GrMoNAS: A granularity-based multi-objective NAS framework for efficient medical diagnosis.

Neural Architecture Search (NAS) has been widely applied to automate medical image diagnostics. However, traditional NAS methods require significant computational resources and time for performance evaluation. To address this, we introduce the GrMoNAS framework, designed to balance diagnostic accuracy and efficiency using proxy datasets for granularity transformation and multi-objective optimization algorithms. The approach initiates with a coarse granularity phase, wherein diverse candidate neural architectures undergo evaluation utilizing a reduced proxy dataset. This initial phase facilitates the swift and effective identification of architectures exhibiting promise. Subsequently, in the fine granularity phase, a comprehensive validation and optimization process is undertaken for these identified architectures. Concurrently, employing multi-objective optimization and Pareto frontier sorting aims to enhance both accuracy and computational efficiency simultaneously. Importantly, the GrMoNAS framework is particularly suitable for hospitals with limited computational resources. We evaluated GrMoNAS in a range of medical scenarios, such as COVID-19, Skin cancer, Lung, Colon, and Acute Lymphoblastic Leukemia diseases, comparing it against traditional models like VGG16, VGG19, and recent NAS approaches including GA-CNN, EBNAS, NEXception, and CovNAS. The results show that GrMoNAS achieves comparable or superior diagnostic precision, significantly enhancing diagnostic efficiency. Moreover, GrMoNAS effectively avoids local optima, indicating its significant potential for precision medical diagnosis.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update.

To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention, diagnosis, and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches for managing each form of acute altitude illness that incorporate these recommendations as well as recommendations on how to approach high altitude travel following COVID-19 infection. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in Wilderness & Environmental Medicine in 2010 and the subsequently updated WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2014 and 2019.

The Molecular Blueprint for Chronic Obstructive Pulmonary Disease (COPD): A New Paradigm for Diagnosis and Therapeutics.

The global prevalence of chronic obstructive pulmonary disease (COPD) has increased over the last decade and has emerged as the third leading cause of death worldwide. It is characterized by emphysema with prolonged airflow limitation. COPD patients are more susceptible to COVID-19 and increase the disease severity about four times. The most used drugs to treat it show numerous side effects, including immune suppression and infection. This review discusses a narrative opinion and critical review of COPD. We present different aspects of the disease, from cellular and inflammatory responses to cigarette smoking in COPD and signaling pathways. In addition, we highlighted various risk factors for developing COPD apart from smoking, like occupational exposure, pollutants, genetic factors, gender, etc. After the recent elucidation of the underlying inflammatory signaling pathways in COPD, new molecular targeted drug candidates for COPD are signal-transmitting substances. We further summarize recent developments in biomarker discovery for COPD and its implications for disease diagnosis. In addition, we discuss novel drug targets for COPD that could be explored for drug development and subsequent clinical management of cardiovascular disease and COVID-19, commonly associated with COPD. Our extensive analysis of COPD cause, etiology, diagnosis, and therapeutic will provide a better understanding of the disease and the development of effective therapeutic options. In-depth knowledge of the underlying mechanism will offer deeper insights into identifying novel molecular targets for developing potent therapeutics and biomarkers of disease diagnosis.

Leveraging School Infection Data to Address Community COVID-19 Data Gaps.

