This week’s flu map from the CDC shows that influenza cases are very high now across the United States. Fortunately, the flu vaccine this year is very well matched to the influenza virus that is circulating. Since we have a “tripledemic” of flu, RSV, and COVID in hospitals now, it is important to get the flu vaccine and the bivalent booster against COVID, wear a mask when indoors, improve air quality, wash hands often and stay home when sick.
Wastewater levels of SARS-CoV-2 are very high in the Bay Area right now. Looking at the curves, it appears that virus levels are higher now than they have been in the 109 weeks since wastewater testing started. Across the US, we see that there is high wastewater virus in Illinois, Ohio, Utah, Arizona, Southern California, NYC, and Washington state. The increase in virus levels may be related to recent Thanksgiving gatherings. Hospitalizations for Covid are also increasing in the United States especially in people over age 70. Only 25% of older Americans have had the bivalent booster in the US. Fortunately, the first real-world data from the CDC on the bivalent booster vaccines find that they are better at preventing symptomatic COVID infections than earlier monovalent boosters. The CDC also reported this week that Paxlovid reduced hospitalization by 51% across all groups studied (all ages, vaccination statuses, histories of prior infection, and variant types.)
Globally, France has an increase in new cases related to the BQ.1.(1) variant and the latest wave is associated with an increase in hospitalizations as well. We are seeing new waves in Japan, Australia and some parts of Europe. In China, protests have erupted across the country after at least ten people died in a fire where residents were locked into their building because of the zero-COVID policy. SARS-CoV-2 cases are rising in China and the Sinovac and Sinopharm vaccines do not protect well against Omicron. As noted in the Economist, the public health crisis is now morphing into a political crisis. A Nature article published last May predicted that if/when the Chinese Zero-COVID policy is lifted, more than 100 million cases of COVID can be expected across China, especially in older people who are not boosted. ICUs and hospitals will be overwhelmed. A new massive SARS-CoV-2 wave in China will affect the world’s supply chain and economy. And if more than 100 million people are infected at the same time, there will be an increased risk of new variants forming.
Kids:
A study from Switzerland shows that 4% of children and 8% of adolescents have Long Covid. Another study from Brazil shows that 25% of asymptomatic children undergoing adenotonsillectomy had SARS-CoV-2 in their tonsils and/or adenoids and that this lymphoid tissue was acting as a viral reservoir. Finally, two other studies (study and study) show that SARS-CoV-2 infections increase the risk of both Type 1 diabetes in children and type 2 diabetes.
PASC, Long COVID:
In a press release from the Radiological Society of North America meeting, researchers found that susceptibility-weighted MRI shows significant brain abnormalities in the brainstem and frontal lobe in patients with PASC/Long Covid. These areas of the brain are associated with fatigue, insomnia, anxiety, depression, headaches and cognitive problems. Magnetic susceptibility in MRI denotes how much certain materials, such as blood, iron and calcium, are magnetized in an applied magnetic field. "Changes in susceptibility values of brain regions may be indicative of local compositional changes.”
We know from a UK Biobank study reported in March 2022, there are changes in brain structure after a SARS-CoV-2 infection including a reduction in grey matter thickness in the orbitofrontal cortex and parahippocampal gyrus, tissue damage in the primary olfactory cortex and a reduction in global brain size. A new study from Mount Sinai, shows that there are similar molecular and cellular changes in the brains of people with SARS-CoV-2 and those with Alzheimer’s disease. SARS-CoV-2 infection mirrors Alzheimer’s Disease (AD)-type transcriptional and cellular neuroinflammatory patterns in a very short time frame. In addition to neuroinflammation, SARS-CoV-2 infection causes changes in gene expression, microglia activation and nodule formation and the blood brain barrier mimicking post-mortem changes seen in the brains of people with Alzheimer’s disease. SARS-CoV-2, like other viruses such as HIV, HSV, and Epstein-Barr virus (EBV), is implicated in cognitive dysfunction.
