COVID-19 Resource Center
COVID-19, Long COVID Syndrome & Post COVID vaccination syndrome
COVID-19 & Long COVID Syndrome
The activation of human endogenous retroviruses and inflammatory mediators in children with COVID-19, Kawasaki disease and multisystem inflammatory syndrome
Activation of HERVs and inflammatory mediators in children with COVID19, multisystem inflammatory syndrome (MIS-C) and Kawasaki disease.
The first genome-wide association study (GWAS) identified genetic variants within the FOXP4 locus as a risk factor for long COVID.
BA.2.86 variant is highly immune evasive and antigenically distinct from XBB.1.5 and previous Omicron variants
BA.2.86 is highly immune evasive and may have advantages over currently circulating variants in its ability to resist XBB-induced humoral immunity.
According to the results of the study, the scientists concluded that the SARS-CoV-2 isolates are formed by a completely new mechanism that cannot be explained by previous biology and that it is highly unlikely that these viruses arose spontaneously.
The presence of the circulating HERV-W ENV protein and elevated plasma levels of anti-SARS-CoV-2 IgE in post-COVID patients
The study showed that the HERV-W ENV protein was expressed in 58% of plasma samples from post-COVID patients, long after the acute SARS-CoV-2 infection was resolved.
The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-2 (IDO2) is expressed in PBMC and brain tissue from patients with PASC and involved in PASC pathology.
Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID, even two years after acute infection.
Spike protein fragment SF5 exhibits strong binding ability and enhances full-length spike protein binding
The fragment SF5 of the SARS-CoV-2 S protein exhibits strong binding ability and mediates the binding of the full-length S protein.
SARS-CoV-2 has the ability to awaken ancient retroviral genes and induce expression of human endogenous retroviruses-W envelope proteins
SARS-CoV-2 induced the expression of the HERV-W envelope proteins, suggesting their involvement in the immunopathogenesis of certain COVID-19-associated syndromes.
This study found that SARS-CoV-2 can enter ACE2-deficient host cells through a TMEM106B-dependent entry mechanism.
Vitamin D3 reduces nucleocapsid protein-induced hyperinflammation by inactivating the NLRP3 inflammasome: results from in vitro and in vivo studies
The in vitro and in vivo findings confirmed that vitamin D3 reduced nucleocapsid protein-caused hyperinflammation by inactivating the NLRP3 inflammasome, partially through the vitamin D receptor-BRCC3 signaling pathway.
The interaction between fecal bacteria and the virus suggests a ‘bacteriophage-like’ behavior of SARS-CoV-2.
The virus was viable for up to five days with and without an environmental biofilm on all surfaces tested. The incubation with SARS-CoV-2 Delta variant increased the biovolume of all three biofilms.
Increased median deformation of red blood cells in children and adolescents following SARS-CoV-2 infection
The median deformation of RBCs was higher in seropositive and vaccinated participants than in seronegative participants, but only within 6 months of SARS-CoV-2-seroconversion.
Early outpatient treatment with metformin was shown to reduce long COVID incidence in the first randomized, placebo-controlled, phase 3 trial
Early outpatient COVID-19 treatment with metformin reduced long COVID incidence by approximately 41%, with an absolute reduction of 4.1%, compared to placebo.
SARS-CoV-2 can infect, replicate, and produce infectious viral particles in primary human hepatocytes.
Long COVID patients have abnormal gas exchange, measured by 129Xe MRI red blood cells-to–alveolar tissue barrier ratio
Results showed that subgroups of nonhospitalized and posthospitalized participants with long COVID had significantly lower 129Xe MRI RBC-to–alveolar tissue barrier ratio than healthy volunteers, but there was no difference between measurements in the subgroups.
The observed rises in blood lactate levels early in the exercise session and decreased rates of FATox during exercise suggest mitochondrial dysfunction and “metabolic reprogramming” in patients with postacute COVID.
The presence of viral antigens, but not infectious virions, in the intestinal mucosa of patients with inflammatory bowel disease and long COVID
The presence of viral antigens, but not infectious virions, was detected in the gut mucosa of 32 /46 patients with inflammatory bowel disease and long COVID symptoms.
SARS-CoV-2 RNAs and spike protein detected in neonatal feces suggest in utero viral transmission to the fetal intestine
The fecal samples of newborns with negative SARS CoV-2 nasal PCR results, born to mothers with COVID-19 infection during pregnancy, at delivery contained SARS-CoV-2 RNAs and S proteins. This suggests the risk of in utero transmission of SARS-CoV-2 to the fetal intestine during gestation.
Spike protein is electrically conductive, it reacts with gold and silicon electrodes and denatures. A method of coronavirus deactivation?
These findings open new venues for developing coronavirus-capturing materials and offer an electrical method for analyzing, detecting and potentially electrically deactivating persistent and future variants of SARS-CoV-2.