BACKGROUND: At-home COVID-19 tests became available in the USA in April 2021 with widespread use by January 2022; however, the lack of infrastructure to report test results to public health agencies created a gap in public health data. Kindergarten through grade 12 (K-12) schools often tracked COVID-19 cases among students and staff; leveraging school data may have helped bridge data gaps. METHODS: We examined infection rates reported by school districts to ABC Science Collaborative with corresponding community rates from March 15, 2021 to June 3, 2022. We computed weekly ratios of community-to-district-reported rates (reporting ratios) across 3 study periods (spring 2021, fall 2021, and spring 2022) and estimated the difference and 95% confidence intervals (CIs) in the average reporting ratio between study periods. RESULTS: In spring 2021, before approval or widespread use of at-home testing, the community-reported infection rate was higher than the school-reported infection rate (reporting ratio: 1.40). In fall 2021 and spring 2022, as at-home testing rapidly increased, school-reported rates were higher than community-reported rates (reporting ratios: 0.82 and 0.66). Average reporting ratios decreased between spring 2021 and fall 2021 (-0.58, 95% CI -0.84, -0.32) and spring 2021 and spring 2022 (-0.73, 95% CI -0.96, -0.48); there was no significant change between fall 2021 and spring 2022 (-0.15, 95% CI -0.36, 0.06). CONCLUSIONS: At-home COVID-19 testing resulted in significant data gaps; K-12 data could have supplemented community data. In future public health emergencies, reporting of school data could minimize data gaps, but requires additional resources including funding to track infections and standardized data reporting methods.

Utility of Bronchoalveolar Lavage for the Diagnosis and Management of COVID-19 in Patients With Cancer.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) on nasopharyngeal swab (NPS), remains the most reliable and practical test to diagnose coronavirus disease 2019 (COVID-19). Current literature is sparse regarding the rates of discordance between NPS and bronchoalveolar lavage (BAL) in patients with cancer. METHODS: We conducted a retrospective cohort study of adult patients with cancer who had BAL samples tested for SARS-CoV-2 at a comprehensive cancer center. Patients without NPS PCR for SARS-CoV-2 before BAL were excluded. RESULTS: In a cohort of 345 patients, 12% and 17% tested positive for SARS-CoV-2 on NPS and BAL, respectively. There was a 6.3% NPS-/BAL+ discordance rate and a 9.5% NPS+/BAL- discordance rate. Patients with lymphoma (adjusted odds ratio [aOR] = 4.06; P = .007) and Hispanic patients (aOR = 3.76; P = .009) were more likely to have NPS-/BAL+ discordance on multivariate analysis. Among patients with NPS- /BAL- for SARS-CoV-2, an alternate infectious (23%) and a noninfectious etiology (16%) were identified in BAL. CONCLUSIONS: Our discordance rates between NPS and BAL were sufficient to recommend BAL in certain patients with cancer with a high clinical suspicion of COVID-19. BAL has value in identifying alternative etiologies of illness in patients with suspected or confirmed COVID-19.

Unmasking the complex roles of hypocalcemia in cancer, COVID-19, and sepsis: Engineered nanodelivery and diagnosis.

Calcium (Ca2+) homeostasis is essential for maintaining physiological processes in the body. Disruptions in Ca2+ signaling can lead to various pathological conditions including inflammation, fibrosis, impaired immune function, and accelerated senescence. Hypocalcemia, a common symptom in diseases such as acute respiratory distress syndrome (ARDS), cancer, septic shock, and COVID-19, can have both potential protective and detrimental effects. This article explores the multifaceted role of Ca2+ dysregulation in inflammation, fibrosis, impaired immune function, and accelerated senescence, contributing to disease severity. Targeting Ca2+ signaling pathways may provide opportunities to develop novel therapeutics for age-related diseases and combat viral infections. However, the role of Ca2+ in viral infections is complex, and evidence suggests that hypocalcemia may have a protective effect against certain viruses, while changes in Ca2+ homeostasis can influence susceptibility to viral infections. The effectiveness and safety of Ca2+ supplements in COVID-19 patients remain a subject of ongoing research and debate. Further investigations are needed to understand the intricate interplay between Ca2+ signaling and disease pathogenesis.

COVID-19 mortality among veterans with serious mental illness in the veterans health administration.