Using machine learning to analyze two EHR databases, a new study shows that there are 4 subphenotypes of Long COVID: Phenotype 1: Cardiac and Renal; Phenotype 2: Respiratory, Sleep and Anxiety; Phenotype 3: Musculoskeletal and Nervous system; and Phenotype 4: Digestive and Respiratory system. Each of the subphenotypes were associated with distinct patient demographics, pre-existing medical conditions and acute infection severity. Another article this week shows that there is a specific proteomic footprint for POTS (postural orthostatic tachycardia syndrome) which includes 19 upregulated proteins and 11 downregulated proteins. The most striking dysregulated proteins found in POTS are related to platelet aggregation and a hypercoagulable state. This may be related to the microclot theory of Long COVID. Time magazine today reviewed research of Drs. Resia Pretorius of South Africa’s Stellenbosch University, David Putrino of Mount Sinai in New York and Akiko Iwasaki of Yale showing that microclots may be to blame, at least in part, for long COVID symptoms. Clinical trials are needed.
Thanks for reading Dr. Ruth’s Newsletter! Subscribe for free to receive new posts and support my work.
Other news:
Medical doctors and debt:
Twitter is allowing misinformation on COVID-19 now.
Pregnancy and Preeclampsia:
11/9/22 Circulating Angiogenic Factor Levels in Hypertensive Disorders of Pregnancy | NEJM Evidence https://buff.ly/3XA7yeV
In the derivation cohort, the median sFlt-1:PlGF ratio was 200 (interquartile range, 53 to 458) among women who developed sPE compared with 6 (interquartile range, 3 to 26) in those who did not (P<0.001).
In women with a hypertensive disorder of pregnancy presenting between 23 and 35 weeks of gestation, measurement of serum sFlt-1:PlGF provided stratification of the risk of progressing to severe Preeclampsia (sPE) within the coming fortnight.
Medicare will limit insulin cost to $35 per month:
FLU:
A step towards making a universal flu vaccine against all subtypes:
11/24/22 Science: A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes https://buff.ly/3ujcqYq
mRNA lipid nanoparticle vaccine encoding all 20 known influenza A and B virus subtypes protected mice and ferrets against matched and mismatched influenza virus strains.
12/2/22 CDC Flu map- It’s bad! (Flu shots are available and are well matched to circulating virus this year.)
It looks like BQ.1.(1) is taking off in the Bay Area.
Palo Alto over the last year. It looks like the wastewater virus levels are higher than the original Omicron wave a year ago.
San Mateo:
12/2/22 Time: Microclots May Be to Blame, At Least In Part, for Long COVID Symptomshttps://buff.ly/3EYtxDJ
Lingering viral remnants may damage the endothelial cells that line the blood vessels, prompting the formation of inflammation and microclots, which could then trigger the immune system attack itself. “It’s connected,” said Dr. Pretorius.
David Putrino, a Long COVID researcher at New York’s Mount Sinai health system agrees that microclots are likely a piece of the larger Long COVID puzzle.
Putrino’s research with Yale University’s Akiko Iwasaki (who has also collaborated with Pretorius) suggests Long COVID patients have high levels of systemic inflammation, which he says could lead to the formation of microclots.
5.6% of patients who took Paxlovid experienced dysgeusia, a bad taste in their mouth, often metallic in nature.
Coating the mouth with chocolate milk or a spoonful of peanut butter before each dose can help mitigate the side effect.
Cinnamon gum, lozenges and mints can help.
Some people feel better if they eat pineapple.
12/1/22 MedRxiv: Clinical, imaging, serological, and histopathological features of pulmonary post-acute sequelae after mild COVID-19 (PASC) https://buff.ly/3UphhBZ
n = 51 Long COVID patients who had mild initial COVID infections
Obstructive lung disease due to T cell bronchiolitis and some scaring found in unvaccinated PASC (Long COVID) patients.
Only 1 patient had residual virus in lungs.
Only 25% of US seniors have gotten the bivalent booster despite their benefit in prevention of hospitalizations and death.
