Persistent viral RNA shedding of SARS-CoV-2 is associated with delirium incidence and six-month mortality in hospitalized COVID-19 patients

Batra, Ayush; Clark, Jeffrey R.; Kang, Anthony K; Ali, Sareen T.; Patel, Tulsi R; Shlobin, Nathan A.; Hoffman, Steven C.; Lim, Patrick H.; Orban, Zachary S.; Visvabharathy, Lavanya; Graham, Edith; Sullivan, David P.; Müller, William A.; Chou, Sherry; Ungvári, Zoltán; Koralnik, Igor J.; Liotta, Eric M.

doi:10.1007/s11357-022-00561-z

Cited by 22 publications

(25 citation statements)

References 65 publications

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“…COVID-19 patients may be particularly prone to agitated encephalopathy. Studies have found that 30% to 51.8% of critically ill COVID-19 patients had at least one episode of hyperactive delirium, which is substantially higher than the pre-pandemic incidence of 12.7% in critically ill patients [50,54,55]. The reason behind this high rate of agitation in COVID-19 patients is unclear; this could be related to the greater severity of COVID-19 lung injury and higher levels of ventilatory support, the frequent use of prone positioning, a relatively higher incidence of young individuals needing critical care during early COVID-19 surges, crisis staffing with providers less experienced in effective sedation management, decreased family visitation, or perhaps biological mechanisms unique to SARS-CoV-2 infection [50,[55][56][57][58].…”

Section: Epidemiology and Presentationmentioning

confidence: 94%

“…The mechanism of persistent cognitive dysfunction in Neuro-COVID is likely a complex interplay of fatigue, sleep disruption, aberrant immune response, and potential persistent infection [156,157]. Lack of oxygen does not seem to be responsible as impaired cognition can occur in patients with mild COVID-19 who were never hypoxic.…”

Section: Pathogenic Mechanismsmentioning

confidence: 99%

“…The rapidly waning T and B cell responses after vaccination, breakthrough infections, and need for booster shots has become painfully apparent, underscoring our persistent knowledge gaps and urgent need for further research on the immune response to SARS-CoV-2 [228]. Pilot studies on the characterization of the T cell response in Neuro-PASC patients and its impact on neuropsychiatric symptoms show an emerging pattern consistent with continuous antigenic stimulation or persistent infection with SARS-CoV-2 [157,229]. Such persistent infection may lead to auto-immunity, driven either by auto-antibodies or auto-reactive T cells.…”

Section: Pathogenic Mechanisms Of Neuro-pasc and Interventionsmentioning

confidence: 99%

“…Such persistent infection may lead to auto-immunity, driven either by auto-antibodies or auto-reactive T cells. Future research should focus on identification of potential hidden reservoirs of SARS-CoV-2 including nasopharyngeal olfactory mucosae, endothelial cells of micro-vessels in the CNS and the gut in PNP and NNP patients [157]. Identification of such reservoirs could justify therapeutic interventions with monoclonal antibodies or antiviral medications.…”

Section: Pathogenic Mechanisms Of Neuro-pasc and Interventionsmentioning

confidence: 99%

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Therapeutic Approaches to the Neurologic Manifestations of COVID-19

2022

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As of May 2022, there have been more than 527 million infections with severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) and over 6.2 million deaths from Coronavirus Disease 2019 (COVID-19) worldwide. COVID-19 is a multisystem illness with important neurologic consequences that impact long-term morbidity and mortality. In the acutely ill, the neurologic manifestations of COVID-19 can include distressing but relatively benign symptoms such as headache, myalgias, and anosmia; however, entities such as encephalopathy, stroke, seizures, encephalitis, and Guillain-Barre Syndrome can cause neurologic injury and resulting disability that persists long after the acute pulmonary illness. Furthermore, as many as one-third of patients may experience persistent neurologic symptoms as part of a Post-Acute Sequelae of SARS-CoV-2 infection (Neuro-PASC) syndrome. This Neuro-PASC syndrome can affect patients who required hospitalization for COVID-19 or patients who did not require hospitalization and who may have had minor or no pulmonary symptoms. Given the large number of individuals affected and the ability of neurologic complications to impair quality of life and productivity, the neurologic manifestations of COVID-19 are likely to have major and long-lasting personal, public health, and economic consequences. While knowledge of disease mechanisms and therapies acquired prior to the pandemic can inform us on how to manage patients with the neurologic manifestations of COVID-19, there is a critical need for improved understanding of specific COVID-19 disease mechanisms and development of therapies that target the neurologic morbidities of COVID-19. This current perspective reviews evidence for proposed disease mechanisms as they inform the neurologic management of COVID-19 in adult patients while also identifying areas in need of further research.

