COVID news and more, 10/6/24
This was an very busy week, so I am trying something different. I am posting my COVID news notes with the data and graphs at the top and the research articles individually summarized towards the bottom.
Overall, SARS-CoV-2 levels are going down and are now at a MODERATE level across the U.S. About 1 in every 78 people is infected which is a big improvement over a month ago. The northeast has the highest level for SARS-2 in wastewater, followed by the midwest. We are expected to hit the lowest recent wastewater levels (a lull) the first week of November.
There is an exceptional review on endothelial dysfunction and microclots in Long COVID with great diagrams on the pathophysiology and on possible medications to treat different clotting issues. In addition, there are several articles on Long COVID and cognitive impairment (brain fog) and how this relates to reduced brain connectivity patterns and white matter structural changes. Drs Peluso and Ely discuss in their Nature article, “Many long-COVID patients have neurological problems that meet the criteria for what would normally be considered age-related mild cognitive impairment, or mild to moderate dementia… The large number of long COVID patients presents a unique opportunity for research, potentially leading to better treatments for both long COVID and other chronic neurocognitive disorders.”
In non-COVID news, disability advocate Alice Wong was chosen a MacArthur Fellow, Dolly Parton donated $1 million to Hurricane Helene relief, and a determined father walked 17+ miles through debris from Helene to get to his daughter’s wedding to walk her down the aisle.
Have a great rest of your weekend,
Ruth Ann Crystal MD
COVID news notes:
JP Weiland: https://twitter.com/JPWeiland
9/30/24 https://x.com/JPWeiland/status/1840893362766754162
US Variant tracker: https://covid.cdc.gov/covid-data-tracker/#variant-proportions
Updated every 2 weeks
Variants around the world: https://outbreak.info/
World wastewater maps (reflects COVID cases): https://www.arcgis.com/apps/dashboards/c778145ea5bb4daeb58d31afee389082
CDC COVID data tracker: https://covid.cdc.gov/covid-data-tracker/index.html#datatracker-home
Last updated 10/4/24
COVID Emergency Dept visits: https://covid.cdc.gov/covid-data-tracker/#ed-visits_all_ages_combined
Through 9/30/24
CDC Respiratory es (COVID, Flu, RSV) Hospitalizations (for those states reporting): https://www.cdc.gov/resp-net/dashboard/index.html
Updated 10/4/24. Only some states are reporting. Hospitalization data will be mandatory again on November 1, 2024.
States reporting Hospitalization through 9/14/24 from
https://iowacovid19tracker.org/
Walgreens positivity rate: https://www.walgreens.com/businesssolutions/covid-19-index.jsp
Updated 9/30/24
US Wastewater Monitoring:
CDC wastewater reporting: https://www.cdc.gov/nwss/rv/COVID19-nationaltrend.html
National wastewater now at MODERATE. Updated 10/3/24.
CDC wastewater map: https://www.cdc.gov/nwss/rv/COVID19-currentlevels.html
Last updated 10/3/24. Time Period: 9/22/24 - 9/28/24
National SARS-CoV-2 data from Sara Anne Willette (Maps through 9/22/24):
https://iowacovid19tracker.org/
Wastewater SCAN: https://data.wastewaterscan.org/
MEDIUM levels SARS-CoV-2 nationally
West: MEDIUM
Midwest: HIGH
Northeast: HIGH
South: Low
California statewide view https://buff.ly/3YObiul
Sewer Coronavirus Alert Network (SCAN) project by Stanford University:
Since 4/6/24 (6 month view). Northern California.
