Changing severity and epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) in the United States after introduction of COVID-19 vaccines, March 2021-August 2022

INTRODUCTION: Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies. METHODS: Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed. RESULTS: Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47-72), 47% were women, and 21% non-Hispanic Black. From the Alpha-predominant period (Mar-Jul 2021; N = 1312) to the Omicron BA.4/BA.5 sublineage-predominant period (Jun-Aug 2022; N = 1307): the percentage of patients who had ≥4 categories of underlying medical conditions increased from 11% to 21%; those vaccinated with at least a primary COVID-19 vaccine series increased from 7% to 67%; those ≥75 years old increased from 11% to 33%; those who did not receive any supplemental oxygen increased from 18% to 42%. Median (IQR) highest C-reactive protein and D-dimer concentration decreased from 42.0 mg/L (9.9-122.0) to 11.5 mg/L (2.7-42.8) and 3.1 mcg/mL (0.8-640.0) to 1.0 mcg/mL (0.5-2.2), respectively. In-hospital death peaked at 12% in the Delta-predominant period and declined to 4% during the BA.4/BA.5-predominant period. CONCLUSIONS: Compared to adults hospitalized during early COVID-19 variant periods, those hospitalized during Omicron-variant COVID-19 were older, had multiple co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death

Notes on syphilis vaccine development

The quest for a syphilis vaccine to provide protection from infection or disease began not long after the isolation of the first Treponema pallidum subspecies pallidum (T. pallidum) strain in 1912. Yet, a practical and effective vaccine formulation continues to elude scientists. Over the last few years, however, efforts toward developing a syphilis vaccine have increased thanks to an improved understanding of the repertoire of T. pallidum outer membrane proteins (OMPs), which are the most likely syphilis vaccine candidates. More has been also learned about the molecular mechanisms behind pathogen persistence and immune evasion. Published vaccine formulations based on a subset of the pathogen’s OMPs have conferred only partial protection upon challenge of immunized laboratory animals, primarily rabbits. Nonetheless, those experiments have improved our approach to the choice of immunization regimens, adjuvants, and vaccine target selection, although significant knowledge gaps remain. Herein, we provide a brief overview on current technologies and approaches employed in syphilis vaccinology, and possible future directions to develop a vaccine that could be pivotal to future syphilis control and elimination initiatives

Implementing and sustaining a mobile medical clinic for prenatal care and sexually transmitted infection prevention in rural Mysore, India

Background In rural India, mobile medical clinics are useful models for delivering health promotion, education, and care. Mobile medical clinics use fewer providers for larger catchment areas compared to traditional clinic models in resource limited settings, which is especially useful in areas with shortages of healthcare providers and a wide geographical distribution of patients. Methods From 2008 to 2011, we built infrastructure to implement a mobile clinic system to educate rural communities about maternal child health, train community health workers in common safe birthing procedures, and provide comprehensive antenatal care, prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV), and testing for specific infections in a large rural catchment area of pregnant women in rural Mysore. This was done using two mobile clinics and one walk-in clinic. Women were tested for HIV, hepatitis B, syphilis, and bacterial vaginosis along with random blood sugar, urine albumin, and anemia. Sociodemographic information, medical, and obstetric history were collected using interviewer-administered questionnaires in the local language, Kannada. Data were entered in Microsoft Excel and analyzed using Stata SE 14.1. Results During the program period, nearly 700 community workers and 100 health care providers were trained; educational sessions were delivered to over 15,000 men and women and integrated antenatal care and HIV/sexually transmitted infection testing was offered to 3545 pregnant women. There were 22 (0.6%) cases of HIV, 19 (0.5%) cases of hepatitis B, 2 (0.1%) cases of syphilis, and 250 (7.1%) cases of BV, which were identified and treated. Additionally, 1755 (49.5%) cases of moderate to severe anemia and 154 (4.3%) cases of hypertension were identified and treated among the pregnant women tested. Conclusions Patient-centered mobile medical clinics are feasible, successful, and acceptable models that can be used to provide quality healthcare to pregnant women in rural and hard-to-reach settings. The high numbers of pregnant women attending mobile medical clinics show that integrated antenatal care with PMTCT services were acceptable and utilized. The program also developed and trained health professionals who continue to remain in those communities

Rapid Training and Implementation of the Pollock Technique, a Safe, Effective Newborn Circumcision Procedure, in a Low-Resource Setting

Male circumcision is highly protective against urinary tract infections, inflammatory conditions of the penis, sexually transmitted infections, and urogenital cancers. We aimed to reintroduce newborn male circumcision through the creation of a training program in Port-au-Prince, Haiti?an area with a considerable burden of preventable urogenital infections, sexually transmitted infections, and low circumcision rate?after an earlier study reported that a majority of Haitian medical providers were in need of and wanted newborn circumcision training. The program was conducted at the GHESKIO Health Centers, a large, non-governmental clinic offering comprehensive pediatric and adult health services. Two Haitian obstetricians and seven nurses learned circumcision procedures. On training completion, one of two obstetricians achieved surgical competence. Introduction of a newborn male circumcision training program was feasible, achieving an acceptable rate of procedural competency and high-quality services. Permanent resources now exist in Haiti to train additional providers to perform newborn male circumcisions

