T cell enhanced by BCG/TB is the key to fight against C19 and Dectin-2+TB/BCG may prevent the severe stage of C19, cytokine storm.

T cell immunity is the key to fight against COVID-19 and it is enhanced by BCG/TB.

I wrote a post below trying to get more attention on T cell and macrophage instead of antibodies.

Don't care about antibodies. Let's care for innate immunity; T cell and macrophage.

https://www.jsatonotes.com/2020/05/dont-care-antibodies-lets-care-innate.html

And here comes a groundbreaking paper that shifts people's attention to T cell from Karolinska, Sweden.

Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19

https://www.biorxiv.org/content/10.1101/2020.06.29.174888v1

I summarize the points of this paper. Please read them and check the charts below.

• There are SARS-CoV-2-specific memory T cells
• SARS-CoV2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19.
• While there are few SARS-CoV-2-specific memory T cells in blood donors of 2019, there are a substantial number of SARS-CoV-2-specific memory T cells in blood donors of 2020.
  -> These suggest that human can generate SARS-CoV-2-specific memory T cells just by exposing themselves to SARS-CoV-2 without getting infected.

One question remains with this paper. This paper states the T cell feature of the patients with acute moderate or severe COVID-19 as below, but are these the causes or the results?

Our preliminary analyses showed that the absolute numbers and relative frequencies of CD4+ and CD8+ T cells were unphysiologically low in patients with acute moderate or severe COVID-19

T cell immunity strengthened by BCG/TB would be the key to understand COVID-19 and BCG/TB correlation. There are many shreds of evidence that BCG/TB enhances innate and T cell immunity.

Dectin-2+TB/BCG may prevent cytokine storm

However, the major cause of COVID-19 deaths is a cytokine storm, which is that our immune system attacks ourselves, and strengthened immunity is not necessarily positive in case of a cytokine storm.

So, how does BCG/TB relate to a cytokine storm? I have found a very interesting paper answering this question.

Dectin-2 Is a Direct Receptor for Mannose-Capped Lipoarabinomannan of Mycobacteria

https://www.sciencedirect.com/science/article/pii/S1074761314002763

 

Mycobacteria possess various immunomodulatory molecules on the cell wall. Mannose-capped lipoarabinomannan (Man-LAM), a major lipoglycan of Mycobacterium tuberculosis, has long been known to have both inhibitory and stimulatory effects on host immunity. However, the direct Man-LAM receptor that explains its pleiotropic activities has not been clearly identified. Here, we report that a C-type lectin receptor Dectin-2 (gene symbol Clec4n) is a direct receptor for Man-LAM. Man-LAM activated bone-marrow-derived dendritic cells (BMDCs) to produce pro- and anti-inflammatory cytokines, whereas it was completely abrogated in Clec4n–/– BMDCs. Man-LAM promoted antigen-specific T cell responses through Dectin-2 on DCs. Furthermore, Man-LAM induced experimental autoimmune encephalitis (EAE) as an adjuvant in mice, whereas Clec4n–/– mice were resistant. Upon mycobacterial infection, Clec4n–/– mice showed augmented lung pathology. These results demonstrate that Dectin-2 contributes to host immunity against mycobacterial infection through the recognition of Man-LAM.

Anti-cytokines such as IL-10 can be produced profoundly if Dectin-2 of human/mice receives Man-LAM of Mycobacterium tuberculosis or BCG as the chart below says. This may prevent cytokine storm!

Also, Man-LAM promoted antigen-specific T cell responses through Dectin-2 on DCs though SARS-CoV-2 is of course not examined in this 2014 paper.

BCG/TB can enhance not only pro-inflammatory cytokines but also anti-inflammatory cytokines. In other words, a human can get better accelerator and brake of the immune system with BCG/TB.

I believe we are getting close to knowing how BCG/TB works against COVID-19.