Santa Clara County wastewater: https://publichealth.santaclaracounty.gov/health-information/health-data/disease-data/covid-19/covid-19-wastewater
Marin county: https://coronavirus.marinhhs.org/surveillance
10/3/24
COVID deaths per week: https://covid.cdc.gov/covid-data-tracker/#trends_weeklydeaths_weeklypctdeaths_00
https://x.com/BNOFeed/status/1840590694055813588
9/29/24
CDC Forecasting of expected EPIDEMIC GROWTH of SARS-CoV-2: https://www.cdc.gov/forecast-outbreak-analytics/about/rt-estimates.html
Puerto Rico COVID-19 dashboard: https://covid-19-puerto-rico.org/2024-06-29/index.html
Canada:
Tara Moriarty Canadian COVID data: https://x.com/MoriartyLab
9/29/24 Forecast https://x.com/MoriartyLab/status/1840537843883544987
France:
UK
UKHSA Dashboard: https://ukhsa-dashboard.data.gov.uk/
UK COVID PCR Test Positivity Map: https://jamestindall.info/skeuomorphology/ladb_covid/index.html
Research Articles
Variants
10/1/24 Lancet: A novel SARS-CoV-2 recombinant transmitted from a patient with an acute co-infection https://buff.ly/3TVkRX6
This is the first report of a patient co-infected with 2 SARS-CoV-2 lineages who transmitted a novel recombinant COVID variant (a combination of the 2 variants) to another patient while in the hospital.
Acute COVID infections, General COVID info
10/1/24 TIME: How COVID-19 Messes Up Your Gut Health https://buff.ly/4etOaYX
"These days, when someone complains of nausea, diarrhea, or vomiting, “I always get a COVID test on that patient,” Jain says.
"Loss of appetite, nausea, vomiting, diarrhea, and stomach pain are common GI symptoms of COVID-19, according to Jain’s research. Some people experience these issues as their first signs of infection, he says, while others initially experience cold-like symptoms and develop gastrointestinal issues as their illness progresses."
9/10/24 Frontiers in Immunology | Alterations in the plasma proteome persist ten months after recovery from mild to moderate SARS-CoV-2 infection https://buff.ly/3XUg4WY
The NIH COVID-ARC group put out a paper on effects of COVID vaccination on the plasma proteome during acute COVID infection and at 10 months after infection. Unvaccinated patients had higher levels of inflammation and immune responses, while vaccinated individuals had more adaptive immune responses and less inflammation with COVID infection. Up to 10 months after acute COVID infection, both vaccinated and unvaccinated people had persistent underexpression of proteins involved in essential cell functions, signaling, and angiogenesis. This suggests that SARS-CoV-2 infection “can lead to long-lasting proteomic changes, with potential implications for understanding post-acute viral syndromes.”
9/23/24 PNAS (Rockefeller, Paris): A sensitive assay for measuring whole-blood responses to type I IFNs https://buff.ly/3zIqHEh
https://www.pnas.org/doi/epub/10.1073/pnas.2402983121
Type I interferon is important for fighting viral infections. A group from Rockefeller University made a new lab test that measures IP-10 which can detect people with autoantibodies to Type I interferon and those with rare inborn errors of the Type I IFN response pathway. This is important because about 10% of people who develop a severe COVID infection have autoantibodies to Type I interferon.
Social and Advocacy
https://x.com/NohaAboelataMD/status/1840208115373093316
Bernie Sanders in the Senate had proposed a Long COVID Moonshot Bill for $10 Billion for research and assistance services. Now, congresspeople from the House of Representatives has done the same.
9/27/24 KQED: Bay Area's Long COVID Community Celebrates Moonshot Bill for $10 Billion in Funding https://buff.ly/3XM7AkB
"The Long COVID Research Moonshot Act, proposed by Rep. Ilhan Omar (D-Minn.) and co-sponsored by Rep. Barbara Lee (D-Oakland), is a companion bill to one that Sen. Bernie Sanders (I-Vt.) introduced in the Senate in August."
“There are political reasons to deny that there are any long-term effects of COVID, to allow for us to ‘get back to normal.’” said Kim Rhoads, co-founder of Umoja Health, which serves the COVID-19 and health needs of people of color.
