Characterizing Macrophages Diversity in COVID-19 Patients Using Deep Learning.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for coronavirus disease 2019 (COVID-19), has affected the lives of billions and killed millions of infected people. This virus has been demonstrated to have different outcomes among individuals, with some of them presenting a mild infection, while others present severe symptoms or even death. The identification of the molecular states related to the severity of a COVID-19 infection has become of the utmost importance to understanding the differences in critical immune response. In this study, we computationally processed a set of publicly available single-cell RNA-Seq (scRNA-Seq) data of 12 Bronchoalveolar Lavage Fluid (BALF) samples diagnosed as having a mild, severe, or no infection, and generated a high-quality dataset that consists of 63,734 cells, each with 23,916 genes. We extended the cell-type and sub-type composition identification and our analysis showed significant differences in cell-type composition in mild and severe groups compared to the normal. Importantly, inflammatory responses were dramatically elevated in the severe group, which was evidenced by the significant increase in macrophages, from 10.56% in the normal group to 20.97% in the mild group and 34.15% in the severe group. As an indicator of immune defense, populations of T cells accounted for 24.76% in the mild group and decreased to 7.35% in the severe group. To verify these findings, we developed several artificial neural networks (ANNs) and graph convolutional neural network (GCNN) models. We showed that the GCNN models reach a prediction accuracy of the infection of 91.16% using data from subtypes of macrophages. Overall, our study indicates significant differences in the gene expression profiles of inflammatory response and immune cells of severely infected patients.

Cannabinoid hyperemesis syndrome in North America: evaluation of health burden and treatment prevalence.

BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is a poorly understood vomiting disorder associated with chronic cannabis use. AIMS: To characterise patients experiencing CHS in North America and to obtain a population-based estimate of CHS treatment prevalence in Canada before and during the Covid-19 pandemic METHODS: Internet survey of 157 CHS sufferers in Canada and the United States. Administrative health databases for the province of Alberta (population 5 million) were accessed to measure emergency department (ED) visits for vomiting, with a concurrent diagnostic code for cannabis use. Three time periods of 1 year were assessed: prior to recreational cannabis legalisation (2017-2018), after recreational legalisation (2018-2019) and during the first year of the Covid-19 pandemic (2020-2021). RESULTS: Problematic cannabis use (defined as a CUDIT-R score ≥8) was universal among the survey cohort, and 59% and 68% screening for moderate or worse anxiety or depression, respectively. The overall treatment prevalence of CHS across all ages increased from 15 ED visits per 100,000 population (95% CI, 14-17) prior to legalisation, to 21 (95% CI, 20-23) after legalisation, to 32 (95% CI, 31-35) during the beginning of the Covid-19 pandemic (p < 0.001). Treatment prevalence among chronic cannabis users was as high as 6 per 1000 in the 16-24 age group. CONCLUSION: Survey data suggest patients with CHS almost universally suffer from a cannabis use disorder, which has significant treatment implications. Treatment prevalence in the ED has increased substantially over a very short time period, with the highest rates seen during the Covid-19 pandemic.

Multisystem inflammatory syndrome in a fully vaccinated 18-year-old without known SARS-CoV-2 infection.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a febrile syndrome that is observed in the pediatric population following severe acute respiratory syndrome 2 (SARS-CoV-2) infection. Vaccines have prevented or lessened the severity of the initial acute respiratory infection, while their effectiveness against severe MIS-C is just beginning to be reported. CASE PRESENTATION: Here we report a fully vaccinated teenage female with no known history of SARS-CoV-2 infection who presented with shock and heart failure. Her presentation was initially thought secondary to a retropharyngeal abscess but was later identified as MIS-C after confirmed nucleocapsid antibody. CONCLUSIONS: Given the recent Omicron waves, the ongoing international outbreaks with evolving variants and the continued evolution of the COVID-19 pandemic, this case emphasizes the need to include MIS-C in the differential diagnosis, even in a fully vaccinated, previously healthy child.

Long-Term Sequelae in Young Convalescent COVID-19 Patients.

