Category: Covid-19

Karen Bulik, RN, left, administers a vaccine for James McNeill inside a walk-in clinic for the newest COVID-19 boosters at the Kaiser Permanente Highlands Ranch Medical Office on October 1, 2022 in Highlands Ranch, Colorado. (Photo By Kathryn Scott/Special to The Denver Post)

COVID-19 hospitalizations across Colorado have increased steadily since August and are nearly at their highest point of 2023, though there are indications this latest wave which is much smaller than earlier surges could be starting to wane.

At the same time, the season doesnt appear to have started in earnest locally for the other major respiratory viruses.

Data from the Colorado Department of Public Health and Environment showed 257 people statewide were hospitalized with COVID-19 as of Tuesday, up from 236 a week earlier and a nearly 360% increase since this years low point on Aug. 1.

Still, thats significantly fewer than when more than 1,500 people were hospitalized with COVID-19 during each of the pandemics largest spikes in December 2020, November 2021 and January 2022.

Its possible some of the current COVID-19 patients were admitted for other reasons and tested positive, but since hospitals no longer routinely test everyone for the virus, thats likely not driving the current increase.

The number of people receiving hospital care for COVID-19 was at its highest level in 2023 during the first week of January. In the fall of 2022, COVID-19 hospitalizations peaked at 440 during a wave that crested in late November.

There is some indication that COVID-19 may have peaked for now, because emergency department visits for the virus are down somewhat from mid-October, said Dr. Thomas Campbell, a professor of medicine in the infectious diseases division at the University of Colorados Anschutz Medical Campus.

With new variants continuing to emerge and immunity waning, however, its likely well see more of the virus in the coming months, he said.

I would expect that even if this current COVID wave is declining, well have another COVID wave this winter, Campbell said.

Unlike last year, there isnt much activity from flu and respiratory syncytial virus in Colorado yet. In the week starting Oct. 22, the state health department reported 17 hospitalizations for flu and 19 for RSV. Both were down slightly from the prior week, though that may reflect incomplete data.

In Colorado, respiratory viruses accounted for about 2.8% of emergency department visits as of Oct. 21, with the majority of those attributed to COVID-19, according to the Centers for Disease Control and Prevention. In comparison, about 11% of emergency room visits in Colorado were for respiratory viruses at the worst point last November.

Nationwide, the percentage of emergency department visits for respiratory viruses was comparable to Colorados, though COVID-19 accounted for a lower percentage of visits.

Last year, flu activity started unusually early. The early circulation may have contributed to a higher hospitalization rate among children and teens, because more people got infected before receiving the vaccine than in a typical year, according to the CDC. This year, it looks like the season wont peak until December or January, Campbell said.

This fall, there are shots available for the three major respiratory viruses: the annual flu vaccine, a COVID-19 shot updated to protect against newer variants, and two shots for RSV. The flu and COVID-19 shots are recommended for everyone six months and older, but the RSV shots are only available for people over 60 and pregnant women. There is also an antibody drug available to protect infants from RSV, but because of a shortage, it may only be available for babies at elevated risk.

While the vaccines dont protect against all infections, they significantly reduce the odds of severe illness, Campbell said. In the Southern Hemispheres flu season earlier this year, the vaccine cut the risk of hospitalization roughly in half. People at high risk can also protect themselves by getting antiviral treatment for flu or COVID-19, he said.

Nationwide, hospital admissions for COVID-19 remained essentially level over the past week, with no clear geographic pattern to where they were increasing or decreasing.

Flu activity was still low, though it has started to pick up in New Mexico, Florida, Alaska and Hawaii, according to the CDC. RSV prevalence is starting to rise in all regions, though it is significantly more widespread in the South than in the rest of the country.

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Colorados COVID hospitalizations keep rising, while flu and RSV stay low - The Denver Post

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Yet another version of Omicron has taken hold in the United States.

The variant, called HV.1, now comprises a quarter of all COVID-19 infections in the U.S., according to CDC estimates. It is most prominent in the mid-Atlantic region, where it makes up about a third of the cases.

The recent dominance of the variant comes as health providers are administering a newly formulated COVID-19 vaccine. Some 99% of the variants now circulating in the U.S.including HV.1are part of the same viral family as the XBB variants that the updated vaccines are designed to target.

Of people who are eligible for the updated COVID-19 vaccines, only 7.1% of adults and 2.1% of children have received a dose since they became available in mid-September.

While many Americans now have some immunity to COVID-19, the slow uptake of vaccines could leave many high-risk people vulnerable to severe illness in the coming months, said William Schaffner, MD, a professor of infectious diseases at the Vanderbilt University School of Medicine.

The general lack of acceptance of this new updated vaccine plus these new variants that are highly transmissible may come together this winter, Schaffner told Verywell. If the immunity from previous vaccines has waned substantially by this winter, and has not been boosted by the new updated vaccine, then I think we could see, once again, a surge in hospitalizations.

The COVID-19 variants that gain dominance over others typically do so because they have evolved to become more transmissible.

My general sense is that the Omicron progenythe children, grandchildren, and great-grandchildren of Omicronare, in general, pretty darn transmissible, Schaffner said.

However, he added, theyre not severe. The reassuring information still comes from the immunologists telling us that so far, the vaccine that was created will continue to provide substantial protection against severe disease.

HV.1 evolved from EG.5, which is a member of the XBB. The updated vaccine is expected to protect against serious illness from HV.1 and other circulating strains, according to Kate Grusich, a public affairs specialist at the CDC. COVID-19 cases also havent become notably more severe since the variants emergence.

Although HV.1 represents an increasing proportion of infections, indicators such as test positivity, hospitalization, and emergency department visits currently indicate an overall decreasing number of infections, Grusich told Verywell via an email.

As is true with all versions of the COVID-19 virus, vaccination is one of the best ways to protect yourself against the most serious outcomes of infection by HV.1. Getting an updated shot can ensure your immune system is primed to recognize and attack against the currently circulating strains.

While the CDC said that all people 6 months and older can be vaccinated, the agency especially recommends the shot for anyone who is older than 65, is immunocompromised, or has a chronic medical condition like heart disease, lung disease, and diabetes.

Wearing a well-fitting face mask can effectively reduce your risk of getting sick or getting others sick if you feel unwell. Testing yourself for COVID-19 and staying home when you experience symptoms of respiratory illness can also slow the spread.

