Post-COVID-19 neuropsychiatric manifestations: a suggested therapeutic approach to 'long COVID' with azithromycin.
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ABSTRACT:
SUBMITTER: Schwartz RA
PROVIDER: S-EPMC10894889 | biostudies-literature | 2023 Dec
REPOSITORIES: biostudies-literature
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Post-COVID-19 neuropsychiatric manifestations: a suggested therapeutic approach to 'long COVID' with azithromycin.
Schwartz Robert A RA Suskind Robert M RM
Epidemiology and infection 20231215
The devastating effects of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may not end when the acute illness has terminated. A subset of COVID-19 patients may have symptoms that persist for months. This condition has been described as 'long COVID'. From a historical perspective, it has been recognized that serious long-term neurological sequelae have been associated with RNA viruses such as influenza viruses and coronaviruses. A potentia ...[more]
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Project description:ImportanceNeurological and neuropsychiatric symptoms that persist or develop three months after the onset of COVID-19 pose a significant threat to the global healthcare system. These symptoms are yet to be synthesized and quantified via meta-analysis.ObjectiveTo determine the prevalence of neurological and neuropsychiatric symptoms reported 12 weeks (3 months) or more after acute COVID-19 onset in adults.Data sourcesA systematic search of PubMed, EMBASE, Web of Science, Google Scholar and Scopus was conducted for studies published between January 1st, 2020 and August 1st, 2021. The systematic review was guided by Preferred Reporting Items for Systematic Review and Meta-Analyses.Study selectionStudies were included if the length of follow-up satisfied the National Institute for Healthcare Excellence (NICE) definition of post-COVID-19 syndrome (symptoms that develop or persist ≥3 months after the onset of COVID-19). Additional criteria included the reporting of neurological or neuropsychiatric symptoms in individuals with COVID-19.Data extraction and synthesisTwo authors independently extracted data on patient characteristics, hospital and/or ICU admission, acute-phase COVID-19 symptoms, length of follow-up, and neurological and neuropsychiatric symptoms.Main outcome(s) and measure(s)The primary outcome was the prevalence of neurological and neuropsychiatric symptoms reported ≥3 months post onset of COVID-19. We also compared post-COVID-19 syndrome in hospitalised vs. non-hospitalised patients, with vs. without ICU admission during the acute phase of infection, and with mid-term (3 to 6 months) and long-term (>6 months) follow-up.ResultsOf 1458 articles, 19 studies, encompassing a total of 11,324 patients, were analysed. Overall prevalence for neurological post-COVID-19 symptoms were: fatigue (37%, 95% CI: 24%-50%), brain fog (32%, 9%-55%), memory issues (27%, 18%-36%), attention disorder (22%, 10%-34%), myalgia (18%, 4%-32%), anosmia (12%, 7%-17%), dysgeusia (11%, 4%-17%) and headache (10%, 1%-21%). Neuropsychiatric conditions included sleep disturbances (31%, 18%-43%), anxiety (23%, 13%-33%) and depression (12%, 7%-21%). Neuropsychiatric symptoms substantially increased in prevalence between mid- and long-term follow-up. Compared to non-hospitalised patients, patients hospitalised for acute COVID-19 had reduced frequency of anosmia, anxiety, depression, dysgeusia, fatigue, headache, myalgia, and sleep disturbance at three (or more) months post-infection. Conversely, hospital admission was associated with higher frequency of memory issues (OR: 1.9, 95% CI: 1.4-2.3). Cohorts with >20% of patients admitted to the ICU during acute COVID-19 experienced higher prevalence of fatigue, anxiety, depression, and sleep disturbances than cohorts with <20% of ICU admission.Conclusions and relevanceFatigue, cognitive dysfunction (brain fog, memory issues, attention disorder) and sleep disturbances appear to be key features of post-COVID-19 syndrome. Psychiatric manifestations (sleep disturbances, anxiety, and depression) are common and increase significantly in prevalence over time. Randomised controlled trials are necessary to develop intervention strategy to reduce disease burden.
| S-EPMC8798975 | biostudies-literature
Project description:Corona Virus Disease 2019 (COVID-19) emerged in December 2019 from Wuhan, China. It typically presents with mild upper respiratory tract infection symptoms and may have life threatening complications, including acute respiratory distress syndrome, acute stroke, myocardial infarction, kidney failure, shock, and even death. Coronavirus infections are known to have neuroinvasive potential with consequent neuropsychiatric manifestations. We analyzed COVID-19 adult patients in the TriNetX database, which is a global health collaborative clinical research platform collecting real-time electronic medical records data from a network of health care organizations (HCOs) from January 20, 2020 to June 10th, 2020. 40,469 patients were diagnosed with COVID-19 among whom 9086 (22.5%) patients had neuropsychiatric manifestations. The most common neurologic manifestations included headache (3.7%) and sleep disorders (3.4%), Encephalopathy (2.3%), Stroke and transient ischemic attack (TIA) (1.0%) and 0.6% had seizures. Most common psychiatric manifestations included anxiety and other related disorders (4.6%), mood disorders (3.8%), while 0.2% patients had suicidal ideation. Early recognition and prompt management of neuropsychiatric manifestations in these patients have a potential to decrease overall morbidity and mortality.
