Is it feasible to actively "vaccinate" by picking a good strain? Why do some people have mild symptoms while others have severe ones?

Recently, as the number of COVID-19 infections has gradually increased, COVID-19 symptoms have become the focus of many people's attention, and some news about "asymptomatic strains" has begun to circulate in WeChat groups. These news reports say that some people who were infected with COVID-19 only felt mild discomfort, without even a fever, and were full of energy again in a few days.

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Some netizens also joked that they might as well take the initiative to infect themselves with these strains, allowing the immune system to have close contact with the new coronavirus at the lowest health cost, and just treat it as a natural vaccine injection.

Is this approach worth recommending? Why do some people have almost no symptoms after being infected with the new coronavirus, while others develop severe symptoms?

Since the outbreak of the COVID-19 pandemic, scientists have conducted a lot of research on these issues, trying to find various factors related to the severity of COVID-19 symptoms. For doctors, this valuable information can help determine which infected people are at risk of severe illness, so that they can intervene early and control the disease before it worsens. This article will introduce 6 known potential factors.

01

Age

Age can be said to be one of the most important factors affecting COVID-19 symptoms. Compared with young people, the elderly are more likely to develop severe symptoms and have a relatively higher risk of death . According to Hong Kong's analysis of the COVID-19 epidemic, more than 95% of deaths this year have occurred in people aged 60 and above.

It sounds easy to understand that older people are more likely to develop severe COVID-19, but the reasons behind it are quite complicated.

Some people believe that the immune system of the elderly has declined and is not as effective in fighting the virus. Others point out that in addition to the direct damage caused by the virus, severe COVID-19 is also related to the "immune storm" caused by inflammatory factors - due to the abnormal activity of the immune system, a large number of inflammatory factors secreted by the body will damage the lungs and other organs. Compared with young people, the elderly are more fragile and less able to withstand the impact of these immune storms.

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In contrast, young people have relatively milder symptoms after being infected with the coronavirus. A study published in The Lancet in 2020 showed that even in the early stages of the epidemic, when there was no immune barrier, even in the face of the more toxic original strain, the death rate among those around 30 years old was less than 0.15%. Among those under 20 years old, this number was almost zero.

In addition, children are less likely to develop severe symptoms after being infected with the new coronavirus. This may be because their immune systems have not yet matured, and they will not experience a dangerous "immune storm".

02

Vaccination

With the advent of multiple new coronavirus vaccines, we can say with certainty that whether or not the new coronavirus vaccine is administered can greatly affect the severity of the final symptoms .

Data from Hong Kong also shows that among the elderly aged 80 and above, the mortality rate of unvaccinated infected people is as high as 14.56%; as long as three doses of vaccine are received, whether it is an inactivated vaccine, an mRNA vaccine, or a mixed vaccination, the mortality rate can be sharply reduced to around 1% or 2%. In other age groups, we can also see a significant drop in mortality after vaccination.

Image source: Reference [3]

03

Biological sex

Unfortunately, the coronavirus does not promote equality between men and women. On the contrary, although no obvious gender-related differences have been observed in terms of infection with the coronavirus, in terms of symptoms, the coronavirus is very "severe" in men and "light" in women .

In fact, in many countries, most of the patients who died from the new coronavirus disease were men. In Italy and Ireland at the beginning of the outbreak, men accounted for nearly 70% of the deaths! Recent data from Hong Kong also showed that the male-to-female ratio of the dead was 1.39:1, which means that men accounted for nearly 60%.

Similar to age, there may be multiple reasons why men are more likely to fall victim to COVID-19. The first is physiological. Due to differences in the number of X chromosomes (some COVID-19-related genes are located on the X chromosome) or differences in androgen levels , women are at a lower risk of contracting COVID-19, which can explain to some extent why women may be better protected.

There are also some lifestyle reasons. For example, men are the main users of tobacco. Long-term smoking can damage the immune system and lung function, and can also amplify the effects of COVID-19 infection. A Chinese research team mentioned in a paper in May 2020 that a history of smoking is a very strong factor in predicting a poor prognosis of the disease. Men are also more likely to drink alcohol, which also weakens the immune system.

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04

Underlying disease

During the epidemic, we may have also heard the term underlying disease. If a COVID-19 patient also suffers from diabetes, hypertension, obesity, cardiovascular disease, asthma, chronic obstructive pulmonary disease and other diseases, the risk of severe illness or death will be higher .

Some of these diseases are clearly associated with severe illness, such as diabetes and obesity, which can weaken the body's resistance to viral infections, while asthma or chronic obstructive pulmonary disease can affect lung function. What's more, patients with these underlying diseases are often treated with corticosteroids, which suppress immune function.