In addition to COVID, influenza is just starting out there. RSV is smoldering at the moment. It hasnt taken off yet. But were now nosing into November, and thats when both of those viruses frequently also get going, Schaffner said.

Influenza vaccines are available for all people 6 months and older, and new RSV vaccines are available for people older than 60 years and for newborns.

HV.1 has now overtaken EG.5, which was dominant in the summer. FL.1.5.1 now makes up about 12% of U.S. cases.

For months, the CDCs variant proportion table has been cramped with the dozens of different variants that have emerged this year. Each variant has some mutations that distinguish it from the others, but none has evolved past Omicron.

I would think that the Omicron pattern is now well established. We can expect continuous mutation and a succession of variants coming up, each one succeeding others, creating a mix of sub-variants, Schaffner said.

Virologists are constantly on the lookout for variants that can cause more severe disease or can better escape natural and vaccine-induced immunity.

At the end of the summer, some scientists expressed concern about BA.2.86, a highly mutated Omicron subvariant that popped up on surveillance systems then. Early sequencing showed the variant to have certain mutations that made it potentially more likely to evade our immune defenses and become a variant of concern deserving of a new Greek letter.

However, BA.2.86 never took offcases attributed to the variant remain low and studies now show that the updated COVID-19 vaccines can sufficiently neutralize it.

However, its close relative, JN.1, is now the fastest-growing lineage, according to Cornelius Roemer, MS, a computational biologist at the University of Basel.

Theres only one change between BA.2.86 and JN.1 in the spike proteinthe outermost protein that allows the virus to enter the cell and JN.1 makes up fewer than 0.1% of the COVID-19 cases now. The CDC said it expects that vaccines will be able to protect against JN.1, just as they do against BA.2.86.

Despite the scientific interest in these new variants, the CDC emphasized that 99% of the circulating variants are part of the XBB familywhich is targeted by the updated COVID-19 vaccine.

If you have not yet received the updated COVID-19 vaccine, you can find a vaccination site through the governments website, Vaccines.gov. You can also order four free at-home COVID-19 tests at COVID.gov.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit ourcoronavirus news page.

By Claire Bugos Claire Bugos is a staff writer at Verywell Health.

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What You Need to Know About the New HV.1 Variant - Verywell Health

The results of this exploratory questionnaire-based study of the effect of treatment with an SSRI in PCS show that an SSRI contributes significantly to the reduction of PCS symptoms. 63.4% (n=95) of patients reported a reasonably good to strong decrease in symptoms and an improvement in functioning. This increased quality of life can contribute to social participation. Four patients had developed clinical depression or anxiety disorder during PCS. Treatment with an SSRI also eliminated these disorders. People who had felt despondent due to PCS also felt less gloomy after an SSRI, but all attributed this to the reduction in their PCS symptoms.

An explanation for the skewed gender distribution in this studyalso found in other research in PCSmay be that many genes for the immune system lie on the X chromosome so that men are more likely to have severe Covid-19 infections, but women are more likely to have more severe PCS symptoms that last longer7,49.

The high level of education in this study compared to other studies1 can probably be explained by the recruitment of patients through LinkedIn. The overrepresentation of female patients from healthcare and education could be caused by the predominance of female workers in these professions on the front lines of the pandemic. Moreover, they returned to work quickly after their Covid-19 infection which is a risk factor for PCS1. Many other risk factors for PCS in this study are consistent with Daviss review article1, such as: asthma, allergies, connective tissue diseases, Epstein-Barr virus etc. A notable addition to the known risk factors is factor V Leiden thrombophilia. In this study, there were two patients with this coagulation disorder, while the prevalence in the general population is only 1:500050. Patients with this coagulation disorder have an 80-fold increased risk of thrombosis.

All patients in our group (n=95) were chronically fatigued during PCS while in a German study11 only 19/42 patients of the PCS study population reported chronic fatigue such as in ME/CFS. An explanation for this difference could be that fatigue in PCS increases with time. While the duration of PCS in the German study was only six months, in our study it averaged 15months. Also, in this German study, of the other PCS patients without chronic fatigue (23/42), only 15 had a neurological or cognitive impairment. In our study, 100% had a neurological or cognitive impairment. However, neurocognitive symptoms begin only a month to a few months after Covid-19 infection and worsen over time51.

No validated questionnaires are yet available for PCS. However, with a new disease, it is important to learn about all symptoms, so we used a questionnaire that included open-ended questions. Thus, we discovered that symptoms can shift over time. Dyspnoea and decrease in smell seem to decrease over time, while fatigue and brainfog seem to increase. Through the open-ended questions we also discovered new symptoms, such as dissociatieve symptoms and not being able to chew properly.

Using three different instruments to determine treatment effectiveness is a further strength of this study. There is strong evidence for the reliability of these measures. The Bell score is a widely used instrument in research on (chronic) fatigue, although not validated. Furthermore, the rating of the Open question outcomes was found to be reliable. Importantly, the three effect measures correlated strongly with each other, supporting the reliability of the individual measures.

The main weakness of this study is that it is not a randomized controlled trial (RCT). We had no control group. Therefore, a placebo effect cannot be ruled out. However, it is known that 85% of patients who have symptoms two months after Covid-19 infection still have them after one year1. ME/CFS and dysautonomia are usually lifelong1. So without treatment with an SSRI, many PCS patients may suffer from these conditions in permanently.

And there is more evidence that a placebo effect may not fully explain the positive results. A placebo effect usually occurs shortly after the start of an intervention and diminishes again after a few weeks, unless a positive expectation is given again52. However, 72 patients (n=95) still had no response in the first weeks, but instead suffered side effects. The 24 patients who used the SSRI for more than six months reported that the effect was maintained, while they were not asked by us to do so, as we had no treatment relationship with the patients. A cohort study without a control group also does not exclude natural recovery. However, because the participants had been seriously ill for 1.5years and deteriorated over time, it seems highly unlikely that, if they had received an SSRI and recovered after a few weeks, this would have been due to natural recovery.

Working with self-reporting is always vulnerable to biases. However, self-report often expresses the experience of patients better. In psychiatry not all physiological parameters can be measured. We also asked the patients to rate their complaints on a scale of 1 to 10. By inviting them to compare the severity of their complaints, we introduced more structure into the self-report.

Finally, low-cost SSRIs are covered by insurance and there is no cost to the patient, which argues against a placebo effect53. However, the possibility of a placebo effect can only be completely ruled out by an RCT.