California Dept Public Health: Resources for people with Post-COVID Conditions (Long COVID) https://buff.ly/3Fljr1i
12/1/22 Nature: Data-driven identification of post-acute SARS-CoV-2 infection (PASC) subphenotypeshttps://buff.ly/3B27kne
Machine learning analysis of EHR data from 2 databases (INSIGHT and OneFlorida+) shows there are 4 sub phenotypes of PASC (Long COVID):
PASC subPhenotype 1: Cardiac and Renal
PASC subPhenotype 2: Respiratory, Sleep and Anxiety
PASC subPhenotype 3: Musculoskeletal (msk) and nervous system
PASC subPhenotype 4: Digestive and Respiratory system
These subphenotypes were associated with distinct patient demographics, underlying conditions before SARS-CoV-2 infection and acute infection phase severity.
11/30/22 CNBC: Why long Covid could be 'the next public health disaster'— with a $3.7 trillion economic impact rivaling the Great Recession https://buff.ly/3AXmyK0.
Long COVID is/could be a public health and financial disaster.
Up to 30% of Americans who get Covid-19 have developed long-haul symptoms, and long COVID has affected 23 million Americans, according to the U.S. Department of Health and Human Services.
Beyond its medical impact, Long COVID has financial impact: the labor gap to disability benefits, life insurance, household debt, forfeit retirement savings and financial ruin.
Long Covid is a $3.7 trillion drag on the U.S. economy — about 17% of our nation’s pre-pandemic economic output. This doesn’t account for future caseloads.
“Long Covid will be around long after the pandemic subsides, impacting our communities, our health care system, our economy and the well-being of future generations,” the HHS report said.
11/30/22 Reuters: FDA pulls U.S. authorization for Eli Lilly's COVID drug Bebtelovimabhttps://buff.ly/3UoSRsm
Bebtelovimab is not effective against BQ.1.(1) which was 57% of cases last week.
Remaining drugs with EUA include Paxlovid, Lagevrio (Molnupiravir) and Veklury (Remdesivir) as treatments for the disease, besides convalescent plasma for some patients.
Evusheld is available for some immunocompromised patients.
11/30/22 Nature (Switzerland): A population-based serological study of post-COVID syndrome prevalence and risk factors in children and adolescents https://buff.ly/3XQEoIn
4% of all children and 8% of teens had Long COVID.
Risk factors for post-COVID syndrome were older age, having a lower socioeconomic status and suffering from chronic health conditions, especially asthma.
Early screening and detection and health promotion are important to assist children and adolescents with Long COVID who may experience long term physical and mental adverse consequences.
11/28/22 Radiological Society of North America: MRI Reveals Significant Brain Abnormalities Post-COVIDhttps://buff.ly/3EOZ3E1
46 COVID-recovered patients and 30 healthy controls. Among patients with long COVID, the most commonly reported symptoms were fatigue, trouble sleeping, lack of attention and memory issues. Long COVID.
Changes in magnetic susceptibility of the brain seen on special MRI 6 months after COVID infection.
Magnetic susceptibility denotes how much certain materials, such as blood, iron and calcium, will become magnetized in an applied magnetic field.
"Changes in susceptibility values of brain regions may be indicative of local compositional changes," Sapna S. Mishra said.
MRI results showed that patients who recovered from COVID-19 had significantly higher susceptibility values in the frontal lobe and brain stem compared to healthy controls. The clusters obtained in the frontal lobe primarily show differences in the white matter.
"These brain regions are linked with fatigue, insomnia, anxiety, depression, headaches and cognitive problems," Mishra said.
Portions of the left orbital-inferior frontal gyrus (a key region for language comprehension and production) and right orbital-inferior frontal gyrus (associated with various cognitive functions including attention, motor inhibition and imagery, as well as social cognitive processes) and the adjacent white matter areas made up the frontal lobe clusters.
The researchers also found a significant difference in the right ventral diencephalon of the brain stem.
This region is associated with many crucial bodily functions, including coordinating with the endocrine system to release hormones, relaying sensory and motor signals to the cerebral cortex and regulating circadian rhythms (the sleep-wake cycle).
"This study points to serious long-term complications that may be caused by the coronavirus, even months after recovery from the infection," Mishra said. "The present findings are from the small temporal window. However, the longitudinal time points across a couple of years will elucidate if there exists any permanent change."
