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Background: Nirmatrelvir/ritonavir (NM/r) is a safe and effective oral antiviral therapeutic used for treatment of mild-to-moderate COVID-19. Case reports described a clinical rebound syndrome whereby individuals experience a relapse of symptoms shortly after completing successful treatment. There is a lack of information on frequency of COVID-19 rebound after NM/r in routine clinical care, contributing factors, and clinical outcomes., Methods: We reviewed electronic medical records to verify COVID-19 diagnosis, symptoms, and treatment with NM/r from January-June 2022. We defined COVID-19 clinical rebound as clear improvement in symptoms followed by recurrence or worsening of symptoms within 30 days of a five-day course of NM/r., Results: We studied 268 adults with median age 57 (IQR 47, 68), 80% White race, 85% non-Hispanic ethnicity, 55% female, 80% vaccinated and boosted against SARS-CoV-2, and 68% with any co-morbidity. Sixteen (6.0%) of studied patients were determined to have COVID-19 clinical rebound. The median time from starting NM/r to rebound was 11 days (IQR 9, 13). Notable demographic and clinical factors with higher proportion (not statistically significant) among COVID-19 rebound patients were female sex (75% rebound vs. 54.5% no rebound), Black race (12.5% rebound vs. 4.9% no rebound), presence of at least one co-morbidity (81.3% rebound vs. 67.5% no rebound), and lack of prior SARS-CoV-2 infection (100% rebound vs. 92.9% no rebound). Only one patient (6.25%) was hospitalized after COVID-19 rebound., Conclusions: COVID-19 clinical rebound after treatment with NM/r is mild with favorable outcomes and more common than previously reported from real-world clinical care studies., (© 2024. The Author(s).)

Background: This study updates the COVID-19 pandemic surveillance in Central Asia we conducted during the first year of the pandemic by providing 2 additional years of data for the region. The historical context provided through additional data can inform regional preparedness and early responses to infectious outbreaks of either the SARS-CoV-2 virus or future pathogens in Central Asia., Objective: First, we aim to measure whether there was an expansion or contraction in the pandemic in Central Asia when the World Health Organization (WHO) declared the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aim to provide historical context for the course of the pandemic in Central Asia., Methods: Traditional surveillance metrics, including counts and rates of COVID-19 transmissions and deaths, and enhanced surveillance indicators, including speed, acceleration, jerk, and persistence, were used to measure shifts in the pandemic. To identify the appearance and duration of variants of concern, we used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID). We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether regional speed was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period., Results: Speed for the region had remained below the outbreak threshold for 7 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant, the coefficients were relatively small in magnitude (0.125 and 0.347, respectively). Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, were both significant and negative, meaning the clustering effect of new COVID-19 cases became even smaller in the 2 weeks around the WHO declaration. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of speed equal to 10 became entirely insignificant for the first time in March 2023., Conclusions: Although COVID-19 continues to circulate in Central Asia, the rate of transmission remained well below the threshold of an outbreak for 7 months ahead of the WHO declaration. COVID-19 appeared to be endemic in the region and no longer reached the threshold of a pandemic. Both standard and enhanced surveillance metrics suggest the pandemic had ended by the time of the WHO declaration., (©Alexander L Lundberg, Egon A Ozer, Scott A Wu, Alan G Soetikno, Sarah B Welch, Yingxuan Liu, Robert J Havey, Robert L Murphy, Claudia Hawkins, Maryann Mason, Chad J Achenbach, Lori A Post. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 28.08.2024.)

