SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice

Cell Reports, Journal Year: 2023, Volume and Issue: 42(3), P. 112189 - 112189

Published: Feb. 17, 2023

Cognitive dysfunction is often reported in patients with post-coronavirus disease 2019 (COVID-19) syndrome, but its underlying mechanisms are not completely understood. Evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein or fragments released from cells during infection, reaching different tissues, including the CNS, irrespective of presence viral RNA. Here, we demonstrate brain infusion mice has a late impact on cognitive function, recapitulating post-COVID-19 syndrome. We also show neuroinflammation and hippocampal microgliosis mediate Spike-induced memory via complement-dependent engulfment synapses. Genetic pharmacological blockage Toll-like receptor 4 (TLR4) signaling protects animals against synapse elimination induced by infusion. Accordingly, cohort 86 who recovered mild COVID-19, genotype GG TLR4-2604G>A (rs10759931) associated poor outcome. These results identify TLR4 as key target to investigate long-term after COVID-19 infection humans rodents.

Language: Английский

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Cognition and Memory after Covid-19 in a Large Community Sample

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 390(9), P. 806 - 818

Published: Feb. 28, 2024

BackgroundCognitive symptoms after coronavirus disease 2019 (Covid-19), the caused by severe acute respiratory syndrome 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist unclear.MethodsWe invited 800,000 adults in a study England to complete an online assessment of function. We estimated global score across eight tasks. hypothesized that participants with persistent (lasting ≥12 weeks) infection onset would have impairments executive functioning memory be observed such participants, especially those who reported recent poor or difficulty thinking concentrating ("brain fog").ResultsOf 141,583 started assessment, 112,964 completed it. In multiple regression analysis, had recovered from Covid-19 whom resolved less than 4 weeks at least 12 similar small cognition as compared no–Covid-19 group, not been infected SARS-CoV-2 unconfirmed (−0.23 SD [95% confidence interval {CI}, −0.33 −0.13] −0.24 CI, −0.36 −0.12], respectively); larger group were seen unresolved (−0.42 SD; 95% −0.53 −0.31). Larger during periods which original virus B.1.1.7 variant was predominant later variants (e.g., −0.17 for vs. B.1.1.529 variant; −0.20 −0.13) hospitalized intensive care unit admission, −0.35 −0.49 −0.20). Results analyses propensity-score–matching analyses. comparison memory, reasoning, function tasks associated largest (−0.33 SD); these correlated weakly symptoms, including brain fog. No adverse events reported.ConclusionsParticipants measured shorter-duration although short-duration still recovery. Longer-term persistence any clinical implications remain uncertain. (Funded National Institute Health Care Research others.)

Language: Английский

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Long-term gastrointestinal outcomes of COVID-19

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 7, 2023

Abstract A comprehensive evaluation of the risks and 1-year burdens gastrointestinal disorders in post-acute phase COVID-19 is needed but not yet available. Here we use US Department Veterans Affairs national health care databases to build a cohort 154,068 people with COVID-19, 5,638,795 contemporary controls, 5,859,621 historical controls estimate set pre-specified incident outcomes. We show that beyond first 30 days infection, exhibited increased spanning several disease categories including motility disorders, acid related (dyspepsia, gastroesophageal reflux disease, peptic ulcer disease), functional intestinal acute pancreatitis, hepatic biliary disease. The were evident who hospitalized during graded fashion across severity spectrum (non-hospitalized, hospitalized, admitted intensive care). consistent comparisons vs control group as referent category. Altogether, our results SARS-CoV-2 infection are at risk COVID-19. Post-covid should involve attention

Language: Английский

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Social participation and risk of developing dementia

Nature Aging, Journal Year: 2023, Volume and Issue: 3(5), P. 532 - 545

Published: May 18, 2023

The increasing number of people with dementia globally illustrates the urgent need to reduce dementia's scale and impact. Lifetime social participation may affect risk by cognitive reserve, through brain maintenance reducing stress improving cerebrovascular health. It therefore have important implications for individual behavior public health policy aimed at burden. Observational study evidence indicates that greater in midlife late life is associated 30–50% lower subsequent risk, although some this not be causal. Social interventions led improved cognition but, partly due short follow-up small numbers participants, no reduction dementia. We summarize linking dementia, discuss potential mechanisms which likely mitigate impact neuropathology brain, consider future clinical prevention interventions. This Review provides evidence-based update on association between interaction authors propose a framework promote as preventative strategy against

Language: Английский

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Risks and burdens of incident dyslipidaemia in long COVID: a cohort study

The Lancet Diabetes & Endocrinology, Journal Year: 2023, Volume and Issue: 11(2), P. 120 - 128

Published: Jan. 6, 2023

Language: Английский

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Postacute Sequelae of SARS-CoV-2 Infection in the Pre-Delta, Delta, and Omicron Eras

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 391(6), P. 515 - 525

Published: July 17, 2024

Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) can affect many organ systems. However, temporal changes during the disease 2019 (Covid-19) pandemic, including evolution SARS-CoV-2, may have affected risk and burden PASC. Whether PASC changed over course pandemic is unclear.