From The Pandemic RoundUp https://www.patreon.com/posts/pandemic-roundup-113265900
“When the federal government’s pandemic-era protections ended last year, Texas moved swiftly, kicking off more people faster from Medicaid than any other state… Nearly 1.4 million people who lost coverage were disenrolled for reasons like failing to return a form.” [ProPublica]
“Millions of people are missing from U.S. disability data… because there is “No Box to Check” to indicate their particular disability on surveys from the U.S. Census Bureau and other federal agencies… [including] between 32% and 53% of people with chronic health conditions, such as long Covid.” [STAT]
Pediatrics
9/26/24 JAMA: Rates of Sudden Unexpected Infant Death Before and During COVID-19 https://buff.ly/3ZNfMUx
During the COVID-19 pandemic, the patterns of sudden unexpected infant death (SUID) and sudden infant death syndrome (SIDS) shifted significantly. Starting in July 2020, SUID rates increased, with a more noticeable rise between June and December 2021, correlating with a surge in Respiratory Syncytial Virus (RSV) hospitalizations. SIDS rates were elevated throughout the pandemic, peaking in July and August 2021. These findings suggest that off-season resurgences of infections like RSV may have contributed to the increase in SUID and SIDS during the pandemic.
10/1/24 Pediatric Infect Dis Journal (Buonsenso): Cytokine Profile in Children Following SARS-CoV-2 Infection: Preliminary Findings https://buff.ly/4dwRrFC
Danielo Buonsenso and colleagues from Italy did a very small study (more like a case series) on children with Long COVID with only 10 pediatric Long COVID patients, 7 COVID recovered children and 4 healthy controls were enrolled. They found that “children with long COVID had statistically significant differences in the levels of Flt3L, CD5, uPA, CCL23, CD40 and TGFα. When adjusted for age, CCL23 levels remained statistically significant.” Because this study was so small, it will be important to repeat it with a larger cohort of children to see if findings are consistent.
“Children with previous SARS-CoV-2 infection, and particularly those with Long COVID, exhibit altered cytokine expression patterns involved in T cell homeostasis and coagulation, in line with adult studies.”
9/29/24 Buonsenso&theKids: Long Covid is real also in children https://buff.ly/4evv1WB
Discusses Pediatric Long COVID salivary biomarkers study from 5/30/2024.
9/26/24 American Journal of Medicine Open (Yale): Post-Acute sequelae of COVID-19 (PASC) in pediatric patients within the United States: A Scoping Review https://buff.ly/3zpHWu8
This review looked at 29 different studies on Post-Acute Sequelae of COVID-19 (PASC or Long COVID) in children and teens. Risk factors for pediatric Long COVID included older age (teens), female sex and severe initial acute COVID infection, although 80% of pediatric Long COVID patients initially had a mild COVID infection. Pre-existing asthma, atopy and obesity were often reported in children with PASC. “Common symptoms were dyspnea, fatigue, headaches, and chest pain… Most studies had a high risk of bias and were limited by a lack of standardized definitions and short follow-up duration.” More research on the long term effects of COVID on children and adolescents are needed.
Figure 4: Pediatric Long COVID symptoms in 529 children and teens
From: https://www.sciencedirect.com/science/article/pii/S2667036424000153
9/11/24 Frontiers in Immunology: Increased incidence of seronegative autoimmune hepatitis in children during SARS-CoV-2 pandemic period https://buff.ly/3zNWzay
A small, retrospective, observational study of 32 children showed a 3.3-fold increase of pediatric seronegative autoimmune hepatitis during the SARS-CoV-2 pandemic (2020-2022) as compared to the 9 years prior (2010-2019).
Antiviral treatments
Resistance to Antiviral Medications
9/25/24 JAMA: Emerging SARS-CoV-2 Resistance After Antiviral Treatment https://buff.ly/3TYNByh
"In this cohort study of 156 participants, treatment-emergent nirmatrelvir resistance mutations were commonly detected, especially in individuals who were immunosuppressed. However, these mutations were generally present at low frequencies and were transient in nature, suggesting a low risk for the spread of nirmatrelvir resistance in the community with the current variants and drug usage patterns."