Background: This study updates our findings from the COVID-19 pandemic surveillance we first conducted in South Asia in 2020 with 2 additional years of data for the region. We assess whether COVID-19 had transitioned from pandemic to endemic at the point the World Health Organization (WHO) ended the public health emergency status for COVID-19 on May 5, 2023., Objective: First, we aim to measure whether there was an expansion or contraction in the pandemic in South Asia around the WHO declaration. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aim to provide historical context for the course of the pandemic in South Asia., Methods: In addition to updating the traditional surveillance data and dynamic panel estimates from our original study, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether regional weekly speed or transmission rate per 100,000 population was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period., Results: Speed for the region had remained below the outbreak threshold for over a year by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1-day persistence coefficients remained statistically significant and positive (1.168), the 7-day persistence coefficient was negative (-0.185), suggesting limited cluster effects in which cases on a given day predict cases 7 days forward. Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, did not indicate any overall change in the persistence measure around the time of the WHO declaration. From December of 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of speed equal to 10 was statistically insignificant across the entire pandemic., Conclusions: While COVID-19 continued to circulate in South Asia, the rate of transmission had remained below the outbreak threshold for well over a year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had ended by the time of the WHO declaration. Prevention policies should be a focus ahead of future pandemics. On that point, policy should emphasize an epidemiological task force with widespread testing and a contact-tracing system., (©Lori A Post, Alan G Soetikno, Scott A Wu, Claudia Hawkins, Maryann Mason, Egon A Ozer, Robert L Murphy, Sarah B Welch, Yingxuan Liu, Robert J Havey, Charles B Moss, Chad J Achenbach, Alexander L Lundberg. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 26.08.2024.)

Background: SARS-CoV-2 vaccines are safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. This study was performed to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population., Methods and Findings: A retrospective clinical cohort study was performed utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. The primary outcome was the incidence and time to the first positive SARS-CoV-2 molecular test in the Omicron predominant era. Multivariable Cox modeling analyses to determine the hazard of SARS-CoV-2 infection were stratified by calendar time (Period 1: January 1 -June 30, 2022; Period 2: July 1 -December 31, 2022) due to violations in the proportional hazards assumption. In total, 133,191 patients were analyzed. During Period 1, having 3+ comorbidities was associated with increased hazard for breakthrough (HR = 1.16 CI 1.08-1.26). During Period 2 of the study, having 2 comorbidities (HR = 1.45 95% CI 1.26-1.67) and having 3+ comorbidities (HR 1.73, 95% CI 1.51-1.97) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in Period 1 of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period., Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age plays an important role in breakthrough infection with the highest incidence among young adults, which may be due to age-related behavioral factors. These findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Moreno Echevarria et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Pre-exposure prophylaxis (PrEP) is an effective, yet underutilized tool for HIV prevention. We sought to understand practice patterns and opportunities for prescribing PrEP across two large, urban, academic healthcare institutions in Chicago, Illinois., Methods: We analyzed electronic medical record data from two institutions including encounters for persons ≥18 years of age with ≥1 negative HIV test between 1/1/2015-12/31/2021 who had indications for PrEP. Eligible encounters were those within a six-month window after STI diagnosis, or as long as injection drug use (IDU) was documented. We categorized encounters as inpatient, emergency department (ED), primary care, infectious disease (ID), obstetrics and gynecology/women's health (OBGYN) and other outpatient settings. We performed bivariable and multivariable mixed effects regression models to examine associations, reporting odds ratios (or adjusted odds ratios) and 95% confidence intervals (OR, aOR, 95% CI)., Results: In total, 9644 persons contributed 53031 encounters that resulted in 4653 PrEP prescriptions. The two healthcare institutions had differing patient demographics; institution A had more 18-24 year-olds (58.3% vs 31.3%), more African Americans (83.8% vs 27.9%), and more women (65.7% vs 46.3%). Institution B had more White (40.6% vs 7.1%) and Hispanic persons (14.0% vs 4.2%), and more men who have sex with men (MSM) (15.2% vs 3.3%). Institution A had more eligible encounters in the ED (30.8% vs 7.3%) as well as in infectious disease, inpatient, OBYGN, and primary care settings. Institution B accounted for the majority of PrEP prescriptions (97.0%).Adjusted models found lower odds of PrEP prescriptions in non-Hispanic Black (aOR 0.23 [0.16, 0.32]) and Latino (aOR 0.62 [0.44, 0.89]) patients, those with injection drug use (aOR 0.01 [0.00, 0.09]), men who have sex with women (aOR 0.36 [0.23, 0.56]), women who have sex with men (aOR 0.11 [0.06, 0.19]), and in the ED (ref) or OBGYN (0.11 [0.04, 0.27]) settings; while increased odds of PrEP prescription were associated with non-Hispanic White (ref) and MSM (aOR 24.87 [15.79, 39.15]) patients, and encounters at Institution B (aOR 1.78 [1.25, 2.53]) and in infectious disease (aOR [11.92 [7.65, 18.58]), primary care (aOR 2.76 [1.90, 4.01]), and other outpatient subspecialty settings (aOR 2.67 [1.84, 3.87])., Conclusions: Institution A contained persons historically underrepresented in PrEP prescriptions, while institution B accounted for most PrEP prescriptions. Opportunities exist to improve equity in PrEP prescribing and across ED and OBGYN settings.

