Long COVID/ Post-COVID-vaccination syndrome
& Nervous System
Chorea, a hyperkinetic movement disorder, develops after COVID-19 infection or COVID vaccination
Two systematic reviews examined the existing literature on chorea associated with COVID-19 infection or vaccination.
SARS-CoV-2 infection in vitro triggered the inflammation and senescence pathways in A9 dopaminergic neurons (mostly affected by Parkinson’s disease in the substantia nigra) derived from human pluripotent stem cells. Increased risk of viral-induced parkinsonism?
This study demonstrated selective in vitro vulnerability of A9 DA neurons derived from human pluripotent stem cells to SARS-CoV-2 infection and the associated inflammatory and cellular senescence response.
“Neurotoxin-like region” of the SARS-CoV-2 spike protein modulates nicotinic acetylcholine receptors (with a high preference for the α7 subtype linked with aggression, anxiety, and depression)
Neurotoxin-like region of the SARS-CoV-2 interact with the nicotinic acetylcholine receptors. The α7 nAChR is a target for the SARS-CoV-2.
Reversible cerebral vasoconstriction syndrome after mRNA COVID vaccination (autopsy report)
Case report of patient who died of radiographically and pathologically confirmed reversible cerebral vasoconstriction syndrome (RCVS) one day after the third mRNA COVID (BNT162b2) vaccination.
Prion-like domains in the SARS-CoV-2 spike protein
Different beta-coronaviruses (β-CoVs) contain prion-like domains in the S proteins. However, SARS-CoV-2 is the only β-CoV with prion-like domains identified within the receptor-binding domain (RBD) of the S protein.
Multifocal necrotizing encephalitis, mild myocarditis, and endothelitis after COVID-19 vaccination (autopsy report)
Autopsy report of multifocal necrotizing encephalitis, mild myocarditis, and endothelitis that developed after a third COVID-19 vaccination.
The role of hypothalamic circuits and the median eminence, not completely protected by the blood-brain barrier, in brain infection with SARS-CoV-2
Some CNS structures, like the choroid plexus and the circumventricular organs including the hypothalamus, are not completely protected by the BBB and can serve as virus entry points.
Hypotestosteronemia in COVID-19 or post COVID syndrome could be of hypothalamic origin
A persistent hypotestosteronemia in certain patients with COVID-19 or long COVID syndrome could be of hypothalamic origin due to impaired GnRH function, or hypogonadotropic hypogonadism.
Correlation between increased [11C]PBR28 PET/MR binding across a wide range of brain regions, as an indicator of neuroinflammation, and parameters of vascular health could partially reflect variations in vascular anatomy and perivascular immune infiltration in post-acute COVID-19
The results provide indirect evidence that differences in PET signal across brain regions, as an indicator of neuroinflammation, could partially reflect variations in vascular health and perivascular immune infiltration in individuals with PASC.
A new-onset small fiber neuropathy in individuals with post-acute COVID-19 syndrome
A case series of a new onset small fiber neuropathy with symptoms of dysautonomia and neuropathy, that developed after COVID-19.
Individuals with post-COVID syndrome have reduced corneal innervation and increased density of corneal dendritic cells more than 20 months after acute COVID-19
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.
SARS-CoV-2 spike protein and its receptor-binding domain stimulate human microglia through different receptors to secrete various proinflammatory mediators
Recombinant full-length S protein and its RBD stimulate human microglia via activation of different receptors. This suggests that the SARS-CoV-2 S protein contributes to neuroinflammation via several mechanisms involved in CNS pathologies.
Case series of hemorrhagic myelitis with poor clinical recovery after the SARS-CoV-2 infection
An uncommon disease, hemorrhagic myelitis was presented in three cases following SARS-CoV-2 infection, with minimal or no improvement during follow-up.
Systemic reaction with predominant neurological and skin manifestations following the third dose of the mRNA-1273 COVID vaccine (case report)
A case of a systemic reaction, characterized by predominant neurological (electroencephalography and MRI findings) and skin manifestations (tinea inguinalis and tinea capitis) that occurred following the third dose of the mRNA-1273 vaccine,
Selected Topics
Cognitive Impairment
A Korean nationwide study with 558,017 participants found that COVID-vaccinated individuals had a higher incidence of Alzheimer’s disease and mild cognitive impairment
The findings showed an increased incidence of Alzheimer’s disease and its prodromal stage, mild cognitive impairment, in COVID-vaccinated individuals, particularly those receiving mRNA vaccines, within three months post-vaccination.
