XBB1.16 is slowly rising and is now at 12.5% of cases. The CDC will no longer be tracking COVID levels in communities and Walgreen’s has stopped reporting COVID cases since April 11, 2023. The good news is that we are now at some of the lowest levels of COVID hospitalizations, deaths and wastewater levels since the beginning of the pandemic. It is expected that we are entering a “wavelet” era of COVID. Because vaccine efficiency and infection immunity against Omicron does not last as long as with prior variants, we can probably expect some small waves of COVID infections several times a year unlike influenza which happens more seasonally.
Despite the end of the global health emergency, several experts interviewed in the Washington Post expect that there is a 20% to 40% chance of a new variant that will cause an Omicron-like large wave of infection in the next two years. In the past, some viral mutations and new variants have formed in immunocompromised people with chronic Covid infections. There are also animal reservoirs of SARS-CoV-2 such as deer and minks that will need to be followed. Congress has allotted $5 billion for Covid research looking at how we can protect ourselves in the future. Research on nasal vaccines that stop a COVID infection from entering the body and pan-coronavirus vaccines that can protect against a variety of coronaviruses will be important. Some representatives in Congress have said that they want to take away this funding, but that would be shortsighted. Preparation is key for protecting against another SARS-CoV-2 variant.
This week in JAMA, a systematic review and meta-analysis of 40 studies looking at waning vaccine efficiency against Omicron infections showed significant waning of efficiency against Omicron within six months after vaccination and boosters. For the primary vaccination, vaccine efficiency was only at 20% by six months for symptomatic infections and was less than 30% at six months after a booster dose. Vaccine efficiency waned more quickly against Omicron infections than prior Delta infections.
David Putrino wrote a long Twitter thread on why Long Covid is not a Functional Neurological Disorder (FND) as some doctors believe. He reviewed many different articles, and some of the most striking showed that patients with Long Covid often have SARS-CoV-2 spike protein in their blood up to 12 months after acute infection, thus pointing to a possible reservoir of virus hidden in the body. Spike protein added to microfluidic channels lined with endothelial cells were found to cause microclots to form using blood from people without Long COVID. An article in NPR reviewed one of the main causes that is thought to be responsible for Long Covid – a viral reservoir of SARS-CoV-2 in the body. A combination of several pathophysiologies (viral reservoir, gut dysbiosis, microclots) may combine to cause Long COVID symptoms, but further research is needed.
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Other news:
4/25/23 Science Daily (M.I.T.): A simple paper test could offer early cancer diagnosis: The new diagnostic, which is based on analysis of urine samples, could also be designed to reveal whether a tumor has metastasized. https://buff.ly/3nuWVgb
Original study:
Nature Nanotechnology: CRISPR-Cas-amplified urinary biomarkers for multiplexed and portable cancer diagnostics in micehttps://buff.ly/423eLpw
4/28/23 HealthDay: Hair Relaxer Chemicals May Affect a Woman's Fertility https://buff.ly/42ewZ7m
Hair relaxers, often used by Black and Hispanic individuals, may compromise fertility, especially if used frequently or long term.
Phthalates, phenols and parabens may be involved.
4/29/23 NPR: Lonely pet parrots find friendship through video chats, a new study finds https://buff.ly/3Vl7yik
5/2/23 KFF: After Idaho’s Strict Abortion Ban, OB-GYNs Stage a Quick Exodushttps://buff.ly/3Vv5J2l
The state law did not allow physicians to terminate ectopic pregnancies, which are never viable and which can be fatal if they rupture.
75 of 117 Idaho OB-GYNs recently surveyed said they were considering leaving the state because of Idaho’s restrictive abortion laws.
Maternity and Labor and Delivery wards are closing across the state as Ob/Gyns leave.
5/3/23 BBC: US Surgeon General Vivek Murthy recounts bout of profound loneliness https://buff.ly/3AWC74m
Dr. Murthy warned that the U.S. is facing an epidemic of loneliness which is as dangerous to health as smoking 15 cigarettes a day.
US health authorities are calling for social isolation to be treated as seriously as obesity or drug abuse. Nearly 50% of all Americans are thought to have been affected.
The issue has been exacerbated by the Covid pandemic, which led many people to reduce the size of their social circles.
