COVID news & more, 9/28/24
Nationally, COVID wastewater levels continue to decrease, although SARS-CoV-2 levels are still HIGH in some places, especially in the midwest. According to the CDC, the very highest levels of SARS-2 seen in wastewater now are in Colorado, Minnesota, New Hampshire and Washington state. Most places in California now show LOW to MEDIUM levels of COVID virus in wastewater after a recent large COVID wave.
Approximately 600,000 Americans are infected by COVID daily at this point which translates to about 1 in every 57 people currently infected. COVID test positivity is decreasing overall, as are emergency department visits for COVID.
CDC wastewater SARS-CoV-2 levels as of 9/21/24
From: https://www.cdc.gov/nwss/rv/COVID19-nationaltrend.html
The new XEC variant has been found in many countries now, but it may not have quite as large an effect as other variants have had. JP Weiland believes that XEC has a 40 to 45% growth advantage over KP.3.1.1 (the current top variant). This is significantly less of a growth advantage as compared to JN.1 which caused last year’s winter wave and had a 120% growth advantage over the prior SARS-CoV-2 variant. This is good news.
Cellular Pathways
This week, there were several interesting articles about the different cellular pathways the SARS-CoV-2 virus uses to affect different organ systems.
COVID and the Heart:
A new study from India analyzed RNA-seq data from 54 human heart tissue samples across four studies to identify gene expression changes specific to SARS-CoV-2 infection and heart failure. They found that SARS-CoV-2 infects heart muscle cells (cardiomyocytes) through the TNF-NF-κB pathway, potentially triggering acute cardiovascular complications and elevating long-term cardiovascular risk.
Figure 1: Putative signaling pathway of SARS-COV-2 interaction with heart tissue causing heart damage and heart failure.
From: https://www.nature.com/articles/s41598-024-69635-6/figures/1
COVID and Cancer
A comprehensive new review looks at cellular pathways that may allow SARS-CoV-2 to trigger cancers. "Unlike classical oncogenic viruses, which transform cells through viral oncogenes or by activating host oncogenes, SARS-CoV-2 appears to promote tumorigenesis by inhibiting tumor suppressor genes and pathways while activating survival, proliferation, and inflammation-associated signaling cascades." The figures in this review examine different pathways that the SARS-CoV-2 virus may use to promote cancer.
Graphical Abstract
From: https://biosignaling.biomedcentral.com/articles/10.1186/s12964-024-01818-0
Figure 1: Key oncogenic signaling molecules or pathways targeted by SARS-CoV-2 NSP, N, M and S proteins.
From: https://biosignaling.biomedcentral.com/articles/10.1186/s12964-024-01818-0/figures/1
Figure 5: The SARS-CoV-2 N protein activates NLRP3 inflammasomes and the dysregulation of the Renin–Angiotensin–Aldosterone System (RAAS) which leads to deregulated cellular metabolism, tumor-promoting inflammation, angiogenesis and metastasis.
From: https://biosignaling.biomedcentral.com/articles/10.1186/s12964-024-01818-0/figures/1
Another review looked at SARS-CoV-2 viral load and cytokine levels in acute COVID infection and the subsequent development of Long COVID (PASC). It found that certain cytokines including IL-10, IL-13, IL-17 and IL-1RA resolve within 3 weeks of acute COVID infection, but others including IL-6, IFN-γ, TNF-α, IL-1β, IL-10, IFN-β may remain elevated in Long COVID. They discussed that Long COVID was associated with higher levels of SARS-2 virus in the blood early in the acute phase of the disease, especially in people who develop neurological Long COVID symptoms like brain fog and memory issues.
Figure 3. Graphical representation of cytokines and chemokines during acute phase of COVID-19 disease and subsequent PASC phase
From: https://www.mdpi.com/2227-9059/12/9/1941
Pediatrics
A new report from the CDC shows that babies under age 6 months are hospitalized with COVID more than any other group except adults age ≥75 years. Maternal vaccination works to decrease the risk of infant hospitalization from COVID. The CDC recommends that pregnant individuals be vaccinated against COVID to protect themselves and their babies.