Younger and middle-aged patients with neuro-post-COVID syndrome were found to have poorer cognitive performance and executive functions and more prevalent neurological symptoms than older patients
Age-related differences in neuro-long COVID showed that younger and middle-aged patients were more severely affected than older patients.
An abnormal accumulation of Alzheimer’s disease-like hyperphosphorylated tau proteins in postmortem brain samples of COVID-19 convalescents who died within 4-13 months after acute COVID-19
This study found abnormal accumulation of hyperphosphorylated tau proteins in the postmortem human brain samples of hippocampus and medial entorhinal cortex within 4-13 months after acute COVID-19.
Cognitive-linguistic difficulties in individuals with post-COVID syndrome
Participants diagnosed with Long COVID performed worse than healthy controls in delayed and immediate verbal recall, informativeness of spoken discourse, letter fluency, and category fluency for animals.
Cognitive dysfunction is associated with changes in the brain functional connectivity in individuals with neuro-post-COVID syndrome
These findings demonstrate characteristics and changes of the complex network known as brain functional connectome in individuals with primarily neurological symptoms of post-COVID syndrome.
Visuospatial deficits were found to correlate with brain neuroimaging findings and upregulation of certain biomarkers in COVID-19 convalescents 4 months after infection
Visuospatial deficit was associated with brain neuroimaging findings, and correlated with the upregulation of certain immune markers in approximately one-quarter of participants four months after acute COVID-19.
Individuals with neuro-post-COVID syndrome and poorer cognitive performance have a distinct immunological signature
Individuals with neuro-PASC had a distinct pattern of T cell activation and specific immune responses against the SARS-CoV-2 nucleocapsid protein.
Transcranial magnetic stimulation demonstrated abnormal GABAergic and glutamatergic regulation of the motor cortex excitability in individuals with post-COVID syndrome and cognitive deterioration
Patients diagnosed with long COVID syndrome and cognitive deterioration had significantly reduced long-interval intracortical inhibition that depends on slow inhibitory post-synaptic potentials mediated through GABA receptors and an abnormal pattern of intracortical facilitation, which is associated with glutamatergic excitatory signaling.
Neuroimmune Diseases
Autoantibodies against peripheral nerve structures have been found in 18% of patients with post-COVID-19 vaccination syndrome
This study has shown that serum prevalence of autoreactive IgGs against peripheral nerve structures was significantly higher in PCVS patients than in healthy controls. IgG binding was directed against axons, paranodes, Schmidt-Lanterman incisures, and Schwann cell nuclei.
The first onset or relapse of optic neuritis in COVID-19 vaccinated individuals positive for SARS-CoV-2
De novo onset or relapse of optic neuritis in vaccinated individuals infected with SARS-CoV-2.
Differences in the concentrations of autoantibodies against receptors involved in autonomic regulation between individuals with post-COVID-19 vaccination syndrome and vaccinated healthy subjects could be related to dysautonomia
The concentrations of autoantibodies against receptors involved in autonomic regulation and serum levels of IL-6/IL-8 can distinguish individuals with post-COVID-19 vaccination syndrome from healthy vaccinated individuals.
Acute disseminated encephalomyelitis (ADEM) can develop after acute SARS-CoV-2 infection or COVID-19 vaccination
A systematic review of the medical literature on cases of acute disseminated encephalomyelitis (ADEM) and acute hemorrhagic leukoencephalitis (AHLE) that occurred after severe acute SARS-CoV-2 infection or CoVID-19 vaccination.
Neuromyelitis optica spectrum disorder (NMOSD) can develop after acute SARS-CoV-2 infection or COVID-19 vaccination
The infection with SARS-CoV-2 and COVID-19 vaccination are associated with de novo onset or relapse of neuromyelitis optica spectrum disorder.
Brain Structural and Functional Changes
Quantitative susceptibility mapping revealed microstructural abnormalities in several medullary clusters associated with respiratory function and body homeostasis in COVID-19 survivors over months after hospitalization
Non-invasive ultra-high-field 7 T QSM showed imaging evidence of pathophysiological changes and microstructural abnormalities in the brainstem over months after COVID-19 hospitalization.
Neurometabolite concentrations show neuronal injury and glial dysfunction in the frontal brain regions of patients with neuropsychiatric symptoms of long COVID (proton MR spectroscopy study)
Brain proton MR spectroscopy demonstrated decreased tNAA and Glu/Gln levels, increased Cho and tCr levels, and altered MI levels (decreased or increased depending on the severity of acute COVID-19) in the frontal brain regions of long COVID patients with neuropsychiatric symptoms.
