Rapid Lineage Assignment of Severe Acute Respiratory Syndrome Coronavirus 2 Cases through Automated Library Preparation, Sequencing, and Bioinformatic Analysis.

The coronavirus disease 2019 (COVID-19) pandemic has provided a stage to illustrate that there is considerable value in obtaining rapid, whole-genome-based information about pathogens. This article describes the utility of a commercially available, automated severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) library preparation, genome sequencing, and a bioinformatics analysis pipeline to provide rapid, near-real-time SARS-CoV-2 variant description. This study evaluated the turnaround time, accuracy, and other quality-related parameters obtained from commercially available automated sequencing instrumentation, from analysis of continuous clinical samples obtained from January 1, 2021, to October 6, 2021. This analysis included a base-by-base assessment of sequencing accuracy at every position in the SARS-CoV-2 chromosome using two commercially available methods. Mean turnaround time, from the receipt of a specimen for SARS-CoV-2 testing to the availability of the results, with lineage assignment, was <3 days. Accuracy of sequencing by one method was 100%, although certain sites on the genome were found repeatedly to have been sequenced with varying degrees of read error rate.

Neuropsychiatric sequelae of long COVID-19: Pilot results from the COVID-19 neurological and molecular prospective cohort study in Georgia, USA.

Background: As the coronavirus disease 2019 (COVID-19) pandemic continues, there has been a growing interest in the chronic sequelae of COVID-19. Neuropsychiatric symptoms are observed in the acute phase of infection, but there is a need for accurate characterization of how these symptoms evolve over time. Additionally, African American populations have been disproportionately affected by the COVID-19 pandemic. The COVID-19 Neurological and Molecular Prospective Cohort Study in Georgia (CONGA) was established to investigate the severity and chronicity of these neurologic findings over the five-year period following infection. Methods: The CONGA study aims to recruit COVID-19 positive adult patients in Georgia, United States from both the inpatient and outpatient setting, with 50% being African American. This paper reports our preliminary results from the baseline visits of the first 200 patients recruited who were on average 125 days since having a positive COVID-19 test. The demographics, self-reported symptoms, comorbidities, and quantitative measures of depression, anxiety, smell, taste, and cognition were analyzed. Cognitive measures were compared to demographically matched controls. Blood and mononuclear cells were drawn and stored for future analysis. Results: Fatigue was the most reported symptom in the study cohort (68.5%). Thirty percent of participants demonstrated hyposmia and 30% of participants demonstrated hypogeusia. Self-reported neurologic dysfunction did not correlate with dysfunction on quantitative neurologic testing. Additionally, self-reported symptoms and comorbidities were associated with depression and anxiety. The study cohort performed worse on cognitive measures compared to demographically matched controls, and African American patients scored lower compared to non-Hispanic White patients on all quantitative cognitive testing. Conclusion: Our results support the growing evidence that there are chronic neuropsychiatric symptoms following COVID-19 infection. Our results suggest that self-reported neurologic symptoms do not appear to correlate with associated quantitative dysfunction, emphasizing the importance of quantitative measurements in the complete assessment of deficits. Self-reported symptoms are associated with depression and anxiety. COVID-19 infection appears to be associated with worse performance on cognitive measures, though the disparity in score between African American patients and non-Hispanic White patients is likely largely due to psychosocial, physical health, and socioeconomic factors.

A potential role for cannabichromene in modulating TRP channels during acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome whose potential to become one of the most grievous challenges of the healthcare system evidenced by the COVID-19 pandemic. Considering the lack of target-specific treatment for ARDS, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve quality of life and outcomes for ARDS patients. ARDS is a systemic inflammatory disease starting with the pulmonary system and involves all other organs in a morbid bidirectional fashion. Mounting evidence including our findings supporting the notion that cannabinoids have potential to be targeted as regulatory therapeutic modalities in the treatment of inflammatory diseases. Therefore, it is plausible to test their capabilities as alternative therapies in the treatment of ARDS. In this study, we investigated the potential protective effects of cannabichromene (CBC) in an experimental model of ARDS. METHODS: We used, for the first time, an inhalant CBC treatment as a potential therapeutic target in a murine model of ARDS-like symptoms. ARDS was induced by intranasal administration of Poly(I:C), a synthetic mismatched double-stranded RNA, into the C57BL/6 mice (6-10 male mice/group, including sham, placebo, and CBC treated), three once-daily doses followed by a daily dose of inhalant CBC or placebo for the period of 8 days starting the first dose 2 h after the second Poly(I:C) treatment. We employed histologic, immunohistochemistry, and flow cytometry methods to assess the findings. Statistical analysis was performed by using one way analysis of variance (ANOVA) followed by Newman-Keuls post hoc test to determine the differences among the means of all experimental groups and to establish significance (p < 0.05) among all groups. RESULTS: Our data showed that CBC was able to reverse the hypoxia (increasing blood O2 saturation by 8%), ameliorate the symptoms of ARDS (reducing the pro-inflammatory cytokines by 50% in lung and blood), and protect the lung tissues from further destruction. Further analysis showed that CBC may wield its protective effects through transient receptor potential (TRP) cation channels, TRPA1 and TRPV1, increasing their expression by 5-folds in lung tissues compared to sham and untreated mice, re-establishing the homeostasis and immune balance. CONCLUSION: Our findings suggest that inhalant CBC may be an effective alternative therapeutic target in the treatment of ARDS. In addition, Increased expression of TRPs cation channels after CBC treatment proposes a novel role for TRPs (TRPA1 and TRPV2) as new potential mechanism to interpret the beneficial effects of CBC as well as other cannabinoids in the treatment of ARDS as well as other inflammatory diseases. Importantly, delivering CBC through an inhaler device is a translational model supporting the feasibility of trial with human subjects, authorizing further research.