Language: Английский

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Molnupiravir and risk of post-acute sequelae of covid-19: cohort study

BMJ, Journal Year: 2023, Volume and Issue: unknown, P. e074572 - e074572

Published: April 25, 2023

Abstract Objective To examine whether treatment with the antiviral agent molnupiravir during first five days of SARS-CoV-2 infection is associated reduced risk post-acute adverse health outcomes. Design Cohort study. Setting US Department Veterans Affairs. Participants 229 286 participants who tested positive for between 5 January 2022 and 15 2023, had at least one factor progression to severe covid-19, survived 30 after testing were enrolled. 11 472 received a prescription within test result 217 814 no covid-19 or antibody (no group). Main outcome measures Risks sequelae (PASC, defined based on prespecified set 13 sequelae), death, hospital admission, each individual sequela group examined application inverse probability weighting balance groups. Post-acute outcomes ascertained from until end follow-up. relative scale (relative hazard ratio) absolute (absolute reduction 180 days) estimated. Results Compared treatment, use was PASC 0.86 (95% confidence interval 0.83 0.89); 2.97% 2.31% 3.60%)), death (hazard ratio 0.62 (0.52 0.74); 0.87% (0.62% 1.13%)), admission (0.86 (0.80 0.93); 1.32% (0.72% 1.92%)). Molnupiravir eight sequelae: dysrhythmia, pulmonary embolism, deep vein thrombosis, fatigue malaise, liver disease, acute kidney injury, muscle pain, neurocognitive impairment. also in people not vaccine, two vaccine doses, booster dose, primary reinfection. Conclusions In compared those Among high may be viable approach reduce PASC.

Language: Английский

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Three-year outcomes of post-acute sequelae of COVID-19

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(6), P. 1564 - 1573

Published: May 30, 2024

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes post-acute sequelae of disease 2019 (COVID-19) (PASC) in many organ systems. Risks these have been characterized up to years after infection, but longer-term follow-up is limited. Here we built a cohort 135,161 people with SARS-CoV-2 and 5,206,835 controls from the US Department Veterans Affairs who were followed for 3 estimate risks death PASC. Among non-hospitalized individuals, increased risk was no longer present first year incident PASC declined over still contributed 9.6 (95% confidence interval (CI): 0.4–18.7) disability-adjusted life (DALYs) per 1,000 persons third year. hospitalized remained significantly elevated (incidence rate ratio: 1.29 CI: 1.19–1.40)). Risk years, substantial residual year, leading 90.0 55.2–124.8) DALYs persons. Altogether, our findings show reduction time, burden mortality health loss remains among individuals.

Language: Английский

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Incident autoimmune diseases in association with SARS-CoV-2 infection: a matched cohort study

Clinical Rheumatology, Journal Year: 2023, Volume and Issue: 42(10), P. 2905 - 2914

Published: June 19, 2023

To investigate whether the risk of developing an incident autoimmune disease is increased in patients with prior COVID-19 compared to those without COVID-19, a large cohort study was conducted.A selected from German routine health care data. Based on documented diagnoses, we identified individuals polymerase chain reaction (PCR)-confirmed through December 31, 2020. Patients were matched 1:3 control COVID-19. Both groups followed up until June 30, 2021. We used four quarters preceding index date end follow-up analyze onset diseases during post-acute period. Incidence rates (IR) per 1000 person-years calculated for each outcome and patient group. Poisson models deployed estimate incidence rate ratios (IRRs) conditional diagnosis COVID-19.In total, 641,704 included. Comparing (IR=15.05, 95% CI: 14.69-15.42) (IR=10.55, 10.25-10.86), found 42.63% higher likelihood acquiring autoimmunity who had suffered This similar common diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR observed vasculitis more severe course at greater disease.SARS-CoV-2 infection associated new-onset after acute phase infection. Key Points • In 3 15 months infection, 43% (95% 37-48%) first-onset disease, meaning absolute increase 4.50 over showed strongest association vascular diseases.

Language: Английский

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Long-term outcomes following hospital admission for COVID-19 versus seasonal influenza: a cohort study

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 24(3), P. 239 - 255

Published: Dec. 15, 2023

Language: Английский

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