Last year, we had a “tripledemic” of COVID, Flu and RSV infections that all challenged the healthcare system at once. This year, it appears that it is a “syndemic” per Dr. Raj Rajnarayanan, as there are more than three pathogens that will impact our healthcare systems this winter. Specifically, we are seeing COVID, Flu, RSV and an atypical bacterial pneumonia in children caused by Mycoplasma Pneumoniae. An epidemic of Mycoplasma Pneumoniae lung infections are being seen in children in China, France, the Netherlands, Denmark, Ireland and Warren County, Ohio.
We know that prior COVID infections can increase the risk of RSV infections in young children, so it may be that past or present COVID infections are increasing the spread of Mycoplasma Pneumoniae in many countries now. Mycoplasma Pneumoniae pneumonia (MPP) is also known as “walking pneumonia”. According to Dr. Annie Sparrow, associate professor at the Icahn School of Medicine at Mount Sinai, the Mycoplasma Pneumoniae bacteria in China may be resistant to azithromycin, the only antibiotic approved for children under 8. I have not seen reports of antibiotic-resistant MPP from other sources and I cannot confirm that this is true.
Sick children receive IV drips on the stairs at a children's hospital in Beijing on Nov. 23., (photo credit: ForeignPolicy.com.)
Per Dr. Celine Gounder, Warren County Ohio is reporting an outbreak of pediatric pneumonia cases. This is similar to the "white lung syndrome" (aka ARDS) that is being seen in Europe and China. She notes that the increase in pneumonia in children is not due to a new pathogen, but rather, it is due to a combination of typical winter viral infections (RSV, Flu, COVID, adenovirus, rhinovirus) and bacterial Mycoplasma Pneumoniae. She tweeted “If this were a novel pathogen, adults wouldn't have immunity & would also be getting sick. That's NOT what we're seeing. Kids are getting sick because they haven't been as exposed to these respiratory illnesses as adults & aren't immune.” She recommends that parents “Take action to prevent RSV, COVID & flu – the 3 big viral respiratory illnesses.” by vaccinating children against these viruses.
The healthcare infrastructure in the U.S., and in many places around the world, has been severely stressed by high hospitalizations and severe healthcare worker burnout, so we need to prepare for this winter's respiratory illnesses. Vaccination against flu and COVID, improving air quality with air filtration, masking indoors with an N95 or KN95 mask, staying home when sick, testing for COVID every 48 hours if exposed or if you have symptoms, are all important ways to reduce the spread of respiratory viruses this season.
The JN.1 variant is spreading rapidly around the world and is causing increased COVID hospitalizations. JN.1 is not expected to cause more severe disease than other Omicron variants according to the WHO, but the upcoming large surge in cases could really stress our hospitals and healthcare systems. Consider getting the updated vaccine now in preparation for a new JN.1 wave that will be very high in mid to late December. Per JP Weiland, another COVID wave has started and the combination of the FLip variants + HV.1 wave happening as the JN.1 variant takes off, will cause anywhere from 1 million to 1.5 million new COVID cases per day in the U.S. by late December. Yikes!
A new article in PNAS warns of a “second pandemic of mood and anxiety disorders, including major depression, anxiety and PTSD." The authors reviewed scientific findings on the neurobiology of stress and reviewed the roles of scientific discovery in both the short term and long term. Dr. Blitshteyn responded with an interesting viewpoint, “We can't talk about a second pandemic of mental health disorders without talking about the first pandemic: COVID-19 has significant neuropsychiatric manifestations, for which we have NO EFFECTIVE treatment. No amount of psychotherapy or positive self-talk is going to fix neuroinflammation.”
There have been several studies linking COVID infection with premature birth. A new population level study shows that maternal COVID vaccination reverses this trend, thus preventing premature births. Preterm birth can have lifelong consequences for the health and socioeconomic well being of the child, so this is welcome news.