As of March 2022, over 78 million cases of COVID-19 and 900,000 deaths have been reported in the United States. The consequences in the acute phase due to the SARS-COV-2 infection are well defined. Beyond the direct effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) involving the lung parenchyma, the post-viral complications within the central nervous system are still largely unknown, and a comprehensive evaluation regarding the long-term neuropsychological sequelae from this disease is not well characterized. An increasing number of patients previously diagnosed with COVID-19 have now presented with ongoing symptoms of inattention, executive function, and memory difficulties. These symptoms are collectively and commonly known by the public as 'brain fog', with many expressing concerns over their inability to engage in the workplace due to these symptoms. Here, we describe three patients who were seen in the Memory Disorders Clinic at Duke University to characterize the long-term neuropsychological symptoms, neuropsychological test results and brain MRI findings after infection with SARS-CoV-2 in a cohort of patients under the age of 60.

Reconstructing SARS-CoV-2 infection dynamics through the phylogenetic inference of unsampled sources of infection.

The COVID-19 pandemic has illustrated the importance of infection tracking. The role of asymptomatic, undiagnosed individuals in driving infections within this pandemic has become increasingly evident. Modern phylogenetic tools that take into account asymptomatic or undiagnosed individuals can help guide public health responses. We finetuned established phylogenetic pipelines using published SARS-CoV-2 genomic data to examine reasonable estimate transmission networks with the inference of unsampled infection sources. The system utilised Bayesian phylogenetics and TransPhylo to capture the evolutionary and infection dynamics of SARS-CoV-2. Our analyses gave insight into the transmissions within a population including unsampled sources of infection and the results aligned with epidemiological observations. We were able to observe the effects of preventive measures in Canada's "Atlantic bubble" and in populations such as New York State. The tools also inferred the cross-species disease transmission of SARS-CoV-2 transmission from humans to lions and tigers in New York City's Bronx Zoo. These phylogenetic tools offer a powerful approach in response to both the COVID-19 and other emerging infectious disease outbreaks.

The major worldwide stress of healthcare professionals during the first wave of the COVID-19 pandemic - the international COVISTRESS survey.

INTRODUCTION: The COVID-19 pandemic has initiated an upheaval in society and has been the cause of considerable stress during this period. Healthcare professionals have been on the front line during this health crisis, particularly paramedical staff. The aim of this study was to assess the high level of stress of healthcare workers during the first wave of the pandemic. MATERIALS AND METHODS: The COVISTRESS international study is a questionnaire disseminated online collecting demographic and stress-related data over the globe, during the pandemic. Stress levels were evaluated using non-calibrated visual analog scale, from 0 (no stress) to 100 (maximal stress). RESULTS: Among the 13,537 individuals from 44 countries who completed the survey from January to June 2020, we included 10,051 workers (including 1379 healthcare workers, 631 medical doctors and 748 paramedical staff). The stress levels during the first wave of the pandemic were 57.8 ± 33 in the whole cohort, 65.3 ± 29.1 in medical doctors, and 73.6 ± 27.7 in paramedical staff. Healthcare professionals and especially paramedical staff had the highest levels of stress (p < 0.001 vs non-healthcare workers). Across all occupational categories, women had systematically significantly higher levels of work-related stress than men (p < 0.001). There was a negative correlation between age and stress level (r = -0.098, p < 0.001). Healthcare professionals demonstrated an increased risk of very-high stress levels (>80) compared to other workers (OR = 2.13, 95% CI 1.87-2.41). Paramedical staff risk for very-high levels of stress was higher than doctors' (1.88, 1.50-2.34). The risk of high levels of stress also increased in women (1.83, 1.61-2.09; p < 0.001 vs. men) and in people aged <50 (1.45, 1.26-1.66; p < 0.001 vs. aged >50). CONCLUSIONS: The first wave of the pandemic was a major stressful event for healthcare workers, especially paramedical staff. Among individuals, women were the most at risk while age was a protective factor.