OBJECTIVE: Persons with serious mental illness (SMI: schizophrenia-spectrum disorders, bipolar disorder) experience increased risk of mortality after contracting COVID-19 based on the results of several international evaluations. However, information about COVID-19 mortality risk among patients with SMI in the Veterans Health Administration (VHA) has been limited, precluding identification of protective factors. The current evaluation was conducted to assess COVID-19 mortality risk among VHA patients with SMI and to evaluate potential protective factors in mitigating mortality risk following a positive COVID-19 diagnosis. METHODS: National VHA administrative data was used to identify all patients (N = 52,916) who received a positive COVID-19 test result between March 1, 2020, and September 30, 2020. Mortality risk was assessed by SMI status via bivariate comparisons and multivariate regression analyses. RESULTS: In unadjusted analyses, VHA patients with SMI overall and patients with bipolar disorder in particular did not experience increased mortality risk in the 30 days following a positive COVID test, although patients with schizophrenia had increased risk. Within adjusted analyses, patients with schizophrenia remained at increased mortality risk (OR = 1.38), but at reduced levels relative to previous evaluations in other healthcare settings. CONCLUSIONS: Within VHA, patients with schizophrenia, but not those with bipolar disorder, experience increased mortality risk in the 30 days following a positive COVID-19 test. Large integrated healthcare settings such as VHA may offer services which may protect against COVID-19 mortality for vulnerable groups such as persons with SMI. Additional work is needed to identify practices which may reduce the risk of COVID-19 mortality among persons with SMI.

Topological data analysis of antibody dynamics of severe and non-severe patients with COVID-19.

The COVID-19 pandemic is a significant public health threat with unanswered questions regarding the immune system's role in the disease's severity level. Here, based on antibody kinetic data of severe and non-severe COVID-19 patients, topological data analysis (TDA) highlights that severity is not binary. However, there are differences in the shape of antibody responses that further classify COVID-19 patients into non-severe, severe, and intermediate cases of severity. Based on the results of TDA, different mathematical models were developed to represent the dynamics between the different severity groups. The best model was the one with the lowest average value of the Akaike Information Criterion for all groups of patients. Our results suggest that different immune mechanisms drive differences between the severity groups. Further inclusion of different components of the immune system will be central for a holistic way of tackling COVID-19.

Changes to Birth Plans Due to COVID-19: A Survey of Utah Midwives and Doulas.

INTRODUCTION: This study seeks to understand the experiences of Utah midwives and doulas caring for patients during the recent coronavirus disease 2019 (COVID-19) pandemic. Specifically, the goal of the study was to describe the perceived impact on the community birth system and explore differences in the access and use of personal protective equipment (PPE) between in- and out-of-hospital births. METHODS: This study used a cross-sectional, descriptive study design. A 26-item survey developed by the research team was sent via email to Utah birth workers, including nurse-midwives, community midwives, and doulas. Quantitative data were collected during December 2020 and January 2021. Descriptive statistics were used in the analysis. RESULTS: Of the 409 birth workers who were sent a link to the survey, 120 (30%) responded: 38 (32%) CNMs, 30 (25%) direct-entry or community midwives, and 52 (43%) doulas. The majority (79%) reported changes to clinical practice during the COVID-19 pandemic. Community midwives (71%) who responded indicated practice volume increased. Survey participants reported an increased patient preference for home births (53%) and birth center births (43%). Among those with one or more patient transfers to the hospital, 61% experienced a change in the process. One participant reported that it took 43 minutes longer to transfer to the hospital. Community midwives and doulas reported poor access to a regular source of PPE. DISCUSSION: Survey participants reported changes to planned birth locations during the COVID-19 pandemic. When necessary, transfers to hospitals were reported to be slower. Community midwives and doulas reported having insufficient access to PPE and reported limited knowledge about COVID-19 testing resources and resources for educating patients on COVID-19. This study adds an important perspective to the existing literature on COVID-19 by indicating that policymakers should include community birth partners in community planning for natural disasters and future pandemics.

Design and analysis of outcomes following SARS-CoV-2 infection in veterans.

