CNS Damage #
Certain Long Covid symptoms may come from direct damage to certain organ systems at the time of acute infection. Direct damage to organ systems is most prevalent in COVID patients who were hospitalized / in the ICU during the acute infection.
- long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI.
- They found white matter-selective microglial reactivity, a pattern observed in CRCI.
- Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity.
- In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function. Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects).
- UK Biobank scanned over 40,000 participants before the start of the COVID-19 pandemic
- Studied the effects of the disease in the brain using multimodal data from 782 participants from the UK Biobank COVID-19 re-imaging study, with 394 participants having tested positive for SARS-CoV-2 infection between their two scans.
- Used structural and functional brain scans from before and after infection, to compare longitudinal brain changes between these 394 COVID-19 patients and 388 controls who were matched for age, sex, ethnicity and interval between scans.
- Identified significant effects of COVID-19 in the brain with a loss of grey matter in the left parahippocampal gyrus, the left lateral orbitofrontal cortex and the left insula. When looking over the entire cortical surface, these results extended to the anterior cingulate cortex, supramarginal gyrus and temporal pole
- Our findings thus consistently relate to loss of grey matter in limbic cortical areas directly linked to the primary olfactory and gustatory system
Despite early speculation that SARS-CoV-2 may enter the central nervous system (CNS) via migration through the nasal cavity and the olfactory pathway or trafficking across the blood-brain barrier, analysis of cerebrospinal fluid (CSF) from living patients with neuropsychiatric manifestations has almost uniformly failed to detect viral RNA by reverse transcription polymerase chain reaction. Instead, the preponderance of evidence from CSF and brain tissue suggests that immune activation and inflammation within the CNS is the primary driver of neurologic disease in acute COVID-19
histopathological studies of brain tissue from patients who died with acute COVID-19 reveal only limited detection of SARS-CoV-2 nucleic acid or viral protein in the brain
- profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control individuals (including 1 patient with terminal influenza) and 8 patients with COVID-19
- systematic analysis yields no molecular traces of SARS-CoV-2 in the brain, we observe broad cellular perturbations indicating that barrier cells of the choroid plexus sense and relay peripheral inflammation into the brain and show that peripheral T cells infiltrate the parenchyma.
- We discover microglia and astrocyte subpopulations associated with COVID-19 that share features with pathological cell states that have previously been reported in human neurodegenerative disease
- Synaptic signalling of upper-layer excitatory neurons—which are evolutionarily expanded in humans7 and linked to cognitive function8—is preferentially affected in COVID-19.
- Across cell types, perturbations associated with COVID-19 overlap with those found in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia and depression
- We discover microglia (cortical T cells) and astrocyte subpopulations associated with COVID-19 that share features with pathological cell states that have previously been reported in human neurodegenerative disease
- Aberrant T cell infiltration into the mouse brain has previously been reported to be sufficient to promote neuroinflammation and impair neurogenesis & there is a precedent for acute viral infections causing long-term inflammation and dysfunction that predisposes individuals to neurodegenerative disease
- Kidney involvement is common in patients with acute SARS-CoV-2 infection, and subclinical inflammation and injury may persist for many months, resulting in a progressive decline in kidney function that leads to chronic kidney disease.
- the relationship between COVID-19 and CKD is likely to be bidirectional
- beyond the acute phase of illness, 30-day survivors of COVID-19 exhibited higher risks of AKI, eGFR decline, ESKD, major adverse kidney events (MAKE), and steeper longitudinal decline in eGFR.
- The risks of kidney outcomes increased according to the severity of the acute infection (categorized by care setting into non-hospitalized, hospitalized, and admitted to intensive care).
- One year after moderate COVID, the incidence rate of impaired DLCO and persistent lung damage still exceeds 30%, and one-third of the patients have severe DLCO impairment and fibrotic lung damage.
- The persistent respiratory complications may cause substantial population morbidity, long-term disability, and even death due to the lung fibrosis progression
- The incidence rate of post-COVID lung fibrosis can be estimated at 2-6% after moderate illness.
- We discuss the use of antifibrotic therapy for idiopathic pulmonary fibrosis, the IN01 vaccine, glucocorticosteroids as well as the stromal vascular fraction for the treatment and rehabilitation of patients with COVID-associated pulmonary damage
- sought to evaluate the spectrum of cardiac involvement among soldiers with cardiopulmonary symptoms in the late convalescent phase of recovery from SARS-CoV-2 compared to a healthy soldier control group, and to determine the rate of progression to CV PASC.
- All soldiers referred for cardiovascular magnetic resonance (CMR) imaging for cardiopulmonary symptoms following COVID-19 were enrolled and matched by age, gender, and athletic phenotype 1:1 to soldiers undergoing CMR in the year prior to the first case of COVID-19 at our institution.
- Fifty soldier cases and 50 healthy soldier controls were included.
- The majority of cases experienced moderate symptoms (N = 43, 86%), while only 10% required hospitalization
- Cardiovascular pathology was diagnosed in 6 symptomatic soldiers (12%) after recovery from SARS-CoV-2, with myocarditis found in 4 (8%).
- RVEF was reduced in soldier cases compared to controls.
- CV PASC occurred in over one-third of soldiers surveyed, but did not occur in any soldiers with asymptomatic acute SARS-CoV-2 infection