Cognitive dysfunction is associated with changes in the brain functional connectivity in individuals with neuro-post-COVID syndrome
These findings demonstrate characteristics and changes of the complex network known as brain functional connectome in individuals with primarily neurological symptoms of post-COVID syndrome.
Transcranial magnetic stimulation demonstrated abnormal GABAergic and glutamatergic regulation of the motor cortex excitability in individuals with post-COVID syndrome and cognitive deterioration
Patients diagnosed with long COVID syndrome and cognitive deterioration had significantly reduced long-interval intracortical inhibition that depends on slow inhibitory post-synaptic potentials mediated through GABA receptors and an abnormal pattern of intracortical facilitation, which is associated with glutamatergic excitatory signaling.
Individuals with neuropsychiatric symptoms of post-acute COVID syndrome have abnormal brain activation during working memory tasks and performed worse in the domains of endurance, locomotion, and the manual dexterity of the dominant hand (BOLD-fMRI study)
The first task-activated BOLD-fMRI study conducted in individuals diagnosed with post-COVID neuropsychiatric symptoms discovered a different brain activity and reorganized working memory network in post-COVID participants.
& Cardiovascular System
Recurrent venous thromboembolism in patients who discontinued anticoagulant therapy for COVID-19-associated venous thromboembolism after at least three months of treatment
After discontinuation of anticoagulation therapy, recurrent VTE occurred in 3.5% of patients, with a rate of 3.1 per 100 patient-years, and no fatal pulmonary embolism.
Orthostatic intolerance, a cardiovascular autonomic disorder, and decreased circulating growth hormone levels have been found in young patients with long COVID syndrome
This study showed a high rate (38%) of standing test positivity in patients with long COVID. The ST-positive long COVID patients under 20 years of age had decreased circulating growth hormone levels.
The SARS-CoV-2 spike protein acts as an allosteric agonist of β-adrenergic receptors and contributes to sympathetic hyperactivity
This study is the first to show that the SARS-CoV-2 spike protein activates β-adrenergic receptors in cardiomyocytes, contributes to cardiac sympathetic hyperactivity and increases activation of downstream β-adrenergic receptor signaling induced by epinephrine.
Spontaneous dissection of the internal carotid artery in a fully vaccinated woman infected with SARS-CoV-2 (case report)
This case report describes a fully vaccinated woman positive for a non-Omicron variant of SARS-CoV-2 who experienced a spontaneous internal carotid dissection. A dissection was treated successfully with a flow-diverter stent.
Extensive thrombosis of cerebral venous sinuses and similar organization of cerebral thrombi were found in all three patients who died of vaccine-induced immune thrombotic thrombocytopenia
The authors performed the immunohistological analysis of clots from three people who died from cerebral venous thrombosis (CVT) related to vaccine-induced immune thrombotic thrombocytopenia (VITT) after receiving a single dose of ChAdOX1-nCoV-19, AstraZeneca/Oxford vaccines.
The mRNA COVID-19 vaccination increases the risk of retinal vascular occlusion
The overall risk of all forms of retinal vascular occlusion was 2.19 times higher in the vaccinated cohort than in the unvaccinated cohort within two years after COVID-19 vaccination.
Selected Topic: Cardiac Sequelae
A Korean nationwide study conducted on more than 44 million vaccinated individuals found that the incidence of myocarditis associated with COVID vaccination was highest in males aged 12 to 17 years, and the most serious adverse effect was sudden cardiac death
The authors concluded that the findings of sudden cardiac deaths attributable to COVID vaccine-related myocarditis warrant the careful monitoring or warning of sudden cardiac death as a potentially fatal complication of COVID-19 vaccination, especially in individuals younger than 45 years of age who received the mRNA vaccines.
SARS-CoV-2 S1 protein activates human cardiac fibroblasts by priming NLRP3 inflammasomes through NF-κB signaling in an ACE2-dependent way and promotes cardiac fibrosis
The S1 protein activates human CFs by priming NLRP3 inflammasomes through NF-κB signaling in an ACE2-dependent way.
The mRNA-1273 and BNT162b2 COVID-19 vaccines induce different cardiotoxic effects and dysfunction in isolated rat left ventricular cardiomyocytes
This study showed for the first time that mRNA-1273 and BNT162b2 COVID-19 vaccines induced cardiotoxic effects with disturbances of normal contractile function in rat cardiomyocytes. The effects of vaccines differed fundamentally in their pathophysiological mechanisms.