FIGURE 2. Maternal vaccination status among infants aged <6 months hospitalized with laboratory-confirmed SARS-CoV-2 infection, October 2022–April 2024
From: https://www.cdc.gov/mmwr/volumes/73/wr/mm7338a1.htm
Looking at the immune response to COVID infection in children, researchers found that preschool-age children had a different adaptive immune response, with a lower frequency of antiviral CD4+ T cells, compared with older children and adults. Young children also made phenotypically distinct memory T and B cell responses after recovery compared with older children and adults. "This study highlights that responses to SARS-CoV-2 infection in young children are unique and reflect the ongoing maturation of the immune system into adulthood."
Vaccines
Long lived plasma cells (LLPC) in the bone marrow produce long-term circulating IgG antibodies (and IgA antibodies) to protect against infection. A new study from Emory University shows something surprising- mRNA SARS-CoV-2 vaccination, even when combined with SARS-CoV-2 infection, does not cause specific LLPCs that could provide IgG antibodies against the virus long term. This may be part of the reason that immunity to COVID wanes so quickly after vaccination. As Dr. Akiko Iwasaki tweeted, “current vaccines are still important, as they boost short-term antibody responses, restimulate memory cells, generate variant-matched immune responses...etc. But we can do better.” Using different vaccine platforms such as nasal vaccine boosters or adding adjuvants may be helpful to reduce waning immunity.
Figure 5b: Graphical summary: Unlike Influenza and Tetanus vaccination, the majority of SARS-CoV-2 plasma cells are not established from the bone marrow LLPC compartment 33 months after mRNA vaccination.
From: https://www.nature.com/articles/s41591-024-03278-y/figures/5
Mitigations and COVID Testing
The US government is sending out another set of 4 free COVID tests. You can sign up at https://covidtests.gov/.
Long COVID
Drs. Peluso and Deeks from UCSF just published an amazing, comprehensive review of the possible biologic and physiologic mechanisms of Long COVID, as well as possible treatments. Kudos to this team for this excellent review!
Figure 6. Mechanistic targets of long COVID prevention and treatment
A)Viral targets, B)Immunologic targets, C) Clotting targets, D) Human herpesvirus targets
From: https://www.sciencedirect.com/science/article/pii/S0092867424008869#fig4
COVID and the Brain
This week, there were two new eye-opening articles on COVID and the brain. The first study showed that young, healthy people had cognition and memory deficits seen on testing one year after mild COVID infection even though they were unaware of these problems. In 2021, thirty-four young healthy, unvaccinated people aged 18 to 30 volunteered to be infected with the original strain of SARS-CoV-2 and were followed with cognitive testing for a year. Eighteen of the volunteers became COVID positive (17 with mild symptoms, 1 with no symptoms). None of the infected individuals thought that they had brain fog or cognitive dysfunction, but cognitive testing showed that they actually did. Memory and executive function tasks such as decision-making skills were the most affected one year after mild COVID infection.
From: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00421-8/fulltext
A second study looked at 351 people who were hospitalized with COVID infection compared to 2,927 matched controls. One-year after moderate to severe COVID infection, cognitive deficits were global and were associated with elevated blood biomarkers consistent with ongoing brain injury. The anterior cingulate cortex volume in the brain was reduced and cognitive deficits were noted to be equivalent to 20 years of brain aging. The authors concluded that the ongoing brain injury appeared to be immune-mediated.
Dr. Eric Topol summarized these two articles and several others in a new post called COVID Brain.
From:
Reinfection Risks
In a new preprint from the Patient-Led Research Collaborative, 3,382 people from different countries were surveyed about outcomes from COVID reinfections. The risk of Long COVID more than doubled if someone had two COVID infections compared to one. “Those who had 2 COVID infections were 2.14 times more likely, and those who had 3 or more COVID infections were 3.75 times more likely to report Long COVID than those with one infection.” Vaccinations reduced the risk of Long COVID, but reinfections decreased this protection. Few people with Long COVID went into remission and the chance of recovery from Long COVID decreased with each additional COVID infection. Sex differences were noted, with males tending to have more improvement than females. This study highlights the importance of preventing COVID reinfections.