| S-EPMC7297688 | biostudies-literature
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Project description:ObjectiveTo evaluate and characterize the cognitive changes in COVID-19 participants at 6-month follow-up, and to explore a possible association with clinical symptoms, emotional disturbance and disease severity.MethodsThis single-center longitudinal cohort study included participants aged 20 and 60 years old to exclude cognitive impairment age-associated with confirmed COVID-19 infection. The initial evaluation occurred 10 to 30 days after hospital or ambulatory discharge, with a subsequent follow-up at 6 months. Patients who had a history of cognitive impairment, neurological conditions, or serious psychiatric disorders were not included. Information on demographics and laboratory results was gathered from medical records. Cognitive outcomes were assessed with a neuropsychological battery including attention, verbal and visual memory, language and executive function tests.ResultsA total of 200 participants were included in the study, and 108 completed the follow-up visit. At the 6-month follow-up, comparing the means from baseline with those of the follow-up evaluation, significant overall improvement was observed in verbal and visual memory subtests (p = 0.001), processing speed (p = 0.001), executive function (p = 0.028; p = 0.016) and naming (p = 0.001), independently of disease severity and cognitive complaints. Anxiety and depression were significantly higher in groups with Subjective Cognitive Complaints (SCC) compared to those without (p < 0.01 for both).ConclusionsPersistent symptoms are common regardless of disease severity and are often linked to cognitive complaints. Six months after COVID-19, the most frequently reported symptoms included headache, dyspnea, fatigue, cognitive complaints, anxiety, and depression. No cognitive impairment was found to be associated with the severity of COVID-19. Overall, neuropsychological and psychopathological improvement was observed at 6 months regardless of disease severity and cognitive complaints.
| S-EPMC11357167 | biostudies-literature
Project description:The expressive number of deaths and confirmed cases of SARS-CoV-2 call for an urgent demand of effective and available drugs for COVID-19 treatment. CD147, a receptor on host cells, is a novel route for SARS-CoV-2 invasion. Thus, drugs that interfere in the spike protein/CD147 interaction or CD147 expression may inhibit viral invasion and dissemination among other cells, including in progenitor/stem cells. Studies suggest beneficial effects of azithromycin in reducing viral load of hospitalized patients, possibly interfering with ligand/CD147 receptor interactions; however, its possible effects on SARS-CoV-2 invasion has not yet been evaluated. In addition to the possible effect in invasion, azithromycin decreases the expression of some metalloproteinases (downstream to CD147), induces anti-viral responses in primary human bronchial epithelial infected with rhinovirus, decreasing viral replication and release. Moreover, resident lung progenitor/stem are extensively differentiated into myofibroblasts during pulmonary fibrosis, a complication observed in COVID-19 patients. This process, and the possible direct viral invasion of progenitor/stem cells via CD147 or ACE2, could result in the decline of these cellular stocks and failing lung repair. Clinical tests with allogeneic MSCs from healthy individuals are underway to enhance endogenous lung repair and suppress inflammation.
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Project description:Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache, neuroinflammatory or cerebrovascular disease. These conditions - here termed Neuro-COVID - are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared to patients with non-inflammatory and autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells. Neuro-COVID CSF leukocytes featured an enriched interferon signature; however, this was less pronounced than in viral encephalitis. Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in severe compared to mild Neuro-COVID patients. Collectively, our findings document the CSF immune compartment in Neuro-COVID patients and suggest compromised antiviral responses in this setting.
2020-12-11 | GSE163005 | GEO
Project description: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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Project description:The post COVID-19 syndrome (PCS) is an emerging phenomenon worldwide with enormous socioeconomic impact. While many patients describe neuropsychiatric deficits, the symptoms are yet to be assessed and defined systematically. In this prospective cohort study, we report on the results of a neuropsychiatric consultation implemented in May 2021. A cohort of 105 consecutive patients with merely mild acute course of disease was identified by its high symptom load 6 months post infection using a standardized neurocognitive and psychiatric-psychosomatic assessment. In this cohort, we found a strong correlation between higher scores in questionnaires for fatigue (MFI-20), somatization (PHQ15) and depression (PHQ9) and worse functional outcome as measured by the post COVID functional scale (PCFS). In contrast, neurocognitive scales correlated with age, but not with PCFS. Standard laboratory and cardiopulmonary biomarkers did not differ between the group of patients with predominant neuropsychiatric symptoms and a control group of neuropsychiatrically unaffected PCS patients. Our study delineates a phenotype of PCS dominated by symptoms of fatigue, somatisation and depression. The strong association of psychiatric and psychosomatic symptoms with the PCFS warrants a systematic evaluation of psychosocial side effects of the pandemic itself and psychiatric comorbidities on the long-term outcome of patients with SARS-CoV-2 infection.
| S-EPMC9552839 | biostudies-literature
Project description:Fatigue in its many forms of physical, mental, and psychosocial exhaustion is a common symptom of post-COVID-19 condition, also known as "Long COVID." Persistent fatigue in COVID-19 patients is frequently accompanied by cognitive dysfunction and neuropsychiatric symptoms; however, less is known about the relationships between these components of post-COVID-19 condition and fatigue itself. Consequently, the present study sought to (1) distinguish the types of fatigue experienced by participants, and (2) investigate whether cognitive deficits across various domains and neuropsychiatric conditions predicted these different types of fatigue. The study included 136 COVID-19 patients referred for neuropsychological evaluation due to cognitive complaints 8 months on average after SARS-CoV-2 infection. Measures included self-reported fatigue (physical, cognitive, and psychosocial), neuropsychiatric questionnaires (assessing symptoms of depression, anxiety, apathy, and executive functioning), a comprehensive neuropsychological assessment, and self-reported quality of life and everyday functioning. Results showed that reports of clinical significant fatigue were pervasive in our sample (82.3% of participants), with physical fatigue rated highest on average relative to the subscale maximum. Elevated levels of apathy, anxiety, and executive dysfunction in neuropsychiatric measures along with executive and attentional difficulties on cognitive tests were found to be consistently important predictors among different types of fatigue. This implicates both cognitive and neuropsychiatric symptoms as predictors of fatigue in post-COVID-19 condition, and stresses the importance of a holistic approach in assessing and considering potential treatment for COVID-19 patients experiencing fatigue.
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Project description: Not available
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