C-19 Resource Page (Acute COVID-19)
& Nervous System
Clinical and radiological findings of cytotoxic lesions of the corpus callosum (CLOCCs) associated with COVID-19
This study presented clinical, radiological and laboratory features of cytotoxic lesions of the corpus callosum (CLOCCs) in eight COVID-19 patients.
In a mouse model of transient focal brain ischemia, the recombinant SARS-CoV-2 spike protein disrupted the RAAS balance, increased coagulation, and decreased fibrinolysis, which worsened ischemic stroke outcome
This study provides new evidence that SARS-CoV-2 S protein injection given to hACE2 KI mice seven days before transient focal brain ischemia disrupted the RAAS balance by increasing Ang II/AT1R signaling in the brain’s cells at the expense of the Ang II/AT2R protective arm.
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.
COVID-19-associated unilateral encephalitis (case report)
A rare case of COVID-19-associated unilateral encephalitis, characterized by severe involvement of the left cerebral hemisphere.
The inoculation of the SARS-CoV-2 S1 protein in the olfactory cavity resulted in brain inflammation and reduced acetylcholine level in the mouse brain
This investigation shows a link between the S1 subunit of the spike protein, brain inflammation, and reduced production of acetylcholine.
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.
The neurons of the peripheral nervous system serve as an alternative route for SARS-CoV-2 invasion of the central nervous system, independent of viremia
After intranasal SARS-CoV-2 inoculation, the findings demonstrated susceptibility of sensory and autonomic neurons of the PNS and CNS to productive infection with SARS-CoV-2 through direct neural invasion that preceded viremia.
SARS-CoV-2 can infect and replicate in human motor neurons differentiated from induced pluripotent stem cells
SARS-CoV-2 is able to infect and replicate in an in vitro model of human motor neurons differentiated from induced pluripotent stem cells.
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. These findings confirmed that the SARS-CoV-2 S protein contributes to neuroinflammation via several mechanisms involved in CNS pathologies.
The Wuhan wild-type strain and five variants of SARS-CoV-2 differently affect the viability of various brain cells (pericytes, astrocytes, endothelial cells, and microglia) and the integrity of the blood-brain barrier
The wild-type Wuhan strain and five variants Alpha, Beta, Delta, Eta, and Omicron, carrying specific mutations that modulate their infectivity and transmissibility, affect the brain cells and the blood-brain barrier differently.
The presence of the SARS-CoV-2 S1 protein in the skull and meninges might show an alternative route for S protein entry into the CNS
The findings of this study suggest an alternative route for the SARSCoV-2 S protein entry into the CNS, wherein it might reache first the skull marrow and meninges before entering the brain.
& Cardiovascular System
Severe vascular remodeling (including severe thickening and fibrosis of the vessel walls, smooth muscle cell proliferation, and vessel lumen occlusion) was found in the placental arteries of women infected with SARS-CoV-2 during pregnancy
The results show severe vascular remodeling of placental arteries, including severe thickening of the vessel walls and the occlusion of the vessel lumen, in women with COVID-19 during pregnancy.
SARS-CoV-2 can infect and replicate in macrophages within atherosclerotic plaques in the human coronary artery wall
SARS-CoV-2 was detected and replicated in the coronary arteries sampled at autopsy of severe COVID-19 cases. The virus targeted plaque macrophages and demonstrated a stronger tropism for arterial wall lesions than for perivascular fat.
Selected topic: SARS-CoV-2 & Cardiac Tissue
Marked neovascularization in the form of intussusceptive angiogenesis, associated with a significant infiltration of CD11b+/TIE2+ macrophages, may be the main driver for a specific cardiac injury induced by SARS-CoV-2
The most remarkable finding in the cardiac remodeling triggered by the SARS-CoV-2 infection was a marked neovascularization in the form of intussusceptive angiogenesis, which was associated with a significant infiltration of CD11b+/TIE2+ macrophages, which are drivers of intussusceptive angiogenesis.