Higher 18F-FDG uptake was detected in the myocardium, axilla, liver, and spleen of asymptomatic vaccinated individuals up to 6 months after the second mRNA COVID-19 vaccination (PET/CT study)
Individuals who were asymptomatic and underwent PET/CT within a period of 180 days following their second vaccination had increased 18Fluorine-fluorodeoxyglucose uptake in the myocardium, axilla, liver, and spleen as compared to unvaccinated individuals.
The VAERS reporting rates of myocarditis/pericarditis after mRNA COVID-19 vaccination demonstrate a higher reporting rate mainly after the second dose, particularly among young males
In this retrospective pharmacovigilance study of safety signals associated with myocarditis/pericarditis after the primary and up to three booster doses of mRNA COVID-19 vaccines, the second dose of the vaccines showed the strongest signal in vaccinated individuals under 25 years old.
Cardiac MRI showed signs of non-ischemic myocardial fibrosis in a significant portion of the cohort diagnosed with long COVID syndrome (30%)
30% of patients diagnosed with long COVID syndrome had cardiac MRI signs of non-ischemic fibrosis, exceeding the prevalence of this disease in the normal adult population.
Myocardial inflammation and edema have been found in a small proportion of patients diagnosed with acute myocarditis within 14 days of mRNA COVID-19 vaccination (PET and MRI study)
PET and MRI visualization of myocardial tissue has shown localized myocardial inflammation and edema in a small proportion of patients with symptomatic myocarditis approximately two months after COVID-19 vaccination.
Patients with acute COVID-19 and convalescents who recovered after severe COVID-19 were found to have elevated levels of anti-desmoglein 2 autoantibodies
The results showed the possible association between anti-Dsg2 autoantibodies and post-COVID-19 cardiac sequelae.
& Other Body Systems
SARS-CoV-2-related inflammation found in the epipharynx of patients with post-COVID syndrome suggests the therapeutic potential of epipharyngeal abrasive therapy
These results suggest a possible link between long COVID and chronic epipharyngitis and emphasize the therapeutic potential of EAT in treating the symptoms of long COVID.
A case series of 30 patients with newly diagnosed or relapsing glomerular diseases (immunoglobulin A nephropathy as the most common) after COVID vaccination
The most common glomerular disease after COVID-19 vaccination was immunoglobulin A nephropathy (IgAN). The absolute risk of glomerular diseases increased after the second or third COVID-19 mRNA vaccination.
Sex-specific differences in gene transcriptomics in peripheral blood cells of vaccinated patients with post-COVID syndrome
Sex-specific differences in the transcriptome of peripheral blood cells in vaccinated patients with PACS indicate possible sex-specific differences in the pathophysiology of PACS.
Higher serum ferritin levels distinguish long COVID patients who subsequently developed a clinical diagnosis of ME/CFS from those who did not meet the ME/CFS criteria
This study revealed that patients with long COVID who developed ME/CFS based on all of the three internationally standardized criteria had increased serum ferritin levels, identifyng serum ferritin as a possible biomarkers for detecting the transition to an ME/CFS condition, especially in female patients.
De novo onset or exacerbation of psoriasis following the SARS-CoV-2 infection or COVID vaccination
This study described a case series of 28 patients who experienced de novo onset or flares of psoriasis following infection with the SARS-CoV-2 or vaccination. All of these patients were successfully managed with anti-IL-17 or anti-IL-23 medications.
The BNT162b2 mRNA vaccine alters the activity of human ovarian granulosa cells, which support the oocytes during folliculogenesis (possible link with menstrual disorders)
The BNT162b2 mRNA COVID-19 vaccine directly affects the activity of ovarian granulosa cells, which is a unique, independent mechanism for vaccine-related menstrual abnormalities.
The receptor binding domain of SARS-CoV-2 S1 subunit binds to kidney injury molecule-1, which is highly expressed upon kidney injury
The receptor binding domain (RBD) of SARS-CoV-2 binds to kidney injury molecule-1 (KIM1), which is highly expresed only upon kidney injury.
Various time modes of proteomic recovery within two years after acute COVID-19
The results showed that different biological processes recovered in different time modes within two years after COVID-19, providing insights into the biological processes of the different long COVID syndrome phenotypes.
Leprosy following COVID-19 vaccination
This study investigated leprosy or immune-mediated complications known as leprosy reactions diagnosed in the Leprosy Clinic at the Hospital for Tropical Diseases, London, within 12 weeks following COVID-19 vaccination.
A case series of Stevens-Johnson syndrome/toxic epidermal necrolysis associated with SARS-CoV-2 infection and COVID-19 vaccination
The largest case series of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) associated with SARS-CoV-2 infection and COVID-19 vaccination.