Figure 1. Group analysis on susceptibility-weighted imaging exhibiting higher susceptibility-weighted imaging values in the COVID group when compared to healthy controls. Three significant clusters were found primarily in the white matter regions of the pre-frontal cortex and in the brainstem. The clusters (a) and (b) are observed bilaterally in the cerebral white matter near the orbitofrontal gyrus, whereas (c) lies in the midbrain region.
China's vaccines (Sinovac and Sinopharm) don't protect well vs Omicron and elderly are not boosted.
Nature article from 5/2022 https://buff.ly/3wgHZTq predicted that opening up China (relaxing Zero-COVID) policy could be a public health and economic catastrophe.
Mathematical modeling at that time predicted 112 million cases, 2.7 ICU admissions (exceeding China’s ICU capacity by 15.6 times) and 1.55 million deaths.
Global implications: China has 1.2 Billion people (20% of the world’s population) and anything that affects China will affect the world’s supply chain and economy. Plus, if COVID runs rampant in China, new variants may form.
12/1/22 The Economist: Xi Jinping’s zero-covid policy has turned a health crisis into a political onehttps://buff.ly/3VKVvtj
Demonstrations erupted across China after at least ten people died in a fire in Urumqi, capital of Xinjiang, where residents were allegedly sealed in a building because of covid.
"The party is willing to lock down millions for weeks on end, but it has failed to deal with vaccine skepticism among the elderly. The government initially licensed vaccines for the under-60s only. It cast doubt on the safety of foreign vaccines while promoting traditional medicine."
By making the zero-covid policy into a test of loyalty, Mr Xi has turned a health crisis into a political one.
11/23/22 Nutrients (Italy): Effects of L-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial https://buff.ly/3Uh9AOa
L-arginine plus vitamin C (n = 25) or placebo (n = 25)
Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis.
A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19 outpatient clinic.
Twice-daily orally either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C (Bioarginina® C, Farmaceutici Damor, Naples, Italy) or a placebo for 28 days.
L-arginine plus vitamin C supplementation improved 6 minute walking performance (p = 0.001), muscle strength, endothelial function, and fatigue (p < 0.0001) in adults with long COVID.
11/27/22 FT: Blood clot drug Eliquis (Apixaban) totally ineffective to prevent hospital readmission as post-Covid treatment after, research finds https://buff.ly/3Vwf7RT
Eliquis (Apixaban) , widely prescribed to Covid-19 patients after discharge from hospital, does not lessen their chances of readmission or improve survival.
HEAL-COVID study: "Helping to Alleviate the Longer-term consequences of Covid-19" — led by Prof Charlotte Summers, an intensive care specialist at Addenbrooke’s in Cambridge.
11/25/22 BioRxiV (Mount Sinai Neurology): Molecular and cellular similarities in the brain of SARS-CoV-2 and Alzheimer’s disease individualshttps://buff.ly/3F4MuWP
Neurological symptoms of neuro-PASC/ Long COVID.
Authors compared post-mortem brain tissue samples from patients with:
SARS-CoV-2,
Alzheimer's disease (AD),
SARS-CoV-2 and AD.
Findings:
Similar alterations of neuroinflammation and blood-brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2 infected AD individuals.
Microglia activation and microglial nodule formation in SARS-CoV-2 infected AD individuals.
HIF-1α is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status.
SARS-CoV-2 is not the first virus to be implicated in cognitive dysfunction. This is a facet shown with other viruses such as HIV, HSV, and Epstein-Barr virus (EBV).
SARS-CoV-2 infection can recapitulate Alzheimer’s Disease (AD)-type transcriptional and cellular neuroinflammatory patterns among others in a very short time frame makes it critical to understand how SARS-CoV-2 impacts long-term cognition.
Several key areas of overlap between the neurological effects of SARS-CoV-2 infection and AD (Alzheimer’s Disease) including neuroinflammation, gene expression, microglia activation and nodule formation and effects on the blood brain barrier.
Most of the measured salivary IgA was secretory IgA (sIgA) that was produced locally in the salivary glands.