The S1 subunit of spike protein and its receptor-binding domain increased the expression of the anti-apoptotic protein survivin
Both the spike 1S protein and its receptor-binding domain increased the expression and the activation of the anti-apoptotic protein survivin in a time-dependent manner. Survivin belongs to the inhibitor of apoptosis family, and is considered a the key marker for the activation of the survival pathway in cancer cells.
Quercetin is one of the most important plant molecules, with antioxidant, antiatopic, pro-metabolic, antiinflammatory, antiviral, and immunoprotective effects.
This study reports on the nuclear translocation of the SARS-CoV-2 spike protein and the spike protein mRNA in SARS-CoV-2-infected cells. The translocation of the S mRNA appeared to be assisted by the S protein, which contains the novel nuclear localization signal motif that is unique among human pathogenic beta-coronaviruses.
A free fatty acid–binding pocket stabilizes spike protein in the locked conformation (the “Achilles’ heel of SARS-CoV-2”)
The receptor binding domain in the SARS-CoV-2 spike protein includes a free fatty acid–binding pocket, to which a free fatty acid binds (the Achilles’ heel of SARS-COV-2). The binding of a free fatty acid stabilizes a locked conformation of the S protein that is incompatible with the binding of ACE2 receptor.
Using machine learning analysis, the authors investigated the incidence of 137 symptoms and conditions potentially related to PASC, and identified four reproducible PASC subphenotypes.
SARS-CoV-2 spike protein changes the morphology of platelets and binds directly to the platelet integrin α5β1 and αvβ3 receptors
The spike protein triggers the dynamic deformation of platelets in elongated morphologies, leading in some cases to their irreversible activation, and binds directly to the platelet integrin α5β1 and αvβ3 receptors.
Post COVID vaccination syndrome
Proteomic analyzes showed that 50% of subjects who received mRNA-based vaccines had specific fragments of recombinant S protein in their blood samples 2–6 months after vaccination
50% of subjects who received mRNA-based vaccines had specific fragments of recombinant S protein in their blood samples 2–6 months after vaccination.
Increased T-cell activation in numerous tissues and SARS-CoV-2 spike RNA+ rectosigmoid cells were found in vaccinated individuals up to 2.5 years after acute COVID-19
A whole-body positron emission tomography with a novel radiopharmaceutical [18F]F-AraG showed increased T cell activation in numerous anatomical regions in the post-acute COVID up to 2.5 years after initial infection.
SARS-CoV-2 mRNA vaccine alters cytokine responses to heterologous pathogens and Toll-like receptor agonists in children up to six months after vaccination (in vitro study)
SARS-CoV-2 mRNA vaccine alters cytokine responses to heterologous stimulants (killed pathogens, Toll-like receptor agonists, and SARS-CoV-2 antigens) in children, and that these effects can persist for up to six months after vaccination.
The study presented two cases who met the criteria for a new leprosy adverse event associated with anti-SARS-CoV-2 vaccination.
The study presented two cases who met the criteria for a new leprosy adverse event associated with anti-SARS-CoV-2 vaccination.
The epigenetic crosstalk between the BNT162b2 mRNA vaccine or the original S gene of SARS-CoV-2 with the human genome
The original SARS-CoV-2 S gene and the BNT162b2 mRNA vaccine exhibit Watson-Crick nucleotide complementarity with human coding or noncoding genes. The patterns of sequence complementarity to the human genome of the BNT162b2 mRNA, encoding the S protein of SARS-CoV-2, differed from those of the original SARS-CoV-2 S gene.
The association between the increase in the incidence of Stevens Johnson syndrome/toxic epidermal necrolysis and SARS-CoV-2 infection and anti-SARS-CoV-2 vaccination
In a recent study, Australian authors presented the largest case series of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) that may be associated with SARS-CoV-2 infection and anti-SARS-CoV-2 vaccination.
Prominent Topics of Discussion
COVID-19/ Long COVID & Nervous system
Reduced corneal innervation and increased dendritic cell density in the cornea of long COVID patients 20 months after the infection
These results show a decrease in corneal nerve density and branch density, as well as an increase in dendritic cell density in patients with long COVID in comparison to the control group.
In hamsters infected with the original Wuhan strain, or the three viral variants, anosmia was strongly dependent on the SARS-CoV-2 variant.
Neurometabolites indicative of neuronal damage and glial dysfunction are altered in the brains of patients with long COVID and neuropsychiatric symptoms
Alterations in neurometabolites that indicate neuronal damage and glial dysfunction in the brains of subjects with long COVID syndrome
Spike protein and its receptor-binding domain stimulate different proinflammatory mediators by activating different receptors in cultured microglia
Recombinant full-length S protein and RBD can stimulate human microglia to secrete various proinflammatory mediators via activation of different receptors.