129Xe MRI red blood cells-to-alveolar tissue barrier ratio shows abnormal gas exchange in long COVID patients
A lower 129Xe MRI RBC-to-barrier ratio in long COVID patients suggests that SARS-CoV-2 infection may have caused some microstructural abnormality to one or two volumes, such as pulmonary embolism, pulmonary blood flow alterations, or alveolar membrane thickening, which leads to decreased blood volume.
Selected Topics
Persistent SARS-CoV-2 reservoirs & antigens
The persistence of vaccine-derived S1 protein in CD16+ monocytes and post-acute sequelae of COVID-19 (PASC)-like cytokine profile up to 245 days after vaccination may contribute to post-COVID vaccination syndrome in SARS-CoV-2-uninfected individuals
These findings suggest that the persistence of vaccine-derived S1 protein in CD16+ monocytes, and post-acute sequelae of COVID-19-like cytokine profile, may contribute to persistent post-COVID-19 vaccination syndrome.
SARS-CoV-2 spike and nucleocapsid proteins as well as HIV-GP120 protein were detected in extracellular vesicles or as free proteins in the bronchoalveolar lavage fluids from post-COVID patients up to two years after acute COVID-19 and from HIV-positive subjects on HAART therapy with undetectable blood viral load
Most spike and nucleocapsid proteins were contained in the extracellular vesicles. In contrast, most HIV-GP120 proteins were present as free proteins.
A specific immunological profile, serological evidence of recent Epstein-Barr virus reactivation, and circulating SARS-CoV-2 S1 protein were found in individuals with post-COVID vaccination syndrome up to 700 days after vaccination
This study demonstrated immunological and other characteristics in individuals experiencing persistent symptoms following COVID-19 vaccination.
SARS-CoV-2 antigens can persist in plasma for up to 14 months after acute infection
Analysis of temporal antigen profiles, performed by collecting blood samples at multiple time points, revealed that the prevalence of SARS-CoV-2 plasma antigens was 10.6% 3-6 months after the onset of COVID-19, 8.7% after 6-10 months and 5.4% after 10-14 months.
Residual SARS-CoV-2 RNA and proteins are persistent in solid tissue samples from various organs at one month, two months, and four months after mild COVID-19
This study showed the persistence of SARS-CoV-2 nucleic acid in solid tissue samples from various organs, including lung, liver, kidney, stomach, intestine, brain, breast, thyroid, blood vessels, and skin, in patients who had recovered from mild COVID-19 at one month, two months, and four months post-infection.
In two patients diagnosed with post-COVID syndrome, SARS-CoV-2 RNA and antigens were detected in the appendix and breast tissue, 426 and 175 days after the acute COVID-19
This study investigated the presence of residual SARS-CoV-2 RNA and antigens in tissues of two patients diagnosed with post-COVID syndrome.
The persistence of SARS-CoV-2 antigens, chronic inflammation, reactivation of latent herpes viruses, and decreased cortisol levels were detected in long COVID patients more than one year after acute infection
Biological (immunological, virological and hormonal) features of long COVID syndrome more than one year after acute infection.
Mass spectrometry analysis demonstrated that approximately 50% of those vaccinated against COVID-19 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.
Vaccinated COVID convalescents were found to have increased T-cell activation in many anatomical regions and SARS-CoV-2-specific RNA in rectosigmoid cells up to 2.5 years after initial infection
A whole-body positron emission tomography with a novel radiopharmaceutical [18F]F-AraG showed increased T cell activation in numerous anatomical regions in vaccinated COVID convalescents up to 2.5 years after initial SARS-CoV-2 infection.
The structures of the Eye
The SARS-CoV-2 spike protein impacts the early and late phases of retinal development in retinal organoids derived from human pluripotent stem cells
This work highlights different effects of SARS-CoV-2 S protein on both early and late stages of retinal development, and provides insights into the cellular and molecular mechanisms of these effects.
New-onset or relapse of uveitis within a month after COVID-19 infection or COVID vaccination
These studies found an association between COVID-19 infection or vaccination and newly diagnosed or recurrent uveitis.
Intranasal infection of mice with SARS-CoV-2 led to retinal inflammation and elevated viral titers in the lungs and brain
The prolonged presence of SARS-CoV-2 S protein in ocular tissues (thirty days after the intravitreal injection) resulted in microaneurysms, retinal atrophy, and retinal vein occlusion.
