Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection

JAMA, Journal Year: 2023, Volume and Issue: 329(22), P. 1934 - 1934

Published: May 25, 2023

Importance SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms other health effects occurring after acute infection, termed postacute sequelae of (PASC), also known as long COVID . Characterizing PASC requires analysis prospectively and uniformly collected data from diverse uninfected infected individuals. Objective To develop a definition using self-reported describe frequencies across cohorts, vaccination status, number infections. Design, Setting, Participants Prospective observational cohort study adults without at 85 enrolling sites (hospitals, centers, community organizations) located in 33 states plus Washington, DC, Puerto Rico. who were enrolled the RECOVER adult before April 10, 2023, completed symptom survey 6 months more onset test date. Selection included population-based, volunteer, convenience sampling. Exposure infection. Main Outcomes Measures 44 participant-reported (with severity thresholds). Results A total 9764 participants (89% infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios 1.5 greater (infected vs participants) for 37 symptoms. Symptoms contributing to score postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes sexual desire capacity, loss change smell taste, thirst, chronic cough, chest pain, abnormal movements. Among 2231 first on December 1, 2021, within 30 days 224 (10% [95% CI, 8.8%-11%]) positive months. Conclusions Relevance was developed based prospective study. As step providing framework investigations, iterative refinement that further incorporates clinical features needed support actionable definitions PASC.

Language: Английский

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Therapeutic strategies for COVID-19: progress and lessons learned

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(6), P. 449 - 475

Published: April 19, 2023

Language: Английский

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Long-term neurologic outcomes of COVID-19

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(11), P. 2406 - 2415

Published: Sept. 22, 2022

Abstract The neurologic manifestations of acute COVID-19 are well characterized, but a comprehensive evaluation postacute sequelae at 1 year has not been undertaken. Here we use the national healthcare databases US Department Veterans Affairs to build cohort 154,068 individuals with COVID-19, 5,638,795 contemporary controls and 5,859,621 historical controls; inverse probability weighting balance cohorts, estimate risks burdens incident disorders 12 months following SARS-CoV-2 infection. Our results show that in phase there was increased risk an array including ischemic hemorrhagic stroke, cognition memory disorders, peripheral nervous system episodic (for example, migraine seizures), extrapyramidal movement mental health musculoskeletal sensory Guillain–Barré syndrome, encephalitis or encephalopathy. We estimated hazard ratio any sequela 1.42 (95% confidence intervals 1.38, 1.47) burden 70.69 63.54, 78.01) per 1,000 persons months. were elevated even people who did require hospitalization during COVID-19. Limitations include comprising mostly White males. Taken together, our provide evidence long-term had

Language: Английский

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The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19

Cell Reports Medicine, Journal Year: 2022, Volume and Issue: 3(6), P. 100663 - 100663

Published: June 1, 2022

Language: Английский

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The protein corona from nanomedicine to environmental science

Nature Reviews Materials, Journal Year: 2023, Volume and Issue: 8(7), P. 422 - 438

Published: March 24, 2023

Language: Английский

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Serotonin reduction in post-acute sequelae of viral infection

Cell, Journal Year: 2023, Volume and Issue: 186(22), P. 4851 - 4867.e20

Published: Oct. 1, 2023

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses formulated explain the etiology PASC, including viral persistence, chronic inflammation, hypercoagulability, autonomic dysfunction. Here, we propose mechanism that links all four in single pathway provides actionable insights for therapeutic interventions. We find PASC are associated with serotonin reduction. Viral infection type I interferon-driven inflammation reduce through three mechanisms: diminished intestinal absorption precursor tryptophan; platelet hyperactivation thrombocytopenia, which impacts storage; enhanced MAO-mediated turnover. Peripheral reduction, turn, impedes activity vagus nerve thereby impairs hippocampal responses memory. These findings provide possible explanation neurocognitive symptoms persistence Long COVID, may extend other post-viral syndromes.