A County-Level Analysis of Socioeconomic and Clinical Predictors of COVID-19 Incidence and Case-Fatality Rates in Georgia, March-September 2020.

OBJECTIVES: The global COVID-19 pandemic has affected various populations differently. We investigated the relationship between socioeconomic determinants of health obtained from the Robert Wood Johnson Foundation County Health Rankings and COVID-19 incidence and mortality at the county level in Georgia. METHODS: We analyzed data on COVID-19 incidence and case-fatality rates (CFRs) from the Georgia Department of Public Health from March 1 through August 31, 2020. We used repeated measures generalized linear mixed models to determine differences over time in Georgia counties among quartile health rankings of health outcomes, health behaviors, clinical care, social and economic factors, and physical environment. RESULTS: COVID-19 incidence per 100 000 population increased across all quartile county groups for all health rankings (range, 23.1-51.6 in May to 688.4-1062.0 in August). COVID-19 CFRs per 100 000 population peaked in April and May (range, 3312-6835) for all health rankings, declined in June and July (range, 827-5202), and increased again in August (range, 1877-3310). Peak CFRs occurred later in counties with low health rankings for health behavior and clinical care and in counties with high health rankings for social and economic factors and physical environment. All interactions between the health ranking quartile variables and month were significant (P < .001). County-level Gini indices were associated with significantly higher rates of COVID-19 incidence (P < .001) but not CFRs. CONCLUSIONS: From March through August 2020, COVID-19 incidence rose in Georgia's counties independent of health rankings categorization. Differences in time to peak CFRs differed at the county level based upon key health rankings. Public health interventions should incorporate unique strategies to improve COVID-19-related patient outcomes in these environments.

Altered mental status is an independent predictor of mortality in hospitalized COVID-19 patients.

BACKGROUND/AIMS: Limited data exists on the outcomes of COVID-19 patients presenting with altered mental status (AMS). Hence, we studied the characteristics and outcomes of hospitalized COVID-19 patients who presented with AMS at our hospital in rural southwest Georgia. METHODS: Data from electronic medical records of all hospitalized COVID-19 patients from March 2, 2020, to June 17, 2020, were analyzed. Patients were divided in 2 groups, those presenting with and without AMS. Primary outcome of interest was in-hospital mortality. Secondary outcomes were needed for mechanical ventilation, need for intensive care unit (ICU) care, need for dialysis, and length of stay. All analyses were performed using SAS 9.4 and R 3.6.0. RESULTS: Out of 710 patients, 73 (10.3%) presented with AMS. Majority of the population was African American (83.4%). Patients with AMS were older and more likely to have hypertension, chronic kidney disease (CKD), cerebrovascular disease, and dementia. Patients with AMS were less likely to present with typical COVID-19 symptoms, including dyspnea, cough, fever, and gastrointestinal symptoms. Predictors of AMS included age ≥ 70 years, CKD, cerebrovascular disease, and dementia. After multivariable adjustment, patients with AMS had higher rates of in-hospital mortality (30.1% vs 14.8%, odds ratio (OR) 2.139, p = 0.019), ICU admission (43.8% vs 40.2%, OR 2.59, p < 0.001), and need for mechanical ventilation (27.4% vs 18.5%, OR 2.06, p = 0.023). Patients presenting with AMS had increased length of stay. CONCLUSIONS: Patients with COVID-19 presenting with AMS are less likely to have typical COVID-19 symptoms, and AMS is an independent predictor of in-hospital mortality, need for ICU admission, and need for mechanical ventilation.

