Long COVID: a review and proposed visualization of the complexity of long COVID

Perumal, Rubeshan; Shunmugam, Letitia; Naidoo, Kogieleum; Karim, Salim S. Abdool; Wilkins, Dave; Izumi, Tatsuro; Bréchot, Christian; Parthasarathy, Sairam; Vahlne, Anders; Nikolich, Janko Ž.

doi:10.3389/fimmu.2023.1117464

Cited by 39 publications

(26 citation statements)

References 193 publications

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“…In New York State, approximately 18% of long COVID patients were unable to resume work for more than a year [17,20]. By 2023, an estimated 4 million Americans with long COVID had not returned to work, incurring costs between 2.6 and 3.7 trillion dollars and exacerbating family income losses and health-related quality of life impacts [21].…”

Section: Discussionmentioning

confidence: 99%

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The Impact of Long COVID on Cognitive Performance and Sleep Quality: An Analysis of the Rancagua Chilean Study (RACHIS)

Aceituno,

Barrancas,

Quiroz-Bravo

et al. 2024

Cureus

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BackgroundInfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to prolonged symptoms post-recovery, commonly known as long-term coronavirus disease 2019 or "long COVID." Neuropsychiatric consequences of long COVID include cognitive dysfunction and sleep disturbances, which significantly impair daily living. This study aimed to explore the impact of long COVID on cognitive performance and sleep quality in patients receiving outpatient care. Material and methodsThis study involved a random sample of 138 of 363 patients, corresponding to 38% of the cohort, who tested positive for SARS-CoV-2 via polymerase chain reaction (PCR) between May 2020 and April 2021. These unvaccinated, non-hospitalized individuals, predominantly exhibiting mild disease symptoms, were prospectively assessed 11 months post-positive PCR test. After informed consent, demographic data, memory, and concentration impairment levels were collected through interviews. Participants reporting cognitive symptoms underwent the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MOCA), and the Pittsburgh Sleep Quality Index. Statistical analyses were conducted, including Student's t-test, Chi-square, Fisher's test, Kruskal-Wallis test, and Pearson correlation coefficient, with a significance threshold set at p<0.05. ResultsOf the 138 participants, 76 (55.1%) were female and 62 (44.9%) were male. The mean age was 45.9 years (± 13.0), with an average educational attainment of 10.4 years (± 3.7). Roughly 50% of the patients reported significant memory and concentration issues (p<0.001). Thirty-three participants underwent detailed cognitive assessments, revealing a 2:1 female-to-male ratio and a significantly higher prevalence of depression in female participants. Cognitive deficits were diagnosed in five (15.2%) participants via the MMSE and in 26 (78.8%) via the MOCA test, with notable deficits in visuospatial/executive functions, language repeat, and deferred recall (p<0.001). A lower educational level was correlated with higher cognitive deficits (p=0.03). ConclusionThe study findings reveal that cognitive impairments, as a consequence of COVID-19, can persist up to 11 months post-infection. The MOCA test proved more effective in diagnosing these deficits and requires adjustments based on educational background. Sleep parameters remained largely unaffected in this cohort, likely attributed to the mild nature of the initial symptoms and the outpatient management of the disease.

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Section: Discussionmentioning

confidence: 99%

“…These disparities can influence the disease trajectory. As a pathological condition, long COVID necessitates recognition and collective efforts in research and treatment by the scientific community and public health entities [21].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Long COVID on Cognitive Performance and Sleep Quality: An Analysis of the Rancagua Chilean Study (RACHIS)

Aceituno,

Barrancas,

Quiroz-Bravo

et al. 2024

Cureus

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“…Long COVID [also referred to as 'post-COVID condition' , 'post-COVID syndrome' and 'post-acute sequelae of COVID-19' (PASC)] is a prolonged, often severe condition with diverse symptoms occurring after SARS-CoV-2 infection (reviewed in [7,[223][224][225][226][227]). Symptoms include fatigue, anosmia and dysgeusia, persistent respiratory problems, such as shortness of breath, periodic cognitive difficulties, cardiovascular difficulties, such as chest pain and arrhythmia, gastrointestinal symptoms, rheumatic and dermatological problems, and neurological and psychiatric symptoms (reviewed, for example, in [224]). Because of the multiple, diverse symptoms associated with long COVID, explanations of its causes have been many and varied.…”