Elevated circulating levels of HERV-W ENV and proinflammatory cytokines in SARS-CoV-2-positive patients with psychosis spectrum disorder
This study showed that SARS-CoV-2 is connected with HERV-ENV expression and elevated serum levels of pro-inflammatory cytokines in patients with psychosis spectrum disorder who had no history of acute COVID-19 infection and had not been vaccinated against SARS-CoV-2.
The Wuhan wild-type strain and the Omicron variant induced stress of CNS cells, altered extracellular glutamate concentration, and damaged cellular components of the BBB.
An uncommon disease, hemorrhagic myelitis was presented in three cases following SARS-CoV-2 infection, with minimal or no improvement during follow-up.
Acute demyelinating disease of the CNS (acute disseminated encephalomyelitis) associated with SARS-CoV-2 infection or anti-SARS-CoV-2 vaccination
A systematic review of the medical literature, that included cases of acute disseminated encephalomyelitis (ADEM) and acute hemorrhagic leukoencephalitis (AHLE) which occurred after severe acute SARS-CoV-2 infection or anti-SARS-CoV-2 vaccination.
Case report: a systemic reaction with predominant neurological and skin manifestations after anti-SARS-CoV-2 vaccination
A case of a systemic reaction, characterized by predominant neurological and skin manifestations, which appeared immediately following the third dose of the anti-SARS-CoV-2 mRNA vaccine and lasted for 11 months.
The association between SARS-CoV-2 infection or anti-SARS-CoV-2 vaccination and neuromyelitis optica spectrum disorder
This review article showed that there is association between SARS-CoV-2 infection or anti-SARS-CoV-2 vaccination and de novo onset or relapse of neuromyelitis optica spectrum disorder.
SARS-CoV-2 infection induces fusion between neurons and between neurons and glia in vitro, disrupting their communication.
The patients with neuro long COVID have a distinct pattern of anti-nucleocapsid-specific immune responses
Multimodal analyses revealed a distinct pattern of T cell activation and anti-nucleocapsid specific immune responses in neuro-PASC patients.
TMS study: reduced GABA-ergic and glutamatergic excitability of the motor cortex in patients with neuro long COVID
The patients with neuro long COVID had abnormal GABA-ergic and glutammatergic regulation and normal cholinergic regulation of the motor cortex excitability.
A link between the S1 subunit of spike protein, brain inflammation, and decreased production of acetylcholine in the mouse brain
Inoculation of the S1 protein in the nasal cavity increased apoptosis of the olfactory system and decreased production of acetylcholine in the mouse brain.
The authors from Switzerland discussed the neurorehabilitation of neurological symptoms in post-COVID syndrome. They focused on treating the three most common neurological symptoms: fatigue, pain, and sleep disorders.
Patients with post-COVID syndrome and neuropsychiatric symptoms have different brain activation during the working memory task
This is the first task-activated BOLD-fMRI study in the post-COVID participants with neuropsychiatric symptoms. Results showed that brain activity in the post-COVID participants differed from activity registered in healthy control participants with no prior history of COVID-19.
Neurodevelopmental sequelae in two neonates after in utero exposure to SARS-CoV-2, with the presence of the S1 subunit in the brain of the deceased infant and in both placentas
This report summarizes the severe neurologic lesions in two infants whose mothers tested SARS-CoV-2 positive several weeks before delivery. The S1 protein was detected in both case placentas, and throughout the brain of the deceased infant.
The first case report of prosopagnosia (face blindness) found two months after the onset of symptoms consistent with COVID-19 in a 28-year-old woman.
A disturbance of acetylcholine synaptic transmission in the central and peripheral nervous system could result in pathological findings in the acute period of SARS-CoV-2 infection and in the post-COVID period.
SARS-CoV-2 spike protein can enter the brain and cause death of hippocampal neurons through the glial cell activation
In vivo studies have shown that SARS-CoV-2 spike protein can enter the brain and cause death of hippocampal neurons through the glial cell activation.
The studies have extensively mapped the spectrum of neurological sequelae in patients with long COVID, but, there has been no significant progress in understanding the underlying mechanisms.
COVID-19/ Long COVID & Cardiovascular System
The analysis of VAERS reporting rates of myocarditis/ pericarditis after mRNA anti-SARS-CoV-2 vaccination (pharmacovigilance study)
The retrospective pharmacovigilance study with a comprehensive analysis of potential safety signals associated with myocarditis/pericarditis after the primary and up to three booster doses of mRNA anti-SARS-CoV-2 vaccines in different age groups.
Cardiac outcome in adolescents with COVID-19 vaccine–associated myocarditis up to one 1 after diagnosis
Impaired systolic and diastolic myocardial deformation and the persistent late gadolinium enhancement were found in a significant subset of patients.