In 2022, Nick Beauchamp of Northeastern University reported that when there was an increase in negative Amazon reviews for Yankee Candles saying “This Candle Has No Smell” correlated with rising COVID cases. This week, Salvatore Mattera shared a Reddit thread on r/Millennials starting with "Does anyone else feel like Covid broke their brain / not themselves?" In the thread, millennials discuss how since they had a COVID infection, they cannot think as clearly or they have memory loss, or they sweat a lot more or have loss of balance (dysautonomia), or they have loss of taste/smell. It makes me wonder how many more people have Long COVID and do not realize what it is.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling post-infectious disease that is seen in many Long COVID patients. Although the following articles are not about Long COVID per se, they are about ME/CFS in general.
Ron Davis’ lab from Stanford showed that 47% of 19 ME/CFS patients and 5% of 19 healthy controls had plasma antibodies that could digest MBP (myelin). Glatiramer acetate (copaxone) inhibited this. They postulated that white matter demyelination in ME/CFS may be causing nerve pain and muscle weakness symptoms and that ME/CFS patients with general malaise and fatigue symptoms may have poor energy levels due to other issues including oxidative stress and mitochondrial dysfunction.
Regarding mitochondrial dysfunction and ME/CFS, Simmaron Research is recruiting 100 ME/CFS patients for a pilot study on Rapamycin, a mitochondrial enhancer, to treat ME/CFS. Their hypothesis is that “ME/CFS patients with elevated serum levels of pATG-13 and related autophagy disruption markers who are given low dose rapamycin will have these proteins (ATG-13) normalize and this may trend with a reduction in ME/CFS symptoms including PEM (post-exertional malaise) flairs.”
High ED visits and hospitalizations for COVID in HHS Region 5 (Illinois, Indiana, Michigan, Minnesota, Ohio, and Wisconsin), HHS Region 7 (Iowa, Kansas, Missouri, and Nebraska), and HHS Region 8 (Colorado, Montana, North Dakota, South Dakota, Utah, and Wyoming).
"TLDR: good news as Covid levels are lower than last winter and falling, as we go into the Christmas season. Flu also remains much lower than last year."
Respiratory illnesses:
12/1/23 Forbes: Forget the ‘tripledemic.’ The U.S. is headed for a ‘syndemic’—and experts warn we’re not prepared https://buff.ly/46FmDPy
“Sarah Rudman, deputy health officer for Santa Clara County Public Health Department, said wastewater readings for RSV are higher than this time last year–and COVID-19 wastewater readings have shot up in the last couple of weeks…. ‘It is concerning to see the levels of RSV and COVID and flu all going up right at the same time.'”
Mycoplasma Pneumoniae epidemics in children noted in many places around the world now:
Ohio is reporting an outbreak of pediatric pneumonia cases. This is similar to the "white lung syndrome" (aka ARDS) that is being seen in Europe & China.
THIS IS NOT DUE TO A NOVEL PATHOGEN CAUSING A NEW PANDEMIC.
3/ This seems to be a similar phenomenon to the pediatric pneumonia outbreak in China... but that is NOT to say that they are connected.
It's being caused by a combo of viral (e.g. RSV, COVID, flu, adenovirus, rhinovirus) & bacterial (e.g. Mycoplasma pneumoniae) infections.
4/ If this were a novel pathogen, adults wouldn't have immunity & would also be getting sick.
That's NOT what we're seeing.
Kids are getting sick because they haven't been as exposed to these respiratory illnesses as adults & aren't immune.
5/ Note that viral infections can also predispose to bacterial suprainfections (i.e. infections on top of or subsequent to the viral infection).
6/ What can parents do to protect their kids?
Take action to prevent RSV, COVID & flu – the 3 big viral respiratory illnesses.
7/ Kids are highly UNDERvaccinated for COVID (see most up-to-date data from the CDC below).
Just because they don't die from COVID & we've moved on from COVID doesn't mean COVID can't still be really bad for kids. covid.cdc.gov/covid-data-tra…
8/ After the elderly, infants & kids under 5 were the most likely to end up in the ED or hospitalized from COVID vs other groups.