The Bell score before Covid-19/PCS and the Bell score during PCS before starting an SSRI were completed retrospectively by all patients. This may have led to some bias. The complaint of PEM was not part of the 8 complaints in the Score list; patients had to list and score this on their own under "other complaints". This may have led to underreporting of this important symptom. LinkedIn gave an overrepresentation of patients with a higher level of education, but perhaps also of a group of initially healthy people who were fully employed. It is precisely in this group that the impact of PCS as well as the outcomes of an SSRI may be well observed.

Normally the catabolic kynurenine pathway (KP) degrades 95% of the essential amino acid tryptophan to produce the vital energy cofactor NAD+. The rest of the tryptophan serves as a precursor for serotonin and melatonin. (See Fig.6). In addition to NAD+, the KP generates different metabolites: kynurenine, kynurenic acid, 3OH-kynurenine, quinolinic acid, anthranilic acid and 3OH-anthranilic acid. The KP is stimulated by inflammation and in PCS it is found overactive26,27,28,30,32.

The overactive KP affects the serotonin pathway. The aryl hydrocarbon receptor (AHR) has a role in regulating immunity and induce transcription of indoleamine 2,3-dioxygenase (IDO-2) enzyme. The amount of IDO-2 in PCS is abundant and causes autophagy and reduced mitochondrial functioning28. Because the metabolites kynurenine and kynurenine acid are agonists of the AHR receptor, there is a runaway positive feedback loop producing more and more metabolites28,30,31,32. Several of the metabolites are potentially toxic. Kynurenine and oxidative stress block the enzyme tetrahydrobiopterin (BH4)1,56, inhibiting both the serotonin pathway and the dopamine pathway1,20,55,56. Kynurenic acid is a nicotine-receptor antagonist and a glutaminergic-receptor antagonist28,30,32. Quinolinic acid blocks the glutaminergic receptor28. When we want to intervene: the kynurenine pathway can be inhibited in various ways and the serotonin pathway can be stimulated in various ways. Intervening through an SSRI has been the most important so far.

The overactive KP absorbs more than 95% of the tryptophan in PCS. Research shows that the amount of tryptophan in blood is decreased in PCS patients30,31,32. Tryptophan deficiency is probably already present during the infection with Covid-19, because Covid-19 attaches with its spike proteins to the Angiotensin Converting Enzyme (ACE2) receptors in the intestines, while tryptophan also uses the same receptor to be absorbed from the intestines54. There is a significant relationship between the level of metabolites in blood and the severity of cognitive impairment in PCS28, (p<0.001)30,31. The KP has normally potentially neurotoxic as well as neuroprotective aspects. An overactive KP during a severe infection however, is toxic for neurons, especially for serotonin neurons. Not only does the KP hijack tryptophan away from the serotonin pathway28,30,31, the metabolite kynurenine and oxidative stress also lowers the level of tetrahydrobiopterin (BH4)1,55,56, an important coenzyme of the serotonin pathway. Moreover, BH4 is an important coenzyme of the dopamine pathwayand to the norepinephrine pathway20,55thus the overactive KP damages these two neurotransmitter systems too. When there is no longer enough tryptophan, this can lead to serotonin depletion16.

SSRIs make the serotonin in the neurons more available through inhibition of reuptake and can partly compensate for the deficiency of tryptophan57. Moreover, SSRIs lower oxidative stress58. That could be an explanation for our finding that PCS patients often have fewer complaints due to SSRIs. But that may come to an end when all the serotonin from the neurons is in the synapses. Nevertheless, after half a year or more (in this research 24 patients), many people still felt good when using an SSRI. So we can (hypothetically) conclude that an SSRI probably indirectly contributes towhen there is a lack of serotonin in the neuronsthat these neurons start to pull harder on the available tryptophan. So SSRIs could slow down the overactive KP. There is no theoretical argument against this hypothesis16.

But there are more avenues for future research advancing this line of clinical research based on tryptophan metabolism. IDO2 expression can be halted by an AHR antagonist28, such as the dietary supplement resveratrol59 or the experimental anticancer drug IK-17560. Furthermore, kynurenine is a glutaminergic receptor antagonists and quinolinic acid even blocks this receptor28. N-acetylcysteine (NAC) not only produces the antioxidant glutathione, but is also a glutaminergic receptor agonist61. The poisonous quinolinic acid and kynurenine acid are nicotinic receptor antagonists. Nicotine isa nicotinic receptor agonist. Tostick nicotine patches helps PCS patients. This may be not only because nicotine is a nicotinic receptor agonist and therefore an opponent of these poisonous metabolites, but nicotine is a strong acetylcholine (ACh) agonist as well62. ACh is the most important neurotransmitter in muscles. Furthermore, folic acid (vit. B11)63 can promote the conversion of B2 back into B455,63 in favour of the serotonin and dopamine pathway.

After a stressful event, the hypothalamus secretes corticotropin-releasing hormone (CRH), which causes the pituitary gland to secrete adrenocorticotropic hormone (ACTH), which in turn causes glucocorticoids (GCs) to be released by the adrenal cortex.

In PCS cortisol (glucocorticoids) levels were on average halved19. That is an indication that the HPA axis is disrupted14,19. In comparison, in ME/CFS, the HPA axis is less severely disrupted12. GCs released by the adrenal glands, act on almost all types of immune cells and perform evident immunosuppressive and anti-inflammatory functions14,15,16,17,18. SSRIs affect the HPA axis16,64. For example by increasing GC receptor density in the hypothalamus and hippocampus (the memory control centre). Further on, acute administration of 5-HTP receptor ligands increased the plasma levels of ACTH and cortisol in both animals and humans15,16. But the effect is not one-dimensional. For example: in patients with major depression with high cortisol levels, an SSRI lowers the cortisol level but triggers a higher Cortisol Awaking Response (CAR)14,15,16,17,19. In ME/CFS, an SSRI works moderately in only one-third of patients12. SSRIs seem to work better in PCS than in ME/CFS. This may be an indication that SSRIs are (partly) effective in PCS by influencing this hormone axis. Another indication of this hypothesis is our report of the patient who was given hydrocortisone because PCS caused her only functioning adrenal gland to fail, but who recovered with an SSRI, after which she was able to taper off the hydrocortisone. In this patient, the SSRI apparently restored not only the HPA axis, but also the disrupted hypothalamic-pituitary-thyroid axis15,16. The question is therefore whetherapart from the HPA axismore hormonal axes starting from the hypothalamus are disturbed by Covid-19/PCS. Thus, reported changes in the menstrual cycle after Covid-1965 could also result from a disrupted hypothalamic-pituitarygonadal axis.

