An intersectional perspective on gender/sex disparities in the epidemiology of COVID-19 cascade from testing to mortality: Evidence from Swiss surveillance data (preprint)

Objectives: This study investigates sex and gender disparities in COVID-19 epidemiology in the Canton of Vaud, Switzerland, focusing on interactions with socioeconomic position (SEP) and age. Methods We analyzed COVID-19 surveillance data from March 2020 to June 2021, using an intersectional approach. Negative binomial regression models assessed disparities between women and men, across SEP quintiles and age groups, in testing, positivity, hospitalizations, ICU admissions, and mortality (Incidence Rate Ratios [IRR], 95% Confidence Intervals [CI]). Results Women had higher testing and positivity rates than men, while men experienced more hospitalizations, ICU admissions, and deaths. The higher positivity in women under 50 was mitigated after accounting for higher testing rates. Across SEP quintiles, gender/sex differences in testing and positivity were insignificant. In the lowest quintile, women`s mortality risk was 68% lower (IRR 0.32, CI 0.20-0.52), with no significant disparities in the highest quintile (IRR 0.66, CI 0.41-1.06). Conclusion Our findings underscore diverse epidemiological patterns of COVID-19, shaped by the interactions of gender/sex, SEP, and age, highlighting the need for intersectional perspectives in both epidemiological research and the development of public health strategies.

Unagi: Deep Generative Model for Deciphering Cellular Dynamics and In-Silico Drug Discovery in Complex Diseases (preprint)

Human diseases are characterized by intricate cellular dynamics. Single-cell sequencing provides critical insights, yet a persistent gap remains in computational tools for detailed disease progression analysis and targeted in-silico drug interventions. We introduce UNAGI, a deep generative neural network tailored to analyze time-series single-cell transcriptomic data. This innovative tool captures the complex cellular dynamics underlying disease progression, enhancing drug perturbation modeling and discovery. When applied to a dataset from patients with Idiopathic Pulmonary Fibrosis (IPF), UNAGI adeptly learns disease-informed cell embeddings that sharpen our understanding of disease progression, leading to the identification of potential therapeutic drug candidates. Validation via proteomics reveals the accuracy of UNAGI’s cellular dynamics analyses, and the use of the Fibrotic Cocktail treated human Precision-cut Lung Slices confirms UNAGI’s predictions that Nifedipine, an antihypertensive drug, may have antifibrotic effects on human tissues. UNAGI's versatility extends to other diseases, including a COVID dataset, demonstrating adaptability and confirming its broader applicability in decoding complex cellular dynamics beyond IPF, amplifying its utility in the quest for therapeutic solutions across diverse pathological landscapes.

EFFICACY AND SAFETY OF DAZODALIBEP (VIB4920/HZN4920) IN SUBJECTS WITH SJÖGREN'S SYNDROME: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PROOF OF CONCEPT STUDY