This study is consistent with a large 2022 study from the US Department of Veterans Affairs’ national database, showing that each additional COVID infection increased the cumulative risk and burden of new chronic diseases (diabetes, heart disease, etc.), Long COVID and death. Like the recent Patient-Led study above of a younger population with Long COVID, this study of an older, more male population at the V.A. also shows that repeat COVID infections lead to increased cumulative risk and that preventing COVID reinfections is very important.
Sweden did not require lockdowns to protect its citizens from getting COVID early in the pandemic, unlike many other countries. In a nationwide survey of all Swedish people on sick leave 18 months after COVID infection during the first wave of the pandemic, 85.6% reported experiencing at least one Long COVID symptom affecting a body system and 46% reported that this affected their activities of daily life, while 66% percent reported extreme fatigue. Cognition, sleep and mobility issues were also common. In general, risk factors for Long COVID symptoms causing disability at 18 months after infection were being female and having severe initial COVID infections that required hospitalization.
H5N1
Yesterday, the CDC reported that several additional health care workers exposed to the Missouri patient who was hospitalized with H5 Avian Flu also had a mild respiratory illness that resolved. "To date, only one case of influenza A (H5N1) has been detected in Missouri. No contacts of that case have tested positive for influenza A (H5N1)." The concern is if others test positive for H5N1 infection, there may have been human-to-human transmission. So, this case is being followed closely.
AI:
Eric Topol MD tweeted about his new article in Science Magazine called “The revolution in high-throughput proteomics and AI”:
“What happens when you can assay over 10,000 proteins in the blood, in tens of thousands of people with years of follow-up, and use #AI analytics? An exciting, but largely unrecognized new frontier in medicine.”
Table summarizing the 11 studies reviewed by Dr. Topol
Other news:
This week, I wrote an article entitled “Infant RSV Disease Prevention: Helping Patients Understand the Options to Help Protect Their Baby” in collaboration with Sanofi. It looks at maternal vaccination and monoclonal antibodies to protect infants against RSV.
In a world first, stem cells were used to reverse Type I diabetes. “A 25-year-old woman with type 1 diabetes started producing her own insulin less than three months after receiving a transplant of reprogrammed stem cells. She is the first person with the disease to be treated using cells that were extracted from her own body.” This is a very exciting discovery for people with Type I diabetes and other autoimmune diseases.
GLP-1 receptor agonist drugs like semaglutide are used to treat Type II diabetes and can be used for significant weight loss. An article in Nature magazine entitled “Why do obesity drugs seem to treat so many other ailments?” looks at how GLP-1 drugs also work to reduce cardiovascular disease, kidney disease, addiction, Parkinson’s disease, sleep apnea and other chronic conditions.
From: https://www.nature.com/articles/d41586-024-03074-1
A woman volunteered to have her brain scanned before, during and for 2 years after pregnancy to show changes in neuroanatomy related to pregnancy. “Pronounced decreases in gray matter volume and cortical thickness were evident across the brain, standing in contrast to increases in white matter microstructural integrity, ventricle volume and cerebrospinal fluid, with few regions untouched by the transition to motherhood.”
After starting renovations in 2022, San Pedro High School discovered a "paleontological goldmine" below the school. Many fossils were found dating back 9 million years. The location is “the largest marine bone bed found in Los Angeles and Orange counties,” with millions of fossils, from shells to huge shark species found.
“In a world first, veterinary scientists at Université de Montréal have found a way to scan the brains of cats while they’re awake, using electrodes concealed under specially knitted wool caps.”
Fée, an abandoned cat with chronic osteoarthritis
Aliénor Delsart / Université de Montréal
Have a great rest of your weekend,
Ruth Ann Crystal MD
COVID news notes:
US Variant tracker: https://covid.cdc.gov/covid-data-tracker/#variant-proportions
As of 9/27/24. Well hello, XEC.
