This is a terrific question. If children are said to have strong vagal activity, is it compared with the vagal tone in adults? Or compared with sympathetic nerve?

What is the cause of low infection rate and low mortality in children is not well explained by studies on COVID-19 to date?

It could also be because either children's naive immune system reacts too weakly to cause symptoms. In some respects, this may be more worrisome as asymptomatic people are less likely to be tested. Asymptomatic children with COVID-19 are high risk to spread the infections particularly as they themselves would often not take control precautions compared to adults.

If it is due to strong vagal tone or blunted sympathetic tone then children should also have relative bradycardia (Faget's sign) when affected with COVID-19. No study has noted this aspect, although irrespective of the age some viral infections (Dengue, Yellow fever, and West Nile fever) have been well known to result in this sign. A feature of children with COVID-19 compared with adults was a rise in procalcitonin indicating that children are more likely to develop secondary bacterial infection.

However, unless studies in children having COVID-19 regarding viral load, immune function (igM, IgG antibodies and lymphocyte count and type (CD4 and CD8) are done, the exact reason is only speculative and at best an hypothesis needing testing.

Weiguo Zhang, vagal activity and sympathicovagal ratio (low frequency /high frequency HRV) are both age dependent, with a little stronger age dependency of vagal activity. Children do have most of this inflammation solving (see below) vagal activity, about 3 x more then a 70 year old subject (the scale is logarithmic in the figure attached).

Some researchers think that in COVID-19, the cytokine flush, produced by our own body (autoimmune reaction) is making the troubles in pneumonia, not the virus itself. Therefore a high vagal activity might be beneficial for the outcome and possible complications.

I add two yet unpublished figures we generated from circadian data of heart rate variability of about 1000 healthy subjects of different ages. They show vagal activity (computed from logRSA) and sympathico-vagal balance (computed from ratio of LF to HF activity of HRV). Vagal activity decreases with age, sympathico-vagal balance increases.

I may have to add some information not so known by folks not familiar with the newly discovered functions of the autonomic nervous system, and quote from our recent paper (Article Dynamics of Vagal Activity Due to Surgery and Subsequent Reh...

"Vagus nerve is the longest nerve of the autonomic nervous system (ANS) and the key component of parasympathetic nervous system. Its baseline activity, often refered to as vagal activity, is crucial for maintaining several body functions at rest, including heart, lungs, and digestion. Vagal activity is stronger during sleep, stabilizing the body’s circadian rhythms, which are key for good general health (Mundigler et al., 2002; Moser et al., 2006a; Kastner et al., 2010; Rocha

et al., 2011; Scheiermann et al., 2013; Curtis et al., 2014; Papaioannou et al., 2014; Alamili, 2015; Madrid-Navarro et al., 2015; Wright et al., 2015).

Vagal activity is also the critical factor behind the functionality of the inflammatory reflex, mechanism responsible for resolving the inflammation once its purpose has been served (Tracey, 2002, 2007; Moser et al., 2008; Rosas-Ballina and Tracey, 2009; Leslie, 2014;Mayer, 2015).

...

Vagal afferents carry receptors for these signals and communicate with certain stem brain areas transmitting the information on inflammation location and strength (Andersson and Tracey, 2012). Upon processing this information, vagal efferents respond by release of acetylcholine at the location of the inflamed tissue (Olofsson et al., 2012). Nicotinergic acetylcholine receptors have been identified on the surface of the macrophages, which down-regulate their cytosine production as a response to the cholinergic stimulation (Rosas-Ballina and Tracey, 2009), thereby reducing the attraction of additional inflammatory immune cells. This inflammatory reflex loop prevents over-activity of the immune system enabling the brain to locally control the immune activity. It also represents the “first line” of inflammation control (Olofsson et al., 2012).

In addition to improving the effectiveness and usefulness of the inflammatory reflex, a strong vagal activity protects against several serious or chronic conditions. They include atherosclerosis, ulceral colitis, Hashimoto’s disease, type 2 diabetes, cancer (Donchin et al., 1992; Moser et al., 2006a; Das, 2011; Huston and Tracey, 2011; Chow et al., 2014), and sepsis, which is know to be related to weakening of body’s natural ability to resolve the inflammation (Tracey, 2002; Nguyen et al., 2006; Nathan and Ding, 2010). The vagus nerve can be electrically and pharmacologically stimulated, while its overall activity can be improved via acupuncture, nutritional therapies, and physical exercise (Huang et al., 2005; Moser et al., 2017).

…independent of the origin of inflammation, vagal activity is always reduced in inflammatory conditions (Lujan and DiCarlo, 2013). This may lead to a positive feedback loop or a vicious circle, entangling the inflammation reflex, and the accompanying pathology. Some forms of obesity are indeed known to lead to inflammation, while at the same time the chronic inflammation promotes obesity-associated diabetes (Wang et al., 2003). This indicates that besides in the development of sepsis, dysfunctional vagal control or circadian disturbance of the ANS could play a role in several key diseases of modern society, including cardiovascular diseases, metabolic syndrome and/or even development of cancer (Moser et al., 2006b; Eiró and Vizoso, 2012)."

Thank you Maximilian Moser for your impressive work. A higher heart rate variability indeed represents one of the mechanisms children have in adapting to and bouncing back from some stresses in general.

Children produce much more Melatonin than adults and this is related to vagal activity. In haled Melatonin is useful against lung injury caused by NLRP3 inflammasome "by both suppressing the release of extracellular histones and directly blocking histone‐induced NLRP3 inflammasome activation."

Article Melatonin alleviates acute lung injury through inhibiting th...

In 8579 cases from 30 provinces out of Wuhan, “the median age of cases was 44 years (33-56)... “ though “schools in China were closed for most of the epidemic because of the 2020 Chinese New Year holidays” https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(20)30230-9.pdf

Reduced Heart rate variability is an important prognostic factor predicting sudden arrhythmic death after acute myocardial infarction (AMI). Several studies have demonstrated increased arrhythmic as well as nonarrhythmic mortality in AMI populations with low HRV. Those studies included traditional methods based on time -or frequency- domain analysis and newer fractal analysis techniques which are based on time-domain analysis . The study showed, that the so-called multipole method provides more prognostic information on patients after acute myocardial infarction than previously suggested risk markers. We can therefore state that the multipole method extracts information both in the frequency domain as well as in the time domain, and therefore performs betterin prognostics than the traditional HRV methods. We can conclude that HRV has both diagnostic as well as prognostic power.