IgG4-related ophthalmic disease after COVID-19 vaccination (case report)
The authors present a patient who developed the ocular manifestation of immunoglobulin (Ig)G4-related disease, referred to as IgG4-related ophthalmic disease (IgG4-ROD), after COVID vaccination.
Individuals with post-COVID syndrome have reduced corneal innervation and increased density of corneal dendritic cells more than 20 months after acute COVID-19
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.
The mRNA COVID-19 vaccination increases the risk of retinal vascular occlusion
The overall risk of all forms of retinal vascular occlusion was 2.19 times higher in the vaccinated cohort than in the unvaccinated cohort within two years after COVID-19 vaccination.
Reactivation of Latent Viruses
A specific immunological profile, serological evidence of recent Epstein-Barr virus reactivation, and circulating SARS-CoV-2 S1 protein were found in individuals with post-COVID vaccination syndrome up to 700 days after vaccination
This study demonstrated immunological and other characteristics in individuals experiencing persistent symptoms following COVID-19 vaccination.
The persistence of SARS-CoV-2 antigens, chronic inflammation, reactivation of latent herpes viruses, and decreased cortisol levels were detected in long COVID patients more than one year after acute infection
Biological (immunological, virological and hormonal) features of long COVID syndrome more than one year after acute infection.
Differently expressed human endogenous retroviruses (HERVs) and immune mediators in children diagnosed with COVID-19, Kawasaki disease, or multisystem inflammatory syndrome in children (MIS-C)
HERV-related genes, HERVs, and immune mediators are differently upregulated in children diagnosed with acute COVID-19, acute or subacute KD, and acute or subacute MIS-C, supporting the role of HERVs in inflammatory diseases and their interaction with the immune system.
Increased circulating levels of HERV-W envelope proteins and proinflammatory cytokines in SARS-CoV-2-positive patients hospitalized for psychosis spectrum disorders
This study demonstrated increased expression of HERV-W ENV proteins and proinflammatory cytokines only in hospitalized patients with psychosis spectrum disorders who were positive for SARS-CoV-2, suggesting a strong link between HERV-W activation, cytokine expression and SARS-CoV-2 infection.
Circulating HERV-W envelope proteins and elevated levels of anti-SARS-CoV-2 IgE antibodies were detected in patients with post-COVID syndrome one year after the acute infection
HERV-W ENV protein was expressed in 58% of plasma samples of post-COVID patients, long after the acute SARS-CoV-2 infection was resolved .75% of post-COVID patients had elevated levels of anti-S and anti-N IgE antibodies compared to pre-pandemic controls.
& Immune Dysregulation/ Autoimmunity
Unvaccinated COVID-19 convalescents were found to have multi-lineage reductions of immune cells and a shift from Th1 to Th2 cytokine pattern ten months after the infection
A follow-up study of immune parameters in unvaccinated COVID-19 convalescents 10 weeks and 10 months after a first and mostly mild infection with the Wuhan-strain Hu-1 showed a long-term reduction of innate and adaptive immune cells, associated with a shift from Th1 to Th2 cytokine pattern.
The P3 peptide of the SARS-CoV2 spike protein shares sequence homology with Staphylococcus aureus superantigens and several endogenous mammalian proteins and induces T-cell proliferation
This study identified a small peptide P3 in the S2 subunit of the SARS-CoV2 S protein with sequence homology to bacterial superantigens and the capacity to induce unexpected proliferation of T-cells.
Passive transfer of IgG from patients with long COVID induces mechanical and thermal sensitivity and impairs locomotor activity in mice
These findings demonstrate that transfer of IgG from long COVID patients to mice replicates disease symptoms, underscoring a causative and heterogeneous role of IgG in the pathogenesis of long COVID.
Immune response in people from malaria-endemic regions of Ghana, exposed to Plasmodium falciparum and positive for SARS-CoV-2
Immune modulation associated with exposure to Plasmodium falciparum may contribute to a reduced severity of SARS-CoV-2 infection among people living in malaria-endemic regions.
A diversity of intracellular microbes in immune cells of SARS-CoV-2-positive and COVID-19-recovered individuals
This study demonstrates diversity of intracellular microbes in immune cells of healthy individuals, SARS-CoV-2 positive patients, and COVID-19 recovered individuals.
Temporal dynamics of anti-chemokine autoantibodies in COVID-19 and long-COVID syndrome
The findings suggest that higher levels of autoantibodies directed against specific chemokines are associated with favorable disease outcomes in COVID-19 convalescents.
Individuals with neuro-post-COVID syndrome and poorer cognitive performance have a distinct immunological signature
Individuals with neuro-PASC had a distinct pattern of T cell activation and specific immune responses against the SARS-CoV-2 nucleocapsid protein.