Persistent Chlamydia trachomatis, Neisseria gonorrhoeae or Trichomonas vaginalis positivity after treatment among human immunodeficiency virus-infected pregnant women, South Africa

The objective of this study is to assess the predictors and frequency of persistent sexually transmitted infection (STI) positivity in human immunodeficiency virus (HIV)-infected pregnant women treated for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) or Trichomonas vaginalis (TV) infection. We enrolled HIV-infected pregnant women attending their first antenatal care visit and tested them for urogenital CT, NG and TV infection using Xpert® CT/NG and TV assays (Cepheid, Sunnyvale, CA). Those testing positive were treated. Participants either notified partners to seek treatment or were given extra medication to deliver to partners for treatment. Repeat testing was conducted approximately 21 days post-treatment or treatment initiation. Among 427 participants, 172 (40.3%) tested positive for any STI. Of the 136 (79.1%) that returned for repeat testing, 36 (26.5%) tested positive for the same organism: CT = 27 (26.5%), NG = 1 (6.3%), TV = 11 (16.7%). Persistent CT positivity was independently associated with having more than one sex partner in the preceding 12 months (adjusted-prevalence ratio [aPR] = 3.03, 95% CI: 1.44–6.37) and being newly diagnosed with HIV infection during the first antenatal care visit compared to those currently on antiretroviral therapy (aPR = 3.97, 95% CI: 1.09–14.43). Persistent TV positivity was associated with not knowing if a partner sought treatment following STI disclosure (aPR = 12.6, 95% CI: 2.16–73.5) and prior diagnosis of HIV but not currently on antiretroviral therapy. (aPR = 4.14; 95% CI: 1.25–13.79). We identified a high proportion of HIV-infected pregnant women with persistent CT or TV positivity after treatment. To decrease the risk of re-infection, enhanced strategies for partner treatment programmes are needed to improve the effectiveness of STI screening and treatment in pregnancy. The relationship between not being on antiretroviral therapy and persistent STI positivity needs further study.The Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health (NIH), award R21HD084274 and the President’s Emergency Plan for AIDS Relief through the United States Agency of the Cooperative Agreement AID 674-A-12-00017 funded this study. Noah Kojima was supported by the U.S. NIH Fogarty International Center (award number D43TW009343) and the University of California Global Health Institute. Christina A Muzny was supported by K23AI106957-01A1 from the National Institute of Allergy and Infectious Diseases.https://journals.sagepub.com/home/stdhj2021Medical MicrobiologyPaediatrics and Child Healt

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

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

Impact of COVID-19 on Primary Care Quality Measures in an Academic Integrated Health System.

BackgroundAccess to primary care was hindered by the coronavirus disease 2019 (COVID-19) pandemic.ObjectiveEvaluate changes in health screening rates before and during the pandemic.DesignRetrospective analysis of health maintenance and disease management screening rates among primary care patients before and during the pandemic.ParticipantsOver 150,000 patients of a large, academic health system.Main measuresSix quality measures were analyzed: colon cancer, breast cancer, cervical cancer, diabetes Hgb A1C, diabetes eye, and diabetes nephropathy monitoring. Based on US Preventative Services Task Force screening guidelines, we determined which patients were due for at least one of the quality measures. We tracked completion rates during three time periods: pre-pandemic (January 1-March 3, 2020), stay-at-home (March 4-May 8, 2020), and phased reopening (May 9-July 8, 2020). Differences in quality measure completion rates were evaluated using mixed-effects logistic regression models.Key resultsCompared to pre-pandemic rates, completion of all health screenings declined during the stay-at-home period: mammograms (OR: 0.34; 95% CI: 0.31-0.37), cervical cancer (OR: 0.83; 95% CI: 0.76-0.91), colorectal cancer (OR: 0.25; 95% CI: 0.23-0.28), diabetes eye (OR: 0.34; 95% CI: 0.29-0.41), diabetes Hgb A1c (OR: 0.41; 95% CI: 0.37-0.46), and diabetes nephropathy (OR: 0.46, 95% CI: 0.41-0.53). During phased reopening, completion of all quality measures increased compared to the stay-at-home period, except for cervical cancer screening (OR: 0.83; 95% CI: 0.76-0.92). There was a persistent reduction in completion of all quality measures, except for diabetic nephropathy monitoring (OR: 0.99; 95% CI: 0.89-1.09), during phased reopening compared to pre-pandemic.ConclusionsHealthcare screening rates were reduced during the early part of the COVID-19 pandemic and did not fully recover to pre-pandemic rates by July 2020. Future research should aim to clarify the long-term impacts of delayed health screenings. New interventions should be considered for expanding remote preventative health services