The brain stem, the oldest part of our brain, is responsible for basic functions such as body temperature, sleepwake rhythm, heart rate, breathing, blood pressure, digestion, eye movements, urination, hearing, tasting, chewing, swallowing, and feeling movement and gravity. Neurotransmitters that are especially important there include serotonin, norepinephrine and dopamine10. The serotonergic neurons start in the raphe nuclei in the pons and may exert their influence there10.

The Covid-19 virus enters the brain stem cells easily attaching to the many ACE2 receptors66. Hypometabolic areas in the pons were found in a study of three PCS patients. Typically, SSRIs worsen sleep quality67, though, not always68. In this study, 29 patients reported in the open-ended question that their sleep improved on the SSRI. This could be explained by the influence of the SSRI on the brainstem. But this may not be the only reason that patients sleep better. We saw in Fig.6 that the sleep hormone melatonin originates from serotonin. When the serotonin neurons withdraw more from the available tryptophan, more melatonin can be produced in addition to more serotonin. The decrease in palpitations, shortness of breath, gastrointestinal complaints, better temperature regulation (one patient) and the ability to chew better (one patient) also supports the idea that SSRIs may (partially) restore the neurotransmitter systems disrupted in the brainstem.

Dysautonomia, especially POTS, is often a symptom of PCS. The clinical picture with a Bell score of 20 or less (almost half of the patients in this study) is striking, as shown by the answers to the open questions: overstimulated patients with palpitations lying limp and exhausted on the couch. In this state, the brainstem shows heightened arousal and seems to be in the fight-or-flight response along with the sympathetic nervous system14,69. This is a primitive survival mechanism in the face of danger, in which the sympathetic ANS dominates. The 'fight-or-flight' response activates the HPA axis so that extra cortisol is released and glucose is released into the muscles for action69. Instead, measured cortisol levels in PCS patients average only 50% of normal19 and the muscles are weak rather than ready to contract. The muscle weakness is not only because no glucose is released in the muscles. It is also because PCS is associated with autoantibodies against the G protein-coupled adrenergic receptor and muscarinic acetylcholine receptor70. Acetylcholine is the main neurotransmitter that sets muscles in motion.

The vagus nerve of the (parasympathetic) ANS also originates from the pons in the brainstem. But this nervejust like musclesuses acetylcholine as a neurotransmitter, so an SSRI cannot intervene there. One speaks of a paralyzed vagus nerve, probably because of the autoantibodies against the muscarinic acetylcholine receptor1. The sympathetic ANS predominates over the parasympathetic ANS in PCS, while G protein-coupled autoantibodies against the adrenergic receptor are also present. Perhaps the (nor)epinephrine pathway has fewer problems with the overactive KP, because it does not use tryptophan as a precursor, but phenylalanine. SSRIs often seem to reduce POTS and palpitations. This is unrelated to an inhibition of serotonin reuptake, as serotonin does not affect the ANS. The inhibition of norepinephrine reuptake may reduce POTS, but could theoretically lead to palpitations. The reduction in palpitations must be found in another mechanism, such as the influence of SSRIs on the anterior cingulate cortex (ACC) in the brain61.

Brainfog and sensory overload responded best to treatment with an SSRI. The raphe nuclei (pons) in the brain stem is the location of the origin of the serotoninergic system. From there, axons are sent throughout the CNS10. So SSRIs can intervene throughout the whole brain.

Dissociative symptoms also disappeared. In sensory overload and dissociation, there is sensory overload due to lack of filtering. The primary unimodal sensory brain regions do not cooperate well with the associative sensory brain regions71,72. It is known that an SSRI can sometimes help with this71,73.

Many PCS patients struggle with forgetfulness1. In the hippocampus, the control centre of memory, serotonergic neurons are dominant74 SSRIs also stimulate the production of serotonin cells in the hippocampus74. Possibly partly because of this, the patients forgetfulness decreased.

The SSRIs fluvoxamine and fluoxetine have been shown to have extra anti-inflammatory effects during Covid-19 infection by inhibiting sphingomyelinase acid (ASM)33. Furthermore, an SSRI reduces the pro-inflammatory cytokines Interleukin 2 (IL 2) and IL 17 in the CNS. In this case, the SSRI must be a sigma1 receptor agonist. This opioid receptor is inter alia involved in reducing virus replication and inhibiting reactivation of herpes viruses such as Epstein-Barr Virus (EBV) and subsequent endoplasmic reticulum (ER) stress and inflammation35. We recommended only SSRIs who are sigma1 receptor agonists34,35. One patient was first given sertraline by the GP, with no response. After switching to citalopram, she did respond reasonable good. In five other patients, GPsprescribed the sigma1 receptor antagonists sertraline (n=4) or paroxetine (n=1). These five patients reported good (n=2), reasonable good (n=2) or moderate (n=1) improvement. There was no evidence in favour of or against a difference in effect measured by the open question depending on whether patients received sigma1 agonists or antagonists (BF=0.43). If we include the patient who changed from sertraline (no effect) to citalopram (reasonable good effect), no significant difference remains (BF=0.39) This is only anecdotal evidence that the mechanism via the sigma1 receptor plays a role in the action of SSRI in PCS. However, the group using a sigma1 antagonist in this study is too small for a proper statistical analysis.

Many Covid-19 and PCS patients have microclots indicative of coagulation problems. Microclots impede oxygen and nutrients flow to organs and tissues8. Platelets are involved in clotting. Platelets transport serotonin, because serotonine has a function in clotting. With serotonin deficiency, platelets become less functional. Because SSRIs inhibit the reuptake of serotonin in platelets, they prolong clotting time and could theoretically dissolve microclots75,76. The two patients with factor V Leiden thrombophilia responded well and moderately, respectively. This could mean that the anticoagulant effect of SSRIsassuming that microclots played a role in these patientsmight contribute to their response. If it were confirmed that PCS is more common in factor V Leiden thrombophilia, this coagulation disorder should be added to the list of risk factors.