Unique monocyte signatures in subgroups of long COVID patients indicate that long COVID phenotypes could be driven by distinct mechanisms
Unique monocyte signatures define subgroups of long COVID patients and confirm prolonged changes in innate immunity during COVID-19 convalescence. Given the heterogeneity of clinical presentations, it seems likely that distinct pathophysiological pathways cause different long COVID phenotypes
Immunocompromised patients with advanced HIV infection have high levels of SARS-CoV-2 spike protein genetic diversity
According to the authors, high levels of SARS-CoV-2 S protein genetic diversity in individuals with advanced poorly controlled HIV infection markedly increase the risk for the emergence of new VOCs in these individuals.
Selected Topics
Immune Dysregulation in post-COVID-19-vaccination syndrome
The persistence of vaccine-derived S1 protein in CD16+ monocytes and post-acute sequelae of COVID-19 (PASC)-like cytokine profile up to 245 days after vaccination may contribute to post-COVID vaccination syndrome in SARS-CoV-2-uninfected individuals
These findings suggest that the persistence of vaccine-derived S1 protein in CD16+ monocytes, and post-acute sequelae of COVID-19-like cytokine profile, may contribute to persistent post-COVID-19 vaccination syndrome.
One year after mRNA COVID-19 immunization, the young people show elevated cytokine levels, suggesting ongoing stimulation of the immune system
The results showed that vaccination led to increased cytokine levels even one year after vaccination. Furthermore, the results indicated differences in cytokine levels based on gender and age.
Autoantibodies against peripheral nerve structures have been found in 18% of patients with post-COVID-19 vaccination syndrome
This study has shown that serum prevalence of autoreactive IgGs against peripheral nerve structures was significantly higher in PCVS patients than in healthy controls. IgG binding was directed against axons, paranodes, Schmidt-Lanterman incisures, and Schwann cell nuclei.
The rapid waning of serum antibodies after mRNA vaccination is due to the inability of mRNA vaccines to induce long-lived plasma cells in the bone marrow
This study showed the exclusion of SARS-CoV-2 specificity from the bone marrow long-lived plasma cell (LLPC) compartment and the inability of mRNA vaccines to induce necessary precursor programs to fully mature into the bone marrow LLPC.
COVID-19 vaccination increased concentrations of IgE specific for the SARS-CoV-2 receptor binding domain and IgG4
This study revealed increased IgE levels specific for the receptor binding domain (RBD) of the SARS-CoV-2 in individuals who had been immunized with the ChAdOx1, CoronaVac and mRNA BNT162b2 vaccines. Additionally, IgG4 levels detected after booster mRNA BNT162b2 vaccination, showed a moderate correlation with IgE levels.
Elevated levels of non-inflammatory IgG4 antibodies specific for the SARS-CoV-2 spike protein were found in children aged 5 to 11 years one year after the BNT162b2 mRNA COVID-19 vaccination
This study found, for the first time in children, that levels of IgG4 antibodies specific for S1 and RBD significantly increased one year after the second vaccination compared to baseline.
IgG4-related diseases (sialadenitis, pancreatitis, and hepatopathy) after COVID-19 vaccination
Two cases of immunoglobulin (Ig)G4-related diseases that developed after COVID vaccination.
IgG4-related ophthalmic disease after COVID-19 vaccination (case report)
The authors present a patient who developed the ocular manifestation of immunoglobulin (Ig)G4-related disease, referred to as IgG4-related ophthalmic disease (IgG4-ROD), after COVID vaccination.
Differences in the concentrations of autoantibodies against receptors involved in autonomic regulation between individuals with post-COVID-19 vaccination syndrome and vaccinated healthy subjects could be related to dysautonomia
The concentrations of autoantibodies against receptors involved in autonomic regulation and serum levels of IL-6/IL-8 can distinguish individuals with post-COVID-19 vaccination syndrome from healthy vaccinated individuals.
A significant proportion (29%) of healthcare workers developed de novo production of antinuclear antibodies after three mRNA COVID-19 vaccinations
A significant proportion (29%) of healthcare workers developed de novo production of antinuclear antibodies after three mRNA COVID-19 vaccines. The most prevalent was a homogeneous pattern of ANA.
Vaccinated COVID convalescents were found to have increased T-cell activation in many anatomical regions and SARS-CoV-2-specific RNA in rectosigmoid cells up to 2.5 years after initial infection
A whole-body positron emission tomography with a novel radiopharmaceutical [18F]F-AraG showed increased T cell activation in numerous anatomical regions in vaccinated COVID convalescents up to 2.5 years after initial SARS-CoV-2 infection.