5/2/23 Surgeon General’s Advisory: Our Epidemic of Loneliness and Isolationhttps://buff.ly/426cLwU
Six pillars to improve connection:
Strengthen Social Infrastructure
Enact Pro-Connection Public Policies
Mobilize the Health Sector
Reform Digital Environments
Deepen Our Knowledge
Cultivate a Culture of Connection
5/3/23 Nature: Women’s health research lacks funding – these charts show how https://buff.ly/3VBcxLH
Interactive charts show how diseases that affect women more are underfunded compared to the disease burden.
AI:
4/30/23 ChatGPT Outperforms Doctors In Answering Patient Messages, Study Shows - MedCity News https://buff.ly/3nk7uTb
A panel of licensed healthcare professionals preferred ChatGPT’s responses 79% of the time over that of physicians.
Last week, healthcare software giant Epic announced that it will integrate GPT-4, the latest version of the AI model, into its electronic health record.
4/28/23 JAMA: Comparing Physician and Chatbot Responses to Patient Questions https://buff.ly/3oSdH9f
A team of licensed health care professionals compared physician’s and chatbot’s responses to patient’s questions asked publicly on a public social media forum. The chatbot responses were preferred over physician responses and rated significantly higher for both quality and empathy.
Scientists trained AI using functional MRI (fMRI) to translate people's thoughts. The decoder trained on one person’s brain activity was not able to read another person’s thoughts.
The A.I. decoder appeared to capture words and their meaning.
"Scientists recorded M.R.I. data from three participants as they listened to 16 hours of narrative stories to train the model to map between brain activity and semantic features that captured the meanings of certain phrases and the associated brain response."
h/t Daniel Kraft
5/1/23 Nature Neuroscience (UT Austin): Semantic reconstruction of continuous language from non-invasive brain recordings https://buff.ly/40UCCq4
The human must cooperate in order to both train and apply the AI decoder.
"Our findings demonstrate the viability of non-invasive language brain–computer interfaces."
5/1/23 NY Times: Geoffrey Hinton, ‘The Godfather of A.I.’ Leaves Google and Warns of Danger Ahead https://t.co/vPAiGQuc83
The transition to the new XBB variants in the US continues, with XBB.1.16 leading the way, while wastewater levels, Covid hospitalizations and deaths are at or near pandemic lows.
Cross-border transmission can’t (and won’t) be stopped.
COVID-19 does not require a coordinated international response.
What it does not mean:
This doesn’t mean the end of a pandemic.
This doesn’t mean that COVID-19 is gone.
SARS-CoV-2 is currently mutating 2 times faster than the flu. We will get future waves, but hopefully these will be “wavelets” given the population-level immunity from vaccines and infections. And wavelets will happen several times a year. The probability of a variant of concern (which would be named Pi) is still ~20% in the next 1.5 years.
This doesn’t mean that we can go back to pre-pandemic times.
3/7/23 Eric Topol MD: A break from Covid waves and a breakthrough for preventing Long Covid https://buff.ly/427QoqF
An Omicron-like event has about a 20% chance of happening in the next 2 years.
5/5/23 Wash Post: Disease experts warn White House of potential for omicron-like wave of illness https://buff.ly/3M0lICg
Eric Topol predicts 20% risk, Trevor Bedford predicts 40% risk by 2025 of a new variant that could cause a large wave like Omicron did because our immunity might now work against it. Dan Barouch hopes that our T cells may help to stop a new variant.
An immunocompromised person may get a chronic COVID infection that could incubate new viral mutations as has happened in the past.
Congress may want to rescind the $5 billion for COVID research, but we need nasal vaccines and pan-coronavirus vaccines to protect us against potential new variants.
“Even if the pandemic is over, endemic COVID is still going to be a major public health concern,” Bedford said.
5/5/23 Reuters: CDC chief Dr. Rochelle Walensky stepping down in June https://buff.ly/44wQWrT
New vaccines/boosters should not include the wild type (Wuhan, original virus) to avoid immune imprinting, but should include Omicron XBB.
Those who haven’t been exposed to Omicron yet should receive two updated vaccine boosters.
5/5/23 BioRxiV: A bivalent ChAd nasal vaccine protects against SARS-CoV-2 BQ.1.1 and XBB.1.5 infection and disease in mice and hamsters https://buff.ly/3AUxlo5
People under age 20 or over age 50 had greater protection from SARS-CoV-2 vaccinations administered between late morning and early afternoon.
5/2/23 NPR: Why viral reservoirs are a prime suspect for long COVID sleuths https://buff.ly/44jmHEN
Review of studies pointing to viral persistence in some people with Long COVID.
Authors note that there may be more than one cause including viral persistence, immune dysregulation, autoimmunity, microclots and endothelialitis, reactivation of dormant viruses like EBV, and signaling problems with the brainstem and the vagus nerve, among others.