But an SSRI can benefit blood circulation in other ways, too. They may show an anti-inflammatory effect on endothelial cells. SSRIs reduce the expression of cytokine-induced endothelial adhesion. This makes it difficult for circulating adhesion molecules, such as monocytes, to adhere77. This mechanism may partially explain their cardioprotective effects76.

Muscle pain and weakness decreased the least in the total group (n=95). We also see this in the patients with fibromyalgia (n=5) who reported little or no improvement after using an SSRI.

The group of non-responders (n=9) were more severely ill with Covid-19 infection than those who did report good response to SSRIs. It is possible that the cascade of severe inflammation caused by Covid-19 in the CNS78 released much histamine. Inhibitory histamine receptors lower serotonin in the CNS, preventing an SSRI from effectively releasing extracellular serotonin40. By adding Histamine1 and 2 antagonists to treatment, an SSRI could in principle still become effective40. However, the lack of response to an SSRI may also have been caused by a serious factor: namely, neuropathology similar to Alzheimers disease is found in Covid-19 infections. In the CNS -amyloid aggregations, plaque formations, tauopathy and cell death have been described79. In these conditions, an SSRI cannot possibly be effective anymore.

Our hypothesis is that for many PCS symptoms, neurotransmitter systems are not damaged but dysregulated and most likely suffering from a tryptophan deficiency due to an overactive KP. But after a chronic course of PCS lasting two years, SSRIs cannot be expected to reset these systems in a short time as long as the kynurenine pathway is still overactive. By comparison, the treatment duration for initial depression is six months to one year and for recurrent depression usually at least 3years80. In toxic drug-induced depersonalization disorder, sometimes 6years of treatment is advised (first authors clinical experience)73. Drug-induced depersonalization disorder is phenomenologically similar to PCS, excluding fatigue and muscle pain. Poor stimulus selection, sensory overload, derealization and brainfog are similar in the two conditions. The preliminary recommendation is to continue treatment with an SSRI for at least 1.52years. More research is needed to support our hypothesis regarding the resetting of neurotransmitter systems by SSRIs. Another possibility could be that SSRIs only suppress symptoms because of the tryptophan deficiency. Contrary to this is the experience of two patients (the first one with a very low Bell score of 20 at the start of SSRI treatment) who discontinued the SSRI after 8months and a year, respectively, because they felt completely healthy for 2 and 7months, respectively. They continue to do well (seven and four months after discontinuation). However, most patients mention that, despite the good response to the SSRI, they must be cautious of not exceeding their limits. The PEM had become much less, but with too many activities in a row, a relapsealbeit shorter and less severe than beforecould follow.

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Treatment of 95 post-Covid patients with SSRIs | Scientific Reports - Nature.com

Summary: A recent study reveals that individuals who experienced childhood adversity, such as neglect or abuse, faced higher chances of COVID-19 hospitalization or mortality in adulthood.

Analyzing over 151,200 adults from the UK Biobank, researchers linked increased reports of early life adversity to 12-25% elevated odds of severe COVID-19 outcomes. This connection remained significant even after accounting for other known risk factors.

The findings underscore the far-reaching impacts of early-life trauma on health outcomes, even decades later.

Key Facts:

Source: University of Pittsburgh

People who endured childhood adversity, like abuse or neglect, were more likely to be hospitalized or die from COVID-19 in adulthood, a new University of Pittsburgh study found. Specifically, higher self-reported childhood adversity was linked to 12-25% higher odds of COVID-19 hospitalization and mortality.

While age, sex, ethnicity, health, and sociodemographic factors have been related to such outcomes throughout the pandemic, this was the first study finding a link between these COVID-19 outcomes and childhood neglect and abuse.

Using the UK Biobank in Great Britain, a team lead byJamie L. Hanson, a researcher in Pitts Learning Research & Development Center and an assistant professor in psychology in the Kenneth P. Dietrich School of Arts & Sciences took a deep dive into information provided by more than 151,200 adults of middle age or older.

What the numbers showed was that people who reported adversity such as abuse or neglect while children were more likely to die or be hospitalized from COVID-19.

The study was published Nov. 1 in theJournal of Epidemiology and Community Health,the British Medical Associations journal focusing on different social determinants of health.

These findings highlight how trauma early in life can have long-lasting impacts on health decades later, Hanson said.

We know that COVID-19 is related to excessive hospitalization and death in the UK and in the United States. And theres emerging research finding that facing adversity, abuse or neglect, early in life, could have sizeable effects on physical health.

But no one had tried to connect these two trends. Knowing a bit more about someones early development could be important to help reduce disparities in COVID-19.

While Hanson and his co-authors maintain that their work opens the door for more pinpointed and global studies, they believe their findings show there could be a need for policies and interventions to lessen COVID-19 impacts in people who have suffered from such childhood adversity.

We may need targeted interventions for individuals and certain communities affected by childhood adversity to lessen the pandemics lasting impact, Hanson said.

Adversity may lead to risk for negative outcomes and the potential to have long-COVID. We need to complete more work to understand how adversity gets under the skin and increases vulnerability to poor health after COVID-19 infections.

In other words, as the co-authors wrote, not just COVID-19 but such findings could be used to limit adversity-related negative outcomes with future pandemics.

Author: Nicholas France Source: University of Pittsburgh Contact: Nicholas France University of Pittsburgh Image: The image is credited to Neuroscience News

Original Research: Open access. Childhood adversity and COVID-19 outcomes in the UK Biobank by Jamie L. Hanson et al. Journal of Epidemiology & Community Health

Abstract

Childhood adversity and COVID-19 outcomes in the UK Biobank

Objectives

This study aims to investigate the association between childhood adversity and COVID-19-related hospitalisation and COVID-19-related mortality in the UK Biobank.

Design

Cohort study.

Setting

UK.

Participants

151200 participants in the UK Biobank cohort who had completed the Childhood Trauma Screen were alive at the start of the COVID-19 pandemic (January 2020) and were still active in the UK Biobank when hospitalisation and mortality data were most recently updated (November 2021).

Main outcome measures

COVID-19-related hospitalisation and COVID-19-related mortality.

Results

Higher self-reports of childhood adversity were related to greater likelihood of COVID-19-related hospitalisation in all statistical models. In models adjusted for age, ethnicity and sex, childhood adversity was associated with an odds ratio (OR) of 1.227 of hospitalisation (95% CI 1.153to 1.306, childhood adversityz=6.49, p<0.005) and an OR of 1.25 of a COVID-19-related death (95% CI 1.11to 1.424, childhood adversityz=3.5, p<0.005). Adjustment for potential confounds attenuated these associations, although associations remained statistically significant.