Cannabidiol (CBD) modulation of apelin in acute respiratory distress syndrome.

Considering lack of target-specific antiviral treatment and vaccination for COVID-19, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve COVID-19-infected patient outcomes. In a follow-up study to our recent findings indicating the potential of Cannabidiol (CBD) in the treatment of acute respiratory distress syndrome (ARDS), here we show for the first time that CBD may ameliorate the symptoms of ARDS through up-regulation of apelin, a peptide with significant role in the central and peripheral regulation of immunity, CNS, metabolic and cardiovascular system. By administering intranasal Poly (I:C), a synthetic viral dsRNA, while we were able to mimic the symptoms of ARDS in a murine model, interestingly, there was a significant decrease in the expression of apelin in both blood and lung tissues. CBD treatment was able to reverse the symptoms of ARDS towards a normal level. Importantly, CBD treatment increased the apelin expression significantly, suggesting a potential crosstalk between apelinergic system and CBD may be the therapeutic target in the treatment of inflammatory diseases such as COVID-19 and many other pathologic conditions.

Neurological consequences of COVID-19: what have we learned and where do we go from here?

The coronavirus disease-19 (COVID-19) pandemic is an unprecedented worldwide health crisis. COVID-19 is caused by SARS-CoV-2, a highly infectious pathogen that is genetically similar to SARS-CoV. Similar to other recent coronavirus outbreaks, including SARS and MERS, SARS-CoV-2 infected patients typically present with fever, dry cough, fatigue, and lower respiratory system dysfunction, including high rates of pneumonia and acute respiratory distress syndrome (ARDS); however, a rapidly accumulating set of clinical studies revealed atypical symptoms of COVID-19 that involve neurological signs, including headaches, anosmia, nausea, dysgeusia, damage to respiratory centers, and cerebral infarction. These unexpected findings may provide important clues regarding the pathological sequela of SARS-CoV-2 infection. Moreover, no efficacious therapies or vaccines are currently available, complicating the clinical management of COVID-19 patients and emphasizing the public health need for controlled, hypothesis-driven experimental studies to provide a framework for therapeutic development. In this mini-review, we summarize the current body of literature regarding the central nervous system (CNS) effects of SARS-CoV-2 and discuss several potential targets for therapeutic development to reduce neurological consequences in COVID-19 patients.

Cannabidiol Modulates Cytokine Storm in Acute Respiratory Distress Syndrome Induced by Simulated Viral Infection Using Synthetic RNA.

Introduction: In the absence of effective antivirals and vaccination, the pandemic of COVID-19 remains the most significant challenge to our health care system in decades. There is an urgent need for definitive therapeutic intervention. Clinical reports indicate that the cytokine storm associated with acute respiratory distress syndrome (ARDS) is the leading cause of mortality in severe cases of some respiratory viral infections, including COVID-19. In recent years, cannabinoids have been investigated extensively due to their potential effects on the human body. Among all cannabinoids, cannabidiol (CBD) has demonstrated potent anti-inflammatory effects in a variety of pathological conditions. Therefore, it is logical to explore whether CBD can reduce the cytokine storm and treat ARDS. Materials and Methods: In this study, we show that intranasal application of Poly(I:C), a synthetic analogue of viral double-stranded RNA, simulated symptoms of severe viral infections inducing signs of ARDS and cytokine storm. Discussion: The administration of CBD downregulated the level of proinflammatory cytokines and ameliorated the clinical symptoms of Poly I:C-induced ARDS. Conclusion: Our results suggest a potential protective role for CBD during ARDS that may extend CBD as part of the treatment of COVID-19 by reducing the cytokine storm, protecting pulmonary tissues, and re-establishing inflammatory homeostasis.

COVID-19-Related Stroke.

The COVID-19 pandemic is associated with neurological symptoms and complications including stroke. There is hypercoagulability associated with COVID-19 that is likely a "sepsis-induced coagulopathy" and may predispose to stroke. The SARS-CoV-2 virus binds to angiotensin-converting enzyme 2 (ACE2) present on brain endothelial and smooth muscle cells. ACE2 is a key part of the renin angiotensin system (RAS) and a counterbalance to angiotensin-converting enzyme 1 (ACE1) and angiotensin II. Angiotensin II is proinflammatory, is vasoconstrictive, and promotes organ damage. Depletion of ACE2 by SARS-CoV-2 may tip the balance in favor of the "harmful" ACE1/angiotensin II axis and promote tissue injury including stroke. There is a rationale to continue to treat with tissue plasminogen activator for COVID-19-related stroke and low molecular weight heparinoids may reduce thrombosis and mortality in sepsis-induced coagulopathy.