Section: Long Covid and Dna Damagementioning

confidence: 99%

SARS-CoV-2 and the DNA damage response

Grand

2023

Journal of General Virology

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The recent coronavirus disease 2019 (COVID-19) pandemic was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is characterized by respiratory distress, multiorgan dysfunction and, in some cases, death. The virus is also responsible for post-COVID-19 condition (commonly referred to as ‘long COVID’). SARS-CoV-2 is a single-stranded, positive-sense RNA virus with a genome of approximately 30 kb, which encodes 26 proteins. It has been reported to affect multiple pathways in infected cells, resulting, in many cases, in the induction of a ‘cytokine storm’ and cellular senescence. Perhaps because it is an RNA virus, replicating largely in the cytoplasm, the effect of SARS-Cov-2 on genome stability and DNA damage responses (DDRs) has received relatively little attention. However, it is now becoming clear that the virus causes damage to cellular DNA, as shown by the presence of micronuclei, DNA repair foci and increased comet tails in infected cells. This review considers recent evidence indicating how SARS-CoV-2 causes genome instability, deregulates the cell cycle and targets specific components of DDR pathways. The significance of the virus’s ability to cause cellular senescence is also considered, as are the implications of genome instability for patients suffering from long COVID.

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“…1 Long-COVID is characterized by a range of persistent symptoms, including respiratory issues, cardiovascular symptoms, and cognitive impairments such as brain fog, fatigue, insomnia, and memory problems. 2 However, our understanding of long-COVID remains limited due to the scarcity of suitable animal models for research.…”

Section: Introductionmentioning

confidence: 99%

Generation and characterization of a humanized ACE2 mouse model to study long‐term impacts of SARS‐CoV‐2 infection

Choi,

Gadhave,

Villano

et al. 2024

Journal of Medical Virology

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Although the COVID‐19 pandemic has officially ended, the persistent challenge of long‐COVID or post‐acute COVID sequelae (PASC) continues to impact societies globally, highlighting the urgent need for ongoing research into its mechanisms and therapeutic approaches. Our team has recently developed a novel humanized ACE2 mouse model (hACE2ki) designed explicitly for long‐COVID/PASC research. This model exhibits human ACE2 expression in tissue and cell‐specific patterns akin to mouse Ace2. When we exposed young adult hACE2ki mice (6 weeks old) to various SARS‐CoV‐2 lineages, including WA, Delta, and Omicron, at a dose of 5 × 105 PFU/mouse via nasal instillation, the mice demonstrated distinctive phenotypes characterized by differences in viral load in the lung, trachea, and nasal turbinate, weight loss, and changes in pro‐inflammatory cytokines and immune cell profiles in bronchoalveolar lavage fluid. Notably, no mortality was observed in this age group. Further, to assess the model's relevance for long‐COVID studies, we investigated tau protein pathologies, which are linked to Alzheimer's disease, in the brains of these mice post SARS‐CoV‐2 infection. Our findings revealed the accumulation and longitudinal propagation of tau, confirming the potential of our hACE2ki mouse model for preclinical studies of long‐COVID.

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Long COVID: a review and proposed visualization of the complexity of long COVID

Cited by 39 publications

References 193 publications

The Impact of Long COVID on Cognitive Performance and Sleep Quality: An Analysis of the Rancagua Chilean Study (RACHIS)

The Impact of Long COVID on Cognitive Performance and Sleep Quality: An Analysis of the Rancagua Chilean Study (RACHIS)

SARS-CoV-2 and the DNA damage response

Generation and characterization of a humanized ACE2 mouse model to study long‐term impacts of SARS‐CoV‐2 infection

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