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Section: Epidemiology and Presentationmentioning

confidence: 94%

Section: Pathogenic Mechanismsmentioning

confidence: 99%

Section: Pathogenic Mechanisms Of Neuro-pasc and Interventionsmentioning

confidence: 99%

Section: Pathogenic Mechanisms Of Neuro-pasc and Interventionsmentioning

confidence: 99%

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Therapeutic Approaches to the Neurologic Manifestations of COVID-19

2022

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“…The study by Batra et al (60) demonstrated that persistent viral shedding in patients was associated with in-hospital delirium episodes and a higher mortality rate. Notably, in the study by Dias et al (61), delirium was not found to have a higher prevalence in the COVID-19 group compared with the non-COVID-19, while it appeared to manifest in a more severe form in the COVID-19 group.…”

Section: Introductionmentioning

confidence: 99%

Delirium during COVID‑19: A report of eight cases and a review of the literature

et al. 2022

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Delirium is an acute confusional state, often associated with long-term hospitalization, oxygen supplementation, the male sex and an older age. Since the start of the coronavirus disease 2019 (COVID-19) pandemic, there was an abrupt increase in intensive care unit (ICU) admissions and hospitalization in general, as well as in the need for oxygen therapy and enforced isolation due to the contagion risk. This caused a sudden increase in the episodes of delirium. The diagnosis of delirium, however, remains a difficult task, as it can often be misdiagnosed or confused with underlying dementia, particularly among the elderly. The present study describes present eight cases of patients admitted to hospital due to severe acute respiratory syndrome coronavirus 2 infection, who manifested delirium. Notably, only one of the patients had psychiatric comorbidities prior to hospitalization. The most prevalent sex was the male (7:1) one, the mean age of the patients was 81.7±4 years, and the mean duration of hospitalization was 23.6±6 days. In total, 3 patients had a virological recovery and were discharged, 3 had a clinical recovery and were transferred to a lower intensity COVID-19 facility and 2 patients did not survive. In the eight cases described herein, the mortality rate was 25%. Delirium was found to be commonly associated with a higher mortality rate and a longer hospitalization period. Therefore, it is imperative to develop protocols and tools with which to rapidly assess delirium and treat it accordingly. In addition, it is fundamental to improve the quality of life of hospitalized patients, supporting behavioral therapy and the environmental factors that can affect patients, to prevent delirium as well.

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Factors affecting prolonged SARS‐CoV‐2 infection and development and validation of predictive nomograms

Guo

Zhang

et al. 2023

Journal of Medical Virology

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Prolonged severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has received much attention since it is associated with mortality and is hypothesized as the cause of long COVID‐19 and the emergence of a new variant of concerns. However, a prediction model for the accurate prediction of prolonged infection is still lacking. A total of 2938 confirmed patients with COVID‐19 diagnosed by positive reverse transcriptase‐polymerase chain reaction tests were recruited retrospectively. This study cohort was divided into a training set (70% of study patients; n = 2058) and a validation set (30% of study patients; n = 880). Univariate and multivariate logistic regression analyses were utilized to identify predictors for prolonged infection. Model 1 included only preadmission variables, whereas Model 2 also included after‐admission variables. Nomograms based on variables of Model 1 and Model 2 were built for clinical use. The efficiency of nomograms was evaluated by using the area under the curve, calibration curves, and concordance indexes (C‐index). Independent predictors of prolonged infection included in Model 1 were: age ≥75 years, chronic kidney disease, chronic lung disease, partially or fully vaccinated, and booster. Additional independent predictors in Model 2 were: treated with nirmatrelvir/ritonavir more than 5 days after diagnosis and glucocorticoid. The inclusion of after‐admission variables in the model slightly improved the discriminatory power (C‐index in the training cohort: 0.721 for Model 1 and 0.737 for Model 2; in the validation cohort: 0.699 for Model 1 and 0.719 for Model 2). In our study, we developed and validated predictive models based on readily available variables of preadmission and after‐admission for predicting prolonged SARS‐CoV‐2 infection of patients with COVID‐19.

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Persistent viral RNA shedding of SARS-CoV-2 is associated with delirium incidence and six-month mortality in hospitalized COVID-19 patients

Cited by 22 publications

References 65 publications

Therapeutic Approaches to the Neurologic Manifestations of COVID-19

Therapeutic Approaches to the Neurologic Manifestations of COVID-19

Delirium during COVID‑19: A report of eight cases and a review of the literature

Factors affecting prolonged SARS‐CoV‐2 infection and development and validation of predictive nomograms

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