BackgroundSjögren's syndrome (SS) is a chronic, systemic autoimmune disease affecting exocrine glands, primarily the salivary and tear glands, with potentially severe manifestations in multiple organs. No approved disease-modifying therapies exist. Dazodalibep (DAZ) is a biologic antagonist of CD40L.ObjectivesThe objective of this study was to evaluate the efficacy and safety of DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity (NCT04129164).MethodsWe conducted a randomized, double-blind, placebo-controlled, crossover study to evaluate DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity, as defined by a EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ≥ 5. Eligible subjects were randomized 1:1 to receive intravenous DAZ 1500 mg or placebo (PBO) Q2W x 3 doses, then Q4W x 4 additional doses. Starting on Day 169, subjects initially randomized to DAZ received PBO Q4W x 5 doses and subjects randomized to PBO received DAZ Q4W x 5 doses and were then followed for 12 weeks. The primary endpoint was the change from Baseline in ESSDAI at Day 169. Safety assessments included the incidence of adverse (AEs), serious AEs (SAEs), and AEs of special interest (AESIs).ResultsThe 74 randomized subjects all received ≥1 dose of study medication (DAZ, N=36;PBO, N=38). The baseline demographics and disease characteristics were balanced between the two groups. The change from Baseline to Day 169 in ESSDAI score (LS mean ± SE), was -6.3 ± 0.6 in DAZ-treated subjects compared to -4.1 ± 0.6 in the PBO group, a difference of -2.2 (p = 0.0167). Compared to the PBO group, the DAZ group showed positive trends in the EULAR Sjögren's Syndrome Patient Reported Index score, and Functional Assessment of Chronic Illness Therapy-Fatigue score at Day 169. A post-hoc responder analysis of subjects achieving high levels (5 and 6 points) of improvement on ESSDAI favored DAZ (61.1% and 60.0%) over PBO (35.1% and 34.3%).The reported AEs were generally mild through Day 169 and similar in frequency between treatment groups. The most frequently reported AEs occurring in ≥5% of DAZ-treated subjects and >PBO were COVID-19, diarrhea, dizziness, ligament sprain, upper respiratory tract infection, contusion, device allergy, fatigue, hypertension, and oropharyngeal pain. Two SAEs were reported in a single DAZ-treated subject: this subject was a 59-year-old female who experienced a grade 3 SAE of COVID-19 infection and later died of unknown cause 46 days after last administration of DAZ (12 days after COVID-19 diagnosis). There was a single AESI of herpes zoster in a DAZ-treated subject.ConclusionDAZ is a potential new therapy for the treatment of systemic disease activity in patients with SS. SS subjects with moderate-to-high systemic disease receiving DAZ experienced a statistically significant reduction in disease activity relative to PBO as measured by the improvement in ESSDAI score. Except for a case of severe COVID-19 infection, DAZ therapy in SS subjects appeared to be well tolerated. Larger controlled trials of DAZ therapy for SS are warranted to further explore its safety profile and confirm its clinical efficacy.Table 1.Efficacy and Safety DataPBO N=38DAZ 1500 mg N=36EfficacyΔESSDAI, LS mean (SE) †-4.1 (0.6)-6.3 (0.6)*ΔESSPRI, LS mean (SE) †-1.12 (0.29)-1.80 (0.31)ΔFACIT-Fatigue, LS mean (SE) †5.8 (1.6)8.1 (1.6)AE Summary, n (%)≥1 AE23 (60.5)28 (77.8)≥1 related AE8 (21)10 (27.8)≥1 SAE01 (2.8)≥1 related SAE00≥1 AE leading to discontinuation00≥1 AESI01 (2.8)≥1 Death01 (2.8)Efficacy endpoints as of Day 169;† Analyzed using MMRM;Comparisons vs PBO;*p<0.05;AE summaries based on AEs that occurred through Day 169;AE, adverse event;AESI, adverse event of special interest;ESSDAI, EULAR Sjögren's Syndrome Disease Activity Index;ESSPRI, EULAR Sjögren's Syndrome Patient Reported Index;FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue;PBO, placebo;SAE, serious adverse eventFigure 1.AcknowledgementsFunded by Horizon herapeutics. Medical writing support provided by B Lujan, PhD, an employee of Horizon Therapeutics.Disclosure of InterestsE. William St. Clair Consultant of: Horizon Therapeutics, Bristol Myers Squibb, CSL Behring, Resolve Therapeutics, Sonoma Biotherapeutics. Royalties: UpToDate, Liangwei Wang Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Ilias Alevizos Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, William Rees Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Alan Baer Consultant of: Bristol Myers Squibb, Wan Fai Ng Consultant of: Novartis, GlaxoSmithKline, Abbvie, BMS, Sanofi, MedImmune, Janssen and UCB, Ghaith Noaiseh Consultant of: Novartis, Chiara Baldini Consultant of: GSK, and Sanofi.

High-Throughput SARS-CoV-2 Antiviral Testing Method Using the Celigo Image Cytometer.