Background: Nirmatrelvir/ritonavir (NM/r) is a safe and effective oral antiviral therapeutic used for treatment of mild-to-moderate COVID-19. Case reports described a clinical rebound syndrome whereby individuals experience a relapse of symptoms shortly after completing successful treatment. There is a lack of information on frequency of COVID-19 rebound after NM/r in routine clinical care, contributing factors, and clinical outcomes., Methods: We reviewed electronic medical records to verify COVID-19 diagnosis, symptoms, and treatment with NM/r from January-June 2022. We defined COVID-19 clinical rebound as clear improvement in symptoms followed by recurrence or worsening of symptoms within 30 days of a five-day course of NM/r., Results: We studied 268 adults with median age 57 (IQR 47, 68), 80% White race, 85% non-Hispanic ethnicity, 55% female, 80% vaccinated and boosted against SARS-CoV-2, and 68% with any co-morbidity. Sixteen (6.0%) of studied patients were determined to have COVID-19 clinical rebound. The median time from starting NM/r to rebound was 11 days (IQR 9, 13). Notable demographic and clinical factors with higher proportion (not statistically significant) among COVID-19 rebound patients were female sex (75% rebound vs 54.5% no rebound), Black race (12.5% rebound vs 4.9% no rebound), presence of at least one co-morbidity (81.3% rebound vs 67.5% no rebound), and lack of prior SARS-CoV-2 infection (100% rebound vs 92.9% no rebound). Only one patient (6.25%) was hospitalized after COVID-19 rebound., Conclusions: COVID-19 clinical rebound after treatment with NM/r is mild with favorable outcomes and more common than previously reported from real-world clinical care studies., Competing Interests: Conflicts of interest/Competing interests All authors declare that they have no conflicts of interest.

Significance: Little is known about the mechanisms by which medication adherence promotes smoking cessation among adults with MDD. We tested the hypothesis that early adherence promotes abstinence by increasing behavioral treatment (BT) utilization., Methods: Data for this post-hoc analysis were from a randomized trial of 149 adults with current or past MDD treated with BT and either varenicline (n = 81) or placebo (n = 68). Arms were matched on medication regimen. Early medication adherence was measured by the number of days in which medication was taken at the prescribed dose during the first six of 12 weeks of pharmacological treatment (weeks 2-7). BT consisted of eight 45-minute sessions (weeks 1-12). Bioverified abstinence was assessed at end-of-treatment (week 14). A regression-based approach was used to test whether the effect of early medication adherence on abstinence was mediated by BT utilization., Results: Among 141 participants who initiated the medication regimen, BT utilization mediated the effect of early medication adherence on abstinencea) an interquartile increase in early medication days from 20 to 42 predicted a 4.2 times increase in abstinence (Total Risk Ratio (RR) = 4.24, 95% CI = 2.32-13.37; p <.001); b) increases in BT sessions predicted by such an increase in early medication days were associated with a 2.7 times increase in abstinence (Indirect RR = 2.73, 95% CI = 1.54-7.58; p <.001); and c) early medication adherence effects on abstinence were attenuated, controlling for BT (Direct RR = 1.55, 95% CI = 0.83-4.23, p =.17)., Conclusions: The effect of early medication adherence on abstinence in individuals with current or past MDD is mediated by intensive BT utilization., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brian Hitsman, PhD, has served on scientific advisory boards for Pfizer and received medication and placebo free of charge from Pfizer for the parent study (NCT02378714). Robert A. Schnoll, PhD, has received varenicline and placebo free of charge from Pfizer for National Institutes of Health-funded trials and has served as a consultant for Pfizer, GlaxoSmithKline, and PalliaTech. David C. Mohr, PhD, has accepted honoraria and consulting