9/18/24 Nature Communications: Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections https://buff.ly/4gWo1E2
"We investigated the impact of antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients (n = 15). All patients received remdesivir and some also received nirmatrelvir-ritonavir (n = 3) or therapeutic monoclonal antibodies (n = 4).
"This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibility in vivo" to hamsters.
Obeldesivir
8/12/24 Antimicrobial Agents and Chemotherapy: Clinical pharmacodynamics of obeldesivir versus remdesivir https://buff.ly/4ewuXGe
Remdesivir is FDA approved for hospitalized COVID patients. It has to be given intravenously because of extensive hepatic metabolism of the drug. "While the efficacy of remdesivir in hospitalized COVID-19 patients is mixed, its efficacy in mild-to-moderate COVID-19 in an outpatient setting is clear: 87% lower risk of hospitalization or death compared to placebo." Obeldesivir, also made by Gilead, is an oral drug that works like Remdesivir, but is more bioavailable. “Obeldesivir recently completed phase 3 trials in the treatment of mild-to-moderate COVID-19 outpatient S (NCT05715528).”
Fig 2 Plasma pharmacokinetics and PBMC pharmacodynamics of remdesivir and obeldesivir in humans.
Long COVID
Long COVID Phenotypes
10/2/24 Nature Preprint (Patient-Led): Multi-method phenotyping of Long COVID patients using high-dimensional symptom data https://buff.ly/4eQCWgS
Using the three different machine learning models to evaluate symptoms in 6,031 people with Long COVID, researchers were not able to find reproducible Long COVID clusters. Analysis did show higher symptom burden clusters in women and in younger individuals, and in those with more severe physical and cognitive post-exertional malaise (PEM). The authors concluded that patient symptoms may not be the best way to sort Long COVID phenotypes, highlighting the complexity of the condition and the need for more detailed, personalized approaches to understanding and grouping patients.
Long COVID and ME/CFS
9/29/24 Journal of Infection: The persistence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis https://buff.ly/3N9bwqX
A new meta-analysis looked at 13 studies that reported a total of 1,973 Long COVID patients. They found that 51% of Long COVID patients have Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) which is characterized by fatigue, sleep disruption, and muscle/joint pain and post-exertional malaise.
Long COVID and the Brain
10/2/24 Nature (M. Peluso, E. Wes Ely): How long COVID could lift the fog on neurocognitive disorders https://buff.ly/3zSKQHK
“Many long-COVID patients have neurological problems that meet the criteria for what would normally be considered age-related mild cognitive impairment, or mild to moderate dementia… Brain studies of COVID patients have been among the most revealing science to emerge from the pandemic.” Long COVID affects more than 5% of people infected with SARS-CoV-2, and some of these patients will develop a rapidly acquired ADRD. “The large number of long COVID patients presents a unique opportunity for research, potentially leading to better treatments for both long COVID and other chronic neurocognitive disorders.”
9/27/24 Nature (UT Austin): Altered functional brain connectivity, efficiency, and information flow associated with brain fog after mild to moderate COVID-19 infection https://buff.ly/3ZZxUdI
n =49 adults with prior COVID infection and n = 24 controls without previous COVID infection.
This study from UT Austin looked at how mild to moderate COVID infection can lead to brain fog and cognitive impairments. Researchers used neuroimaging to compare brain activity and cognitive performance in people who had a prior COVID infection as compared to controls. They found that the group that previously had a COVID infection had reduced brain connectivity, especially in areas linked to fatigue and cognitive function, suggesting that brain fog is associated with lower efficiency in processing information due to changes in the brain's connectivity.