The COVID-19 pandemic has created a worldwide public health crisis that has since resulted in 6.8 million reported deaths. The pandemic prompted the immediate response of researchers around the world to engage in rapid vaccine development, surveillance programs, and antiviral testing, which resulted in the delivery of multiple vaccines and repurposed antiviral drug candidates. However, the emergence of new highly transmissible SARS-CoV-2 variants has renewed the desire for discovering new antiviral drug candidates with high efficacy against the emerging variants of concern. Traditional antiviral testing methods employ the plaque-reduction neutralization tests (PRNTs), plaque assays, or RT-PCR analysis, but each assay can be tedious and time-consuming, requiring 2-3 days to complete the initial antiviral assay in biologically relevant cells, and then 3-4 days to visualize and count plaques in Vero cells, or to complete cell extractions and PCR analysis. In recent years, plate-based image cytometers have demonstrated high-throughput vaccine screening methods, which can be adopted for screening potential antiviral drug candidates. In this work, we developed a high-throughput antiviral testing method employing the Celigo Image Cytometer to investigate the efficacy of antiviral drug candidates on SARS-CoV-2 infectivity using a fluorescent reporter virus and their safety by measuring the cytotoxicity effects on the healthy host cell line using fluorescent viability stains. Compared to traditional methods, the assays defined here eliminated on average 3-4 days from our standard processing time for antiviral testing. Moreover, we were able to utilize human cell lines directly that are not typically amenable to PRNT or plaque assays. The Celigo Image Cytometer can provide an efficient and robust method to rapidly identify potential antiviral drugs to effectively combat the rapidly spreading SARS-CoV-2 virus and its variants during the pandemic.

Mammals responded to reduced road traffic.

COVID-19 restrictions in 2020 reduced traffic worldwide and altered animal movement.

Adeno-associated virus 2 infection in children with non-A-E hepatitis.

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.

Survey of the Adequacy of Brazilian Children and Adolescents to the 24-Hour Movement Guidelines before and during the COVID-19 Pandemic.

The 24-Hour Movement Guidelines provide specific recommendations on movement behaviors for children and adolescents. The objective of this study was to verify the adequacy of children and adolescents to the guidelines for moderate to vigorous physical activity, recreational screen time, and sleep duration, and the overall adequacy to the guidelines, before and during the COVID-19 pandemic. A cross-sectional study was conducted with parents or guardians of children or adolescents from different regions of Brazil using a digital interview form including sociodemographic characteristics of families, moderate to vigorous physical activity, recreational screen time, and sleep duration before and during the pandemic. Statistically significant variation was observed in both groups in relation to moderate to vigorous physical activity and recreational screen time between the two periods evaluated. Overall adequacy to the guidelines before the pandemic was 19.28% for children from Group 1 (0-5 years old) and 39.50% for those from Group 2 (6 to 17 years old). During the pandemic, it corresponded to 3.58% in Group 1 and 4.94% in Group 2 (p-value between periods ≤0.001). This study showed the significant impact of pandemic restrictions on reducing overall compliance and physical activity, and increasing screen time among Brazilian children and adolescents.

Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.

Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. Funding: None.

Persistent post-COVID-19 dysosmia: Practices survey of members of the French National Union of Otorhinolaryngology-Head and Neck Surgery Specialists. CROSS analysis.

INTRODUCTION: Persistent dysosmia more than 3 months after SARS-CoV-2 disease (COVID-19) is considered as long-COVID olfactory disease (LCOD). The primary objective of this study was to evaluate the diagnostic and therapeutic management of LCOD in the daily clinical practice of members of the National Union of Otorhinolaryngology-Head and Neck Surgery Specialists (Syndicat national des médecins spécialisés en ORL et chirurgie cervico-faciale) (SNORL). The secondary objective was to identify factors influencing management within the descriptive survey data. MATERIALS AND METHODS: A questionnaire was designed (GoogleForm®) and e-mailed to all 715 SNORL members in January 2022. RESULTS: The response rate was 7.4% (n=53/715). In total, 94.3% of respondents (n=50) had managed LCOD cases, and 56% (n=28) used psychophysical olfactory tests. Specific olfactory medical therapy involved local corticosteroid nasal sprays in 49.1% of cases (n=26) and oral corticosteroids in 32.1% (n=17). Olfactory self-training was prescribed by 81.1% of respondents, with associated speech pathologist therapy in 15.1% (n=8) of cases. No predictive factors for specific management were identified. CONCLUSION: Olfactometry is currently under-applied. Consistent with guidelines, non-drug therapy (olfactory training) is the first-line treatment for LCOD.

