Hi Everyone!
Welcome to this week's Long COVID Newsletter. This edition, while brief due to ongoing database creation, highlights developments in the understanding and treatment of Long COVID.
Recently, the National Academies of Sciences, Engineering, and Medicine proposed a comprehensive definition for Long COVID aimed at standardizing its diagnosis and treatment across various sectors. This initiative seeks to alleviate the challenges faced by patients, including inconsistent medical care and social stigma. Additionally, we explore impactful studies like the PROMIS study's insights into immune function and the persistent neurological effects observed in post-COVID mice.
We will be skipping the article of the week this week for brevity purposes.
Media
SUMMARY:
The National Academies of Sciences, Engineering, and Medicine propose a new definition for Long COVID as a chronic condition following a SARS-CoV-2 infection, lasting at least three months, and affecting one or more organ systems.
The lack of a unified definition has led to difficulties in diagnosis, treatment, and support for patients, contributing to social stigma and inconsistent medical care.
he new definition aims to be used for clinical care, insurance coverage, disability benefits, public health, research, and public awareness, helping to standardize and improve care and understanding of Long COVID.
The report recommends that the Office of Long COVID Research and Practice, along with the Long COVID Coordination Council, lead the dissemination and implementation of the new definition, with periodic reviews to update it as new evidence emerges.
SUMMARY:
Natacha Gray shares her experience with long Covid, detailing the challenges she faced after contracting COVID-19 in 2021.
Despite initially feeling better, Natacha's symptoms resurfaced, leading to debilitating fatigue, cognitive difficulties, and breathing problems.
The impact of long Covid on Natacha's life, relationships, and mental health is profound, highlighting the complexities of living with a chronic condition.
Article: Pennington Biomedical researchers partner on award-winning long COVID study
SUMMARY:
The PROMIS study, receiving over $802,000 in funding, focuses on uncovering the drivers of Long COVID and enhancing immune function in affected individuals.
Researchers hypothesize that inflammation induced by COVID-19 may lead to immune system stress, triggering secondary complications like fatigue, brain fog, and headaches in Long COVID patients.
The nationwide RECOVER initiative, which includes the PROMIS study, seeks to understand and find treatments for Long COVID, as the causes of this condition remain unknown.
Dr. Kirwan's research team aims to analyze blood and tissue samples to determine if the virus is still present in Long COVID patients and investigate its impact on immune responses.
Research
DEFINITIONS:
Olfactory Bulb (OB): A brain structure involved in the sense of smell, where olfactory sensory neurons send signals.
Olfactometry: The measurement of the sense of smell, often using standardized tests like the Sniffin’ Sticks test.
Neuropsychological Testing: Assessments that measure cognitive functions, such as memory, attention, and problem-solving skills.
Sniffin’ Sticks Test: A standardized test used to assess olfactory function by having participants identify different odors.
SUMMARY:
This study aimed to investigate the relationship between olfactory bulb (OB) volume and olfactory dysfunction in individuals who had recovered from mild to moderate COVID-19.
The study included 233 non-vaccinated COVID-19 convalescents from the Hamburg City Health Study. Participants underwent MRI, neuropsychological testing, and olfactory function assessment through a structured questionnaire and the Sniffin’ Sticks test.
Participants with self-reported olfactory dysfunction had significantly lower OB volumes at baseline compared to those with normal olfaction.
OB volume at baseline predicted olfactometry scores at follow-up, suggesting its potential use as a marker for long-term olfactory function.
The prevalence of self-reported olfactory dysfunction declined over time: 67.1% during acute infection, 21.0% at baseline, and 17.5% at follow-up.
OB volume was not significantly associated with performance in neuropsychological tests, indicating that olfactory dysfunction may not correlate with broader cognitive impairments in mild to moderate COVID-19 cases.
SUMMARY:
The Johns Hopkins COVID Long Study (JHCLS) aims to investigate the short-term and long-term consequences of COVID-19 through a nationwide prospective cohort study using self-reported data from an online survey.
The study includes 16,764 adults with a history of SARS-CoV-2 infection and 799 adults without such a history. Of the infected participants, 75% reported very good or excellent health prior to infection, and 63% were defined as having long COVID according to the WHO definition.
Among participants with a history of SARS-CoV-2 infection, 99% reported experiencing at least one symptom during the acute phase, with 9.9% reporting hospitalization. Long COVID symptoms included cardiopulmonary, systemic, neuropsychiatric, and gastrointestinal issues.
he study will analyze longitudinal data to understand the progression and resolution of long COVID symptoms over time. This will help identify individuals at risk of long-term sequelae and characterize the physical and mental health disabilities associated with long COVID.
DEFINITIONS:
DKA (Diabetic Ketoacidosis): A serious diabetes complication where the body produces excess blood acids (ketones) due to insulin deficiency, leading to hyperglycemia and metabolic acidosis.
Type 1 Diabetes Mellitus: An autoimmune condition where the pancreas produces little or no insulin, leading to high blood sugar levels.
Hyperglycemia: Elevated blood glucose levels.