BACKGROUND: Understanding how SARS-CoV-2 infection impacts long-term patient outcomes requires identification of comparable persons with and without infection. We report the design and implementation of a matching strategy employed by the Department of Veterans Affairs' (VA) COVID-19 Observational Research Collaboratory (CORC) to develop comparable cohorts of SARS-CoV-2 infected and uninfected persons for the purpose of inferring potential causative long-term adverse effects of SARS-CoV-2 infection in the Veteran population. METHODS: In a retrospective cohort study, we identified VA health care system patients who were and were not infected with SARS-CoV-2 on a rolling monthly basis. We generated matched cohorts within each month utilizing a combination of exact and time-varying propensity score matching based on electronic health record (EHR)-derived covariates that can be confounders or risk factors across a range of outcomes. RESULTS: From an initial pool of 126,689,864 person-months of observation, we generated final matched cohorts of 208,536 Veterans infected between March 2020-April 2021 and 3,014,091 uninfected Veterans. Matched cohorts were well-balanced on all 39 covariates used in matching after excluding patients for: no VA health care utilization; implausible age, weight, or height; living outside of the 50 states or Washington, D.C.; prior SARS-CoV-2 diagnosis per Medicare claims; or lack of a suitable match. Most Veterans in the matched cohort were male (88.3%), non-Hispanic (87.1%), white (67.2%), and living in urban areas (71.5%), with a mean age of 60.6, BMI of 31.3, Gagne comorbidity score of 1.4 and a mean of 2.3 CDC high-risk conditions. The most common diagnoses were hypertension (61.4%), diabetes (34.3%), major depression (32.2%), coronary heart disease (28.5%), PTSD (25.5%), anxiety (22.5%), and chronic kidney disease (22.5%). CONCLUSION: This successful creation of matched SARS-CoV-2 infected and uninfected patient cohorts from the largest integrated health system in the United States will support cohort studies of outcomes derived from EHRs and sample selection for qualitative interviews and patient surveys. These studies will increase our understanding of the long-term outcomes of Veterans who were infected with SARS-CoV-2.

Curcumin Confers Anti-Inflammatory Effects in Adults Who Recovered from COVID-19 and Were Subsequently Vaccinated: A Randomized Controlled Trial.

COVID-19 infection and vaccination offer disparate levels of defense against reinfection and breakthrough infection. This study was designed to examine the effects of curcumin supplementation, specifically HydroCurc (CURC), versus placebo (CON) on circulating inflammatory biomarkers in adults who had previously been diagnosed with COVID-19 and subsequently received a primary series of monovalent vaccine doses. This study was conducted between June 2021 and May 2022. Participants were randomized to receive CURC (500 mg) or CON capsules twice daily for four weeks. Blood sampling was completed at baseline and week-4 and analyzed for biomarkers. Linear regression was utilized to examine the between-group differences in post-trial inflammatory biomarker levels, adjusting for baseline and covariates including age, sex, race/ethnicity, and interval between COVID-19 diagnosis and trial enrollment. The sample (n = 31) was 71% female (Age 27.6 ± 10.4 y). The CURC group exhibited significantly lower post-trial concentrations of proinflammatory IL-6 (ß = -0.52, 95%CI: -1.03, -0.014, p = 0.046) and MCP-1 (ß = -0.12, 95%CI: -0.23, -0.015, p = 0.027) compared to CON, adjusting for baseline and covariates. Curcumin intake confers anti-inflammatory activity and may be a promising prophylactic nutraceutical strategy for COVID-19. These results suggest that 4 weeks of curcumin supplementation resulted in significantly lower concentrations of proinflammatory cytokines in adults who recovered from COVID-19 infection and were subsequently vaccinated.

Effects of the COVID-19 pandemic on general health and malaria control in Ghana: a qualitative study with mothers and health care professionals.