Conceptualizing the Episodic Nature of Disability among Adults Living With Long COVID: Qualitative Study...American Congress of Rehabilitation Medicine (ACRM) 99th Annual Conference, November 8-11, 2022, Chicago, Illinois

To describe experiences of disability among adults living with Long COVID. We conducted a community-engaged qualitative descriptive study involving online semi-structured interviews. We recruited participants via collaborator community networks in Canada, United Kingdom, United States and Ireland. Adults who self-identified as living with Long COVID, defined as signs and symptoms that develop during or following an infection consistent with COVID-19, which continue for 12-weeks or more and not explained by an alternative diagnosis. We purposively recruited for diversity in country, gender, age, sexual orientation, and duration since initial COVID-19 infection. Not applicable. We used a semi-structured interview guide to explore experiences of disability living with Long COVID, specifically health-related challenges and how they were experienced over time. We asked participants to draw their health trajectory. We conducted a group-based content analysis. Among the 40 participants (10 per country), the median age was 39 years;majority were women (63%), white (73%), heterosexual (75%), and living with Long COVID for ≥1 year (83%). Participants described their disability experiences as episodic in nature, characterized by fluctuations in presence and severity of health-related challenges (disability) that may occur within the day to over the long-term living with Long COVID. They described living with 'ups and downs', 'flare-ups', and 'peaks' followed by 'crashes', 'troughs', and 'valleys', likened to a 'yo-yo' 'rolling hills', and 'rollercoaster ride' with 'relapsing/remitting', 'waxing/waning', 'fluctuations' in health. Illustrations demonstrated trajectories of health dimensions, some more episodic than others. Uncertainty intersected with the episodic nature of disability, characterized as unpredictability of episodes, their length, severity and triggers, and process of long-term recovery, which had implications on broader health. Experiences of disability were described as episodic in nature, characterized by fluctuating health challenges, which may be unpredictable among this sample of adults living with Long COVID. Results will help to better understand experiences of disability among adults living with Long COVID and inform approaches for rehabilitation. None.

Conceptualizing the Episodic Nature of Disability among Adults Living With Long COVID: Qualitative Study

To describe experiences of disability among adults living with Long COVID. We conducted a community-engaged qualitative descriptive study involving online semi-structured interviews. We recruited participants via collaborator community networks in Canada, United Kingdom, United States and Ireland. Adults who self-identified as living with Long COVID, defined as signs and symptoms that develop during or following an infection consistent with COVID-19, which continue for 12-weeks or more and not explained by an alternative diagnosis. We purposively recruited for diversity in country, gender, age, sexual orientation, and duration since initial COVID-19 infection. Not applicable. We used a semi-structured interview guide to explore experiences of disability living with Long COVID, specifically health-related challenges and how they were experienced over time. We asked participants to draw their health trajectory. We conducted a group-based content analysis. Among the 40 participants (10 per country), the median age was 39 years;majority were women (63%), white (73%), heterosexual (75%), and living with Long COVID for ≥1 year (83%). Participants described their disability experiences as episodic in nature, characterized by fluctuations in presence and severity of health-related challenges (disability) that may occur within the day to over the long-term living with Long COVID. They described living with 'ups and downs', 'flare-ups', and 'peaks' followed by 'crashes', 'troughs', and 'valleys', likened to a 'yo-yo' 'rolling hills', and 'rollercoaster ride' with 'relapsing/remitting', 'waxing/waning', 'fluctuations' in health. Illustrations demonstrated trajectories of health dimensions, some more episodic than others. Uncertainty intersected with the episodic nature of disability, characterized as unpredictability of episodes, their length, severity and triggers, and process of long-term recovery, which had implications on broader health. Experiences of disability were described as episodic in nature, characterized by fluctuating health challenges, which may be unpredictable among this sample of adults living with Long COVID. Results will help to better understand experiences of disability among adults living with Long COVID and inform approaches for rehabilitation. None.

Unified Protocol vs Trauma-Focused Cognitive Behavioral Therapy among Adolescents with PTSD