Ketoacidosis: A condition characterized by high levels of ketones in the blood, leading to acidic blood pH.
ACE2 (Angiotensin-Converting Enzyme 2): A receptor on cell surfaces that SARS-CoV-2 uses to enter cells; it also plays a role in regulating blood pressure and inflammation.
Polyuria: Excessive urination.
Polydipsia: Excessive thirst.
SUMMARY:
The study investigates the relationship between COVID-19 and the development of diabetic ketoacidosis (DKA) and new-onset type 1 diabetes mellitus.
A case of a 24-year-old male developing DKA after a COVID-19 infection is presented to highlight this potential link.
DKA is an acute diabetes complication characterized by hyperglycemia and ketoacidosis, often triggered by factors like infection, myocardial infarction, or certain drugs.
The study details the symptoms and diagnostic process of DKA, including the critical role of immediate evaluation and stabilization.
The patient had a history of COVID-19 infection 12 weeks prior to presenting with DKA symptoms like malaise, polyuria, polydipsia, headache, and fatigue.
Laboratory findings confirmed hyperglycemia, ketonuria, and acidosis. Treatment included an insulin drip, IV fluids, and electrolyte correction.
Two main hypotheses explain the relationship between COVID-19 and DKA: (1) SARS-CoV-2 interacts with the ACE2 receptor, causing pancreatic inflammation and damage; (2) Direct binding of the virus to pancreatic islet cells, leading to cell modification and hyperglycemia.
The case highlights a possible genetic predisposition, as the patient had a family history of type 1 diabetes, suggesting that COVID-19 might act as a catalyst in genetically susceptible individuals.
DEFINITIONS:
Prothrombotic changes: Changes associated with blood clotting that increase the risk of clot formation.
Amyloid fibrinogen: Abnormal protein involved in clot formation.
Thromboembolism: Formation of a clot that blocks a blood vessel.
Macrovacular: Refers to blood vessels of larger diameter.
Microvascular: Refers to small blood vessels, such as capillaries.
SUMMARY:
The text challenges the prevailing hypothesis that thrombosis causes the post-COVID-19 condition, emphasizing that there is a lack of evidence linking clotting abnormalities to persistent symptoms.
The "microclots" theory suggests that prothrombotic changes in acute COVID-19 are not necessarily present in the post-COVID-19 condition, highlighting the need to differentiate between the two states.
A study linking clotting disturbances to cognitive deficits is critiqued for methodological flaws and lack of epidemiological soundness.
Plausible alternative hypotheses, such as an inflammatory response mediating hemostatic changes in PCC, are proposed as explanations for persistent symptoms.
The objective of this population-based cohort study of 3,946 participants was to assess the association between SARS-CoV-2 seropositivity and symptoms consistent with long COVID.
Among people with laboratory-confirmed COVID-19, there was no association between antibody positivity (+Ab/+RNA vs. -Ab/+RNA) and any symptoms, physical health, mental health, or cognitive function.
As expected, among people with laboratory-confirmed prior infection and positive serology (+Ab/+RNA) compared to those without reported or confirmed prior infection and negative serology (-Ab/-RNA/no reported COVID-19), physical health, cognitive function, and fatigue were worse, and palpitations and headaches limiting the ability to work were more prevalent.
Among people with laboratory-confirmed COVID-19, SARS-CoV-2 serology from practice settings were not associated with long COVID symptoms and health status suggesting limited utility of serology testing for long COVID.
SUMMARY:
The study looks at how people with long COVID utilize healthcare services over a 12-month period post-diagnosis in comparison to those without long COVID using EHR data from the OpenSAFELY platform.
Patients diagnosed with long COVID showed significantly higher healthcare utilisation and costs, especially in primary care and medication prescriptions, indicating a substantial burden on healthcare systems.
The average number of healthcare visits per year for individuals with long COVID was nearly double that of the comparator group, with associated costs of around £2,500 per person per year compared to £1,500 for the comparators.
Factors associated with high healthcare utilisation in the long COVID group included female sex, obesity, asthma, mental health issues, comorbidities, and prior hospitalisation due to COVID-19.
My Take:
This is unsurprising and matches many experiences of people i know of with LC. I think a large drain is that most people with LC have no idea what is wrong with them at first, so this leads to them visiting many healthcare specialists.
DEFINITIONS:
GPCR (G protein-coupled receptor): A large family of cell surface receptors that respond to various external signals and activate internal signal transduction pathways.
Autoantibodies: Antibodies produced by the immune system that mistakenly target and react with a person's own tissues or organs.
Hypovolemia: A condition where there is a decreased volume of blood in the body.
Autonomic Neuropathy: A condition where the autonomic nerves are damaged, affecting body functions like heart rate, blood pressure, and digestion.
Hyperadrenergic State: A condition characterized by increased activity of the adrenergic nervous system, often resulting in elevated heart rate and blood pressure.
SUMMARY:
Postural orthostatic tachycardia syndrome (POTS) involves an exaggerated heart rate increase upon standing without orthostatic hypotension. Its pathophysiology includes hypovolemia, autonomic neuropathy, a hyperadrenergic state, and cardiovascular deconditioning.
