Detection of SARS-CoV-2 and HHV-8 from a large pericardial effusion in an HIV-positive patient with COVID-19 and clinically diagnosed Kaposi sarcoma: a case report

BACKGROUND: Pericardial effusion is a late manifestation of HIV more commonly observed in individuals with depressed CD4 counts. Although Mycobacterium tuberculosis remains to be one of the most frequently identified pathogens in the pericardial fluid among people living with HIV, less commonly described etiologies include SARS-CoV-2 that causes coronavirus disease and human herpesvirus-8 which is associated with Kaposi sarcoma. Isolation of more than one pathogen in normally sterile sites remains challenging and rare. We report the first documentation of both SARS-CoV-2 and HHV-8 in the pericardial fluid. CASE PRESENTATION: We present the case of a young man in his 20s with a recent history of clinically diagnosed pulmonary tuberculosis who was admitted for progressive dyspnea and cough. He had multiple violaceous cutaneous lesions on the face, neck, and trunk and diffused lymphadenopathies. He tested positive for SARS-CoV-2 on admission. The patient was clinically diagnosed with pneumonia, Kaposi sarcoma, and HIV/AIDS. Empiric broad spectrum antimicrobial regimen was subsequently initiated. HIV with low CD4 count was confirmed during hospitalization. Echocardiography revealed a large pericardial effusion, in impending cardiac tamponade. Frond-like fibrin strands, extending to the parietal pericardium, were also observed. Pericardiostomy yielded hemorrhagic, exudative effusion with lymphocytic predominance. SARS-CoV-2 and HHV-8 were detected in the pericardial fluid, and bacterial, fungal, and tuberculous studies were negative. The patient had clinical improvement after pericardial drainage. However, despite our best clinical care, he developed a nosocomial infection leading to clinical deterioration and death. CONCLUSION: Detection of SARS-CoV-2 and HHV-8 in the pericardial fluid is rare, and interpretation of their significance in clinical care is challenging. However, coronavirus disease and Kaposi sarcoma must be considered and adequately addressed in immunocompromised adults presenting with large pericardial effusion

Detection of SARS-CoV-2 and HHV-8 from a large pericardial effusion in an HIV-positive patient with COVID-19 and clinically diagnosed Kaposi sarcoma: a case report

Background: Pericardial effusion is a late manifestation of HIV more commonly observed in individuals with depressed CD4 counts. Although Mycobacterium tuberculosis remains to be one of the most frequently identified pathogens in the pericardial fluid among people living with HIV, less commonly described etiologies include SARS‑CoV‑2 that causes coronavirus disease and human herpesvirus‑8 which is associated with Kaposi sarcoma. Isolation of more than one pathogen in normally sterile sites remains challenging and rare. We report the first documentation of both SARS‑CoV‑2 and HHV‑8 in the pericardial fluid.Case presentation: We present the case of a young man in his 20s with a recent history of clinically diagnosed pul‑monary tuberculosis who was admitted for progressive dyspnea and cough. He had multiple violaceous cutaneous lesions on the face, neck, and trunk and diffused lymphadenopathies. He tested positive for SARS‑CoV‑2 on admission. The patient was clinically diagnosed with pneumonia, Kaposi sarcoma, and HIV/AIDS. Empiric broad spectrum antimi‑crobial regimen was subsequently initiated. HIV with low CD4 count was confirmed during hospitalization. Echocardi‑ography revealed a large pericardial effusion, in impending cardiac tamponade. Frond‑like fibrin strands, extending to the parietal pericardium, were also observed. Pericardiostomy yielded hemorrhagic, exudative effusion with lympho‑cytic predominance. SARS‑CoV‑2 and HHV‑8 were detected in the pericardial fluid, and bacterial, fungal, and tubercu‑lous studies were negative. The patient had clinical improvement after pericardial drainage. However, despite our best clinical care, he developed a nosocomial infection leading to clinical deterioration and death.Conclusion: Detection of SARS‑CoV‑2 and HHV‑8 in the pericardial fluid is rare, and interpretation of their signifi‑cance in clinical care is challenging. However, coronavirus disease and Kaposi sarcoma must be considered and adequately addressed in immunocompromised adults presenting with large pericardial effusion

A call to protect non-clinical frontliners in the fight against COVID-19: evidence from a seroprevalence study in the Philippines.

