What is Long COVID?
The National Academies of Sciences, Engineering and Medicine created this consensus definition: “Long COVID (LC) is an infection-associated chronic condition (IACC)
that occurs after SARS-CoV-2 infection and is present for at least 3
months as a continuous, relapsing and remitting, or progressive disease
state that affects one or more organ systems.”
Current Research and Understanding of Long COVID
(see also Mast Cell Disease and Long COVID (aka PACS)
Solving the puzzle of Long Covid
"From an extensive body of mechanistic research in people affected by Long Covid, there appear to be multiple potential pathogenic pathways, including persistence of the virus or its components in tissue reservoirs; autoimmune or an unchecked, dysregulated immune response; mitochondrial dysfunction; vascular (endothelial) and/or neuronal inflammation; and microbiome dysbiosis."
Biological mechanisms underpinning the development of long COVID
This study lists the following underlying biological mechanisms for Long COVID- microvascular thrombosis, auto-immunity, dysbiosis, persistent metabolic derangement, viral persistence, Mast Cell Activation Syndrome (MCAS), Postural Orthostatic Tachycardia Syndrome (POTS), CNS Inflammation and dysfunction, and reactivation of latent viruses.
"Microclots may accumulate and disseminate within the microcirculation, eventually obstructing capillaries and circulatory pathways, leading to hypoperfusion of tissues. Recently, it has been shown that the SARS-CoV-2 spike protein can induce the formation of microclots by binding to soluble fibrinogen molecules causing structural changes to complement 3, prothrombin, β and γ fibrin/fibrinogen, thereby rendering the molecule insoluble. Furthermore, the ACE2 and TMPRSS receptors are found universally on platelets and vascular endothelium, to which the virus readily binds to infect host cells."
"The pattern of the hyperinflammation that occurs during COVID-19 is consistent with an inflammatory response mediated through SARS-CoV-2-mediated MC (Mast Cell) activation, and such a hyperactivation of MCs has been widely demonstrated in COVID-19 postmortem studies. Persistent MCA is associated with extensive systemic inflammatory pathologies seen in LC (Long COVID), including myocardial infarction, compromised microvasculature, endothelial damage, and intravascular coagulation. In histopathological studies, MCs were observed to organize themselves along the blood vessel walls, placing them in an optimal location to directly exert their effects on the vasculature."
Insights into early recovery from Long COVID—results from the German DigiHero Cohort
"We performed multivariable logistic regression to identify factors associated with early recovery from Long COVID... Men, younger participants, individuals with mild course of acute infection, individuals infected with the Omicron variant, and individuals who did not seek medical care in the 4–12 week period after infection had a higher chance of early recovery."
Post COVID-19 Neurological Syndrome
What we now know about long COVID and our brains
Long COVID is also called Post-COVID-19 Neurological Syndrome (PCNS) in research.
What is Post-COVID-19 Neurological Syndrome?
"The
physical stress of infection might end, but COVID-19 patients can carry
emotional and neurological scars from the experience for months and
years, often in the form of post-traumatic stress disorder (PTSD). For
example a large Chinese study earlier this year revealed that an
alarming 96.2 per cent of recovering COVID-19 patients have clinical
evidence of severe post-traumatic stress disorder (PTSD).... COVID-19
and acute stroke share common pathobiology at a cellular level."
Long-term neurological manifestations are being seen in people who have recovered from COVID 19, including in children. These can include acute encephalitis but may also appear as more general symptoms such as headache, fatigue, confusion, and more serious problems such as memory problems, problems with speech, psychotic symptoms, even seizures. In some cases this seems to be part of the Multisystem Inflammatory Syndrome in Children that can be one presentation of COVID 19. References and relevant studies:
Other Long COVID Considerations
Invasive Aspergillosis as an Under-recognized Superinfection in COVID-19
"Taken together, these early findings suggest that invasive aspergillosis
may be an important, yet under-recognized, complication of SARS-CoV-2
infection. The frequency of post-COVID-19 aspergillosis is likely to
differ significantly between hospitals and geographic sites, as has been
observed with postinfluenza aspergillosis"
"We are living in an unprecedented era of fungal infections,
characterized by the emergence of previously unrecognized human
pathogens and well-recognized pathogens causing new manifestations of
disease. The spectrum of “at-risk” populations for invasive Aspergillus
infections is expanding, with increased appreciation of diseases such
as chronic pulmonary infection and postinfluenza aspergillosis. Fungal
superinfections are difficult to distinguish from severe COVID-19 based
on clinical or imaging findings, and a high index of suspicion is
necessary to diagnose aspergillosis. If aspergillosis is a complication
of COVID-19 in a significant minority of critically ill hospitalized
patients, failure to recognize or diagnose the disease will likely lead
to excess mortality. For this reason, it is imperative to establish the
incidence, clinical characteristics, and outcomes of COVID-19-associated
aspergillosis as quickly as possible."