BACKGROUND: COVID-19 has severely impacted health systems and the management of non-COVID-19 diseases, including malaria, globally. The pandemic has hit sub-Saharan Africa less than expected; even considering large underreporting, the direct COVID-19 burden was minor compared to the Global North. However, the indirect effects of the pandemic, e.g. on socio-economic inequality and health care systems, may have been more disruptive. Following a quantitative analysis from northern Ghana, which showed significant reductions in overall outpatient department visits and malaria cases during the first year of COVID-19, this qualitative study aims to provide further explanations to those quantitative findings. METHODS: In the Northern Region of Ghana, 72 participants, consisting of 18 health care professionals (HCPs) and 54 mothers of children under the age of five, were recruited in urban and rural districts. Data were collected using focus group discussions with mothers and through key informant interviews with HCPs. RESULTS: Three main themes occurred. The first theme-general effects of the pandemic-includes impacts on finances, food security, health service provision as well as education and hygiene. Many women lost their jobs, which increased their dependance on males, children had to drop out of school, and families had to cope with food shortages and were considering migration. HCPs had problems reaching the communities, suffered stigmatisation and were often barely protected against the virus. The second theme-effects on health-seeking-includes fear of infection, lack of COVID-19 testing capacities, and reduced access to clinics and treatment. The third theme-effects on malaria-includes disruptions of malaria preventive measures. Clinical discrimination between malaria and COVID-19 symptoms was difficult and HCPs observed increases in severe malaria cases in health facilities due to late reporting. CONCLUSION: The COVID-19 pandemic has had large collateral impacts on mothers, children and HCPs. In addition to overall negative effects on families and communities, access to and quality of health services was severely impaired, including serious implications on malaria. This crisis has highlighted weaknesses of health care systems globally, including the malaria situation; a holistic analysis of the direct and indirect effects of this pandemic and an adapted strengthening of health care systems is essential to be prepared for the future.

Assessment of the Risk of Venous Thromboembolism in Nonhospitalized Patients With COVID-19.

Importance: Patients hospitalized with COVID-19 have higher rates of venous thromboembolism (VTE), but the risk and predictors of VTE among individuals with less severe COVID-19 managed in outpatient settings are less well understood. Objectives: To assess the risk of VTE among outpatients with COVID-19 and identify independent predictors of VTE. Design, Setting, and Participants: A retrospective cohort study was conducted at 2 integrated health care delivery systems in Northern and Southern California. Data for this study were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Participants included nonhospitalized adults aged 18 years or older with COVID-19 diagnosed between January 1, 2020, and January 31, 2021, with follow-up through February 28, 2021. Exposures: Patient demographic and clinical characteristics identified from integrated electronic health records. Main Outcomes and Measures: The primary outcome was the rate per 100 person-years of diagnosed VTE, which was identified using an algorithm based on encounter diagnosis codes and natural language processing. Multivariable regression using a Fine-Gray subdistribution hazard model was used to identify variables independently associated with VTE risk. Multiple imputation was used to address missing data. Results: A total of 398 530 outpatients with COVID-19 were identified. The mean (SD) age was 43.8 (15.8) years, 53.7% were women, and 54.3% were of self-reported Hispanic ethnicity. There were 292 (0.1%) VTE events identified over the follow-up period, for an overall rate of 0.26 (95% CI, 0.24-0.30) per 100 person-years. The sharpest increase in VTE risk was observed during the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% CI, 0.51-0.67 per 100 person-years vs 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days). In multivariable models, the following variables were associated with a higher risk for VTE in the setting of nonhospitalized COVID-19: age 55 to 64 years (HR 1.85 [95% CI, 1.26-2.72]), 65 to 74 years (3.43 [95% CI, 2.18-5.39]), 75 to 84 years (5.46 [95% CI, 3.20-9.34]), greater than or equal to 85 years (6.51 [95% CI, 3.05-13.86]), male gender (1.49 [95% CI, 1.15-1.96]), prior VTE (7.49 [95% CI, 4.29-13.07]), thrombophilia (2.52 [95% CI, 1.04-6.14]), inflammatory bowel disease (2.43 [95% CI, 1.02-5.80]), body mass index 30.0-39.9 (1.57 [95% CI, 1.06-2.34]), and body mass index greater than or equal to 40.0 (3.07 [1.95-4.83]). Conclusions and Relevance: In this cohort study of outpatients with COVID-19, the absolute risk of VTE was low. Several patient-level factors were associated with higher VTE risk; these findings may help identify subsets of patients with COVID-19 who may benefit from more intensive surveillance or VTE preventive strategies.