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.
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.
SARS-CoV-2 infection and additional hypoxic stress deteriorates cardiac function and disrupts vascular network formation in human cardiac tissue model
Human iPS cell-based cardiac tissue model shows that cardiac tissue exposed to persistent SARS-CoV-2 infection is at high risk for cardiac dysfunction.
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
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.
Testosterone, TMPRSS-2 and P450 aromatase are markers for the severity of COVID-19 (testosterone as a regulator of TMPRSS2 expression)
Hospitalized patients with COVID-19 were found to have higher TMPRSS-2 and P450 aromatase levels and lower testosterone levels, suggesting that TMPRSS2, testosterone, and P450 aromatase can be used as markers of poor prognosis or increased disease severity in COVID-19.
Highly expressed markers of vascular impairment and autophagy are co-localized with SARS-CoV-2 spike protein in placenta samples of unvaccinated women positive for SARS-CoV-2
Increased expression of VEGF and the endothelial cell marker CD34 indicates alterations, disarrangements, or remodeling of normal vasculature, associated with vascular endothelial injury and endothelitis.
SARS-CoV-2 enters human erythrocytes but does not affect the development of Plasmodium falciparum
SARS-CoV-2 enters human erythrocytes, but in a low percentage of cells (10.9%) compared to SARS-CoV-2 permissive cell lines. The presence of SARS-CoV-2 in blood culture did not affect the survival or growth rate of the malaria parasite.
Tuberculous pericarditis with pericardial tamponade in SARS-CoV-2-positive patients (Two case reports)
These case reports presented individuals who were diagnosed with COVID-19 and who developed tuberculous pericarditis with tamponade.
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.
SARS-CoV-2 preferentially infects intestinal cells via their apical side and causes damage to the intestinal epithelial barrier
Inoculation of SARS-CoV-2 at the apical pole resulted in the severe damage to the integrity of the intestinal epithelial barrier, suggesting that the virus present in the intestinal lumen could damage the intestinal epithelial barrier, enter the blood vessels and spread to various organs.
HERV-W envelope proteins detected in plasma, blood cells and postmortem tissues of severe COVID-19 patients could serve as biomarkers of COVID-19 severity
SARS-CoV-2 can induce the expression of the HERV-W envelope proteins, suggesting their involvement in COVID-19-associated pathology.
SARS-CoV-2 can infect hepatocytes and stimulate hepatic glucose production through gluconeogenesis
SARS-CoV-2 can infect, replicate, and produce infectious viral particles in primary human hepatocytes and stimulate their production of glucose through gluconeogenesis.
Acute COVID-19 in Children & Adolescents
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.
Selected Topics
SARS-CoV-2 & The Feto-Placental Pathology
Highly expressed markers of vascular impairment and autophagy are co-localized with SARS-CoV-2 spike protein in placenta samples of unvaccinated women positive for SARS-CoV-2
Increased expression of VEGF and the endothelial cell marker CD34 indicates alterations, disarrangements, or remodeling of normal vasculature, associated with vascular endothelial injury and endothelitis.
Neurodevelopmental disorders and microcephaly after in utero SARS-CoV-2 exposure (case reports)
Clinical findings, placental pathology, and immunohistochemical analysis strongly suggest that second-trimester maternal SARS-CoV-2 infection and placentitis triggered an inflammatory response in the fetoplacental unit that affected the fetal brain.
Maternal-fetal transmission of SARS-CoV-2, viral tropism for various fetal brain cells, and a concerning degree of brain gliosis were observed in the brains of in utero-infected mouse fetuses
The results showed significant level of maternal-fetal transmission of delta variant SARS-CoV-2 in later stages of mice pregnancy, and viral tropism for various fetal brain cells, like endothelial cells of blood vessels, barrier cells of the choroid plexus, neurons, and glial cells.