fees from Otsuka Pharmaceuticals, Optum Behavioral Health, Centerstone Research Institute, and the One Mind Foundation; royalties from Oxford Press, and has an ownership interest in Adaptive Health, Inc. Mark D. Huffman, MD, MPH, has patents for combination therapy for the treatment of heart failure. The George Institute for Global Health has a patent, license, and has received investment funding with the intent to commercialize fixed-dose combination therapy through its social enterprise business, George Medicines. Jacqueline K. Gollan has accepted royalties from the American Psychological Association., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with enhanced transmissibility and immune escape have emerged periodically throughout the coronavirus disease 2019 (COVID-19) pandemic, but the impact of these variants on disease severity has remained unclear. In this single-center, retrospective cohort study, we examined the association between SARS-CoV-2 clade and patient outcome over a two-year period in Chicago, Illinois. Between March 2020 and March 2022, 14,252 residual diagnostic specimens were collected from SARS-CoV-2-positive inpatients and outpatients alongside linked clinical and demographic metadata, of which 2,114 were processed for viral whole-genome sequencing. When controlling for patient demographics and vaccination status, several viral clades were associated with risk for hospitalization, but this association was negated by the inclusion of population-level confounders, including case count, sampling bias, and shifting standards of care. These data highlight the importance of integrating non-virological factors into disease severity and outcome models for the accurate assessment of patient risk., Competing Interests: Declaration of interests M.G.I. has received research support, paid to Northwestern University, from AiCuris, GlaxoSmithKline Janssen, and Shire. M.G.I. is a paid consultant for Adagio, AlloVir, Celltrion, Cidara, Genentech, Roche, Janssen, Shionogi, Takeda, and Viracor Eurofins. M.G.I. is a paid member of the data and safety monitoring boards (DSMBs) of CSL Berhring, Janssen, Merck, SAB Biotherapeutics, Sequiris, and Takeda. J.F.H. has received research support, paid to Northwestern University, from Gilead Sciences and is a paid consultant for Merck., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute coronavirus disease 2019 (COVID-19) and may affect clinical management., Methods: In this retrospective cohort study, we applied the US Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at 6 academic medical centers from 1 March 2020 to 31 December 2021. Patients MIS-A were matched by age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographic characteristics, presenting symptoms, laboratory and imaging results, treatments administered, and outcomes between cohorts., Results: Through medical record review of 10 223 patients hospitalized with SARS-CoV-2-associated illness, we identified 53 MIS-A cases. Compared with 106 matched patients with COVID-19, those with MIS-A were more likely to be non-Hispanic black and less likely to be non-Hispanic white. They more likely had laboratory-confirmed COVID-19 ≥14 days before hospitalization, more likely had positive in-hospital SARS-CoV-2 serologic testing, and more often presented with gastrointestinal symptoms and chest pain. They were less likely to have underlying medical conditions and to present with cough and dyspnea. On admission, patients with MIS-A had higher neutrophil-to-lymphocyte ratio and higher levels of C-reactive protein, ferritin, procalcitonin, and D-dimer than patients with COVID-19. They also had longer hospitalization and more likely required intensive care admission, invasive mechanical ventilation, and vasopressors. The mortality rate was 6% in both cohorts., Conclusions: Compared with patients with acute symptomatic COVID-19, adults with MIS-A more often manifest certain symptoms and laboratory findings early during hospitalization. These features may facilitate diagnosis