutralization test, and then two IgG tests and one IgM were performed. The Chinese study also conducted IgM and IgG tests on samples that were negative in the neutralization experiments.

Armed with this background knowledge and information, let's now compare the results of the SARS-COV-2 antibody test of archived serum samples from China and the United States. The following summary comes from the two papers mentioned earlier.

Let's look at the data from China first. The blood samples in the Chinese paper dated between January and April 2020, all 38,144 blood donors from three blood centers in Wuhan, Shenzhen and Shijiazhuang, including 17,794 from Wuhan, 6810 from Shenzhen, and 13,540 from Shijiazhuang. In the first round of total antibody tests, 544 samples were found to be positive. In the second round, 398 cases were confirmed to be positive by virus neutralization test (these continued to undergo IgG and IgM antibody tests).

Among the 1,385 serum samples taken from Wuhan one week before January 23, 2020,  the day when the city was placed under quarantine, the number of confirmed positive for new coronavirus antibody was zero. Throughout January 2020, only one of 2208 blood donors in Wuhan was positive, which appeared on January 20, 2020. The positive rate was thus less than one in 1,000. With the spread of COVID-19 in Wuhan, between February and March 2020, the antibody positive rate of blood donors in Wuhan reached 3%. After partial lifting of the lockdown on April 8, 2020, 225 of over 10,000 serum samples from Wuhan tested positive, with a ratio of 2.24%. Of the thousands of samples in Shenzhen, only one was positive, in March 2020. The situation in Shijiazhuang was similar, with only one positive sample at the end of February. As of April 2020, out of a total of more than 19,000 serum samples from Shenzhen and Shijiazhuang, only one positive sample was found in each of the two cities.

It can be seen from the above that during January 2020, the rough proportion of Wuhan blood donors positive for the SARS-COV-2 antibodies was less than 0.05% (five out of then thousand). Wuhan has a population of 11.21 million. According to this ratio (and assuming that the number of asymptomatic infections is much greater than that of symptomatic patients), the total number of Wuhan coronavirus infections in January 2020 would be around 5,000. This number is close to the results of an analysis conducted by Neil M. Ferguson of Imperial College in the United Kingdom on January 22, 2020 based on the number of confirmed COVID cases, the incubation period and transmission characteristics of the virus (Ref. 3). In that analysis, Ferguson estimated that the number of infected people in Wuhan at that time was about 4,000, and the range was 1,000 to 9,000. In turn, this also shows that blood donors are a very good sampling section for studying the spread of the novel coronavirus - after all, it seems that there is no correlation between the infectivity of the novel coronavirus and a person's health, although the symptoms after infection differ. In addition, we can also see that early January 2020 is still the initial stage of the spread of the novel coronavirus in Wuhan, and the spread had been suppressed in its budding stage before it has had time to spread to other parts of China on a large scale. This is why until April 2020, the positive rate of SARS-CoV-2 antibodies in nearly 20,000 serum samples from Shenzhen and Shijiazhuang was less than one in ten thousand.

So what about the data in the US CDC paper?

A total of 7,389 serum samples from blood donors in the United States archived by the American Red Cross were tested . Among them, 1912 samples were from California, Oregon, and Washington state, and the blood donation dates were from December 13, 2019 to December 16, 2019. Of these 1912 serum samples, 39 were tested positive by two rounds of antibody tests, and 37 were further confirmed to be positive by neutralization tests (see the US testing procedures above). In other words, about two percent of these U.S. serum samples from December 13 to 16, 2019 were determined to be positive for novel coronavirus antibodies. The other 5,477 serum samples tested in the United States came from five eastern and midwestern states (MA, WI, IA, MI, CT, RI). The blood donation dates were between December 30, 2019 and January 17, 2020. After three rounds of testing (two rounds of antibody testing + neutralization test), the number of positive cases was 47, and the proportion was 9 per thousand (0.9%). It is worth noting that in the second round of testing, 30% of serum samples from the United States were IgG positive but IgM negative, so the infection of their donors occured two weeks before the blood donation or earlier.

The population of California is 39.5 million, Oregon 4.2 million, and Washington 7.6 million, for a total of 51.3 million. According to the analysis of Wuhan above, at a ratio of 2%, we conclude that the number of people infected with the novel coronavirus in these three states before December 16, 2019 was about 1 million. Similarly, before January 17, 2020, the number of people infected with the novel coronavirus among the 30 million people in the states of MA, WI, IA, MI, CT, RI was about 300,000.

At this point, a dynamic picture comparing the spread of the novel coronavirus between China and the United States should have surfaced. By the end of December 2019, when Wuhan confirmed the cases of pneumonia with unknown causes (notice by Wuhan Health Commission on December 30), there were probably already 1 million people infected with the novel coronavirus in the western United States. Moreover, the virus had spread rapidly in the United States. By mid-January 2020, the infection rate of the novel coronavirus in the eastern states of the United States had been close to 1%. In contrast, until late January 2020, the number of people infected in Wuhan is only a few thousand at most according to the serum antibody test and the analysis of the Imperial College. We can conclude that at the end of 2019, the total number of people infected with the novel coronavirus in the United States was at least 100 times the number of people infected in China at that time.

It is hoped that the above comparative analysis can be a source of inspiration for further studies, with more complete and more detailed data (including data from other countries), combined with mathematical analysis of the infection model, to obtain a more complete and clearer picture of the spread of the novel coronavirus.

Ref 1:  Sridhar V Basavaraju, et al. Serologic Testing of US Blood Donations to Identify Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)--Reactive Antibodies: December 2019--January 2020,  Clinical Infectious Diseases , 2020;, ciaa1785,  https://doi.org/10.1093/cid/ciaa1785


Ref 2:  Chang, L., Hou, W., Zhao, L.  et al.  The prevalence of antibodies to SARS-CoV-2 among blood donors in China.  Nat Commun 12,  1383 (2021). https:// doi .org/10.1038/s41467-021-21503-x  

Ref 3.  https:// spiral.imperial.ac.uk:8443/handle/10044/1/77150; https:// doi.org/10.25561/77150

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