Why is COVID-19 Less Severe in Children?

Levi-28by Gertrud U. Rey

The prevalence of SARS-CoV-2, the virus that causes COVID-19, is steadily increasing around the world. Yet despite this unsettling fact, one statistic continues to hold true: most infected children experience mild symptoms, respond well to treatment, recover more quickly than adults, and have a better prognosis.

An initial report from China showed that only 965 out of 44,672 confirmed COVID-19 patients were under the age of  19. A letter to the editor of the New England Journal of Medicine reported only six cases of COVID-19 out of 366 hospitalized children. Only one of these children required admission to the intensive care unit, and all six patients recovered after an average of 8 days. According to the largest study of COVID-19 in children to date, more than 90% of children with laboratory-confirmed COVID-19 had asymptomatic, mild, or moderate disease. A comprehensive review of COVID-19 in children published on March 23 shows that even in Italy, the country with the highest number of COVID-19-related deaths so far, only 1.2% of patients were children, and none of these children died.

What is the reason for this low morbidity and mortality in children? Although the answer isn’t clear, there are a few possible explanations. Children are thought to have fewer underlying disorders and healthier respiratory tracts because of less exposure to cigarette smoke and air pollution. There is speculation that the non-specific, innate immune response that occurs upon an initial encounter with a pathogen is stronger in children. This type of immune response seems to be delayed in the elderly, and in an effort to “catch up,” may result in excessive inflammation, thereby ultimately causing more severe damage.

Another possible explanation is tied to angiotensin-converting enzyme 2 (ACE2), the host cell surface protein that serves as a receptor for SARS-CoV-2 entry into cells. ACE2 is prevalent on lung, kidney, intestinal, and arterial cells, where it normally controls blood pressure by regulating the volume of fluids in the body. ACE2 is also an important regulator of the immune response, especially in the context of inflammation. Some suggest that ACE2 is less mature in young children and thus may not function properly as a receptor for SARS-CoV-2. Furthermore, it is more abundant on cells of the lower respiratory tract, which is typically the site of severe COVID-19 disease. Consistent with this observation, data indicate that children experience more SARS-CoV-2 infections in the upper respiratory tract than the lower respiratory tract.

It has also been suggested that ACE2 is expressed more abundantly on senescent cells, which have stopped dividing and exist predominantly in the elderly. Considering that senescent cells are still metabolically active and contain all the factors necessary for virus replication, this hypothesis seems plausible.

It is also possible that early childhood vaccines provide some protective immunity against SARS-CoV-2. For example, a study from 2008 shows that the measles vaccine elicits neutralizing (virus-inactivating) antibodies against SARS-CoV, the virus responsible for the 2003 coronavirus epidemic. Immunity derived from childhood vaccines typically wanes with age, thereby possibly increasing the risk of severe COVID-19 in the elderly.

As is typical of newly emerging pathogens, many characteristics of the diseases they cause are largely unknown. As such, the exact reasons for why COVID-19 is less severe in children remain ambiguous. Hopefully the answer will become clearer as more data emerge over the next few months.

17 thoughts on “Why is COVID-19 Less Severe in Children?”

  1. Pingback: Why is COVID-19 Less Severe in Children? – Virology Hub

  2. Ritesh Tandon

    Amother possibility is frequent exposure of children to other coronaviruses in school/daycare settings. We don’t know for sure yet but there could be some cross-protection from antibodies generated against other coronaviruses.

  3. Giuseppe Pontrelli

    The reference on protection of Measles vaccine reported results of immunogenicity of a modified RECOMBINANT Measles vaccine with gene of SARS-Cov virus. There is no evidence showed that routine Measles Vaccine is protective vs Coronavirus!

  4. ok. we, us and them need the potential vaccine that could distroy the commond virus in present time (convid-19). ,and thank you………….

  5. If the population of senescent cells in old people is indeed making them more vulnerable to the virus, then Azithromycin, which got quite a bit of recent attention before the virus broke upon the scene as an anti-aging drug because it kills senescent cells:

    “Genetic experiments that eliminate “senescent” cells – older cells, which lose the ability to divide – have already been proven to alleviate age-related dysfunction in model organisms.

    Now, scientists have shown for the first time that an FDA-approved antibiotic – Azithromycin – can effectively target and eliminate senescent cells in culture.

    Publishing in the journal Aging (US), a team from the University of Salford’s Translational Medicine Laboratories compared the effects of a panel of FDA-approved drugs, on i) normal cells and ii) senescent cells, derived from human skin and lungs.

    At a single low-dosage, Azithromycin was shown to effectively kill and eliminate the senescent cells, with an efficiency of 97 percent.

    Moreover, the normal healthy cells thrived in the presence of Azithromycin.

    “It was an astonishing result, and one that got us thinking about the implications for treating or preventing a variety of ageing-associated diseases,” said Professor Michael P. Lisanti, the research lead.

    “Azithromycin is a relatively mild antibiotic that has been proven to extend lifespan in cystic fibrosis patients by several years.

    “Originally, the thinking was that Azithromycin is killing harmful bacteria in cystic fibrosis patients – but our tests now shed a new light on what might be actually going on.

    “Our new interpretation is that the antibiotic is probably eliminating the “inflammatory” fibroblasts, in other words, the senescent cells that are normally associated with ageing.

    “If that is the case, then we may have unearthed a very inexpensive and readily available method of eliminating ageing cells that are toxic to the body.”

    might be useful as a preventative treatment for older people as well as a treatment for people who already have the virus, as the French are doing.