Persistence of S1 Spike Protein in CD16+ Monocytes up to 245 Days in SARS-CoV-2 Negative Post COVID-19 Vaccination Individuals with Post-Acute Sequalae of COVID-19 (PASC)-Like Symptoms
preprint
by Dr. Bruce Patterson and his team. In this small study Dr. Patterson et. al
find that the individuals suffering from long COVID like symptoms after
vaccination have persistent spike protein S1, S2, and even a mutant S1 in their
non-classical and intermediate (CD16+) monocytes. These monocytes have an
affinity to bind with the blood vessel endothelium. Hence, vascular
damage/inflammation and clotting will ensue.
Management approach they offer is CCR5 antagonists (like Maraviroc) and
Statins to reduce the binding of CD16+ monocytes to endothelium.
In Long COVID, GI and Mental Health Symptoms 'Go Hand in Hand'
"In an analysis of nearly 750 individuals who had COVID-19, those with mental health symptoms either before or after their infection were more than 16 times more likely to have post-COVID GI symptoms (adjusted odds ratio [aOR] 16.5, 95% CI 6.97-38.9), reported John Blackett, MD, MS, of the Mayo Clinic in Rochester, Minnesota, and colleagues."
EWAS of post-COVID-19 patients shows methylation differences in the immune-response associated gene, IFI44L, three months after COVID-19 infection.
"We explored the epigenetic signatures of COVID-19 in peripheral blood
using data from an ongoing prospective observational study of COVID-19
called the Norwegian Corona Cohort Study. A series of EWASs were
performed to compare the DNA methylation profiles between COVID-19 cases
and controls three months post-infection. We also investigated
differences associated with severity and long-COVID. Three
CpGs-cg22399236, cg03607951, and cg09829636-were significantly
hypomethylated (FDR < 0.05) in COVID-19 positive individuals.
cg03607951 is located in IFI44L which is involved in innate response to
viral infection and several systemic autoimmune diseases. cg09829636 is
located in ANKRD9, a gene implicated in a wide variety of cellular
processes, including the degradation of IMPDH2. The link between ANKRD9
and IMPDH2 is striking given that IMPDHs are considered therapeutic
targets for COVID-19. Furthermore, gene ontology analyses revealed
pathways involved in response to viruses. The lack of significant
differences associated with severity and long-COVID may be real or
reflect limitations in sample size. Our findings support the involvement
of interferon responsive genes in the pathophysiology of COVID-19 and
indicate a possible link to systemic autoimmune diseases."
Long COVID and employment
USDHHS Guidance on “Long COVID” as a Disability Under the ADA, Section 504, and Section 1557
"This
guidance explains that long COVID can be a disability under Titles II
(state and local government) and III (public accommodations) of the
Americans with Disabilities Act (ADA),3 Section 504 of the
Rehabilitation Act of 1973 (Section 504),4 and Section 1557 of the
Patient Protection and Affordable Care Act (Section 1557).5 Each of
these federal laws protects people with disabilities from
discrimination.6 This guidance also provides resources for additional
information and best practices. This document focuses solely on long
COVID, and does not address when COVID-19 may meet the
legal
definition of disability. The civil rights protections and
responsibilities of these federal laws apply even during emergencies.7
They cannot be waived."
COVID-19 Workplace Safety Plan | PDF version
Job Accommodation Network, definition of a disability
EEOC What You Should Know About COVID-19 and the ADA, the Rehabilitation Act, and Other EEO Laws
EEOC Coronavirus 19
Long COVID Background
Long COVID: major findings, mechanisms and recommendations
"Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field."
Is ‘Long Covid’ similar to ‘Long SARS’?
Some long Covid patients may have hidden damage to their lungs - BBC News
A
special type of MRI, which measures how well oxygen can get into a
person's bloodstream from the lungs, is showing some sort of widespread
inflammation in the lungs that can seriously reduce oxygen exchange.
