January 16th, 2023

This week we look at new data on viral cell infiltration, mask efficacy, hyperlipidemia, micro and macronutrient metabolism post moderate to severe disease and then we switch over to random acts of kindness and then onto social media use and outcomes in teens.

 Omicron US strains: as of January 14th data - variants make up:

BA.5 @ 3%, BQ.1 @ 16%, BQ1.1 @ 29% - New strains XBB.1.5 @ 43%, XBB @ 4% and BN.1 @ 2%

XBB.1.5 the dominant strain where there was no increased risk of hospitalization or death in countries like Singapore where data has been tracked. The US data so far appears to be the same. Highly infectious, no increased death risk.

None of these VOC's are showing signs of increased disease morbidity.

Little else to report here. (CDC Variants)

Quick Hits and other musings -

1) Very interesting study looking at Covid 19 severity and the risk for downstream metabolic dysfunction. From Cell: "For a large cohort of patients representing the full spectrum of disease severities, we constructed a cross-omic interaction network (Figure 1E) that revealed, for example, COVID-19 severity-dependent connections between specific elevated cytokines and the downregulation of certain classes of metabolites and metabolic processes, suggesting an orchestration between increasing disease severity, elevated inflammation, and loss of key circulating nutrients. Further, the plasma multi-omic profiles captured a surprising similarity between moderate and severe COVID-19 and a sharp difference between mild and moderate infections. This major shift is marked by the preferential loss of lipids, amino acids, and xenobiotic metabolism (Figure 1D) and significant elevation of inflammatory cytokines (Figure 1C). The net implication is that of a stressed pro-inflammatory environment accompanied by decreased metabolic resources and signatures of possible hepatic dysfunction. Similarly, a sharp difference between mild and moderate cases is observed in peripheral immune cells. This is characterized by the significant elevation of activated adaptive immune cells, and the emergence of unusual phenotypes. An interesting example is that of CD4+ T cells, which exhibit both a proliferative exhausted phenotype and a clonally expanded CD4+cytotoxic phenotype. In fact, these two CD4+ phenotypes exhibit distinct functional signatures, distinct TCR sharing patterns, and may represent two divergent destinations for naive CD4+ T cells. Whether these phenotypes are harmful or protective remains unclear, but their relative abundances increase with infection severity, starting at the transition between mild and moderate disease." (Su et. al. 2022) Look at the figures in the paper as they are very illustrative of the shift in immune metabolic function.

What this paper details is the reality that mild disease from COVID19 is vastly different from moderate to severe disease in the downstream damage. Moderate or severely infected individuals have major shifts in macronutrient metabolism as well as clearing toxins due to damaged cellular machinery from the hyper inflammation induced by SARS2.

What this tells me is this: if you suffer moderate to severe Covid disease, you must begin a process of healing yourself. I would counsel myself to begin time restricted eating in a 16 hours off 8 on cycle. I would lean toward a keto style diet with whole foods mostly plants as the added non keto foods. I would exercise to tolerance while avoiding all toxins, especially alcohol and drugs that are metabolized by the liver. I would begin meditation and prayer daily for sympathetic and inflammation down regulation.

I can personally say that I had moderate disease in 2020 and it did take a toll on my system that I am still coming out from under. These studies help us plan for the future post illness.

2) Hyperlipidemia noted post acute covid illness. "In the post-acute phase of the SARS-CoV-2 infection, compared with the non-infected contemporary control group, those in the COVID-19 group had higher risks and burdens of incident dyslipidaemia, including total cholesterol greater than 200 mg/dL, triglycerides greater than 150 mg/dL, LDL cholesterol greater than 130 mg/dL, and HDL cholesterol lower than 40 mg/dL. The risks and burdens of these post-acute outcomes increased in a graded fashion corresponding to the severity of the acute phase of COVID-19 infection (ie, whether patients were non-hospitalised, hospitalised, or admitted to intensive care). The results were consistent in analyses comparing the COVID-19 group to the non-infected historical control group.""Experimental evidence suggests that the immune and inflammatory response following the initial infection could alter hepatic lipoprotein metabolism, which might transiently result in depressed levels during the acute phase with putative over compensatory rebound in the post-acute phase... Studies also suggest substantial changes in oral and gut microbiome and proteomic and metabolomic profiles of individuals infected with SARS-CoV-2 that could last well beyond the acute phase and contribute to changes in lipid profiles." (Xu et. al. 2022)

For me this is a clear indication that the immunolipidmetabolic system is mobilized to fight the acute SAR2 illness and takes time to revert to pre illness levels assuming that tissue was not permanently damaged and or post infectious lifestyle changes are maintaining the dysfunction. The graded response to the infectious disease burden is in line with what would be expected. More disease equals more immune cell/lipid cell involvement and more damage leading to longer time to recovery. It behooves everyone seeing these changes to recheck levels in a few months to assess long term damage as opposed to acute responses.

3) Are N95 masks superior to surgical masks? That has been the going belief for 2 + years. A study, says that maybe this is not so true. "In the intention-to-treat analysis, RT-PCR–confirmed COVID-19 occurred in 52 of 497 participants in the medical mask group versus 47 of 507 in the N95 respirator group. An unplanned subgroup analysis by country found that in the medical mask group versus the N95 respirator group RT-PCR–confirmed COVID-19 occurred in 8 of 131 (6.11%) versus 3 of 135 (2.22%) in Canada, 6 of 17 (35.29%) versus 4 of 17 (23.53%) in Israel, 3 of 92 (3.26%) versus 2 of 94 (2.13%) in Pakistan, and 35 of 257 (13.62%) versus 38 of 261 (14.56%) in Egypt." (Loeb et. al. 2022) This study was a multi country study over a 22 month time frame which means it covered multiple variants. This is reassuring for those in the high risk pools including healthcare workers exposed to actively ill persons and those with metabolic and immunologic risk.

