Emerging epidemiologic reports on COVID-19 in children in China show that, while they are less likely than adults to be infected and have severe illness, they are still vulnerable to the pandemic coronavirus.

This will very beneficial

Thanks Dr Kamal M Alsaad and Saswatik Tripathy for your reply, yes children are labile to infection but still mild. Moreover, on 21/march, Max Planck institute for infection biology in Germany, announced that they will test vaccine candidate called VPM1002, which originally developed from BCG vaccine, the large-scale study is to be carried out at several hospitals in Germany and will include older people and health care workers. Both groups are particularly at risk from the disease. VPM1002 could thus help bridge the time until a vaccine specifically effective against SARS co-virus 2 is available.

https://www.mpg.de/14610776/immune-boost-corona-virus

I hope their vaccine trail will success. Because I think the pediatric compulsive vaccines have some answers, as they enable children to resist the COVID-19 severity with their native immune systems.

A useful list of recent articles with some on pediatric COVID-19 is at https://www.jwatch.org/pediatric-infections?query=topic_pedinf&jwd=000012305116&jspc=

Robert John Wolff thanks professor for your reply. Those recent articles also show that the majority of infected children have a mild to moderate clinical pictures, which in turn support the theoretical possibility of cross immunity provided by compulsive pediatric vaccines.

I am not a specialist on lung immunology, but children have some lung immune tissue that at least in Western countries tends to be absent in healthy adults. For the children-specific consideration see my comment of May 8th (today) in the thread

https://www.researchgate.net/post/Could_hay_fever_help_protect_against_COVID-19

For a better understanding of that comment, please see the whole thread.

Johannes M Dijkstra Your discussion is very interesting

Your idea is based on increased Th2 polarization and the subsequent decreased Th1 polarization protect from COVID-19 severity, However, theoretically, decreased Th1 differentiation increase the susceptibility to/persistent/severity of viral infection, which are supported by delayed viral clearance, persistent virus-induced inflammation and amplification of the allergic inflammation in asthmatic patients (https://erj.ersjournals.com/content/18/6/1013).

Moreover, Th1 might mediates a protective immune response against COVID-19, which is supported by the probability of decreased mortality rate and increased recovery rates accompanied by BCG vaccines (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31025-4/fulltext). It is well known that BCG induce strong Th1 response, which might mediates a non-specific immune response against COVID-19.

Interestingly, COVID-19 mortality rates in countries that have BCG in their routine vaccine programs, are obviously less than other countries, for example, the total death in Africa and Asia is about 23,000, while in Europe and North america is 237,000 (the rate is 1:10).

The link for BCG distribution (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062527/), The link for death rate by countries (https://www.worldometers.info/coronavirus/).

Dear Mohamed Hamed Abdelaziz,

Thank you for your contribution to this important discussion.

In this and my next two posts I will reply to your comments. I hope that I summarized your comments correctly.

1. You state that, generally, Type 1 immunity (Th1 polarization) is important for virus clearance, and that, therefore, you are uncomfortable with the model that the Type 2 immunity polarization induced by Asthma may be protective against virus by suppression of Type 1 immunity.

Your chosen reference Article The immunology of virus infection in asthma

Article IgA, IgG and IgM quantification in bronchoalveolar lavage fl...

Although I added hay fever in Japan to the discussion, the model of asthma-induced Type 2 immunity protecting from lethal COVID-19 inflammation had been proposed before (also mentioned earlier in this thread) Article Risk factors for severity and mortality in adult COVID-19 in...

"Interestingly, the prevalence of asthma in COVID-19 patients 365 (0.9%) in our study was markedly lower than that reported in the adult population of Wuhan 366 (6.4%). We thus speculate that Th2 immune response in asthmatic patients may counter the 367 inflammation process induced by SARS-CoV-2 infection. Further studies are required to 368 characterize the immune response and inflammation features of COVID-19."

Dear Mohamed Hamed Abdelaziz,

2. As to your second point "Moreover, Th1 might mediates a protective immune response against COVID-19, which is supported by the probability of decreased mortality rate and increased recovery rates accompanied by BCG vaccines (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31025-4/fulltext). It is well known that BCG induce strong Th1 response, which might mediates a non-specific immune response against COVID-19."

As you know, the article reference that you provide does not provide evidence of BCG vaccines protecting against COVID-19. You are right that BCG vaccines have been shown to have a protective effect against several other viruses, probably through the non-specific enhancement of Type 1 immunity.

Personally, I do not like the experiment in the Netherlands and Australia to immunize health care workers with BCG vaccine. Most of them should be rather well protected by their immune system anyway because of their age, and I feel that giving them sufficient rest and protection wear should be enough (and should be done!!!!!). My expectation is that prophylactic administration of the BCG vaccine in these health care workers will, if they later get infected with SARS-CoV-2, on average lead to a faster clearance of the virus; I do not debate that Type 1 immunity is one of the ways to beat a virus. However, I am afraid that if the SARS-CoV-2 virus breaks through the first line of defense, the Type 1 immune polarization in these health care workers may prohibit them from properly dealing with the inflammation, and the overall death rate may be higher than without the BCG vaccination.