The SARS-CoV-2 proteins were found in the fetal brain cortical hemorrhages during early gestation
This study reported the presence of SARS-CoV-2 in fetal brain tissue, associated with cortical hemorrhages, and linked to reduced blood vessel integrity and monocyte infiltration of the hemorrhagic cortex. SARS-COV-2 antigens were also detected in the placenta, amnion, and umbilical cord during early gestation (the first and second trimesters of pregnancy).
Severe vascular remodeling (including severe thickening and fibrosis of the vessel walls, smooth muscle cell proliferation, and vessel lumen occlusion) was found in the placental arteries of women infected with SARS-CoV-2 during pregnancy
The results show severe vascular remodeling of placental arteries, including severe thickening of the vessel walls and the occlusion of the vessel lumen, in women with COVID-19 during pregnancy.
Stool samples from newborns, born to mothers infected with SARS-CoV-2 during pregnancy, contained SARS-CoV-2 RNA and S protein at delivery, indicating in utero viral transmission to the fetal intestine
The mechanism of in utero transmission to the fetal intestine remains unclear. Since viral RNA was detected in the placenta and amniotic fluid, this might be the pathway of viral transmission.
SARS-CoV-2 & Children’s Brain
Acute necrotizing encephalopathy in children infected with the Omicron variant of SARS-CoV-2
This retrospective study of 4,520 pediatric patients infected with the Omicron variant of SARS-CoV-2 demonstrated that acute necrotizing encephalopathy and pneumonia with comorbidities were the main causes of death.
Cerebrovascular lesions and brain vascular abnormalities in children infected with the Omicron variant of SARS-CoV-2 (MRI study)
This study has shown cerebrovascular lesions and vascular abnormalities in a high proportion (48.4%) of children with severe neurological manifestations of infection with the Omicron variant of SARS-CoV-2.
Acute encephalopathy in unvaccinated children infected with the Omicron variant of SARS-CoV-2 (Japanese nationwide epidemiological study)
A significantly higher number of patients with SARS-CoV-2-associated acute encephalopathy experienced severe disability or even death than patients with acute encephalopathy not associated with SARS-CoV-2.
Pediatric patients with the Omicron variant of SARS-CoV-2 have a higher rate of simple or complex febrile seizures compared to children infected with non-Omicron variants
The Omicron variant of SARS-CoV-2 was associated with a higher rate of febrile seizures and unconsciousness in infected children compared to non-Omicron variants.
Some features of the SARS-CoV-2
The XEC variant of SARS-CoV-2 exhibits higher pseudovirus infectivity and immune evasion
SARS-CoV-2 XEC variant exhibited a higher pseudovirus infectivity and immune evasion compared to KP.3, indicating that XEC will be a predominant SARS-CoV-2 variant in the near future.
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.
Histamine receptor H1 binds directly to the N-terminal domain on the SARS-CoV-2 S1 protein and acts as an ACE2-independent receptor for SARS-CoV-2, but also synergistically interacts with ACE2 and facilitates ACE2-dependent viral entry (antihistamines could be a potential treatment for COVID-19)
Histamine receptor H1 acts as an independent receptor for SARS-CoV-2. The antihistamine drugs effectively inhibited the binding of H1R to the S protein and viral infection.
SARS-CoV-2 variant KP.2 (JN.1.11.1.2) exhibits increased immune resistance
This study showed an increased immune resistance of KP.2 variant and its ability to evade neutralizing antibodies to a greater extent than previous variants, including JN.1.
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.
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.
SARS-CoV-2 spike protein activates the epidermal growth factor receptor (EGFR), its downstream signaling pathways and the anti-apoptotic protein survivin
SARS-CoV-2 S1 subunit and RBD activate the EGFR and its downstream signaling pathways and increase the expression and activation of the anti-apoptotic protein survivin.
The classification of SARS-CoV-2 variants into five serotypes based on the antigenicity of the receptor-binding domain
Chinese researchers propose the classification of SARS-CoV-2 variants into five serotypes based on the antigenicity of the receptor-binding domain
The bacterial lipopolysaccharide binds to the SARS-CoV-2 spike protein and drives the formation of large S protein aggregates
These findings have established a significant link between excessive inflammation during SARS-CoV-2 infection and comorbidities associated with increased levels of bacterial endotoxins. This synergism between LPS and the S protein is of clinical and therapeutic importance.