CDC COVID data tracker: https://covid.cdc.gov/covid-data-tracker/index.html#datatracker-home
COVID Emergency Dept visits: https://covid.cdc.gov/covid-data-tracker/#ed-visits_all_ages_combined
In some states, the descent is slower:
CDC Respiratory viruses (COVID, Flu, RSV) Hospitalizations (for those states reporting): https://www.cdc.gov/resp-net/dashboard/index.html
Walgreens positivity rate: https://www.walgreens.com/businesssolutions/covid-19-index.jsp
US Wastewater Monitoring:
CDC wastewater reporting: https://www.cdc.gov/nwss/rv/COVID19-nationaltrend.html
Data through 9/21/24.
CDC wastewater map: https://www.cdc.gov/nwss/rv/COVID19-currentlevels.html
Updated 9/27/24. Data through 9/21/24.
CDC SARS-CoV-2 Wastewater Levels by State:
National SARS-CoV-2 data from Sara Anne Willette: https://iowacovid19tracker.org/
Through 9/22/24
By County
Wastewater SCAN: https://data.wastewaterscan.org/
Wastewater SCAN now reports SARS-2 at MEDIUM level in wastewater in the USA as a whole.
Midwest and Northeast are higher than other parts of the country
California statewide view https://buff.ly/3YObiul
Sewer Coronavirus Alert Network (SCAN) project by Stanford University:
Marin county: https://coronavirus.marinhhs.org/surveillance
US COVID deaths per week: https://covid.cdc.gov/covid-data-tracker/#trends_weeklydeaths_weeklypctdeaths_00
JP Weiland: 9/27/24 https://x.com/JPWeiland/status/1839795905811071342
September 27th update: Transmission rates cratering after a high summer surge.
XEC growing modestly- relatively positive outlook for winter.
Estimates:
590,000 new infections/day
1 in every 57 people currently infected
3% lower than 12 month avg.
9/25/24 https://x.com/JPWeiland/status/1839066851688534342
Michael Hoerger modeling: http://pmc19.com/data/, https://twitter.com/michael_hoerger
Tara Moriarty Canadian COVID data: https://x.com/MoriartyLab
UK:
9/26/24 Prof Christina Pagel: https://x.com/chrischirp/status/1839427892260069659
“We are now in our fourth or fifth Covid wave of the year with little time between waves.
I think this is a consequence of return to school & work plus a cold and wet September.
The latest subvariant XEC is not yet prevalent enough here to be driving this wave.
I also wrote about it here:
including reflecting on our refusal to learn from the pandemic.”
Cellular Pathways
COVID and the Heart:
9/27/24 Nature Scientific Reports: RNA-Seq analysis of human heart tissue reveals SARS-CoV-2 infection and inappropriate activation of the TNF-NF-κB pathway in cardiomyocytes https://buff.ly/47RmNWs
TNF-NF-κB: Tumor necrosis factor (TNF) and nuclear factor-kappa B (NF-κB)
Figure 1: Putative signaling pathway of SARS-COV-2 interaction with heart tissue causing heart damage and heart failure.
From: https://www.nature.com/articles/s41598-024-69635-6/figures/1
COVID and Cancer
9/26/24 Cell Communication and Signaling: Oncogenic potential of SARS-CoV-2—targeting hallmarks of cancer pathways https://buff.ly/4drwE6p
Graphical Abstract
From: https://biosignaling.biomedcentral.com/articles/10.1186/s12964-024-01818-0
Figure 1: Key oncogenic signaling molecules or pathways targeted by SARS-CoV-2 NSP, N, M and S protein
From: https://biosignaling.biomedcentral.com/articles/10.1186/s12964-024-01818-0/figures/1
Figure 5: The SARS-CoV-2 N protein activates NLRP3 inflammasomes and the dysregulation of the Renin–Angiotensin–Aldosterone System (RAAS) which leads to deregulated cellular metabolism, tumor-promoting inflammation, angiogenesis and metastasis.