Recent studies suggest an autoimmune component in POTS, highlighted by the presence of anti-G protein-coupled receptor (GPCR) antibodies.
GPCRs are essential membrane receptors involved in various physiological processes. Autoantibodies against GPCRs, particularly adrenergic and muscarinic acetylcholine receptors (AChRs), have been linked to POTS.
These autoantibodies may contribute to the symptoms of POTS by disrupting normal receptor function.
POTS and Long-COVID: POTS has been identified as a sequela of COVID-19, often referred to as long-COVID POTS.
This form of POTS shares similarities with non-COVID-related POTS but typically resolves more spontaneously.
Studies have found elevated levels of autoantibodies in POTS patients, suggesting a potential autoimmune etiology.
These autoantibodies, especially against muscarinic AChRs, correlate with disease severity and specific symptoms like persistent gastrointestinal issues.
Article: Persistent Neurological Deficits in Mouse PASC Reveal Antiviral Drug Limitations | bioRxiv
DEFINITIONS:
TH: Tyrosine hydroxylase, an enzyme involved in the production of dopamine.
SN: Substantia nigra, a region of the brain involved in movement control.
Microglia: Immune cells in the brain that play a role in inflammation and neuroprotection.
SUMMARY:
This study looks at the long-term neurological effects of SARS-CoV-2 infection in mice, mirroring findings in human patients.
The persistence of neuroinflammation, dopaminergic neuron loss, and behavioral changes raise concerns about potential neurodegenerative consequences of COVID-19.
The inability of antiviral therapy to reverse these effects underscores the complexity of post-COVID neurological complications and emphasizes the need for further research in this area.
DEFINITIONS:
Probiotics: Live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.
Synbiotics: A combination of probiotics and prebiotics (fibers that feed the beneficial bacteria) designed to support the gut microbiota.
Postbiotics: Non-viable bacterial products or metabolic byproducts from probiotic microorganisms that have biological activity in the host.
Gut-Brain Axis: The bidirectional communication pathway between the gastrointestinal tract and the brain, which involves hormonal, immune, and neural mediators.
SUMMARY:
The review discusses the role of the gut microbiome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and long COVID, noting that disturbances in gut microbiota may contribute to the symptoms experienced in these conditions.
The use of microbial-based preparations, including probiotics, synbiotics, and postbiotics, is explored as a potential therapeutic approach to restore gut homeostasis and manage symptoms like fatigue, cognitive dysfunction, and gastrointestinal issues.
The article evaluates various studies on the effectiveness of microbial preparations in improving symptoms of ME/CFS and long COVID.
It highlights positive outcomes such as reduced inflammation, enhanced cognitive functions, and improved gastrointestinal health, suggesting that these interventions could be beneficial in managing the complex symptomatology of these conditions.
The review details the mechanisms through which the gut microbiome influences ME/CFS and long COVID, including the modulation of the immune system, the production of short-chain fatty acids (SCFAs) that have anti-inflammatory properties, and the impact on the gut-brain axis which affects both neurological and immune responses.
It emphasizes the need for more controlled clinical trials to determine optimal formulations, dosages, and treatment durations for microbial-based therapies. These studies are crucial to confirm the benefits and safety of these interventions in treating post-viral syndromes.
Patients treated for COVID-19 at intensive care units between 3/2020 and 1/2021 were analyzed for complete blood count (CBC) and coagulation biomarkers (prothrombin time activity (%) (PT%), activated partial thromboplastin time (APTT), fibrinogen, coagulation factor VIII (FVIII), antithrombin (AT), and D-dimer) during the 6 months post-hospitalization.
Most CBCs and coagulation biomarkers had median values within the normal range. However, only 21% (15/70) of patients achieved full normalization of all biomarkers.
Compared to acute COVID-19, hemoglobin, PT%, and AT increased, while leukocytes, fibrinogen, FVIII, and D-dimer decreased. Despite decreased levels, FVIII remained elevated in 46% (31/68), leukocytes in 26% (18/70), and D-dimer in 27% (18/67) at 6 months. A weak negative correlation (r = −0.37, p = .036) was found between DLCOc% and FVIII.
Only a few patients had normal CBC and coagulation biomarker values 6 months after critical COVID-19. A weak negative correlation between DLCOc% and FVIII suggests that deranged coagulation activity may be associated with reduced diffusing capacity.
“I think a large drain is that most people with LC have no idea what is wrong with them at first, so this leads to them visiting many healthcare specialists.”
I would add that a large range and number of specialists still don’t have much knowledge about LC, which only exacerbates the costs as patients go from doc to doc. We patients have much more time on our hands to read newsletters like yours than docs in managed care seem to have. The system is broken when doctors don’t have time to keep up on the latest research.
Well, at least (in my experience), these un- and undereducated docs believe us now. I guess that’s a big improvement over 2020-21.
Agree with Amy. The Med professionals are chronically shor of time to keep up with the literature, plus they are driven to diagnose conditions using probability curves that LC completely throws off and skews.