Language: Английский

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Association of Treatment With Nirmatrelvir and the Risk of Post–COVID-19 Condition

JAMA Internal Medicine, Journal Year: 2023, Volume and Issue: 183(6), P. 554 - 554

Published: March 23, 2023

Importance Post–COVID-19 condition (PCC), also known as long COVID, affects many individuals. Prevention of PCC is an urgent public health priority. Objective To examine whether treatment with nirmatrelvir in the acute phase COVID-19 associated reduced risk PCC. Design, Setting, and Participants This cohort study used care databases US Department Veterans Affairs (VA) to identify patients who had a SARS-CoV-2 positive test result between January 3, 2022, December 31, were not hospitalized on day result, at least 1 factor for progression severe illness, survived first 30 days after diagnosis. Those treated oral within 5 (n = 35 717) those received no antiviral or antibody during infection (control group, n 246 076) identified. Exposures Treatment receipt based prescription records. Main Outcomes Measures Inverse probability weighted survival models estimate association (vs control) post–acute death, hospitalization, prespecified panel 13 sequelae (components PCC) reported relative scale (RR) hazard ratio (HR) absolute reduction percentage 180 (ARR). Results A total 281 793 (mean [SD] age, 61.99 [14.96]; 242 383 [86.01%] male) illness studied. Among them, 076 infection, 717 result. Compared control was (RR, 0.74; 95% CI, 0.72-0.77; ARR, 4.51%; 4.01-4.99), including 10 cardiovascular system (dysrhythmia ischemic heart disease), coagulation hematologic disorders (pulmonary embolism deep vein thrombosis), fatigue malaise, kidney disease, muscle pain, neurologic (neurocognitive impairment dysautonomia), shortness breath. Nirmatrelvir death (HR, 0.53; 0.46-0.61); 0.65%; 0.54-0.77), hospitalization 0.76; 0.73-0.80; 1.72%; 1.42-2.01). people unvaccinated, vaccinated, boosted, primary reinfection. Conclusions Relevance found that across spectrum this regardless vaccination status history prior infection; totality findings suggests may reduce adverse outcomes.

Language: Английский

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Immunological memory to SARS‐CoV ‐2 infection and COVID ‐19 vaccines

Immunological Reviews, Journal Year: 2022, Volume and Issue: 310(1), P. 27 - 46

Published: June 22, 2022

Immunological memory is the basis of protective immunity provided by vaccines and previous infections. can develop from multiple branches adaptive immune system, including CD4 T cells, CD8 B long-lasting antibody responses. Extraordinary progress has been made in understanding to SARS-CoV-2 infection COVID-19 vaccines, addressing development; quantitative qualitative features different cellular anatomical compartments; durability each component antibodies. Given sophistication measurements; size human studies; use longitudinal samples cross-sectional head-to-head comparisons between or for 1 year already supersedes that any other acute infectious disease. This knowledge may help inform public policies regarding as well scientific development future against diseases.

Language: Английский

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Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

Science, Journal Year: 2024, Volume and Issue: 383(6680)

Published: Jan. 18, 2024

Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis >6500 proteins in 268 longitudinal samples revealed dysregulated activation the complement system, an innate immune protection and homeostasis mechanism, individuals experiencing Covid. Thus, active was characterized by terminal system dysregulation ongoing alternative classical pathways, latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers hemolysis, tissue injury, platelet activation, monocyte-platelet aggregates were Machine learning thromboinflammatory as top biomarkers, warranting diagnostic therapeutic interrogation these systems.

Language: Английский

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Long COVID: mechanisms, risk factors and recovery

Experimental Physiology, Journal Year: 2022, Volume and Issue: 108(1), P. 12 - 27

Published: Nov. 22, 2022

Abstract Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS‐CoV‐2, is placing an increasing burden on individuals society. A Physiological Society virtual meeting in February 2022 brought clinicians researchers together to discuss current understanding long COVID mechanisms, risk factors recovery. This review highlights themes arising from that meeting. It considers nature exploring its links other post‐viral illnesses such as myalgic encephalomyelitis/chronic syndrome, how research can help us better support suffering all syndromes. started particularly swiftly populations routinely monitoring their physical performance – namely military elite athletes. The high degree diagnosis, intervention success these active suggest management strategies for wider population. We then consider key component populations, cardiopulmonary exercise training, has revealed COVID‐related changes physiology including alterations peripheral muscle function, ventilatory inefficiency autonomic dysfunction. impact dysautonomia are further discussed relation postural orthostatic tachycardia treatment aim combat sympathetic overactivation stimulating vagus nerve. interrogate mechanisms underlie symptoms, focus impaired oxygen delivery due micro‐clotting disruption cellular energy metabolism, before considering indirectly or directly tackle mechanisms. These include remote inspiratory training integrated care pathways combine rehabilitation drug interventions into healthcare access across different populations. Overall, this showcases physiological reveals occur therapeutic being developed tested condition.

Language: Английский

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