From: https://biosignaling.biomedcentral.com/articles/10.1186/s12964-024-01818-0/figures/1
9/23/24 Biomedicines: Uncovering the Contrasts and Connections in PASC: Viral Load and Cytokine Signatures in Acute COVID-19 versus Post-Acute Sequelae of SARS-CoV-2 (PASC) https://buff.ly/3Ya2T5T
https://www.mdpi.com/2227-9059/12/9/1941
Figure 3. Graphical representation of cytokines and chemokines during acute phase of COVID-19 disease and subsequent PASC phase
Pediatrics
9/26/24 CDC: COVID-19–Associated Hospitalizations and Maternal Vaccination Among Infants Aged <6 Months — COVID-NET, 12 States, October 2022–April 2024 https://buff.ly/47ERqy9
https://www.cdc.gov/mmwr/volumes/73/wr/mm7338a1.htm
Babies under age 6 months are hospitalized with COVID more than any other group except adults age ≥75 years. Maternal vaccination works to decrease the risk of infant hospitalization from COVID.
FIGURE 2. Maternal vaccination status among infants aged <6 months hospitalized with laboratory-confirmed SARS-CoV-2 infection, October 2022–April 2024
From: https://www.cdc.gov/mmwr/volumes/73/wr/mm7338a1.htm
9/18/24 Science Translational Medicine: Preschool-age children maintain a distinct memory CD4+ T cell and memory B cell response after SARS-CoV-2 infection https://buff.ly/3MRCbZ6
https://www.science.org/doi/10.1126/scitranslmed.adl1997
Vaccines
9/27/24 Nature (F. Eun-Hyung Lee's lab, Emory): SARS-CoV-2-specific plasma cells are not durably established in the bone marrow long-lived compartment after mRNA vaccination https://buff.ly/4eDGh2S
https://www.nature.com/articles/s41591-024-03278-y
Dr. Akiko Iwasaki tweet thread https://x.com/VirusesImmunity/status/1839739442300424382
Figure 5b: Graphical summary. Unlike Influenza and Tetanus vaccines, the majority of SARS-CoV-2 plasma cells are not established from the bone marrow LLPC compartment 33 months after mRNA vaccination.
From: https://www.nature.com/articles/s41591-024-03278-y/figures/5
Prof Akiko Iwasaki discusses this paper in a tweet thread: https://x.com/VirusesImmunity/status/1839739442300424382
Antiviral treatments
The US government is sending out 4 free COVID tests via https://covidtests.gov/.
Long COVID
9/25/24 Cell (Peluso and Deeks, UCSF): Mechanisms of long COVID and the path toward therapeutics https://buff.ly/4gHuv9q
Drs. Peluso and Deeks from UCSF just published an amazing, comprehensive review of the pathophysiology of and potential treatments for Long COVID.
Figure 5. Potential relationships between the biological mechanisms of long COVID
Figure 6. Mechanistic targets of long COVID prevention and treatment
Viral targets
Immunologic targets
Clotting targets
Human herpesvirus targets
10/2024 Lancet: Changes in memory and cognition during the SARS-CoV-2 human challenge study https://t.co/E6LkFWQ02W
In 2021, thirty-four young healthy, unvaccinated people aged 18 to 30 volunteered to be infected with the original strain of SARS-CoV-2 and were followed with cognitive testing for a year. Eighteen volunteers became COVID positive (17 with mild symptoms, 1 with no symptoms). None of the infected individuals felt that they had brain fog or cognitive dysfunction, but cognitive tests showed that they actually did.
From: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00421-8/fulltext
5/2020 Science: Ethics of controlled human infection to address COVID-19 https://buff.ly/3MVIRp3
The ethics of controlled human infection studies (CHIs)
9/23/24 Nature Medicine: Post-hospitalisation COVID-19 cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction https://buff.ly/3XWeEfY
“Cognitive deficits in patients requiring hospitalization were equivalent in magnitude to 20 years of ageing and associated with objective evidence of ongoing brain injury and reduced grey matter volume.”