10/2024 Psychiatry Research (Madrid, Spain): Neural basis of Fatigue in post-COVID syndrome and relationships with cognitive complaints and cognition https://buff.ly/3zzVseL
Researchers from Madrid, Spain studied brain structural and functional connectivity in 129 people with fatigue from Long COVID. Fatigue is one of the most common and debilitating symptoms of Long COVID and is associated with subjective cognitive complaints. The researchers found that both physical and mental fatigue were associated with distinct patterns of brain connectivity, especially in frontal, temporal, and cerebellar regions. Long COVID fatigue also correlated with changes in white matter of the brain.
Fig. 3. White matter diffusivity associations with fatigue, FLEI and Stroop W-C in PCS.
From: https://www.sciencedirect.com/science/article/pii/S0165178124003986
9/12/24 Frontiers in Neurology (Barcelona, Spain): Multimodal neuroimaging in Long-COVID and its correlates with cognition 1.8 years after SARS-CoV-2 infection: a cross-sectional study of the Aliança ProHEpiC-19 Cognitiu https://buff.ly/3Y3nNDo
“The Aliança ProHEpiC-19 Cognitiu (APC) is a prospective, longitudinal study that explores how Long COVID (LC) affects the brain and cognition using MRI with diffusion tensor imaging (DTI) and functional MRI (fMRI) sequences on 53 LC patients 1.8 years after acute COVID-19 onset.”
The researchers found that cognitive impairments in executive function, attention, and memory were linked to changes in brain structure, particularly in white matter, as well as alterations in functional brain activity and connectivity. In both hemispheres of the brain, reduced axon myelination and lower white matter network integrity was associated with memory impairment, as was a higher resting state activity in the fronto-parietal network. In addition, they found “increased functional connectivity among the bilateral hippocampus, the right hippocampus and the left amygdala, and the right hippocampus and the left middle temporal gyrus” that were inversely related to memory. These findings show that Long COVID leads to changes in the brain that last for almost two years after infection that contribute to memory and cognitive problems.
Figure 1. Increased radial diffusivity (RD) (red-yellow) superimposed on the tract skeleton (green).
From: https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1426881/full
Vascular pathologies in Acute and in Long COVID
9/30/24 Seminars in Thrombosis and Hemostasis (Putrino, Kell, Pretorius): Vascular Pathogenesis in Acute and Long COVID: Current Insights and Therapeutic Outlook https://buff.ly/4dD8ztx
Amazing review. Outline below:
The Interplay between Endothelial Dysfunction and Coagulation
Other Special Investigations to Consider in Patients with Long COVID
Potential Therapeutic Agents that Could be Useful in the Context of Long COVID
Fig. 1 COVID-associated endothelial dysfunction and endothelialitis.
Fig. 2
Figure 4: Ways to measure endothelial health or dysfunction
Given our presentation of evidence for the central role of endothelialitis in Long COVID, clinicians should consider routine assessment of endothelial health using tools such as endothelium-dependent FMD, peripheral arterial tonometry and capillaroscopic analysis. These assessments can help identify individuals at risk for Long COVID or monitor those already affected.
For Medications for Long COVID, see Table 1: Long COVID manifestations, affected organ systems, and therapeutic agents that may be effective in the treatment of Long COVID https://buff.ly/4dD8ztx
Table 2: Take-home pointers for clinicians
***Key Takeaways:
One crucial takeaway from our analysis is the urgent need to recognize the centrality of Endothelial Dysfunction (ED) in Long COVID. Further, the intermittent character of Long COVID symptoms remains a puzzle that requires further investigation. It is evident that host genetic polymorphisms play a pivotal role in determining the diverse clinical symptomatology experienced by Long COVID sufferers, highlighting the need for personalized approaches to treatment and management. A complete understanding of factors such as oral dysbiosis and viral persistence in the upstream causation of ED is yet to be elucidated but should be an urgent focus.