Get their kids vaccinated for influenza & COVID ASAP.
9/ If their infant is eligible for Beyfotus or Synagis to prevent RSV, they should get that, too. Pregnant women should get an RSV shot to protect their newborns after birth.
10/ Consider wearing KN95/N95 masks in crowded places (e.g. shopping malls, public transportation).Make use of indoor ventilation & air filtration (i.e. open windows/doors when possible, get HEPA air filtration units or Corsi boxes).
12/ If someone has COVID or influenza they may be eligible to take Paxlovid, Tamiflu or Xofluza.
And if someone has COVID, influenza or RSV, they should consider isolating away from others if possible, at least as long as they have symptoms.
10/13/23 Family Medicine and Community Health (Ohio): Association of COVID-19 with respiratory syncytial virus (RSV) infections in children aged 0–5 years in the USA in 2022: a multicentre retrospective cohort study https://buff.ly/3FVXEfQ
Cohort study of 228,940 children aged 0–5 years.
Prior COVID-19 infection was associated with a significantly increased risk for RSV infection among young children in 2022. Similar findings were replicated for a study population of children aged 0–5 years in 2021.
11/28/23 Foreign Policy: Chinese Hospitals Are Housing Another Deadly Outbreak https://buff.ly/3QSfWnu
The surge in hospitalization of children in China is Mycoplasma pneumoniae which appears to be antibiotic-resistant to azithromycin, the only antibiotic for children under age 8.
Children are hooked up to IV drips on the stairs at a children's hospital in Beijing on Nov. 23.
11/25/23 Forbes: Mycoplasma Likely Main Culprit Of Outbreak Of Pediatric Cases Of Pneumonia Worldwide https://buff.ly/3Rg0y5K
Among other countries, China, South Korea and France are having serious epidemics of probable mycoplasma pneumonia in children.
“Measures such as masking, ventilating, washing hands, avoiding close contact with others and staying home when sick are recommended to prevent the spread of mycoplasma, but also the viruses that can lead to mycoplasma.
If ill, the pathogen can be treated with a wide variety of antibiotics, including azithromycin, but also tetracycline, macrolides and fluoroquinolones.”
29/11/23 Le Parisien: Flambée de pneumopathies chez les enfants [en France] : la hausse se poursuit, les autorités appellent à la « vigilance » https://buff.ly/3uz312a
"les passages aux urgences chez les moins de 15 ans continue de grimper, en raison — notamment — de la recrudescence de la bactérie Mycoplasma pneumoniae."
Le ministère de la Santé: « recrudescence inhabituelle de cas d’infections respiratoires à Mycoplasma pneumoniae, y compris nécessitant une hospitalisation chez les adultes et les enfants en France ».
« la grande majorité des infections sont modérées et ce ne sera pas aussi dramatique que le VRS (le virus respiratoire syncytial, qui provoque notamment des bronchiolites) »
11/23/23 WHO: The CDC of China reported an increase in outpatient consultations and hospital admissions of children due to Mycoplasma pneumoniae pneumonia since May, and RSV, adenovirus and influenza virus since October. https://buff.ly/3uBV6Bp
Denmark reports epidemic levels of Mycoplasma pneumonia.
Last week, the Netherlands reported a striking rise in pneumonia in children and young people since August.
China reports overwhelmed Children's Hospitals due to a mix of respiratory viruses and M. Pneumoniae.
"Chinese clinicians, quoted in media reports, have said that, before COVID, the country experienced Mycoplasma pneumonia outbreaks every 3 to 7 years."
11/27/23 PNAS: The Neurobiology of Stress: Vulnerability, resilience, and major depression https://buff.ly/47X31HB
"Evidence suggests that we are facing a second pandemic of mood and anxiety disorders, including major depression, anxiety and PTSD."
Scientific review of the neurobiology of stress.
"Mood and anxiety disorders have a common biological underpinning that serves as a starting place for understanding these disorders at a mechanistic level: the Stress System."
