An episode of ‘PGT Biochemistry and Infections’ II

In one of my Program for the Gifted and Talented (PGT) courses titled ‘Biochemistry and Infections’, we cover a topic related to the immunity against viral infection. Let us apply the knowledge for some real life situations below,

First, RNA virus is prompt to mutation; indeed, SARS-CoV-2 was observed to have mutated from D614 to G614 over the past few months. That ‘D614G mutation’ could be linked to the ‘second wave’ of outbreak in Hong Kong, when many travelers returned from Europe and Northern America. That mutation was also believed to make the virus more infectious but less deadly. According to a study led by Prof Yuen Kwok-Yung, the virus continued to evolve, for example, in the ‘third wave’ of outbreak in Hong Kong, more viral mutations were identified in the local cases. Given the nature of RNA virus, I humbly believe that the mutations of the viral genome should facilitate the virus to evolve continually until one dominant form is resulted, potentially during winter of the northern hemisphere (similar pattern to seasonal influenza). We have to be alert to the forth and fifth waves!

Second, antibodies belong to the adaptive immunity and specifically, it is the humoral immune response elicited by B cells. Antibodies are supposed to protect us against viral infections; yet, there is also a concept called ‘antibody-dependent enhancement’ (ADE). Several articles from Nature described the possibility of the damaging effects of ADE, for example, the antibody induced by SARS-CoV-2 infection could lead to more serious clinical problems if the same patient is infected again by another strain of SARS-CoV-2 (possibly resulted from mutation). ADE is particularly important for the development of the vaccine against COVID-19. Not only should we examine whether prior SARS-CoV-2 infection makes subsequent infections more serious (similar to the case of Dengue fever), we also have to check if vaccination makes real SARS-CoV-2 infection even worse!

Third, we learn from immunology courses or textbooks that the memory of immune cells could last for years and even a whole life. Unexpectedly, the team led by Prof KY Yuen has recently demonstrated a counter example, in which a patient was re-infected by SARS-CoV-2 within 142 days! The findings implied that the patient did not develop protective immunity against COVID-19 after the first infection. In theory, there could be several possibilities or hypotheses: 1) the patient recovered without the activation of adaptive immunity; thus, B cells were not triggered to release antibodies and no memory was resulted (it is very very unlikely); 2) the virus significantly changed the antigens within 5 months, such that it was able to escape the host’s stronger secondary immune response (it is possible but not very likely); 3) as reported, the immunity against SARS-CoV-2 remained for a relatively short period of time, for example, the half life of antibodies was estimated to be around 36 days.

It would be quite shocking if there is a 50% decrease in the amount of protective antibodies against COVID-19 in just 36 days on average; in other words, we have to ask if herd immunity is still possible? Will COVID-19 become a more serious kind of influenza? The mechanism behind has to be elucidated as soon as possible! The immunity against COVID-19 is a major consideration for vaccine development; we could not afford to have a vaccine that could only be effective for around one month or two.

(Photo credit: The Chinese University of Hong Kong)

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