Since the COVID-19 pandemic started in 2020, healthcare workers (HCW) and other hospital personnel have been regarded as “frontliners”, and at increased risk of SARS-CoV-2 infection compared to the general population. As such, testing only symptomatic individuals or regular testing of HCWs who directly attend to COVID-19 patients or specimens may underestimate the extent of infection, and actual SARS-CoV-2 seroprevalence. Because of this, the World Health Organization has called for seroepidemiological surveys to assess the extent of infection amongst HCW and other populations to provide timely estimates of COVID-19 virus infection severity and inform public health responses and evidence-based policy decisions

SARS-CoV-2 seroprevalence and infection rate in Manila, Philippines prior to national vaccination program implementation: a repeated cross-sectional analysis

Background: SARS-CoV-2 seroepidemiological studies are used to guide public health decision making and to prepare for emerging infectious diseases. Disease occurrence estimates are limited in the Philippines, the country with the highest reported number of coronavirus disease-related deaths in the Western Pacific region. We aimed to estimate SARS-CoV-2 seroprevalence and infection rate among outpatient clinic attendees in Metro Manila prior to the implementation of the national coronavirus disease vaccination program. Methods: We conducted repeated cross-sectional surveys at the animal bite clinic in San Lazaro Hospital, Manila, the Philippines across four periods, 3 months apart, between May 2020 and March 2021. Multivariable logistic regression was used to assess associations between different characteristics and infection status including seropositivity.Results: In total 615 participants were enrolled, ranging from 115 to 174 per period. Seroprevalence quadrupled between the first (11.3%) and second (46.8%) periods and plateaued thereafter (third—46.0%, fourth—44.6%). Among seropositive participants, total antibody concentration was comparable throughout the first to third periods but declined between the third and fourth periods. Infection prevalence was comparable across enrollment periods (range 2.9–9.5%). Post-secondary education [aOR 0.42 (95% CI 0.26, 0.67)] was protective, and frontline work [aOR 1.81 (95% CI 1.18, 2.80)] was associated with increased odds of seropositivity. Frontline work status [aOR 2.27 (95% CI 1.10, 4.75)] and large household size [aOR 2.45 (95% CI 1.18, 5.49)] were associated with increased odds of infection.Conclusions: The quadrupling of seroprevalence over 3 months between the first and second enrollment periods coincided with the high burden of infection in Metro Manila in early 2020. Our findings suggest a limit to the rise and potential decline of population-level SARS-CoV-2 infection-induced immunity without introduction of vaccines. These results may add to our understanding of how immunity develops against emerging infectious diseases including coronaviruses

SARS-CoV-2 seroprevalence and infection rate in Manila, Philippines prior to national vaccination program implementation: a repeated cross-sectional analysis.

BACKGROUND: SARS-CoV-2 seroepidemiological studies are used to guide public health decision making and to prepare for emerging infectious diseases. Disease occurrence estimates are limited in the Philippines, the country with the highest reported number of coronavirus disease-related deaths in the Western Pacific region. We aimed to estimate SARS-CoV-2 seroprevalence and infection rate among outpatient clinic attendees in Metro Manila prior to the implementation of the national coronavirus disease vaccination program. METHODS: We conducted repeated cross-sectional surveys at the animal bite clinic in San Lazaro Hospital, Manila, the Philippines across four periods, 3 months apart, between May 2020 and March 2021. Multivariable logistic regression was used to assess associations between different characteristics and infection status including seropositivity. RESULTS: In total 615 participants were enrolled, ranging from 115 to 174 per period. Seroprevalence quadrupled between the first (11.3%) and second (46.8%) periods and plateaued thereafter (third-46.0%, fourth-44.6%). Among seropositive participants, total antibody concentration was comparable throughout the first to third periods but declined between the third and fourth periods. Infection prevalence was comparable across enrollment periods (range 2.9-9.5%). Post-secondary education [aOR 0.42 (95% CI 0.26, 0.67)] was protective, and frontline work [aOR 1.81 (95% CI 1.18, 2.80)] was associated with increased odds of seropositivity. Frontline work status [aOR 2.27 (95% CI 1.10, 4.75)] and large household size [aOR 2.45 (95% CI 1.18, 5.49)] were associated with increased odds of infection. CONCLUSIONS: The quadrupling of seroprevalence over 3 months between the first and second enrollment periods coincided with the high burden of infection in Metro Manila in early 2020. Our findings suggest a limit to the rise and potential decline of population-level SARS-CoV-2 infection-induced immunity without introduction of vaccines. These results may add to our understanding of how immunity develops against emerging infectious diseases including coronaviruses

Introduction: Toward an Engaged Feminist Heritage Praxis

We advocate a feminist approach to archaeological heritage work in order to transform heritage practice and the production of archaeological knowledge. We use an engaged feminist standpoint and situate intersubjectivity and intersectionality as critical components of this practice. An engaged feminist approach to heritage work allows the discipline to consider women’s, men’s, and gender non-conforming persons’ positions in the field, to reveal their contributions, to develop critical pedagogical approaches, and to rethink forms of representation. Throughout, we emphasize the intellectual labor of women of color, queer and gender non-conforming persons, and early white feminists in archaeology

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049