Changes in cytokine responses to heterologous pathogens and SARS-CoV-2 antigens were observed in children aged 5 to 11 years up to six months after their second BNT162b2 mRNA vaccination
Since a decrease in immune response to other pathogens makes children more susceptible to other infections, the authors concluded that these findings highlight the need for further consideration of vaccination policy.
Repeated mRNA COVID vaccinations increase the levels of IgG4 antibodies specific for SARS-CoV-2 spike protein and IgG4-switched memory B cells
Irrgang et al were the first to report an increase in the proportion of IgG4 antibodies specific for SARS-CoV-2 spike protein, starting after the second and increasing further after the third mRNA COVID vaccination.
Long COVID/ Post-COVID-vaccination syndrome in Children/ Adolescents
Children and adolescents with post-COVID syndrome (84% COVID-vaccinated) were found to have reduced pulmonary regional ventilation and perfusion (phase-resolved functional lung MRI study)
PREFUL MRI parameters revealed subtle pulmonary changes in children and adolescents with post-COVID syndrome, such as reduced regional ventilation and perfusion.
Orthostatic intolerance, a cardiovascular autonomic disorder, and decreased circulating growth hormone levels have been found in young patients with long COVID syndrome
This study showed a high rate (38%) of standing test positivity in patients with long COVID. The ST-positive long COVID patients under 20 years of age had decreased circulating growth hormone levels.
Hypertrophic tonsils as the SARS-CoV-2 reservoir in children: 23% of tonsil and adenoid tissue samples of children who had undergone adenotonsillectomy, were positive for the SARS-CoV-2 nucleoprotein
A discovery of the structural SARS-CoV-2 protein in situ in adenoids and palatine tonsils, in both epithelial and lymphomononuclear cells of different lymphoid compartments, suggests that the tonsils may be sites of prolonged infection, even without recent COVID-19 symptoms.
Elevated levels of non-inflammatory IgG4 antibodies specific for the SARS-CoV-2 spike protein were found in children aged 5 to 11 years one year after the BNT162b2 mRNA COVID-19 vaccination
This study found, for the first time in children, that levels of IgG4 antibodies specific for S1 and RBD significantly increased one year after the second vaccination compared to baseline.
The adverse events in adolescents aged 12–19 years after COVID-19 vaccination (Norwegian nationwide study)
This nationwide registry-based study has shown increased risks of adverse events, including anaphylactic reaction, lymphadenopathy, and myocarditis/pericarditis in older adolescents aged 12–19 years, after the second mRNA COVID-19 vaccination.
Changes in cytokine responses to heterologous pathogens and SARS-CoV-2 antigens were observed in children aged 5 to 11 years up to six months after their second BNT162b2 mRNA vaccination
Since a decrease in immune response to other pathogens makes children more susceptible to other infections, the authors concluded that these findings highlight the need for further consideration of vaccination policy.
58% of adolescents diagnosed with COVID vaccine-associated myocarditis had subclinical myocardial dysfunction up to one year after the diagnosis
This study showed persistence of residual late gadolinium enhancement in cardiac magnetic resonance imaging in 58% of adolescents with COVID vaccine-associated myocarditis up to one year of follow-up.
Children and adolescents infected with SARS-CoV-2 or vaccinated against COVID-19 were found to have increased median deformation of red blood cells
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.
Treatment
Positive effects of the flavonol quercetin in COVID-19 or post-COVID-19 syndrome
Numerous studies demonstrated the positive effects of quercetin in in COVID-19 or post-COVID-19 syndrome, including direct inhibition of viral entry into the host cells, inhibition of viral replication, anti-inflammatory, antioxidant, immunomodulatory and neuroprotective effects.
Metformin reduces the viral load and the incidence of long COVID syndrome in outpatients infected with SARS-CoV-2
Two randomized, placebo-controlled trials show that metformin reduces the viral load of SARS-CoV-2 and the incidence of long COVID syndrome.
Graded exercise therapy for individuals with long COVID syndrome and postexertional malaise: Pro et Contra
In their recent articles, several authors have discussed the clinical management of autonomic dysfunction and graded exercise therapy for individuals diagnosed with long-COVID or PACS syndrome.
Acyclovir clinically resolved or significantly improved symptoms in patients diagnosed with long COVID syndrome
Two case series studies demonstrated that four patients with long COVID improved with chronic use of acyclovir.