The findings showed that myocardial injury after mRNA-1273 booster vaccination occurred in one out of 35 people (2.8%), which was higher than incidence estimated in meta-analyses of hospitalized cases with myocarditis (incidence of 0.0035%) after the second vaccination.
Cardiac MRI revealed signs of non-ischemic myocardial fibrosis in in 30% of PASC/long COVID patients, exceeding the prevalence in the normal adult population.
Cytokine-dependent pathology and a profibrotic myeloid response in 23 patients with vaccine-associated myocarditis after mRNA SARS-CoV-2 vaccination
The cytokinopathy and profibrotic myeloid cell response suggest cytokine-dependent pathology possibly associated with myeloid cell–associated cardiac fibrosis in myocarditis after mRNA SARS-CoV-2 vaccination.
PET and MRI visualization of myocardial tissue sequelae in patients with myocarditis after anti-SARS-CoV-2 vaccination
PET and MRI visualization of myocardial tissue showed that localized myocardial inflammation and edema is present in a small proportion of patients with symptomatic myocarditis at approximately 2 months after anti-SARS-CoV-2 vaccination.
Results showed that the overall risk of all forms of retinal vascular occlusion was 2.19 times higher in the vaccinated cohort than in the unvaccinated cohort in the 2 years after vaccination.
These findings revealed the possibility that autoimmunity to desmoglein 2 contributes to cardiac sequelae associated with C-19 infection.
SARS-CoV-2 S1 subunit of the spike (S) protein by itself promotes cell signaling in the vasculature. A morphometric analysis of the pulmonary vessels showed wall thickness in patients who died of SARS-CoV-2.
Elevated circulating levels of free full-length SARS-CoV-2 spike protein in adolescents and young adults with myocarditis after mRNA vaccination
Adolescents and young adults with myocarditis after SARS-CoV-2 mRNA vaccination had significantly higher levels of free full-length spike protein in their plasma, whereas asymptomatic vaccinated control subjects had no detectable free spike protein.
COVID-19/ Long COVID, Immunity & Inflammation
Spike protein binds directly to bacterial lipopolysaccharide, boosting the inflammatory response and forming spike protein aggregates
The S protein binds to LPS through multiple sites on the S1 and S2 subunits, and that this interaction enhances the inflammatory response in vitro and in vivo.
The presence of concurrent intracellular pathogens can lead to T-cell exhaustion and potentially severe consequences
This theoretical paper discusses the possible interactions between intracellular pathogens, such as viruses, bacteria, fungi and protozoan parasites when they concurrently infect the same host cells. Concurrent intracellular pathogens can lead to T-cell exhaustion and subvert innate and adaptive immune defenses, with severe consequences.
Autoantibodies against certain chemokines have favorable outcome in recovered COVID-19 convalescents
These findings revealed different patterns of anti-chemokine autoantibodies in recovered convalescents after COVID-19 and patients with long COVID
An immunohistologic analysis of cerebral venous thrombi caused by vaccine-induced immune thrombotic thrombocytopenia
The immunohistological analysis of clots from three people who died from cerebral venous thrombosis related to vaccine-induced immune thrombotic thrombocytopenia after receiving a single dose of ChAdOX1-nCoV-19 vaccines.
Unique monocyte signatures in subgroups of long COVID patients indicate that long COVID phenotypes could be driven by distinct mechanisms
This study shows unique monocyte signatures that define subgroups of long COVID patients. Given the heterogeneity of clinical presentations, it seems likely that different long COVID phenotypes are caused by distinct pathophysiological pathways.
The authors proposed a pathophysiological model of long COVID based on the persistence of SARS-CoV-2 virus. It apears that long COVID is an infection-associated chronic disease that affects every single organ system, and results in multisystem injury in both adults and children.
Graves’ disease after mRNA vaccination against COVID-19, with the presence of autoantibodies one year after the vaccination
A case report of new-onset Graves’ disease after mRNA vaccination against COVID-19, with the presence of autoantibodies one year after the vaccination.
A recent detailed review article discusses the known underlying mechanisms, possible trigger factors and consequences of persistent thromboinflammation in post-acute COVID-19 syndrome.
Repeated SARS-CoV-2 mRNA vaccination results in a class switch to noninflammatory spike-specific IgG4 antibodies
Repeated immunization with SARS-CoV-2 mRNA vaccines can cause an increase in anti-spike IgG4 antibodies and IgG4-switched memory B cells 5 to 7 months after the second mRNA immunization. This class switch has been linked to a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition.
Prolonged SARS-CoV-2 receptor binding domain booster vaccination promotes humoral and cellular immune tolerance in the Balb/c mice
Prolonged vaccination promoted the development of a prominent adaptive immune tolerance and profoundly impaired the immune response established by conventional course.