4) Covid infects the entire body according to new research from Nature. "Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2. However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain. Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months." (Stein et. al. 2023)

This is concrete evidence that can only be seen reliably after death that this virus does in fact cause system wide disease as the virus travels everywhere in those that are ill. Since PACS/Long Covid appears to be systemic, I hypothesize that like Epstein Barr virus, this virus does this even after mild disease. Fascinating is an understatement.

Non Covid stuff:

5) In the Journal of Experimental Psychology we see an article about the Long Distance Love Bombs that I recently wrote about. "Performing random acts of kindness increases happiness in both givers and receivers, but we find that givers systematically undervalue their positive impact on recipients. In both field and laboratory settings (Experiments 1a through 2b), those performing an act of kindness reported how positive they expected recipients would feel and recipients reported how they actually felt. From giving away a cup of hot chocolate in a park to giving away a gift in the lab, those performing a random act of kindness consistently underestimated how positive their recipients would feel, thinking their act was of less value than recipients perceived it to be. Givers’ miscalibrated expectations are driven partly by an egocentric bias in evaluations of the act itself (Experiment 3). Whereas recipients’ positive reactions are enhanced by the warmth conveyed in a kind act, givers’ expectations are relatively insensitive to the warmth conveyed in their action. Underestimating the positive impact of a random act of kindness also leads givers to underestimate the behavioral consequences their prosociality will produce in recipients through indirect reciprocity (Experiment 4). We suggest that givers’ miscalibrated expectations matter because they can create a barrier to engaging in prosocial actions more often in everyday life (Experiments 5a and 5b), which may result in people missing out on opportunities to enhance both their own and others’ well-being." (Kumar et. al. 2022)

The key to this piece is knowing that your little efforts mean a lot to the recipient. Therefore, give it away as frequently as you can.

6) Are phones a drain on our capacity to be? From an article called Brain Drain, Adrian Ward writes, "In this research, we test the “brain drain” hypothesis that the mere presence of one’s own smartphone may occupy limited-capacity cognitive resources, thereby leaving fewer resources available for other tasks and undercutting cognitive performance. Results from two experiments indicate that even when people are successful at maintaining sustained attention—as when avoiding the temptation to check their phones—the mere presence of these devices reduces available cognitive capacity. Moreover, these cognitive costs are highest for those highest in smartphone dependence." (Ward et. al. 2017) They note that over 90% of smartphone users do not leave home without it and most check them almost 100 times a day. Only 20 years ago, this persistent connection was impossible. How does the persistent connection impact our cognitive ability? We know that it takes away from doing other things for our youth like playing an instrument, dating a person in person, reading books frequently (streaming reaction), reduced physical activity and much more.

More: "When these devices are salient in the environment, their status as high-priority (relevant and salient) stimuli suggests that they will exert a gravitational pull on the orientation of attention. And when consumers are engaged in tasks for which their smartphones are task-irrelevant, the ability of these devices to automatically attract attention may undermine performance in two ways. First, smartphones may redirect the orientation of conscious attention away from the focal task and toward thoughts or behaviors associated with one’s phone. Prior research provides ample evidence that individuals spontaneously attend to their phones at inopportune times, and that this digital distraction adversely affects both performance and enjoyment. Second, smartphones may redistribute the allocation of attentional resources between engaging with the focal task and inhibiting attention to one’s phone. Because inhibiting automatic attention occupies attentional resources, performance on tasks that rely on these resources may suffer even when consumers do not consciously attend to their phones. We explore this possibility in the current research.... Similarly, research in the educational sphere demonstrates that using mobile devices and social media while learning new material reduces comprehension and impairs academic performance."

The article is deep and excellent parsing through the data with regard to working memory and fluid memory and how they are affected by the smartphones using up capacity for these actions over time. These issues are way out in the forefront of issues that we are seeing in children. Working memory deficits are a common feedback result of psychoeducational testing in our patients. How much of this is attributable to the use of smartphones and streaming screens is a guess, but it is definitely not zero.

Keep these devices completely away from toddlers and young children. Absolutely, reduce the use in all young kids.

7) More on this same topic: From the study: "In this cohort study of 169 sixth- and seventh-grade students, participants who engaged in habitual checking behaviors showed a distinct neurodevelopmental trajectory within regions of the brain comprising the affective salience, motivational, and cognitive control networks in response to anticipating social rewards and punishments compared with those who engaged in nonhabitual checking behaviors." (Maza et. al. 2023)

Teens that habitually check their social media have brain changes that are concerning for social mood and anxiety over time. The changes were noted in the amygdala which governs emotions and memory. The changes increased over time with continued high social media usage noting a stacking effect over time. Disrupting these amygdala functions could have downstream effects that are lifelong and problematical for life success. The authors noted that the high users became desensitized to positive social cues and punishments from live actions with others

That's all this week!

Dr. M

Su Cell

Xu J Lancet Diabetes and Endocrinology

Loeb Annals Internal Medicine

Stein Nature

Kumar J Exp Psychology

Ward University of Chicago Press Journals

Maza JAMA Pediatrics


CDC Variants Page

CDC Covid Deaths