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A lot of people are wondering why #Japan has so few cases of #COVID19. In this commentary, @NathanGrubaugh and I speculate on some possible reasons. (1/n)

embopress.org/doi/10.15252/e…
An important observation made by @NathanGrubaugh is the recent introduction of #SARSCoV2. Note the earlier infections came from China, while ones in March are predominantly from Europe (plus Egypt, USA). Japan has now tightened travel bans. (2/n)

nextstrain.org/ncov/global?f_…
An intriguing link is the correlation between the #BCG vaccination and #COVID19. In countries that mandate childhood BCG vaccines, cases of #COVID19 and deaths appear to be low. For more discussions see 👇🏽
(3/n)

jsatonotes.com/2020/03/if-i-w…
news.yahoo.co.jp/byline/kimuram… (by Prof. Miyasaka)
We are grateful for Dr. Hiroshi Iwasaki (my father who is a guru on internet searches) for collecting information from Japanese media, and @HironoriFunabi1 for his informative tweets on this issue 🙏🏽 (end)
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Prof. Akiko Iwasaki
@VirusesImmunity
Several studies are coming out saying that blood LDH (lactate dehydrogenase) levels early in #COVID19 disease correlates with severe disease progression. This is a clue that #pyroptosis may be a the core of this disease (1/n).

medrxiv.org/content/10.110…
jci.org/articles/view/…
What is LDH? It is an enzyme found within the cytosol of nearly all cells. Ed Miao's group showed that LDH release is a reliable way to monitor #pyroptosis, a form of cell death that depends on inflammasomes leading to plasma membrane rupture. (2/n)

ncbi.nlm.nih.gov/pubmed/23852598
LDH is not released by apoptosis or even hyperactivation of macrophages. It requires pyroptosis and membrane rupture shown by @jkagan1 's group. (3/n)

sciencedirect.com/science/articl…
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Prof. Akiko Iwasaki
@VirusesImmunity
This is a cautionary tale of how anti-Spike antibody may make COVID disease worse. In this study, the authors show that anti-Spike IgG made SARS-CoV disease worse by switching macrophage from wound-healing to proinflammatory phenotype. A thread (1/n)

insight.jci.org/articles/view/…
When rhesus macaques were immunized with SARS-Spike MVA vaccine, high titers of neutralizing Ab (NAb) generated correlated with severe diffuse alveolar damage NOT protection upon i.n. challenge with SARS-CoV, despite reducing viral load. Loss of disease tolerance by S-IgG. (2/n)
Next, rhesus macaques injected with low or high dose of anti-Spike-IgG (passive transfer) and challenged with SARS developed worse disease. Thus, S-IgG alone can lead to SARS disease exacerbation. (3/n)
Read 8 tweets
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Prof. Akiko Iwasaki
@VirusesImmunity
A few years ago, @HShin_Lab developed a new vaccine strategy called 'Prime & Pull' - T cells are pulled into target tissue with chemokines, as #HSV2 vaccine strategy. Now, @SmitaGopinath shows that topical aminoglycosides = potent 'Pull' agent 👇🏽(1/n)

jimmunol.org/content/early/…
This finding follows @SmitaGopinath's earlier work that aminoglycoside antibiotics applied to the genital mucosa induces potent interferon-stimulated genes including CXCL10. Effector CD8 T cell expressing CXCR3 are recruited to the tissue. (2/n)

nature.com/articles/s4156…
Single application aminoglycoside antibiotics are advantageous over recombinant chemokines because they are 1) approved for human use, 2) cheap, 3) effective. #HSV2 #vaccine

Prime & Pull also is very effective when used therapeutically @peowenlu. (3/n)

nature.com/articles/s4154…
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