Proactive Outreach for At-risk Health Plan Members During COVID-19 Pandemic in New Mexico.

OBJECTIVE: -Explore the impact of proactive outreach to a health plan population during COVID-19 pandemic in New Mexico. BACKGROUND: -By March 2020, the 2019 novel coronavirus (COVID-19) was a global pandemic, circulating in more than 114 countries. As more information about virus transmission, symptoms, and comorbidities were reported over time, recommendations for reducing the spread of the virus within communities was provided by leading health organizations like the Centers for Disease Control and Prevention (CDC). METHODS: -Criteria were developed to identify health plan members most at risk for virus complications. Once members were identified, a health plan representative contacted each member to inquire about member needs, questions, and provide them with resources. Members were then tracked for COVID-19 testing results and vaccination status. RESULTS: -Overall, 50,000+ members received an outreach call (during 8-month timeframe), and 26,000 calls were tracked for member outcomes. Over 50% of the outreach calls were answered by the health plan member. Of the members who were called, 1186 (4.4%) tested positive for COVID-19. Health plan members that could not be reached represented 55% of the positive cases. A chi-square test of the two populations (reached vs unable to reach) showed a significant difference in COVID-19 positive test results (N = 26,663, X2(1) = 16.33, P<0.01). CONCLUSIONS: -Community outreach was related to lower rates of COVID-19. Community connection is important, especially in tumultuous times, and proactive outreach to the community provides an opportunity for information sharing and community bonding.

Prevalence of potential drug-drug interactions with ritonavir-containing COVID-19 therapy.

BACKGROUND: Patients with COVID-19 receiving ritonavir-containing therapies are at risk of potential drug-drug interactions (pDDIs) because of ritonavir's effects on cytochrome P450 3A4. OBJECTIVE: To assess the prevalence of pDDIs with ritonavir-containing COVID-19 therapy in adults with COVID-19 using the Optum Clinformatics Data Mart database. METHODS: In this retrospective, observational cohort study, patients with COVID-19 aged 18 years or older prescribed cytochrome P450 3A4-mediated medications with supply days overlapping the date of COVID-19 diagnosis between January 1, 2020, and June 30, 2021, were classified as having pDDIs. pDDI was classified as contraindicated, major, moderate, or mild using established drug interaction resources. Prevalence of pDDIs with ritonavir-containing COVID-19 therapy was estimated for the entire cohort and in patient groups with high risk of severe COVID-19 progression or pDDIs. Actual COVID-19 treatments received by the patients, if any, were not considered. Outcomes were presented descriptively without adjusted comparisons. RESULTS: A total of 718,387 patients with COVID-19 were identified. The age-sex standardized national prevalence of pDDIs of any severity was estimated at 52.2%. Approximately 34.5% were at risk of contraindicated or major pDDIs. Compared with patients without pDDI, patients exposed to pDDIs were older and more likely to be female, reside in long-term care facilities, and have risk factors for progression to severe COVID-19. Higher prevalence of major/contraindicated pDDIs was observed in older patients (76.1%), female patients (65.0%), and patients with multiple morbidities (84.6%). CONCLUSIONS: Study findings demonstrate that more than one-third of patients with COVID-19 were at risk of significant pDDIs if treated with ritonavir-containing COVID-19 therapy and highlight the need to assess all patients with COVID-19 for pDDIs. Ritonavir-based therapies may not be appropriate for certain patient groups, and alternative therapies should be considered. DISCLOSURES: Drs Igho-Osagie, Puenpatom, and Grifasi Williams are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. Dr Song and Ms He are employees of Analysis Group, Inc., and served as paid consultants for Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. Drs Yi and Wang, and Mr Berman, and Ms Gu were employees of Analysis Group, Inc., at the time of study conduct. Financial support for this study was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. The study sponsor was involved in the design and conduct of the study; collection, management, analysis, interpretation of data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Reducing COVID-19 diagnostic errors with dNTPαSe supplementation.