Harmful consequences of COVID-19 such as prolonged quarantine, lack of social contact, and especially loss of parents or friends can negatively impact children and adolescents' mental health in diverse ways, including engendering post-traumatic stress symptoms. Our study is the first to compare the transdiagnostic Unified Protocol for the Treatment of Emotional Disorders in Adolescents (UP-A;Ehrenreich-May et al., 2009;2017) with Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) in terms of outcomes related to PTSD symptoms (COVID-19-related vs. COVID-19 unrelated PTSD) and comorbid symptoms (i.e., anxiety, depression) and other measures (i.e., emotion regulation, self-injury, anger). Individuals diagnosed with PTSD were randomly assigned to the UP-A (n = 46) or TF-CBT group (n = 47), administered the SCID-5 and a battery of measures and followed-up post-treatment and then after 3, 6, and 9 months. Ninety-three adolescents with PTSD were enrolled, 45% boys and 61% COVID-19-related PTSD. We adopted an intention-to-treat approach. At the initial post-intervention assessment, except for emotion regulation and unexpressed angry feelings, in which UP-A participants reported greater reductions, no significant differences in other variables were secured between the UP-A and TF-CBT. However, at follow-up assessments, the UP-A evidenced significantly better outcomes than TF-CBT. We found support for the UP-A compared with TF-CBT in treating adolescents with PTSD, regardless of COVID-19-related PTSD status, in maintaining treatment effectiveness over time.

High seroprevalence of antibodies against SARS-CoV-2 among healthcare workers 8 months after the first wave in Aden, Yemen

The true burden of COVID-19 in Yemen is underestimated. The healthcare system is dysfunctional and there is a high shortage of health care workers in the country. Testing for SARS-CoV-2 remains limited and official surveillance data is restricted to those who are severe or highly suspected. In this study, Médecins Sans Frontières (MSF) aimed to conduct serological screening using rapid tests for asymptomatic staff at the MSF Aden Trauma Center to determine the SARS-CoV-2 antibody seropositivity. Four months after the peak of the first wave, we offered all the staff at the MSF Aden Trauma Center PCR if symptomatic, and a baseline SARS-CoV-2 serology screening followed by follow-up screenings. A final round was scheduled four months after the baseline. A rapid serology lateral flow test, NG-Test IgM-IgG was used in all rounds and in the final round, an electrochemiluminescence immunoassay (ECLIA) (Elecsys Anti-SARS-CoV-2 assay). Univariate and multivariate analyses were used to identify risk factors for seropositivity. The level of agreement between the different serology assays used was investigated. Overall 69 out of 356 participants (19.4%, 95% CI 17.9–20.8) tested positive by NG-Test between September and November 2020. A sub-sample of 161 staff members were retested in January 2021. Of these, the NG-Test detected only 13 positive cases, whereas the ECLIA detected 109 positive cases. The adjusted seroprevalence by ECLIA was 59% (95%CI 52.2–65.9). The non-medical staff had significantly lower odds of seropositivity compared to the medical staff (AOR 0.43, 95% CI 0.15–0.7, p<0.001). The positive percent agreement between the two tests was very low (11%). Our results suggest a very high SARS-CoV-2 seroprevalence in healthcare workers in Yemen, highlighting the need for regular testing and rapid vaccination of all healthcare workers in the country.

Baseline Demographics and Disease Characteristics of Patients Enrolled in the Registry of the Natural History of Recurrent Pericarditis in Pediatric and Adult Patients (Resonance)

Background The natural history of recurrent pericarditis (RP) and its associated co-morbidity are not well understood. The RESONANCE registry (NCT04687358) was implemented to collect observational data from real-world clinical practice to better understand the presentation, management and outcomes of patients with RP. Methods Enrollment of adult and pediatric patients began March 2021 and continues at 22 participating centers across the US. Patients with RP episodes <=3 years prior to enrollment and currently on treatment were considered to have active disease. Patients with RP related to trauma, malignancy and connective tissue disease were excluded. The current analysis reports interim demographic and disease characteristics at enrollment for the active cohort with complete data records. Results As of 15 August 2022, complete data records were available for 100 adult and 2 pediatric patients. To date, the majority of patients are female (62%, n=64). Mean (SD) age was 47 (15) years. The primary cause of the initial acute pericarditis event was idiopathic/viral (68%, n=70) or post-cardiac injury syndrome (8%, n=8). Median (Q1,Q3) duration of disease at enrollment was 2.7 (1.0, 5.2) years. 70% (n=71) of patients had experienced at least one recurrence in the one-year retrospective period. Comorbidities were low (15%;n=16);of these, 25% (n=4) had hypertension, 25% (n=4) had cardiac arrhythmia, 25% (n=4) had depression, 12.5% (n=2) had COVID-19 and 12.5% (n=2) had anxiety. Concomitant medical management data will be presented. Conclusion RESONANCE is a novel national multicenter registry collecting data relevant for informing treatment strategies for RP. Initial data from the first 103 patients suggest a preponderance of women with active RP;overall, patients are relatively young without significant comorbidities versus other acquired cardiovascular diseases. As enrollment and data collection expands, RESONANCE is designed to reveal important characteristics for RP which can guide clinical practice and improve quality of life of patients with RP.Copyright © 2023 American College of Cardiology Foundation