COVID, the Lungs and Alveolar Macrophages
10/4/24 Nature Immunology: Profibrotic monocyte-derived alveolar macrophages are expanded in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19 https://buff.ly/3NcRNGJ
"Monocyte-derived alveolar macrophages drive lung injury and fibrosis in murine models and are associated with pulmonary fibrosis in humans" after COVID infection.
10/4/24 Nature Immunology: Monocyte-derived macrophages are too much of a good thing in lung fibrosis https://buff.ly/4duZfaR
"Acute lung injury elicits a profibrotic wound healing program in monocyte-derived macrophages. Their abundance is associated with pulmonary fibrosis in individuals recovering from COVID-19 pneumonia."
From: https://www.nature.com/articles/s41590-024-01989-5/figures/1
9/30/24 Immunity: Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection ameliorates secondary influenza A virus disease https://buff.ly/3ZK2GHE
Getting a COVID infection can help a person fight against Influenza A via durable epigenetic innate immune memory in alveolar macrophages.
Graphical Abstract:
From: https://www.cell.com/immunity/abstract/S1074-7613(24)00417-5
Long COVID and Neuropathy
9/30/24 Yale Medicine, Lisa Sanders MD: When Nerve Pain and Numbness Are Linked to Long COVID https://buff.ly/47WB9od
One study (https://buff.ly/4eQnMs3) showed that 56% of COVID-19 patients had symptoms of peripheral neuropathy post-infection.
Neuropathy workup should include tests for B12, autoimmune diseases, possibly for high B6, EMG/nerve conduction test, and possibly a skin biopsy for small fiber neuropathy (SFN).
Long COVID and Surgery
9/12/24 International Journal of Environmental Research and Public Health (UCSD): The Long Haul to Surgery: Long COVID Has Minimal Burden on Surgical Departments https://buff.ly/4eLIs4F
At UCSD, patients with positive COVID tests in 2020 to 2021 were sent surveys 90 days after the positive test. About 10% of patients responded, and of those, about half reported symptoms consistent with Long COVID- weakness/tiredness, sleep disturbances, and difficulty thinking/concentrating (“brain fog”). Of all of the respondents, 174 (17.4%) had undergone a surgery or an invasive procedure in any one of the surgical specialties at UCSD. There were no statistically significant differences between the surgical outcomes (case urgency, hospitalization, ICU stay, or 30 day complication rate) for patients with and without Long COVID symptoms.
Of note, prior studies have shown that anesthesiologists find that people with Long COVID can have problems with oxygen diffusion, as if they were anemic, but they are not.
H5N1
10/3/24 BNO News: 2 dairy workers in California tests positive for H5N1 bird flu https://buff.ly/4eSIY0N
"The workers have only mild symptoms and the risk to the general public is believed to be low."
10/4/24 Los Angeles Times: 'More serious than we had hoped': Bird flu deaths mount among California dairy cows https://t.co/NbXjBu51pd
Although dairy operators had been told to expect a mortality rate of less than 2%, preliminary reports suggest that between 10% and 15% of infected cattle are dying, according to veterinarians and dairy farmers.
Avian Flu H5N1 Influenza A https://www.cdc.gov/nwss/wastewater-surveillance/Flu-A-data.html
AI:
10/2/24 Economist: AI offers an intriguing new way to diagnose mental-health conditions with voice https://archive.is/oH3Ft
Other news:
10/4/24 https://x.com/jburnmurdoch/status/1842163184838250764
This may be due to GLP-1 medications.
10/1/24 Congrats to Alice Wong, disability advocate on being chosen a MacArthur Fellow https://x.com/macfound/status/1841152664039551115
9/30/24 David Jones traveled nearly 27 miles, including 17 miles on foot, through Hurricane Helene's wreckage to make it to his daughter's wedding to walk her down the aisle. https://buff.ly/3TY8bPd
10/5/24 BBC: Dolly Parton donates $1Million to Hurricane Helene recovery efforts https://buff.ly/3XXEuPo
Dolly Parton is a national treasure!
Thank you for your commitment and time. Your round up is essential reading each week.