and management., Competing Interests: Potential conflicts of interest. After this work was conducted, S. G. C. became an employee of the University of Utah, where she received funding from the Pediatric Pandemic Network through her institution. A. G. is a copyright holder of the Hidradenitis Suppurativa–Specific Investigator Global Assessment (HS-IGA) and the Hidradenitis Suppurativa Quality of Life score (HiSQOL); received consulting fees (honoraria for advisory role) from AbbVie, Aclaris Therapeutics, AnaptysBio, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Incyte, Insmed, Janssen Pharmaceuticals, Novartis, Pfizer, Sonoma Biotherapeutics, UCB, UNION Therapeutics, Ventyx Biosciences, and Viela Bio; and was funded by AbbVie, UCB, the National Psoriasis Foundation, and the CHORD COUSIN Collaboration (C3) through grants to his institution. M. N. received consulting fees from Pfizer for serving on a coronavirus disease 2019 task force. C. J. A. participated on a data safety monitoring board for Abivax. L. M. A. was compensated by Regeneron for work as a coinvestigator in clinical trials, participated on a data safety monitoring board for Ferring Pharmaceuticals, and served on the Infectious Diseases Society of America Board of Directors. L. B. participated on a data safety monitoring board for Gilead Sciences (advisory meeting after the Conference on Retroviruses and Opportunistic Infections on 11 April 2022). R. M. received consulting fees from and is a shareholder in Acolyte Health (Cedars Sinai Accelerator) and reports support for attending meetings and/or travel for the 2023 American Medical Informatics Association Clinical Informatics Conference from Cedars Sinai. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Invasive cervical cancer (ICC) is an HIV-associated cancer that is preventable and precancerous stages including early ICC stages could be detected through screening offering opportunities for treatment and cure. The high incidence in women living with HIV and late presentation often at advanced stages of ICC with limited treatment facilities often result in early mortality. We sought to compare the epidemiologic characteristics and survival differences in HIV status of ICC patients in Nigeria., Methods: We conducted a cohort study at two federal academic hospital-based research sites in Jos University Teaching Hospital, and Lagos University Teaching Hospital Nigeria, between March 2018 and September 2022. We enrolled women with histologically confirmed ICC with known HIV status, and FIGO staging as part of the United States of America's National Institutes of Health/National Cancer Institute funded project titled 'Epigenomic Biomarkers of HIV-Associated Cancers in Nigeria'. The primary outcome was all-cause mortality with assessment of overall survival (OS) and time to death after ICC diagnosis. OS distribution was estimated using the method of Kaplan-Meier and compared between groups using the log-rank test., Results: A total of 239 women with confirmed ICC were enrolled and included in this analysis, of whom 192 (80.3%) were HIV-negative (HIV-/ICC +), and 47 (19.7%) were HIV-positive (HIV +/ICC +). The HIV +/ICC + patients were younger with median age 46 (IQR: 40-51) years compared to 57 (IQR: 45-66) among HIV-/ICC + (P < 0.001). Squamous cell carcinoma was the commonest histopathologic variant in 80.4% of ICC diagnosis, moderately differentiated tumor grade in 68.1% in both groups. HIV +/ICC + diagnosis was at FIGO advanced stages in 64.9% compared to 47.9% in HIV-/ICC +. The HIV-/ICC + women had better OS compared to HIV +/ICC + participants (p = 0.018), with 12-month OS 84.1% (95%CI 75-90%) and 67.6% (95%CI 42-84%) respectively., Conclusion: ICC is diagnosed at a relatively young age in women living with HIV, with a significantly lower overall survival probability compared to women without HIV. The trend of presentation and diagnosis at advanced stages in women living with HIV could partly explain the differences in overall survival., (© 2023. The Author(s).)