Good news: the new 2023 updated XBB.1.5 COVID vaccine boosts neutralizing antibodies against XBB.1.5, EG.5.1, and key emergent viruses like HV.1, HK.3, JD.1.1, and JN.1 (13.3-to-27.4-fold).
Since JN.1 is spreading around the world, it would be good to get the updated vaccine now before the Christmas holiday.
The updated 2023 mRNA vaccine (XBB.1.5) boosted serum virus-neutralization antibodies significantly against not only XBB.1.5 (27.0-fold) and the currently dominant EG.5.1 (27.6-fold) but also key emergent viruses like HV.1, HK.3, JD.1.1, and JN.1 (13.3-to-27.4-fold).
In individuals previously infected by an Omicron subvariant, serum neutralizing titers were boosted to highest levels (1,764-to-22,978) against all viral variants tested.
COVID-19 vaccines prevent premature births.
“There are several studies linking preterm delivery with COVID, and this study in PNAS is a bit different. It is a population level study that shows that vaccination reverses the trend.”
11/27/23 PNAS: Vaccination, immunity, and the changing impact of COVID-19 on infant health https://buff.ly/49NV3Cu
Maternal COVID infection was associated with a marked increase in preterm births (< 32 weeks of gestation).
Preterm birth can have lifelong consequences for health and socioeconomic well- being for the child.
Maternal COVID vaccination was linked with preventing preterm births.
“The harmful impact of COVID- 19 infection disappeared almost a year earlier in zip codes with high vaccination rates, suggesting that vaccines might have prevented thousands of preterm births.”
Remember even if you have had a previous Omicron variant infection over the last couple of years, that does not provide very robust immunity unless you have been vaccinated on top of it.
5/18/22 Nature: Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination https://buff.ly/3LwzQj4
11/28/23 K. Jetelina: Vaccine disparities are worse post-emergency in the U.S. https://buff.ly/3uDjW3I
"The gap between Latinx and White residents who are fully protected is more than twice what it was last year. Same with African American/Black residents. Same with residents of low income.
This means two things:
Those who are more likely to lack access to healthcare are even more likely to be infected and get seriously ill once again.
The commercialization of vaccines has only amplified gaps in access and uptake. This is cause for concern about our national vaccine system during non-emergency times."
11/17/23 KFF: With COVID Concerns Lagging, Most People Have Not Gotten Latest COVID Vaccine And Half Say They Are Not Taking Precautions This Holiday Season https://buff.ly/3T3DJUm
11/22/23 BMJ: Covid-19 vaccine effectiveness against post-covid-19 condition among 589 722 individuals in Sweden: population based cohort study https://buff.ly/47vI1rD
Vaccination protection against Long COVID—1 dose 21%, 2 doses 59%, 3 doses 73%.
Strong association between covid-19 vaccination before infection and reduced risk of receiving a diagnosis of PCC (Long COVID).
11/30/23 AMA: The latest long COVID research on symptoms, testing and treatments with Akiko Iwasaki, PhDhttps://buff.ly/47yTW8c
11/30/23 Upcoming Shionogi Ensitrelvir trial for Long COVID planned
11/29/23 Lancet: Long Covid Clinical Severity Types Based on Symptoms and Functional Disability: A Longitudinal Evaluation https://buff.ly/3RoZVqK
prospective longitudinal study design
“The three-level clinical severity pattern remained consistent over time between the two assessments, with 51% of patients switching the clinical severity type between the assessments. The fluctuation was independent of the LC severity and time between the assessments.”
COVID-19 infection in general is associated with long-lasting microstructural brain changes.
Patients with Long COVID had different patterns of brain changes than people who had recovered from COVID-19 infection without any long-term symptoms.
Diffusion microstructure imaging (DMI), a novel MRI technique, can provide detailed information about brain tissues.
COVID-19 infection induced a specific pattern of microstructural changes in various brain regions, and this pattern differed between those who had long COVID and those who did not.
To be presented next week at the Radiological Society of America meeting
People with long COVID exhibit patterns of changes in the brain that are different from fully recovered COVID-19 patients.