"Our results suggest that the development of a mucosal booster vaccine dose should be further exploited to induce a stronger sIgA response."
11/23/22 Nature (Sweden): Plasma proteomic profiling in postural orthostatic tachycardia syndrome (POTS) reveals new disease pathways https://buff.ly/3EvZZ02
n = 65 people with POTS and 65 controls
Proteomic footprint of POTS: 19 upregulated and 11 downregulated proteins
Especially noted upregulated proteins for platelet aggregation and hypercoagulable state in POTS.
Proteomic footprint of significantly dysregulated proteins in POTS. Volcano plot illustrating 30 significantly dysregulated proteins in POTS. Eleven downregulated proteins in blue and 19 upregulated proteins in red. Complete names of proteins are found in Table 2
Table 2 Significantly dysregulated proteins in POTS identified using data-independent acquisition (DIA) label-free quantification mass spectrometry.
11/24/22 PLOS One: Long Covid stigma: Estimating burden and validating scale in a UK-based sample https://buff.ly/3XwoMd3
Those who reported having a clinical diagnosis of Long Covid had higher discrimination and stigma prevalence than those without.
10/26/22 US Census Bureau: Week 50 Household Pulse Survey: October 5 - October 17 https://buff.ly/3EEW0y6
34 million in US with symptoms longer than 3 months
5 million in US unable to carry out activities of daily living
If you have further questions, please contact our study staff at: TreatCOVID@stanford.edu or 650-308-6788
11/22/22 Brazilian J of Otorhinolaryngology: Asymptomatic SARS-COV-2 infection in children's tonsils https://buff.ly/3EjXv4Q
48 children who underwent adenotonsillectomy between October 2020 and September 2021. None of them had experienced signs or symptoms of acute upper airway infection in the month prior to surgery.
25% of asymptomatic children had SARS-CoV-2 in tonsils or adenoids.
Positive immunostaining in adenotonsillar tissue samples suggest that lymphoid tissue can be a reservoir of SARS-CoV-2 and may play an important role in community dissemination.
11/23/22 Nature Metabolism: Increased Type 1 Diabetes Mellitus (T1DM) risk in children infected with SARS-CoV-2 https://buff.ly/3Xvod3f
New diagnoses of T1DM were more frequent in the SARS-CoV-2 cohort than in the respiratory illness cohort at one, three and six months post-infection.
11/18/22 BMC Medicine : Risk for newly diagnosed diabetes after COVID-19: a systematic review and meta-analysis https://buff.ly/3OtsS1r
After COVID-19, patients of all ages and genders had an elevated incidence and relative risk for a new diagnosis of diabetes especially in the first 3 months after COVID-19 infection.
Relative Risk: Type 1 diabetes RR=1.48 and Type 2 diabetes RR=1.70.
11/22/22 BioRxiV: Wildlife exposure to SARS-CoV-2 across a human use gradient https://buff.ly/3i5zaIH
18 different wildlife species in the Eastern U.S. tested.
Virginia opossum was positive for SARS-CoV-2 and one infected opossum had a de novo mutation of SARS-CoV-2 that could bind receptors better.
Squirrels, and raccoons had high seroprevalence, ranging between 62%-71%. Sites with high human use had 3x higher seroprevalence.
11/22/22 Patient Led Research Collaborative announces $4.8 Million in biomedical research awards for 9 projects on Long COVID and associated conditions https://buff.ly/3TUgokE
9 projects chosen by LongCovid & ME/CFS patients on microclots, spinal-structural abnormalities, immunologic dysfunction (T cell), microbiome changes, sleep dysfunction, drug repurposing, multi-omic profiling of Long COVID and a clinical trial on Low Dose Naltrexone (LDN).
11/22/22 CDC: Bivalent COVID-19 Vaccines for Children Aged 6 Months Through 4 or 5 Years May Be Available in Early to Mid-December https://buff.ly/3i8dSKc
11/22/22 CDC MMWR: Bivalent COVID-19 Boosters Better At Preventing Symptomatic COVID-19 Than Previous Shots, CDC Study Finds.