Cognitive consequences of COVID-19 in older adults with cognitive impairment

Introduction Coronavirus disease 2019 (COVID-19) is due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with significant morbidity and mortality that is well documented. This includes significant central nervous system (CNS) involvement that ranges from acute delirium to meningoencephalitis. While acute symptoms and manifestations have been noted, long-term neuropsychiatric and cognitive outcomes remain unclear in convalescent COVID-19 patients. Characterizing the convalescence is particularly important since 80% recover, yet the relationship between exacerbated cognitive dysfunction and COVID-19 remains unclear. We describe 3 adults above age 65 who reported worsening cognitive symptoms in the convalescent stage of COVID-19. Methods Three adults above the age of 65 who noted worsening cognitive difficulties after SARS-CoV-2 infection and COVID-19 were evaluated in the Memory Clinic of the Duke Neurological Disorders Clinic. Electronic medical records were retrospectively reviewed. Exam included a comprehensive neurological evaluation, formal neuropsychological evaluation, and neuroimaging. Prior history was collected for comparison with their current clinical evaluation profile data. Results Patient 1 is a 69 year old diabetic, hypertensive male with a history of depression and a first-order relative and a maternal aunt with late-onset Alzheimer's disease dementia who presented for evaluation of memory loss first noted about one year prior but had significantly worsened in the five months since his recovery from COVID-19. He had documented antibodies to SARS-CoV-2. The patient reported forgetting when he had eaten and now evinces navigation issues even when driving on familiar roads. Head CT without contrast obtained before COVID-19 infection showed mild bilateral hippocampal atrophy. He scored 4/8 on the AD8 Dementia Screening and 20/30 on the Montreal Cognitive Assessment (MoCA). PHQ9 was 10, GAD7 was 0, and NPI was 1. Formal neuropsychological evaluation data were collected. A diagnosis of late-onset Alzheimer's disease without behavioral disturbance was made during his clinic visit. Donezepil was started. Other comorbidities included vitamin B12 deficiency, atrial fibrillation, congestive heart failure, chronic obstructive pulmonary disease, obstructive sleep apnea, and morbid obesity. Patient 2 is a 68 year old male with a history of anxiety, depression, and attention deficit disorder who presented for evaluation of poor memory, inability to “visually map,” and daily “senior moments” as well as a prolonged period of confusion while driving four months after recovering from COVID-19. He had documented antibodies to SARS-CoV-2. He had transient memory problems two years ago that improved after changing his bupropion dosage. He also takes fluoxetine. He now regularly misplaces objects and often stops a task midway through, thinking that he completed it. His GDS score was 5. Head CT was unremarkable. MRI of the brain demonstrated mild hippocampal and biparietal lobe atrophy as well as mild cerebral white matter disease. He scored 7/8 on the AD8 Dementia Screening and 27/30 on the MoCA. A diagnosis of dementia with behavioral disturbance was made. PHQ9 was 9, GAD7 was 6, and NPI was 7. B12 was normal. There is no family history of cognitive impairment. Patient 3 is a 76-year-old female with a history of bipolar 1, diabetes, hypothyroidism, hyperlipidemia who presented for evaluation of memory loss that started 6 months ago but worsened since she had recovered from COVID-19 diagnosed about 8 weeks earlier. After testing positive, she was hospitalized for 3 weeks due to acute encephalopathy attributed to lithium toxicity. She was also taking trazodone. Her GDS score was 7. She scored 8/8 on the AD8 Dementia Screening. MoCA could not be completed. PHQ9 was 3, GAD7 was 9, and NPI was 19. Formal neuropsychological evaluation data were collected. Head CT without contrast three weeks after COVID-19 diagnosis showed calcification in the right basal ganglia, a mild hypodense signal periventricularly, and gray-white differentiation. Brain MRI without contrast showed subtle hippocampal and perisylvian atrophy on T1, mild to moderate parietal lobe atrophy bilaterally, and mild to moderate periventricular leukoaraiosis/white matter hyperintensities on FLAIR sequence. A diagnosis of dementia without behavioral disturbance was made. There is a family history of bipolar disorder in siblings and cognitive impairment in her father but no specific diagnosis of dementia. Conclusions This case series describes the exacerbation of pre-existing psychiatric and cognitive conditions after COVID-19 recovery in 3 older adults with formal neuropsychological evaluation data. Longitudinal investigation of convalescent patients is warranted to better clinically characterize and provide insight into the long-term effects of COVID-19. This will allow further investigation into the pathophysiology regarding the long-term consequences of SARS-CoV-2 infection. Funding Not Applicable.