They used DMI and compared MRI brain scans of three groups: 89 patients with long COVID, 38 patients that had contracted COVID-19 but did not report any subjective long-term symptoms, and 46 healthy controls with no history of COVID-19.
COVID-19 infection induced a specific pattern of microstructural changes in various brain regions, and this pattern differed between those who had long COVID and those who did not.
“Expression of post-COVID symptoms was associated with specific affected cerebral networks, suggesting a pathophysiological basis of this syndrome” Dr. Rau said.
11/26/23 r/Millennials: "Does anyone else feel like Covid broke their brain / not themselves?" https://buff.ly/49YXJxs
Reddit thread in which millennials discuss how since they had a COVID infection, they can’t think as clearly and have memory loss, or they sweat a lot more (dysautonomia), or loss of taste/smell, etc.
10/16/22 NPR: Why did he suspect a COVID surge was coming? He followed the digital breadcrumbs. https://buff.ly/3eEyxo4
The Yankee Candle clues
A wave of negative Amazon reviews for Yankee Candles smell became an early warning sign that COVID cases were rising.
10/31/23 JPM (Blitshteyn): Neuropsychiatric Manifestations of Mast Cell Activation Syndrome (MCAS) and Response to Mast-Cell-Directed Treatment: A Case Series https://buff.ly/4a3JqHF
Case series of 8 patients with psychiatric disease (depression, anxiety, panic disorder, OCD, bipolar disease) that were refractory to standard medical therapeutics.
All eight patients were subsequently diagnosed with MCAS and all patients experienced significant improvements regarding neuropsychiatric and multisystemic symptoms after mast-cell-directed therapy.
In neuropsychiatric patients who have systemic symptoms and syndromes, it is important to consider the presence of an underlying or comorbid MCAS.
SARS-CoV-2 infects peripheral and central nervous system neurons before viremia
11/21/23 Lancet: 3-year outcomes of discharged survivors of COVID-19 following the SARS-CoV-2 Omicron (B.1.1.529) wave in 2022 in China: a longitudinal cohort study https://buff.ly/3sK2ni5
3-year prospective follow up of 1359 people hospitalized in China for COVID.
Lung function restored back to baseline in most
Higher risk of reinfection than people without Long Covid
More than half (54%) had persistent LC symptoms at 3 years
11/20/23 CIDRAP: 10-minute procedure called a CT-guided Stellate Ganglion Block (SGB) may repair distorted sense of smell in COVID survivors https://buff.ly/3GdleoC
59% who responded said their sense of smell had improved by 1 week after SGB.
A second SGB injection on the opposite side at least 6 weeks later showed more improvement.
Stellate Ganglion Block (SGB), Figure from Cleveland Clinic
ME/CFS:
11/27/23 Biochemistry (Ron Davis lab): Catalytic Antibodies May Contribute to Demyelination in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) https://buff.ly/47S7ITc
19 ME/CFS and 19 healthy control plasma samples. Abs were also collected from MS patients.
Some patients with ME/CFS have catalytic autoantibodies in their plasma that cause the breakdown of myelin basic protein (MBP).
Within the ME/CFS samples tested for this particular set, 47% were found to digest MBP, while in the healthy control group, 5% of the samples also showed digestion of MBP.
ME/CFS patients whose plasma Ab samples did not breakdown MBP may have symptoms unrelated to demyelination. They may be experiencing symptoms more related to general malaise and fatigue as might be caused by poor energy levels due to oxidative stress and mitochondrial dysfunction.
Glatiramer acetate (copaxone), an FDA approved immunomodulator to treat multiple sclerosis, inhibits ME/CFS antibody digestion of MBP.
Aprotinin, which is a specific serine protease inhibitor, specifically prevents breakdown of MBP. Catalytic antibodies may have serine protease-like activity.
"Because COVID-19 has been described as a trigger for ME/CFS, demyelination could play a bigger role in patient symptoms for those recently diagnosed with ME/CFS. Therefore, by studying proteolytic antibodies in ME/CFS, their target substrates, and inhibitors, a new mechanism of action could lead to better treatment and a possible cure for the disease."