"These could all actually converge and come together in an interrelated way, so by no means are they necessarily mutually exclusive," says Dr. Linda Geng, co-director of Stanford University's long COVID clinic.
5/2/23 Nature: Algorithm for Optimized mRNA Design Improves Stability and Immunogenicity https://buff.ly/44AvQZV
mRNA vaccines are limited by mRNA instability and degradation which is a major obstacle in the storage, distribution, and efficacy of mRNA vaccine products.
Authors used their algorithm called LinearDesign to improve mRNA half-life and protein expression, and dramatically increase antibody titer by up to 128× in vivo, compared to the codon-optimization benchmark.
5/2/23 Wash Post: CDC opens probe after 35 test positive for Covid following CDC conferencehttps://buff.ly/3ANL67R
Attendees say many people did not mask, socially distance or take other precautions recommended earlier in the pandemic.
Functional Neurological Disorder (FND) is synonymous with a conversion disorder (i.e. “psychosomatic illness”).
Articles referenced in the tweet thread:
1/13/23 Nature (Davis et al): Long COVID: major findings, mechanisms and recommendations https://buff.ly/3Xe7LUi
Immune dysregulation:
5/1/22 Gastroenterology (Zollner et al): Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases https://buff.ly/420Napa
2/28/22 J of Medical Virology (Giannos): Gut dysbiosis and long COVID‐19: Feeling gutted https://buff.ly/3nvoGW4
Long COVID gut dysbiosis:
Decreased anti-inflammatory bacteria Faecalibacterium prausnitzii, Eubacterium rectale, and Bifidobacterium adolescentis.
These changes may underlie the association between lower gut microbiota diversity and higher C‐reactive protein levels in long COVID‐ 19 patients (Figure 1).
References:
8. Yeoh YK, Zuo T, Lui GCY, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID‐19. Gut. 2021;70:698‐706.
10. Chen Y, Gu S, Chen Y, et al. Six‐month follow‐up of gut microbiota richness in patients with COVID‐19. Gut. 2022;71:222‐225.
11. Tian Y, Sun KY, Meng TQ, et al. Gut microbiota may not be fully restored in recovered COVID‐19 patients after 3‐month recovery. Front Nutr. 2021;8:182.
So if you have LC, persistent virus is often found in your GI tract and then gut dysbiosis emerges.
6/16/22 MedRxiV (David Walt lab): Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae https://buff.ly/42oNWMa
9/2/22 Clinical Infectious Disease (David Walt lab): Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae https://buff.ly/42naihm
SARS-CoV-2 spike protein was detected in the plasma of the majority of PASC patients up to 12 months after diagnosis.
Detection of spike at multiple time points 2 to 12 months after infection.
Important to do longitudinal sampling as temporal fluctuations in antigen levels were noted for a subset of individuals with LC.
“The presence of circulating spike [protein] supports the hypothesis that a reservoir of active virus persists in the body.”
Clotting and Endothelial dysfunction
4/18/23 Cell Trends in Endocrinology and Metab: Long COVID: pathophysiological factors and abnormalities of coagulation https://buff.ly/3HyWWGI
When you add spike protein to healthy blood, microclots form.
The Brain
“Every acute COVID infection, Long COVID or not, appears to damage your brain.”
3/7/22 Nature: SARS-CoV-2 is associated with changes in brain structure in UK Biobank https://buff.ly/3sP9zqj
UK Biobank MRIs with MRI scans before and after COVID infection as compared to controls with no COVID infections showed:
(1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus;
(2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and
(3) a greater reduction in global brain size in the SARS-CoV-2 cases.
The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points.
6/12/22 Cell (Monje, Iwasaki): Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation https://buff.ly/3PeizyL
Respiratory COVID induces CSF cytokine elevation and microglial reactivity.
CCL11 activates hippocampal microglia and impairs neurogenesis.
Respiratory COVID causes persistent loss of oligodendrocytes and myelinated axons.
Long COVID symptoms may be related to the extent to which the virus is present in different organ systems.
5/1/23 Nature: COVID's future: mini-waves rather than seasonal surges https://buff.ly/3p4Bsv6
We may be in the "wavelet" era of COVID where new variants cause more mild infection over all. Wavelets may happen three or four times per year in some countries.
The combination of rapid mutation and short-lived human immunity is probably preventing SARS-CoV-2 from settling into seasonal patterns of circulation, says Wenseleers.