Omicron variants may have been artificially synthesized rather than naturally formed
The authors emphasized that the Omicron isolates BA.1, BA.1.1, and BA.2 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.
TMEM106B protein can serve as an alternative receptor for SARS-CoV-2 entry into ACE2-negative host cells
TMEM106B, a lysosomal transmembrane protein, can serve as an alternative receptor for the entry of severe acute respiratory syndrome coronavirus 2 into the angiotensin-converting enzyme 2 receptor-negative cells.
The “bacteriophage-like” behavior of SARS-CoV-2 (the SARS-CoV-2 genome can replicate outside the human body)
The interaction between fecal bacteria and the SARS-CoV-2 suggests a ‘bacteriophage-like’ behavior of SARS-CoV-2.
Delta variant of the SARS-CoV-2 increased the volumes of environmental biofilms and remained viable for up to five days
The virus was viable for up to five days with and without an environmental biofilm on all surfaces tested. The SARS-CoV-2 viability was highly correlated with the microorganisms forming the biofilms.
SARS-CoV-2 S1 protein is electrically conductive and reacts with gold, silicon, copper, and platinum electrodes and denatures. A method of coronavirus deactivation?
These findings provide new opportunities for developing coronavirus-capturing materials that are capable of irreversibly trapping the virus via strong covalent bonds.
Selected topic: Homology between Viral and Human/Other Antigens
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.
The striking molecular mimicry between SARS-CoV-2 and human EnaC-alpha may contribute to reduced reabsorption of alveolar fluid at the air-liquid interface
SARS-CoV-2 S protein may compete for the same processing protease with EnaC-alpha, a sodium permeable ion channel that controls fluid reabsorption at the air–liquid interface.
“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.
Molecular similarities between antigenic sites of the SARS-CoV-2 RBD and 54 antigenic determinants of fifteen pathogens (bacteria, parasites, and viruses)
Seven antigenic sites of SARS-CoV-2 spike RBD showed molecular similarities with 54 antigenic determinants found in fifteen pathogen microorganisms, including bacteria, parasites and viruses.
Treatment
The carbohydrate ProLectin M increased viral clearance in patients with mild to severe COVID-19 by antagonizing the binding of galectin-3 to the S1 subunit of the SARS-CoV-2
The carbohydrate PL-M can reduce the viral load in Vero cells. In clinical studies with COVID-19 patients, PL-M treatment resulted in a rapid reduction of viral load and increased viral clearance, with no adverse effects.
Dose-dependent antiviral effect of probenecid in COVID-19
This study showed a dose-dependent antiviral effect of a uricosuric agent probenecid in patients with symptomatic, mild-to-moderate COVID-19.
Histamine receptor H1 binds directly to the N-terminal domain on the SARS-CoV-2 S1 protein and acts as an ACE2-independent receptor for SARS-CoV-2, but also synergistically interacts with ACE2 and facilitates ACE2-dependent viral entry (antihistamines could be a potential treatment for COVID-19)
Histamine receptor H1 acts as an independent receptor for SARS-CoV-2. The antihistamine drugs effectively inhibited the binding of H1R to the S protein and viral infection.
Anti-SARS-CoV-2 properties of natural products derived from plants, honey, and marine sponges
This study analyzes recent research on natural products derived from plants, honey, and marine sponges with properties against the SARS-CoV-2, as well as several potential mechanisms of their action,
21% of vaccinated COVID-19 outpatients treated with nirmatrelvir-ritonavir had a virologic rebound phenomenon and a substantially prolongated shedding of replication-competent viruses
This study demonstrated that virologic rebound was found in 21% of COVID-19 outpatients treated with nirmatrelvir-ritonavir.