Conclusions

Childhood adversity was significantly associated with COVID-19-related hospitalisation and COVID-19-related mortality after adjusting for sociodemographic and health confounders. Further research is needed to clarify the biological and psychosocial processes

See the original post here:

History of Childhood Adversity Tied to Higher COVID-19 Mortality Risks - Neuroscience News

While the BA.2.86 or "Pirola" variant of SARS-CoV-2 never took off in the U.S., some researchers are now eyeing its descendant, JN.1, which may be more immune-evasive.

JN.1 has yet to appear on the CDC's variant proportions tracker, but it has started cropping up in samples in France, the U.K., and Portugal.

The CDC warned in August that since BA.2.86 had more than 30 new mutations, it could have a growth advantage over other variants. That hasn't yet materialized, but eyes are on JN.1 because it also has a mutation in L455S, which has been problematic for monoclonal antibodies, researchers said.

Amesh Adalja, MD, of Johns Hopkins University Center for Health Security in Baltimore, told MedPage Today that these factors are worth watching, but JN.1 isn't a cause for concern just yet.

"It's not something that has spread very vastly or deeply," he said. "It's a very rare variant and an offshoot of BA.2.86, and it has those mutations that were characteristic of BA.2.86 that are somewhat immune evasive, but BA.2.86 was never really able to take off."

At this time, there is no evidence that JN.1 is going to become a dominant variant, Adalja said: "There's no evidence that it's spreading widely or rapidly or posing any major concern in terms of the metrics that we're tracking. It's just another variant where we don't know what its fate will be, but it's not dominant now."

Adalja noted that even if JN.1 did become dominant, COVID-19 vaccines will very likely still protect against severe disease. In addition, he said, antivirals such as nirmatrelvir-ritonavir (Paxlovid) are "variant agnostic" and will likely continue to be effective.

Currently, HV.1 is estimated to be the dominant variant in the U.S., accounting for about 25% of cases, according to CDC's variant proportions tracker. It's followed closely by EG.5, which accounts for an estimated 22% of cases.

Adalja emphasized that SARS-CoV-2 will continue to mutate and that there shouldn't be much concern about new variants before there's substantial information about transmission and severity of disease. Widespread population immunity is a key driver of viral evolution and will continue to produce new variants, he said.

"This is what respiratory viruses do, they continue to evolve," he added.

Indeed, experts have previously told MedPage Today that they are taking a different approach to monitoring new variants. Shishi Luo, PhD, head of infectious diseases at the population genomics company Helix, said in an earlier interview that experts are now watching hospitalizations "[r]ather than trying to follow what the new mutations are and seeing if neutralization assays or experiments are done to investigate the functional impact of the mutation."

Luo added that scientists treat all new variants with the same caution while monitoring them for signs of increased severity or transmission.

Michael DePeau-Wilson is a reporter on MedPage Todays enterprise & investigative team. He covers psychiatry, long covid, and infectious diseases, among other relevant U.S. clinical news. Follow

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What to Know About the JN.1 Variant - Medpage Today

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Please choose I'm not a medical professional. Allergy and Immunology Anatomy Anesthesiology Cardiac/Thoracic/Vascular Surgery Cardiology Critical Care Dentistry Dermatology Diabetes and Endocrinology Emergency Medicine Epidemiology and Public Health Family Medicine Forensic Medicine Gastroenterology General Practice Genetics Geriatrics Health Policy Hematology HIV/AIDS Hospital-based Medicine I'm not a medical professional. Infectious Disease Integrative/Complementary Medicine Internal Medicine Internal Medicine-Pediatrics Medical Education and Simulation Medical Physics Medical Student Nephrology Neurological Surgery Neurology Nuclear Medicine Nutrition Obstetrics and Gynecology Occupational Health Oncology Ophthalmology Optometry Oral Medicine Orthopaedics Osteopathic Medicine Otolaryngology Pain Management Palliative Care Pathology Pediatrics Pediatric Surgery Physical Medicine and Rehabilitation Plastic Surgery Podiatry Preventive Medicine Psychiatry Psychology Pulmonology Radiation Oncology Radiology Rheumatology Substance Use and Addiction Surgery Therapeutics Trauma Urology Miscellaneous

The rest is here:

A Retrospective Analysis of Hyperlipidemia and COVID-19 Outcomes Investigated in a Rural Midwestern Population - Cureus

Good morning.

Moderna is repositioning itself in the biotechnology space by betting on new innovation based on its mRNA platform. Moderna CFO Jamey Mock will play a major role in mitigating risk in these big investments as demand for the companys only marketable product at this timethe COVID-19 vaccinelags.

Modernas total revenue for Q3 2023 was $1.8 billion, compared to $3.4 billion in the same period in 2022, the company reported on Thursday. This is mainly due to a decrease in sales of the COVID-19 vaccine. Net product sales for the third quarter of 2023 were $1.8 billion, a decrease of 44% compared to the same period in 2022.

The companys 2023 sales guidance has been revised to at least $6 billion overall (previously $6 to $8 billion), and at least $2 billion from the U.S. (previously $2 to $4 billion).

After looking through the month of October, it appears as though vaccinations are really following a trend consistent with last year, which would be on the lower end, Mock says.

The soft demand for COVID-related products also resulted in a drop in sales for the companys competitor, Pfizer.

Moderna has taken steps like reducing manufacturing capacity to make sure the COVID franchise is a continuous and increasing source of income and cash generation next year, Mock says.

But hes seeing these headwinds as a breeding ground for innovation.

Theres a true organic growth opportunity here, Mock says. We still believe that we will launch 15 products by 2028. These will include respiratory, oncology, rare disease and latent disease products, he says.

Among those is the experimental vaccine against respiratory syncytial virus (RSV). Moderna filed with regulators in July for full approval of the one syringe shot for adults ages 60 and older.

Moderna plans on investing approximately $25 billion in research and development (R&D) from 2024 through 2028. This is all geared toward long-term value creation for the company, Mock says.

To support innovation and growth, his number one priority is understanding how much the company can afford to spend, Mock says.

Our view is that were fortunate to have a fair amount of capital right now, he explains. At the end of the third quarter, we have $13 billion in cash. In 2024, our sales will go down to what we think is about $4 billion. So we will most likely make a loss in the year 2024 and deplete some of that capital. We actually think thats the right thing to do. Now, you cant do it forever. But the company is committing to break even by the end of 2026, he says.