Seroprevalence of anti-SARS-CoV-2 antibodies among blood donors from December 2020 to June 2021 in Koutiala district, Mali

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus associated with coronavirus disease (COVID-19). At the time of the study, little data on the level of exposure of the population in Koutiala district in Mali to SARS-CoV-2 was available. Although blood donors are not representative of the general population, a COVID-19 seroprevalence estimate in this population was intended to assess the extent of community transmission, serve as a health alert system, and help guide the public health response. We measured seroprevalence of anti-SARS-CoV-2 antibodies using NG-Biotech SARS-Cov-2 RDT and ECLIA test between January and June 2020. This is a cross-sectional study of volunteer blood donors aged 18 to 60 years, independent of any previous COVID-19 disease. A stratified analysis of seroprevalence by month of sample collection and a comparison of the results of the NG-Biotech SARS-Cov-2 RDT with those of the ECLIA test was performed. The overall prevalence of antibodies to SARS-Cov-2 virus assessed by the NG-Biotech SARS-Cov-2 RDT was 24.6% (95% CI 21.8–27.4) and by the ECLIA test was 70.2 (95% CI 64.9–75.5). Both estimates remained relatively stable over the study period. We observed SARS-CoV-2 exposure much higher than indicated by case-based surveillance. The national surveillance system, as it was, was not able to detect variations in incidence, and as such, we do not recommend it as an alert system. However, the discrepancy between the results of the rapid test and the ECLIA test shows that further research is required to assess the validity of these test before a more solid conclusion can be drawn it their use in surveillance.

A Persistent Nightmare: A Case of Recurrent Brachial Artery Thrombosis

Background Brachial artery thrombosis can be seen with thromboembolism, hypercoagulability, and arterial thoracic outlet syndrome. Case A 33-year-old healthy female construction worker presented with right hand discoloration and pain. She suffered a COVID-19 infection 8 weeks prior with hand symptoms developing shortly thereafter. She could no longer work due to the pain. Duplex ultrasound and CTA of the right upper extremity (Figure) demonstrated localized thrombosis of the right brachial artery. The workup yielded no aortic or intracardiac thrombus, and cardiac event monitor showed no atrial arrhythmia. She underwent thrombectomy with brachial artery stenting and was found, during surgery, to have distal ulnar artery occlusion. Two days post-op, she had recurrent pain and was found to have brachial artery recurrent thrombosis. She underwent urgent brachial-brachial bypass. Arm pain continued despite graft patency, so ulnarpalmar bypass was performed. Decision-making Hypercoagulability workup, including antiphospholipid antibody, protein C, protein S, homocysteine, and Lp(a), was negative. Neither central thrombus on TEE nor evidence of thoracic outlet syndrome was found. As a diagnosis of exclusion, brachial artery thrombosis was ascribed to COVID infection. Despite rivaroxaban, the patient developed gangrene (Panel C) requiring partial digit amputation. Conclusion We present a case of COVID-19-induced recurrent brachial artery thrombosis despite surgical intervention. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

A Survey of Didemnin Depsipeptide Production in Tistrella.

As one of the first families of marine natural products to undergo clinical trials, the didemnin depsipeptides have played a significant role in inspiring the discovery of marine drugs. Originally developed as anticancer therapeutics, the recent re-evaluation of these compounds including synthetically derived dehydrodidemnin B or Aplidine, has led to their advancement towards antiviral applications. While conventionally associated with production in colonial tunicates of the family Didemnidae, recent studies have identified their biosynthetic gene clusters from the marine-derived bacteria Tistrella mobilis. While these studies confirm the production of didemnin X/Y, the low titer and general lack of understanding of their biosynthesis in Tistrella currently prevents the development of effective microbial or synthetic biological approaches for their production. To this end, we conducted a survey of known species of Tistrella and report on their ability to produce the didemnin depsipeptides. These data were used to develop conditions to produce didemnin B at titers over 15 mg/L.

Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe.

Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients.   Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.