Post-acute COVID effects on the Brain
9/26/24 Covid Brain in 2 new publications ranging from mild cases in the young and healthy, to severe Covid among hospitalized patients. And other relevant updates.
From: Eric Topol https://x.com/EricTopol/status/1839688127113474362/photo/1
Reinfection Risks
9/24/24 Nature Portfolio Preprint: Long COVID and associated outcomes following COVID-19 reinfections: Insights from an International Patient-Led Survey https://buff.ly/3XY8Q5s
“Plain language summary
COVID-19 reinfections, or repeat infections with SARS-CoV-2, are common, even in people who have been vaccinated. Long COVID is a chronic health condition without a cure that can develop after a COVID infection. We investigated the impact of reinfections on the odds of reporting Long COVID, its symptoms and related disability. Using expertise from researchers with Long COVID, we developed an online survey that asked about COVID infection history, vaccination, and a suite of Long COVID symptoms. Our results show that COVID reinfections are associated with greater chances of reporting Long COVID, severe fatigue, symptoms in multiple body systems and limitation in physical function. Our findings support the importance of preventing COVID infections and considering reinfections when addressing Long COVID.”
11/2022 Nature (Al-Aly): Acute and postacute sequelae associated with SARS-CoV-2 reinfection https://buff.ly/3hyZp9R
9/18/24 Scandinavian Journal of Public Health: Self-reported body function and daily life activities 18 months after Covid-19: A nationwide cohort study (Sweden) https://buff.ly/3XxGLRc
In this nationwide study, more than 8 out of 10 individuals experienced problems with body function 18 months after being on sick leave due to Covid-19, with women and those initially hospitalised reporting more problems.
H5N1
9/27/24 CDC: Several additional health care workers exposed to the Missouri patient who was hospitalized with H5 Avian Flu had mild respiratory symptoms. "To date, only one case of influenza A(H5N1) has been detected in Missouri. No contacts of that case have tested positive for influenza A(H5N1)." https://buff.ly/4do97Dr
AI:
9/26/24 Science (Eric Topol MD): The revolution in high-throughput proteomics and AI https://www.science.org/doi/10.1126/science.ads5749
9/26/24 Eric Topol: https://twitter.com/EricTopol/status/1839373506049663296
My piece @ScienceMagazine today
“What happens when you can assay over 10,000 proteins in the blood, in tens of thousands of people with years of follow-up, and use #AI analytics?
An exciting, but largely unrecognized new frontier in medicine; open-access”
Eric Topol: A Table summarizing the 11 studies I reviewed
Other news:
This week, I wrote an article entitled “Infant RSV Disease Prevention: Helping Patients Understand the Options to Help Protect Their Baby” in collaboration with Sanofi. It looks at maternal vaccination and monoclonal antibodies to protect infants against RSV.
9/26/24 Nature: Stem cells reverse woman’s Type I diabetes — a world first https://buff.ly/4ezgfxy
“A 25-year-old woman with type 1 diabetes started producing her own insulin less than three months after receiving a transplant of reprogrammed stem cells1. She is the first person with the disease to be treated using cells that were extracted from her own body.”
9/25/24 Nature: Why do obesity drugs seem to treat so many other ailments? https://buff.ly/3ZC9OG1
https://www.nature.com/articles/d41586-024-03074-1
From: https://www.nature.com/articles/d41586-024-03074-1
9/16/24 Nature Neuroscience: Neuroanatomical changes observed over the course of a human pregnancy https://buff.ly/3B5culn
9/23/24 Mental Floss: Millions of Marine Fossils Discovered Beneath Los Angeles High School https://buff.ly/47HHBiQ
9/26/24 Recording the cats in the hats https://buff.ly/4gHKEMg
https://www.eurekalert.org/news-releases/1059386
“In a world first, veterinary scientists at Université de Montréal have found a way to scan the brains of cats while they’re awake, using electrodes concealed under specially knitted wool caps.”
Fée, an abandoned cat with chronic osteoarthritis
Aliénor Delsart / Université de Montréal