11/26/23 Autoimmunity Reviews: Brain-regional characteristics and neuroinflammation in ME/CFS patients from neuroimaging: A systematic review and meta-analysishttps://buff.ly/3QYVm52
11/14/23 Health Rising: Simmaron's ME/CFS Trial of Rapamycin - a Mitochondrial Enhancer - to Begin Soon https://buff.ly/3uuAfzW
Their hypothesis: “ME/CFS patients with elevated serum levels of pATG-13 and related autophagy disruption markers who are given low dose rapamycin will have these proteins (ATG-13) normalize and this may trend with a reduction in ME/CFS symptoms including PEM flairs.” It is based on their research:
5/2022 Molecular and Cellular Neuroscience: Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE) https://buff.ly/3GpML6f
Mitochondrial repair with non-COVID sepsis:
11/23/23 Redox Biology: Restoring the infected powerhouse: Mitochondrial quality control in sepsishttps://buff.ly/49UwDXX
Mitochondrial biogenesis
Other news:
11/30/23 ABC: New study reinforces skin-to-skin contact is critical for premature babies https://buff.ly/46B0S3j
11/9/23 Nature: Risk of hematological malignancies from CT radiation exposure in children, adolescents and young adults https://buff.ly/47AGhh6
Moderate to high dose radiation is known to cause leukemia.
This study looked at almost 1 million children and young adults who underwent lower dose CT examinations before age 22 years.
CT scan radiation was associated with an increased risk of blood cancers with a dose-response relationship.
A clear dose–response between cumulative radiation dose to the active (red) bone marrow (ABM) and the risk of blood cancers such as leukemias and lymphomas. There was increased risk at doses as low as 10–15 mGy for non-Hodgkins Lymphomas and for mature B cell neoplasms.
11/20/23 Healio: Hybrid closed-loop system lowers severe hypoglycemia, DKA rates in Type 1 diabeteshttps://buff.ly/3sGr1QB
The Control-IQ Observational study using the t:slim X2 insulin pump with Control-IQ technology (Tandem Diabetes Care).
At 1 year, adults using the system had a time in range of 70.1%, and the device provided improvements in several self-reported quality of life measures.
CAR T-therapies for cancer may cause a new T cell cancer. But, the FDA says that the benefits still outweigh the risks.
11/28/23 FDA Investigating Serious Risk of T-cell Malignancy after CAR-T cell Immunotherapies https://buff.ly/3T3D2KG
Although the overall benefits continue to outweigh potential risks, FDA is investigating the risk of T cell malignancy with serious outcomes, including hospitalization and death.
11/28/23 JAMA: Self-Sampling Strategy to Increase Cervical Cancer Screening https://buff.ly/46ByP3U
Mailing patients a human papillomavirus (HPV) self-sampling kit increased cervical cancer screening for those due and overdue for screening.
11/29/23 US FDA flags new problem with Philips CPAP machines- fire hazard https://buff.ly/3RmlrMz
“reports of people facing thermal issues such as fire, smoke, burns, and other signs of overheating while using Philips’ DreamStation 2 CPAP machines.”
You might be interested in this thread by Dr. Lisa Iannatotone. She has multiple links to current journal articles.
" We’re in our *3rd* post-lockdown viral respiratory season and admissions for viral resp illness+pneumonia are 6 standard deviations above the historical average. I do not understand how so many reasonable people haven’t figured out that the “immunity debt” scapegoat is disinfo."
You might be interested in this thread by Dr. Lisa Iannatotone. She has multiple links to current journal articles.
" We’re in our *3rd* post-lockdown viral respiratory season and admissions for viral resp illness+pneumonia are 6 standard deviations above the historical average. I do not understand how so many reasonable people haven’t figured out that the “immunity debt” scapegoat is disinfo."
https://twitter.com/lisa_iannattone/status/1730800968999079992