“The first real-world data on the new Omicron vaccines find that they are better at preventing symptomatic COVID infections than the earlier doses...said” the CDC.
These “results are based on more than 360,000 symptomatic adults tested for COVID at pharmacies nationwide from Sept. 14 to Nov. 11.”
11/22/22 CDC MMWR: Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19 — United States, April–September 2022 https://buff.ly/3ub6SPP
Real world data shows Paxlovid reduction of hospitalization by 51% across all groups studied (age, vaccination status, history of prior infection, month of infection which tells which variant.)
11/21/22 MedRxiV: Changes in population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States between December 2021 and November 2022 https://buff.ly/3XnCDm0
As of 10 November 2022, it is estimated that 94% of Americans have had Covid at least once, much of those infections in the past year.
Ranking of states w/ most vulnerability due to lack of vaccines/ boosters.
Higher protection against SARS-CoV-2 infection and severe disease in October 2022, but we still need to be vigilant because new variants can be more immune evasive.
11/21/22 MedRxiV: Immunogenicity and safety of a 4th homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): a phase 2, randomized, placebo-controlled trial https://buff.ly/3Eqc3Qo
Encouraging new data for Novavax boosters (1st and 2nd) for inducing neutralizing antibody response against BA.5.
Antigenic cartography demonstrated a more universal-like response against SARS-CoV-2 variants after a fourth dose of NVX-CoV2373, indicating that updates to the vaccine composition may not be warranted.
11/19/22 MedRxiV: Efficacy of the wild-type/Omicron BA.1 bivalent vaccine as the second booster dose against Omicron BA.2 and BA.5 https://buff.ly/3tLU0zm
2x nAbs against BA.5 with the WT + BA.1 bivalent booster used in other countries.
(3 to 5x nAbs with the BA.5 bivalent booster in several recent studies).
Financial and bureaucratic barriers in the United States mean that the next generation of Covid vaccines may well be designed here, but used elsewhere.
“Foreign rivals have raced ahead in approving long-awaited nasal-spray vaccines, including one invented in St. Louis, creating a scenario in which Americans would have to travel abroad for the latest in American vaccine technology.”
11/18/22 JAMA: National Football League (NFL) Fan Attendance and County-Level COVID-19 Incidence in the 2020-2021 Season https://buff.ly/3TSeUY9
The 2020-2021 National Football League (NFL) season had some games with fans and others without.
Fan attendance was associated with spikes in COVID-19 cases in the surrounding counties in the 14- 21 day postgame period when >20,000 people in attendance.
11/15/22 OK Doomer by Jessica Wildfire: You May Be Early, but You're Not Wrong: A Covid Reading Listhttps://buff.ly/3tV7CZe
The author reviews important studies showing the following:
11/14/22 MedRxiV: Conceptualizing the Episodic Nature of Disability among Adults Living with Long COVID: A Qualitative Study https://buff.ly/3u0Bcwj
Canada, Ireland, United Kingdom, and United States.
Participants described their Long COVID disability experiences as episodic with fluctuations in presence and severity of health-related challenges (disability).
11/18/22 Nature Reviews Neurology: Looking for lights in the fog of long-term neurological COVID https://buff.ly/3EM3DUK
Review of article from 9/22/22 Long-term neurologic outcomes of COVID-19 https://buff.ly/3BzWuEp
Increased risk of central and peripheral nervous system outcomes 1 year after infection.
Neurological syndromes included cerebrovascular diseases, encephalitis, fatigue, cognitive problems, mental health disorders, neuropathies and muscular disorders, especially in older patients.
Younger adults exhibited a higher COVID-19-related risk of memory and cognitive disorders, sensory disorders and other neurological disorders (including Guillain–Barré syndrome and encephalitis or encephalopathy), probably owing to a combination of immunological and psychological factors.
3/7/22 Nature: SARS-CoV-2 is associated with changes in brain structure in UK Biobank https://buff.ly/3sP9zqj
We identified significant longitudinal effects when comparing the two groups, including
(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.
Greater cognitive decline noted.
Imaging and cognitive longitudinal effects were observed in non-hospitalized patients as well.
These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia.
Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.