Another priority is assessing where to spend, he says. For example, Moderna has de-risked infectious disease vaccines due to prior success with COVID, and now with RSV, he says. So its easier to invest there from a probability of success perspective, Mock says.

He continues, We also look at the duration and time to revenue. The way we can innovate more is to actually get more sales to be able to afford more capital to reinvest back in the business. And then theres diversification and risk management, he says. We dont want to put all of our eggs into a respiratory vaccine basket, thats why you see us investing in oncology and latent disease and rare disease, Mock says.

And his third priority is helping with execution, especially in regard to the remaining manufacturing facilities, Mock says. So thats investing in it, making sure that it has a lot of automation, making sure that its super efficient. And when these products are ready to be sold, we have a reliable source of supply.

He adds, finance, communications, and HR also need to support our frontline and make sure that we can do that in the most efficient way.

Have a good weekend.

Sheryl Estrada sheryl.estrada@fortune.com

Some notable moves this week

Jamie Millerwas named EVP and CFO ofPayPal (Nasdaq: PYPL), effective Nov. 6. Miller will succeed Gabrielle Rabinovitch, who is currently acting CFO.Miller most recently served as global CFO of EY, having joined to lead the separation and IPO of its strategy, tax, and consulting business. Between June 2021 and January 2023, she served as CFO of Cargill.

Tony Skiadas was promoted to CFO at Verizon Communications, Reuters reported. Skiadas, who has a 27-year tenure at Verizon, had been serving as the interimCFOsince March 2023.

Troy Ignelzi was named CFO at Rapport Therapeutics, Inc., a clinical-stage biotechnology company, effective Nov. 1. Ignelzi joins Rapport with nearly two decades of financial leadership experience. Most recently, he was CFO at Karuna Therapeutics. Before Karuna, Ignelzi served as CFO at Juventas Therapeutics and scPharmaceuticals.

Beth Howewas named EVPand CFO atSiTime Corporation(Nasdaq: SITM), the precision timing company, effective Nov. 8. Art Chadwick has decided to step down as CFO and retire, effective Nov. 7. During her 17 years at HP Inc., Howe held numerous finance roles, most recently serving as HPs chief audit executive.

Holly Agliowas named CFO atMarchex, Inc.(Nasdaq: MCHX), a conversation intelligence company.Most recently, Aglio was CFO and a member of the board of directors of NetCentrics and led its 2021 acquisition by Cerberus Capital Management.

Brian Unruhwas named CFO and a member of the executive team atABBYY, an intelligent automation company. Unruh brings 20 years of experience serving in executive management positions at public and private equity-backed software and platform-as-a-service companies.

Raime Leebywas named CFO atDHI Group, Inc.(NYSE: DHX), a provider of AI-powered career marketplaces. Leebybrings over 23 years of financial experience. Before joining DHI, she served as chief strategy officer and interim CFO at US Med-Equip, a company that provides medical equipment and solutions to hospitals.

Andrew Jacksonwas appointed CFO atCalidi Biotherapeutics, Inc.(NYSEAM: CLDI), a clinical-stage biotechnology company. Jackson has over 25 years of corporate finance experience. He most recently served asCFO of Eterna Therapeutics Inc. Before that, he served as CFO at Ra Medical Systems for over four years.

E-TRADE from Morgan Stanley has released itsmonthly sector data on net buys and sells on the platform.

With the S&P 500 declining for a third-straight month in October, E-TRADE clients shifted somewhat into single stock selectionpotentially taking advantage of depressed pricing, Chris Larkin, managing director of trading and investing at E-TRADE from Morgan Stanley, said in an emailed statement. Amid a relatively strong earnings season, traders concentrated some of their buying in AMZN, as the company beat expectations. And, as geopolitical tensions deepen, we saw traders eye the industrials sector with particular interest in Boeing. On the flip side, no big surprises on the net selling front, as traders unloaded consumer staples with the economy humming along and real estate with interest rates remaining high.

Here are a fewFortuneweekend reads:

Tim Cook keeps giving the same answer about Apples generative AI plans, and its falling flat with investors by Rachyl Jones

Disney is buying Comcasts stake in streaming service Hulubut the $8.6 billion price tag is just the beginning and could go much higher, by Christiaan Hetzner

CEO of Ozempic prescription startup Calibrate steps down as investors eye rapid down-sizing of consumer business by Jessica Mathews

Starbucks CEO reveals 3 secrets in his daily routine that helped him beat executive burnout by Alexa Mikhail

Sam Bankman-Fried perpetrated one of the biggest financial frauds in American historya multibillion-dollar scheme designed to make him the king of crypto.But heres the thing: The cryptocurrency industry might be new, the players like Sam Bankman-Fried might be new, but this kind of fraud, this kind of corruption, is as old as time. And we have no patience for it.

U.S. AttorneyDamian Williamssaid at a Thursday night press conference after a12-person jury found Sam Bankman-Fried guilty of seven counts, which is the culmination of a year-long criminal proceeding following the November 2022 collapse of the crypto exchange FTX, Fortune reported.

See more here:

Modernas CFO on the $25 billion innovation plan to work past the post-COVID slump - Fortune

DENVER (AP) Dallas Mavericks coach Jason Kidd will miss Friday nights game at Denver with a non-COVID-19 illness.

Kidd didnt make the trip and will be replaced by top assistant Sean Sweeney. Its the second time Sweeney has filled in. He went 3-1 when Kidd was in the health and safety protocols during the 2021-2022 season, Kidds first with the Mavericks.

Dallas goes into its first meeting with the defending NBA champion Nuggets as the only undefeated team in the Western Conference. The Mavs are 4-0 for the first time since 2004-2005.

Continue reading here:

Mavs coach Jason Kidd has non-COVID illness, will miss game in Denver - The Associated Press

Good morning.

Moderna is repositioning itself in the biotechnology space by betting on new innovation based on its mRNA platform. Moderna CFO Jamey Mock will play a major role in mitigating risk in these big investments as demand for the companys only marketable product at this timethe COVID-19 vaccinelags.

Modernas total revenue for Q3 2023 was $1.8 billion, compared to $3.4 billion in the same period in 2022, the company reported on Thursday. This is mainly due to a decrease in sales of the COVID-19 vaccine. Net product sales for the third quarter of 2023 were $1.8 billion, a decrease of 44% compared to the same period in 2022.