Some other point of consideration:

One of the most important comorbidity factors for COVID-19 is obesity. That may have a variety of reasons. However, one of the possible reasons is that obesity induces Type 1 immunity Article The Macrophage Switch in Obesity Development

Dear Mohamed Hamed Abdelaziz,

3. As to your third point "Interestingly, COVID-19 mortality rates in countries that have BCG in their routine vaccine programs, are obviously less than other countries, for example, the total death in Africa and Asia is about 23,000, while in Europe and North america is 237,000 (the rate is 1:10)."

Many of these countries are poor, and I speculate (see earlier posts) that they are protected by a high incidence of helminthiasis by which lungs will have associated BALT lymphoid tissue with Type 2 immune polarization. The major weakness of the BCG vaccine theory is that non-specific immunity is not expected to last for decades. It says about non-specific "trained immunity" (Netea et al., 2020, in Nature Reviews Immunology) https://www.nature.com/articles/s41577-020-0285-6 : "The immunological phenotype of trained immunity has been proven to last at least 3 months and up to 1 year, although heterologous protection against infections induced by live vaccines can last for up to 5 years." Like discussed in this thread about BALT tissue, the creation of "tertiary" lymphoid tissue that can last for months is commonly known. However, a non-specific immune memory that can last for years is, to my knowledge, not known. The statement ".. up to 5 years" by Netea et al. appears to be unfounded, as far as I can see, as it refers to a study in Uganda Article Child survival and BCG vaccination: a community based prospe...

Thanks Johannes M Dijkstra for this continuing discussion

- Your suggestion as the protection against COVID-19 is mediated by IgA induced by IL-5 in allergic rhinitis patients. But, in this case, the non-specific IgA doesn’t contain the enough affinity that is required for viral neuralization, and as you know the high affinity antibodies are needed for efficient neutralization.

- The second suggestion of decreased Th1 polarization will weaken the inflammatory response accompanied by COVID-19. In this case the patient will be vulnerable for various types of infection (bacterial and viral) that require an efficient Th1 response.

Dear Mohamed Hamed Abdelaziz,

Type 2 immunity promotes IgA production, including against SARS-CoV-2 viurs after infection.

I agree that Type 2 immune polarization, in many cases, reduces resistance against viral infection, as is known in pregnant women. However, in the lungs, where IgA is an important part of the immune response, the 1/2 discussion may be less simple.

So far, I have avoided a detailed discussion of the inflammation caused by SARS-CoV-2 in the lung because there are not enough data yet. However, it seems that SARS-CoV-2 prohibits the mounting of a typical Type 1 response by actively interfering with interferon production. If this is true, the IgA production may be even more important. I’ll try to add a more detailed discussion on this when more data are available.

Do you mean the protective IgA is not allergen specific and is COVID-19 specific?

-In case of IgA is allergen specific; it will be low affinity

-In case of IgA is COVID-19 specific; also, it will be low affinity, due to high viral mutation rate.

Secondly, what is the possible pathway for a virus to activate Th2 response?

Normally, the virus is recognized by pattern recognition receptor in cytoplasm of innate immune cells, then it is processed and presented with MHCII to Th0 inducing Th1, or presented by any cell with MHCI to CD8+ cell.

Mohamed Hamed Abdelaziz

The polarization of cells like macrophages or T helper cells, or the type of antibody class switch, depends (also) on the local cytokine concentrations. Thus, in an immune milieu that enhances IgA production, also the production of specific IgA antibodies against SARS-CoV-2 will be enhanced.

So far, I did not discuss the possibility of Th2 cells directed against SARS-CoV-2, but indeed this is possible. For example, whereas helminths usually generate Th2 cells, in an immune milieu polarized towards Type 1 immunity they generate Th1(-like) cells https://www.frontiersin.org/articles/10.3389/fcimb.2017.00341/full . Thus, if in the presence of abundant agents that induce a Type 2 immune response, such as pollen during hay fever, Th2 cells may be generated against SARS-CoV-2 antigens.

IgA is very well known to be important for controlling viral infection. For example, the presence versus absence of IgA induction is thought to explain the success of the OPV versus IPV polio vaccines ( https://science.sciencemag.org/content/368/6489/362/tab-pdf ).

The expression of IgA may be even more important for controlling large viruses like SARS-CoV-2 that appear to have tricks up their sleeves to inhibit interferon production and do not induce a classical Type 1 response (e.g. https://www.medrxiv.org/content/10.1101/2020.04.19.20068015v1.full.pdf ).

SARS-CoV-2 viruses mutate remarkably slow for an RNA virus, presumable because of their possession of an exonuclease.

Johannes M Dijkstra There is no doubt that specific IgA mediate antiviral immunity against stable viruses (consider the mutation rate of COVID-19, which still not clear), and further studies are required to elucidate the pathway of COVID-19 IgA generation.

We see alot of cases in pediatric age group and majority with no underlying comorbidity

We see alot of cases in pediatric age group and majority with no underlying comorbidity

We see alot of cases in pediatric age group and majority with no underlying comorbidity

We see alot of cases in pediatric age group and majority with no underlying comorbidity