  6. Having read the post, I agree with the opinion that “Although the answer isn’t clear, there are a few possible explanations. Children are thought to have fewer underlying disorders and healthier respiratory tracts because of less exposure to cigarette smoke and air pollution. There is speculation that the non-specific, innate immune response that occurs upon an initial encounter with a pathogen is stronger in children. This type of immune response seems to be delayed in the elderly, and in an effort to “catch up,” may result in excessive inflammation, thereby ultimately causing more severe damage”.

    In my opinion, I think the reason is that the disorder and inability of the neuro-signaling subsystem and the improper immune responses. It’s a primary research supposition analysis and needs some proper data analysis.

    I don’t have any full-time degrees. Simplest and Least Legit Work Qualifications for the Globe The Global Federal Union can take the reform of most simplified qualifications to form least qualifications in the form of e-qualification required by GFU basic or constitutional law within GFU via Global E-qualification E-platform. Some of the e-qualifications can be memberships of lawful GFU societies or associations through the GCTS (Global Credit Transfer and Accumulating System), and no other qualified certificates will be requested for positions funded by global budgets except for necessary requirements of the global e-qualifications.

    The global e-qualifications will be only applied, received and verified through the Global E-qualification E-platform that used for work qualifications required within GFU. Except for the global unified e-qualifications, there’ll be no other qualificational certificates or qualified certifications for positions in the public sectors funded by the GFU budgets; there’ll be no limits for other economic and social sectors as long as the limits don’t against the Global Antitrust Law in the aspect of global working qualifications. The GCTS ( Global Credit Transfer and Accumulating System) which should now contain all the forms of life-long learning outcomes can be used for the global unified e-qualifications required by global law and regulations and be in the structure of a subcommittee with global national working personnel involved, including the personal self-learning and practiceship.

    The kernel of this proposal is the unified global E-qualifications, the GFU E-qualification E-platform and the relevant law for the necessary qualifications in the form of e-qualification. Therefore, GFU needs to utilize the proper global budget plan to set up the unified GFU E-qualification E-platform associated with eIDs (It is corresponding to personal ID number which can also be as personal tax and basic credit numbers and for the usage of GFU uniform e-government services; eIDs are for the market and other social activities) as one of the GFU public services sub-E-platform by related GFU committee, according to the GFU Basic Treaty, or the GFU basic or constitutional law when possible later. In addition, the GFU eID system can include the basic eIDs that used also for GFU public services and other eIDs such as the registration number of global unified e-qualification with the working of algorithm functions.

  7. Pingback: TWiV 598: Who was that masked man? Coronavirus update with Daniel Griffin | This Week in Virology

  8. steve hawkins

    Very interesting comment JimM. Sounds like that might be indicating the way azithromycin seemed to help some people. Definitely one to watch.

    Striking a more positive note on possible effects of this ‘lock down’: I wonder if it will mean that we finally beat the measles despite all the Wakefield disciples efforts to keep it plaguing Humanity?

    Come to that: might the lock down finally rid us of even the ‘common cold’? That would really upset the drug cos! 🙂

    Shame we didn’t think of a worldwide lockdown *before* the coronavirus hit us.

  9. Dr. Lisanti, while writing this article, I actually looked for your paper on this topic, but couldn’t find it. If you look, the word “suggested” in the third to last paragraph links to a YouTube video with an interview with you, which is where I got the idea, so I give you full credit! 🙂 Thanks!

  10. Also, as Doxycyline and Azithromycin both inhibit protein synthesis, this would explain why they both experimentally reduced IL-6 levels and have been reported to inhibit viral replication.
    So, these antibiotics behave as anti-viral agents.
    Cheers !!!

  11. There is another idea starting to rise – The virus degrades Hemoglobin. Children and people with Sickle Cell Anemia have higher concentrations and don’t suffer from hypoxia. Here’s a link to a recent study

  12. Covid-19 is but one of a number of viruses that are much less severe in children than they are in adults – the typical “childhood” illnesses, measles, mumps and chickenpox come to mind. For other viruses this is not true, influenza being an example. Would there be a common mechanism whereby these illnesses are relatively minor in children, but more severe in adults? With Covid, an excessive and disordered inflammatory response seems to correlate with a poor outcome. Is this true of the other “childhood” illnesses when they infect the susceptible adult?

  13. Dear Gertrud
    Thanks for writing this informative piece, quite a few ‘hypothesis’ surrounding this subject. Please note that the conclusion derived from the measles virus vaccine in eliciting NA to SARS CoV is NOT correct; the NA was observed in the recombinant measles virus vaccine which expressed SARS CoV proteins. I have to be careful here and do not want to be misquoted. I would like to emphasise the need for vaccination against measles as not only it is is an excellent vaccine against measles, it also prevents the slight period of immuno-suppression followed after measles.
    Best Wishes
    Javeed Ahmed

    Dr J Ahmed
    Consultant Microbiologist & Virologist

  14. To those who commented on the measles vaccine: you are correct and your correction is noted with appreciation! On that note, I would like to point out that my general point in that paragraph still has some merit, especially in light of recent discussions involving the oral polio vaccine (OPV). It is a known fact that there are viruses that are persistently present in the population and that you can always isolate such viruses from healthy children. Back in the polio days when they were conducting clinical trials for OPV, they found that these other viruses were completely wiped out in children who had received OPV. In fact, an initial administration of OPV reduced mortality caused by other pathogens by as much as 30%. And each successive OPV booster increased this favorable effect even further. This was observed in several parts of the world because it stopped outbreaks caused by completely unrelated viruses. This same effect is also observed after vaccination with other live-attenuated vaccines like the measles vaccine, smallpox vaccine, and bacterial vaccines like BCG and others. The effect would most definitely have to be non-specific, which implicates the innate immune response. It may just be possible that recent vaccination simply engages the innate immune response and keeps it “on guard”.

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