The company's 2023 sales guidance has been revised to at least $6 billion overall (previously $6 to $8 billion), and at least $2 billion from the U.S. (previously $2 to $4 billion).

After looking through the month of October, it appears as though vaccinations are really following a trend consistent with last year, which would be on the lower end, Mock says.

The soft demand for COVID-related products also resulted in a drop in sales for the company's competitor, Pfizer.

Moderna has taken steps like reducing manufacturing capacity to make sure the COVID franchise is a continuous and increasing source of income and cash generation next year, Mock says.

But hes seeing these headwinds as a breeding ground for innovation.

Theres a true organic growth opportunity here, Mock says. We still believe that we will launch 15 products by 2028. These will include respiratory, oncology, rare disease and latent disease products, he says.

Among those is the experimental vaccine against respiratory syncytial virus (RSV). Moderna filed with regulators in July for full approval of the one syringe shot for adults ages 60 and older.

Moderna plans on investing approximately $25 billion in research and development (R&D) from 2024 through 2028. This is all geared toward long-term value creation for the company, Mock says.

Story continues

To support innovation and growth, his number one priority is understanding how much the company can afford to spend, Mock says.

Our view is that we're fortunate to have a fair amount of capital right now, he explains. At the end of the third quarter, we have $13 billion in cash. In 2024, our sales will go down to what we think is about $4 billion. So we will most likely make a loss in the year 2024 and deplete some of that capital. We actually think that's the right thing to do. Now, you can't do it forever. But the company is committing to break even by the end of 2026, he says.

Another priority is assessing where to spend, he says. For example, Moderna has de-risked infectious disease vaccines due to prior success with COVID, and now with RSV, he says. So it's easier to invest there from a probability of success perspective, Mock says.

He continues, We also look at the duration and time to revenue. The way we can innovate more is to actually get more sales to be able to afford more capital to reinvest back in the business. And then there's diversification and risk management, he says. We don't want to put all of our eggs into a respiratory vaccine basket, that's why you see us investing in oncology and latent disease and rare disease, Mock says.

And his third priority is helping with execution, especially in regard to the remaining manufacturing facilities, Mock says. So that's investing in it, making sure that it has a lot of automation, making sure that it's super efficient. And when these products are ready to be sold, we have a reliable source of supply.

He adds, finance, communications, and HR also need to support our frontline and make sure that we can do that in the most efficient way.

Have a good weekend.

Sheryl Estrada sheryl.estrada@fortune.com

This story was originally featured on Fortune.com

Read this article:

Moderna's CFO on the $25 billion innovation plan to work past the post-COVID slump - Yahoo Finance

Cruise passengers stroll the waterfront in Juneau on May 9. (Photo by Yereth Rosen/Alaska Beacon)

The state of Alaska broke its 2019 record for cruise ship tourism this summer, with Alaskas capital city recording 1.65 million passengers this year, according to figures released Thursday at a meeting of the Juneau Chamber of Commerce.

Most Alaska tourists arrive via cruise ship, and Juneau sees all but a handful of the cruise ships that visit Alaska each summer, making the citys figures a proxy for the industry as a whole.

The newly published figures mark a rebound and then some from the COVID-19 pandemic emergency.

Juneau recorded 1.2 million cruise ship tourists in 2022, 124,600 in 2021, 48 in 2020, and 1.33 million in 2019. The 2019 figure was the previous record.

This is a 23% increase from our best season ever before, said Meilani Schijvens, director of Rain Coast Data, the economics firm that published the numbers.

It ended up being a really, really strong season here in Southeast Alaska, Schijvens said.

The figures, based on per-passenger head tax figures calculated by the City and Borough of Juneau, were released as part of an annual report commissioned by Southeast Conference, the regional economic development organization for Southeast Alaska.

They include only manifested passenger numbers, said Juneau Port Director Carl Uchytil, so they dont include the thousands of crew aboard ship. The figures also dont differentiate between passengers who disembark in the city and those who stay aboard ship.

Brian Holst, director of the Juneau Economic Development Council, said the figures are absolutely good news for his community because economic sectors like tourism have come back solid since the pandemic emergency.

Businesses are reporting either a good year or a great year, he said.

An annual panel survey of 370 Southeast Alaska business owners found 73% had a positive view of the regions economy, the highest mark since the survey began in 2010.

Almost 80% of survey participants said they have positive expectations for 2024 as well.

Tourism accounts for 15% of Southeast Alaskas jobs but only 9% of its wages; most tourism jobs are seasonal, occurring during the cruise ship season that runs from April through October.

Government work state, federal, local and tribal accounts for more than a third of the regions jobs and wages and is the leading economic sector.

While the number of visiting tourists is above what it was in 2019, the number of tourism-related jobs in Southeast Alaska remains below what it was in the prior record year, as do wages. Tourism-related employment accounted for 12% of all wages in Southeast Alaska in 2019 before declining during the pandemic.

Employers across the region continue to report a workforce shortage, with construction workers in particular being hard to come by.

Really, we could use a lot more foreign workers coming into the United States and coming into Alaska to bolster our economy, Schijvens said.

According to her firms survey, more than half of the regions business leaders said a lack of housing has cost them employees.

Survey respondents also said the cost and availability of child care was a major factor in their inability to hire and retain workers.

Over the past 12 years, the price of an average single family home in Juneau has risen 52%, 22 percentage points above inflation during that period, Schjivens said. Average wages in the city rose 38%, 8 points above inflation, during the same period.

Juneau Mayor Beth Weldon said of the 2023 cruise ship season, We are happy with the numbers for the tourism numbers, but at the same time, we understand that the community has felt a little tension this year.

Concerns about traffic and overcrowding have risen along with passenger volume, and the city has reached a voluntary agreement with the cruise industry to cap the number of ships per day.

No more than five large ships will be permitted on any given day, starting next year. According to preliminary data shared by Schjivens, 50 ships have planned a combined 660 voyages to Southeast Alaska in 2024, with the first ship due in Juneau April 8, and the last on Oct. 26.

Thats an extension of this years record-long cruise ship season, which began in mid-April, and Schjivens expects 1.7 million tourists in the capital city next year, another record.

More here:

Alaska breaks cruise ship passenger record as tourism rebounds from the COVID-19 pandemic - KTOO