In addition, some cancer patients often have weaker immunity than normal people, and some patients who have received organ transplants also need to take drugs that suppress immune function. This will also increase the risk of COVID-19 infection and severe illness.

05

Previous infection

"New crown" is just an abbreviation that stands for "new coronavirus." Before the epidemic, there were other seasonal coronaviruses in our lives that caused mild cold symptoms.

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Stanford University School of Medicine published a study last year, pointing out that if an individual has been infected with other coronaviruses, it may leave a "memory" in some T cells of the immune system . If the emergence of new coronavirus variants will gradually lose the effect of neutralizing antibodies, then the memory effect of T cells will be longer. Even if the common coronavirus is quite different from the new coronavirus, as long as there are some similarities, it can still help the immune system respond faster.

Consistent with this hypothesis, the researchers found that in people with the most severe COVID-19 infections, their T cells lacked the marks of previous exposure to other coronaviruses.

06

"The Chosen One"

In addition to the situations mentioned above, there are also some " super immune people ".

Some medical media have reported on the story of "super immune people", mentioning a couple living under the same roof, the husband was admitted to the ICU due to severe COVID-19, but the wife showed no signs of being affected by COVID-19. Moreover, such "super immune people" are not isolated cases.

The phenomenon of "super-immunes" has also existed in other infectious diseases. For example, in HIV infection, some people have mutations in the CCR5 gene, which prevents the virus from invading cells. Such individuals can be said to be naturally immune to specific viruses.

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Scientists believe that in the bodies of COVID-19 "super-immunes", there may also be some special gene mutations - either changing the characteristics of the immune system or affecting the virus's invasion pathway - making the new coronavirus incapable of them. At present, we do not know whether different super-immunes have the same mutations. This will also be one of the directions for future research.

07

Summarize

In summary, there are many factors that affect the severity of a person's COVID-19 symptoms. In many cases, this involves the interweaving of multiple factors. For example, if a middle-aged person is a male who has never been infected with other coronaviruses and has only received two shots of the vaccine, and a female who has received four shots of the vaccine and has been infected with multiple common seasonal coronaviruses before, even if the two people are infected with the same strain, their symptoms may be very different.

Therefore, the idea mentioned at the beginning - actively infecting the so-called "asymptomatic strain" - is not feasible. Just because others are asymptomatic does not mean that you will also be asymptomatic after being infected .

What's more, even though most of the current COVID-19 symptoms are relatively mild, it is still a disease after all, and it is better not to get it if you can. Even if an individual has mild symptoms after infection, he or she may still infect people around him or her with weaker immunity, causing serious consequences for others.

It is still recommended that everyone take personal protection measures and maintain social distance .

References:

[1] COVID-19: Why is it mild for some, deadly for others? [EB/OL]. 2020-04-17. https://weillcornell.org/news/covid-19-why-is-it-mild-for-some-deadly-for-others

[2] Andrew Thurston. Why Do Some People Get Sicker Than Others from COVID? [EB/OL]. 2022-04-29. https://www.bu.edu/articles/2022/why-do-some-people-get-sicker-from-covid/

[3] Analysis of preliminary data on reported deaths from COVID-19 [EB/OL]. 2022-12-15. https://www.covidvaccine.gov.hk/pdf/death_analysis.pdf

[4] Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis[J]. The Lancet infectious diseases, 2020, 20(6): 669-677. https://doi.org/10.1016/S1473-3099(20)30243-7

[5] Gagliardi, MC, Tieri, P., Ortona, E. et al. ACE2 expression and sex disparity in COVID-19. Cell Death Discov. 6, 37 (2020). https://doi.org/10.1038/s41420-020-0276-1

[6] Foresta, C., Rocca, MS & Di Nisio, A. Gender susceptibility to COVID-19: a review of the putative role of sex hormones and X chromosome. J Endocrinol Invest 44, 951–956 (2021). https://doi.org/10.1007/s40618-020-01383-6

[7] Liu W, Tao ZW, Wang L, et al. Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease[J]. Chinese medical journal, 2020, 133(09): 1032-1038. https://doi.org/10.1097/CM9.0000000000000775

[8] Amitha Kalaichandran. A lucky few seem 'resistant' to Covid-19. Scientists want to know why [EB/OL]. 2021-08-23. https://www.statnews.com/2021/08/23/lucky-few-seem-resistant-to-covid19-scientists-want-to-know-why-2/

Author: Ye Shi

Reviewer: Li Dongzeng, Chief Physician, Department of Infectious Diseases, Beijing You'an Hospital, Capital Medical University

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