Sun, 06/28/2020 - 10:24
- Second wave?
We heard about second waves in Iran and US, but those countries failed to take stringent measures in the first place: there was just a temporary small “dip” between the first massive appearance in the capital + other highly connected areas and the subsequent further spread into the rest of the country.
A nice textbook example of a “second wave” though is Israel. See https://www.worldometers.info/coronavirus/country/israel/ . Scroll down a bit and you see a very nice bimodal curve: on March 7th just 4 cases; on April 2th we reach the top with 765; on May 15th down to 10, but yesterday June 27th back to 621 in a clearly rising curve.
What happened? Unfortunately, I couldn’t find a scientific paper. Just two reports in the general press: one suggesting that school reopening was involved; the other about collaboration with UAE on vaccine development.
https://news.yahoo.com/israel-uae-join-forces-fight-coronavirus-213037946.html
Another country that talks about a second wave is South-Korea. See
https://www.worldometers.info/coronavirus/country/south-korea/
https://news.yahoo.com/coronavirus-south-korea-second-wave-112229586.html
Please note that Korea already starts to fight with all means against a “second wave” when less than 100 cases show up in a country with over 50 million inhabitants, while most people in Belgium (with only 11.5 million), including some of our experts, are very happy with 90 cases daily (hence a five times higher incidence)….
Clearly, there are quite different attitudes towards this virus from “No passaran” in Mongolia and the prudent well-organized East-Asia and (most of) Scandinavia and the “German Empire” to “Laissez faire, laissez passer” in Sweden, UK-US and the self-satisfied West with “superior” health systems. With us in Belgium, nicely in between: a bit slow and rather disorganized, but with many competent people ready to act and self-organize (improvise?), as soon as it becomes really urgent. See the late Jean-Luc Dehaene “We will solve the problems when they arise”. To be read as ”Don’t waste too much time and energy in anticipating”? Belgian “bricolage”?
You could easily imagine that a new scientific ‘trans-discipline” of “socio-anthropo-virology” will emerge from this crisis….
Please note also that “second waves” or “new outbreaks” (whatever you like to call them) are not well-behaved: they do not wait until holidays are over and the Fall begins….
But, I guess I do not need to argue with this audience, rather with some of our policy-makers and a large part of our public opinion, who feel that we should finally stop whining and worrying about COVID and just take up our “normal” life….
Back to more fundamental science.
- Pathophysiological insights, focusing on endotheliitis (endothelialitis) and coagulopathy.
2.1. The ground-breaking letter from Zurich on April 15 in the Lancet shows 3 cases, clearly suggesting that endothelial cell infection and subsequent inflammation. Hence “COVID-19-endotheliitis could explain the systemic impaired microcirculatory function in different vascular beds and their clinical sequelae in patients with COVID-19” and “This hypothesis provides a rationale for therapies to stabilize the endothelium while tackling viral replication, particularly with anti-inflammatory anti-cytokine drugs, ACE inhibitors, and statins.” Especially in vulnerable patients with preexisting endothelial dysfunction, which is associated with male sex, smoking,
hypertension, diabetes, obesity, and established cardiovascular disease…”
2.2. The review by Mueller et al summarizes some hypotheses why ageing is an important risk factor.
- Fig 1: Viral alert signals are initially slow, resulting in greater viral replication. Defective macrophages and T cells with a limited repertoire of receptors are less effective. More cells are infected, inducing high levels of inflammatory cytokine signaling. The endothelial cell lining of the capillary becomes inflamed, fibroblasts are activated, and SARS-CoV-2 viral components and cytokines enter the bloodstream. Fluid fills the alveolus, reducing lung capacity and the virus infects microvascular pericytes in other organs. A cytokine storm initiates microvasculature clotting, causing severe hypoxia, coagulopathy and organ failure.
-Fig 2: Tightly controlled activation of the innate immune system is essential for viral recognition and clearance. Cytokine storm is the result of sustained activation of the inflammatory signaling cascade and can result in hypercoagulation in small blood vessels, which leads to tissue damage, DIC and multi-organ failure. Inflammaging and immunosenescence contribute to the development of cytokine storm
Next, some of the potential mechanisms are discussed: age-related epigenetic changes with a potential role of NAD+ and sirtuins, as well as other “biological clocks” (glycosylation and immune clocks). See Fig 3
Based on these mechanism, some novel approaches are proposed, such as NAD+ precursors, Metformin (known as an insulin stimulator) and even low-dose mTOR inhibitors. I’m a bit skeptical though, since, according to the authors, these products have “a myriad of effect” or even “hormetic effects” (meaning stimulatory at low and inhibitory at high doses). I guess we have all learned from experience that you have to be very careful with this type of products, of which you do not know in advance how they will act on people with a severely dysregulated metabolism, such as severe COVID cases…..
2.3. Conversely, kids avoid COVID complications, probably because of “healthy arteries” (with no tendency to endothelialitis and blood clothing). See Nature ‘News”
Maybe, I’ll be back tomorrow with some reflections on diabetes and COVID or else, it will be after July 10th.
Enjoy life,
Guido Vanham