Timely and accurate diagnosis of COVID-19 is critical for controlling the pandemic. As the standard method to diagnose SARS-CoV-2, the real-time reverse transcription polymerase chain reaction (RT-qPCR) has good convenience. However, RT-qPCR still has a relatively high false-negative rate, particularly in the case of detecting low viral loads. In this study, using selenium-modified nucleoside triphosphates (dNTPαSe) in the RT-PCR reactions, we successfully increased the detection sensitivity and reduced the false-negative rate in COVID-19 diagnosis. By detecting positive controls, pseudovirus, and clinical samples with the commercial kits, we found that the dNTPαSe supplementation to these kits could generally offer smaller Ct values, permit the viral detection even in single-digit copies, and increase the detection specificity, sensitivity, and accuracy, thereby reducing the false-negative rate. Our experimental results demonstrated that dNTPαSe supplementation can make the commercial kits more specific, sensitive, and accurate, and this method is a convenient and efficient strategy for the disease detection and diagnosis.

Detection of anti-feline infectious peritonitis virus activity of a Chinese herb extract using geneLEAD VIII, a fully automated nucleic acid extraction/quantitative PCR testing system.

The geneLEAD VIII is a fully-automated nucleic acid extraction/quantitative PCR equipment developed by Precision System Science Co., Ltd., (PSS). To take advantage of its capability, we developed a quantitative assay system to measure growth of animal viruses. The system was used to assay one of the Chinese herbal extracts whose anti-malarial activities were previously reported and demonstrated its dose-dependent anti-viral activity against feline infectious peritonitis virus (FIPV), a feline coronavirus causing the fatal diseases in cats, and relatively low cell toxicity. The assay developed in this study is useful to screen antiviral drugs and the anti-FIPV activity of the herbal extract identified have a potential to lead to development of new drugs against FIPV and other coronaviruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

[Invasive aspergillosis: definitions, diagnosis, and treatment]. / Aspergilosis invasiva: definiciones, diagnóstico y tratamiento.

Invasive aspergillosis (IA) is a serious disease with high mortality. There are several risk factors and in-hospital outbreaks related with construction have been described. An entity related to COVID-19 infection, known as COVID-19 associated pulmonary aspergillosis (CAPA), has recently appeared. Early and appropriate treatment is of paramount importance, especially in immunocompromised and critically ill patients. Diagnosis is based on recognition of predisposing factors, clinical signs, imaging, direct examination, culture, histopathology, and biomarkers such as galactomannan. The drug of choice is voriconazole, but alternative therapies must be taken into account given the increasing presence of resistant isolates.

La aspergilosis invasiva (AI) es una enfermedad grave y con alta mortalidad. Existen factores de riesgo y se describen brotes intrahospitalarios relacionados con construcciones. También se describe una entidad relacionada con la infección por COVID-19, conocida como aspergilosis pulmonar asociada a COVID-19 (APAC). Es de vital importancia implementar un tratamiento adecuado y precoz, especialmente en pacientes inmunocomprometidos y críticamente enfermos. El diagnóstico se basa en reconocer los factores predisponentes, la clínica, la obtención de imágenes, exámenes directos, cultivos, histopatología y biomarcadores como el galactomanano. La droga de elección es el voriconazol, pero se deben conocer las alternativas terapéuticas dada la creciente presencia de aislamientos resistentes.