Background: Contribution of host factors in mediating susceptibility to extrapulmonary tuberculosis is not well understood., Objective: To examine the influence of patient sex on anatomical localization of extrapulmonary tuberculosis., Methods: We conducted a retrospective cross-sectional study in Mali, West Africa. Hospital records of 1,304 suspected cases of extrapulmonary tuberculosis, available in TB Registry of a tertiary tuberculosis referral center from 2019 to 2021, were examined., Results: A total of 1,012 (77.6%) were confirmed to have extrapulmonary tuberculosis with a male to female ratio of 1.59:1. Four clinical forms of EPTB predominated, namely pleural (40.4%), osteoarticular (29.8%), lymph node (12.5%), and abdominal TB (10.3%). We found sex-based differences in anatomical localization of extrapulmonary tuberculosis, with males more likely than females to have pleural TB (OR: 1.51; 95% CI [1.16 to 1.98]). Conversely, being male was associated with 43% and 41% lower odds of having lymph node and abdominal TB, respectively (OR: 0.57 and 0.59)., Conclusion: Anatomical sites of extrapulmonary tuberculosis differ by sex with pleural TB being associated with male sex while lymph node and abdominal TB are predominately associated with female sex. Future studies are warranted to understand the role of sex in mediating anatomical site preference of tuberculosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC)., Methods: This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC., Results: We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43-58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC., Conclusion: Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control., (© 2023. The Author(s).)

Background: The performance of rapid antigen tests (Ag-RDTs) for screening asymptomatic and symptomatic persons for SARS-CoV-2 is not well established., Objective: To evaluate the performance of Ag-RDTs for detection of SARS-CoV-2 among symptomatic and asymptomatic participants., Design: This prospective cohort study enrolled participants between October 2021 and January 2022. Participants completed Ag-RDTs and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 every 48 hours for 15 days., Setting: Participants were enrolled digitally throughout the mainland United States. They self-collected anterior nasal swabs for Ag-RDTs and RT-PCR testing. Nasal swabs for RT-PCR were shipped to a central laboratory, whereas Ag-RDTs were done at home., Participants: Of 7361 participants in the study, 5353 who were asymptomatic and negative for SARS-CoV-2 on study day 1 were eligible. In total, 154 participants had at least 1 positive RT-PCR result., Measurements: The sensitivity of Ag-RDTs was measured on the basis of testing once (same-day), twice (after 48 hours), and thrice (after a total of 96 hours). The analysis was repeated for different days past index PCR positivity (DPIPPs) to approximate real-world scenarios where testing initiation may not always coincide with DPIPP 0. Results were stratified by symptom status., Results: Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDTs twice 48 hours apart resulted in an aggregated sensitivity of 93.4% (95% CI, 90.4% to 95.9%) among symptomatic participants on DPIPPs 0 to 6. When singleton positive results were excluded, the aggregated sensitivity on DPIPPs 0 to 6 for 2-time serial testing among asymptomatic participants was lower at 62.7% (CI, 57.0% to 70.5%), but it improved to 79.0% (CI, 70.1% to 87.4%) with testing 3 times at 48-hour intervals., Limitation: Participants tested every 48 hours; therefore, these data cannot support conclusions about serial testing intervals shorter than 48 hours., Conclusion: The performance of Ag-RDTs was optimized when asymptomatic participants tested 3 times at 48-hour intervals and when symptomatic participants tested 2 times separated by 48 hours., Primary Funding Source: National Institutes of Health RADx Tech program., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-0385.

The SARS-CoV-2 nucleocapsid (N) protein is highly immunogenic, and anti-N antibodies are commonly used as markers for prior infection. While several studies have examined or predicted the antigenic regions of N, these have lacked consensus and structural context. Using COVID-19 patient sera to probe an overlapping peptide array, we identified six public and four private epitope regions across N, some of which are unique to this study. We further report the first deposited X-ray structure of the stable dimerization domain at 2.05 Å as similar to all other reported structures. Structural mapping revealed that most epitopes are derived from surface-exposed loops on the stable domains or from the unstructured linker regions. An antibody response to an epitope in the stable RNA binding domain was found more frequently in sera from patients requiring intensive care. Since emerging amino acid variations in N map to immunogenic peptides, N protein variation could impact detection of seroconversion for variants of concern. IMPORTANCE As SARS-CoV-2 continues to evolve, a structural and genetic understanding of key viral epitopes will be essential to the development of next-generation diagnostics and vaccines. This study uses structural biology and epitope mapping to define the antigenic regions of the viral nucleocapsid protein in sera from a cohort of COVID-19 patients with diverse clinical outcomes. These results are interpreted in the context of prior structural and epitope mapping studies as well as in the context of emergent viral variants. This report serves as a resource for synthesizing the current state of the field toward improving strategies for future diagnostic and therapeutic design., Competing Interests: The authors declare a conflict of interest. K.J.F.S. has significant financial interest in Situ Biosciences LLC, a contract research organization that conducts coronavirus research unrelated to this work. K.J.F.S. also received payments from Buoy Health during the time of this investigation for consultation on COVID-19 topics unrelated to this work. All other authors declare no conflicts of interest.