Wastewater-based epidemiology for comprehensive community health diagnostics in a national surveillance study: Mining biochemical markers in wastewater.

This manuscript showcases results from a large scale and comprehensive wastewater-based epidemiology (WBE) study focussed on multi-biomarker suite analysis of both chemical and biological determinants in 10 cities and towns across England equating to a population of ∼7 million people. Multi-biomarker suite analysis, describing city metabolism, can provide a holistic understanding to encompass all of human, and human-derived, activities of a city in a single model: from lifestyle choices (e.g. caffeine intake, nicotine) through to health status (e.g. prevalence of pathogenic organisms, usage of pharmaceuticals as proxy for non-communicable disease, NCD, conditions or infectious disease status), and exposure to harmful chemicals due to environmental and industrial sources (e.g. pesticide intake via contaminated food and industrial exposure). Population normalised daily loads (PNDLs) of many chemical markers were found, to a large extent, driven by the size of population contributing to wastewater (especially NCDs). However, there are several exceptions providing insights into chemical intake that can inform either disease status in various communities or unintentional exposure to hazardous chemicals: e.g. very high PNDLs of ibuprofen in Hull resulting from its direct disposal (confirmed by ibuprofen/2-hydroxyibuprofen ratios) and bisphenol A (BPA) in Hull, Lancaster and Portsmouth likely related to industrial discharge. An importance for tracking endogenous health markers such as 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, an oxidative stress marker) as a generic marker of health status in communities was observed due to increased levels of HNE-MA seen at Barnoldswick wastewater treatment plant that coincided with higher-than-average paracetamol usage and SARS-CoV-2 prevalence in this community. PNDLs of virus markers were found to be highly variable. Being very prevalent in communities nationwide during sampling, SARS-CoV-2 presence in wastewater was to a large extent community driven. The same applies to the fecal marker virus, crAssphage, which is very prevalent in urban communities. In contrast, norovirus and enterovirus showed much higher variability in prevalence across all sites investigated, with clear cases of localized outbreaks in some cities while maintaining low prevalence in other locations. In conclusion, this study clearly demonstrates the potential for WBE to provide an integrated assessment of community health which can help target and validate policy interventions aimed at improving public health and wellbeing.

Impact of the Presence Anti-SARS-CoV-2 IgA in the Colostrum of Women Infected by COVID-19 During the Pregnancy in Neonatal Clinical Outcomes: A Cross-Sectional Study.

OBJECTIVES: To describe the presence of anti-SARS-CoV-2 IgA and IgG in the blood and colostrum of women with COVID-19 infection during pregnancy and associate the presence of anti-SARS-CoV-2 IgA in colostrum with clinical symptoms of their newborns. METHODS: A cross-sectional study was developed with 165 participants with COVID-19 infection during pregnancy and their newborns. DATA COLLECTED: characteristics COVID-19 infection in pregnant women, gestational age, and clinical symptoms in their newborns (fever, hypothermia, respiratory distress, hypotonia, hypoactivity, hypoglycemia, cyanosis, vomiting/regurgitation, abdominal distention, and jaundice). Maternal blood and colostrum samples were collected postpartum to to detect the presence of IgA and IgG anti-SARS-CoV-2. RESULTS: The median interval between COVID-19 diagnosis and delivery was 37.5 days (IQ = 12.0, 73.0 days). Clinical symptoms during hospitalization were observed in 55 newborns (33.3%), and two (1.6%) tested RT-PCR positive for COVID-19. Positive colostrum for anti-SARS-CoV-2 IgA was found in 117 (70.9%) women. The presence of anti-SARS-CoV-2 IgA in colostrum was associated independently with lower clinical symptoms in their newborns (OR = 0.42; 95% CI 0.202 to 0.84; p = 0.015). CONCLUSIONS FOR PRACTICE: The presence of anti-SARS-CoV-2 IgA in colostrum was detected in more than two-thirds of the women evaluated and was associated with a lower frequency of clinical symptoms in their newborns.