Importance: Statin use prior to hospitalization for Coronavirus Disease 2019 (COVID-19) is hypothesized to improve inpatient outcomes including mortality, but prior findings from large observational studies have been inconsistent, due in part to confounding. Recent advances in statistics, including incorporation of machine learning techniques into augmented inverse probability weighting with targeted maximum likelihood estimation, address baseline covariate imbalance while maximizing statistical efficiency., Objective: To estimate the association of antecedent statin use with progression to severe inpatient outcomes among patients admitted for COVD-19., Design, Setting and Participants: We retrospectively analyzed electronic health records (EHR) from individuals ≥ 40-years-old who were admitted between March 2020 and September 2022 for ≥ 24 h and tested positive for SARS-CoV-2 infection in the 30 days before to 7 days after admission., Exposure: Antecedent statin use-statin prescription ≥ 30 days prior to COVID-19 admission., Main Outcome: Composite end point of in-hospital death, intubation, and intensive care unit (ICU) admission., Results: Of 15,524 eligible COVID-19 patients, 4412 (20%) were antecedent statin users. Compared with non-users, statin users were older (72.9 (SD: 12.6) versus 65.6 (SD: 14.5) years) and more likely to be male (54% vs. 51%), White (76% vs. 71%), and have ≥ 1 medical comorbidity (99% vs. 86%). Unadjusted analysis demonstrated that a lower proportion of antecedent users experienced the composite outcome (14.8% vs 19.3%), ICU admission (13.9% vs 18.3%), intubation (5.1% vs 8.3%) and inpatient deaths (4.4% vs 5.2%) compared with non-users. Risk differences adjusted for labs and demographics were estimated using augmented inverse probability weighting with targeted maximum likelihood estimation using Super Learner. Statin users still had lower rates of the composite outcome (adjusted risk difference: - 3.4%; 95% CI: - 4.6% to - 2.1%), ICU admissions (- 3.3%; - 4.5% to - 2.1%), and intubation (- 1.9%; - 2.8% to - 1.0%) but comparable inpatient deaths (0.6%; - 1.3% to 0.1%)., Conclusions and Relevance: After controlling for confounding using doubly robust methods, antecedent statin use was associated with minimally lower risk of severe COVID-19-related outcomes, ICU admission and intubation, however, we were not able to corroborate a statin-associated mortality benefit., (© 2023. The Author(s).)

Background: Disparities in access to anti-SARS-CoV-2 monoclonal antibodies have not been well characterized., Objective: We sought to explore the impact of race/ethnicity as a social construct on monoclonal antibody delivery., Design/patients: Following implementation of a centralized infusion program at a large academic healthcare system, we reviewed a random sample of high-risk ambulatory adult patients with COVID-19 referred for monoclonal antibody therapy., Main Measures: We examined the relationship between treatment delivery, race/ethnicity, and other demographics using descriptive statistics, binary logistic regression, and spatial analysis., Key Results: There was no significant difference in racial composition between patients who did (n = 25) and patients who did not (n = 378) decline treatment (p = 0.638). Of patients who did not decline treatment, 64.8% identified as White, 14.8% as Hispanic/Latinx, and 11.1% as Black. Only 44.6% of Hispanic/Latinx and 31.0% of Black patients received treatment compared to 64.1% of White patients (OR 0.45, 95% CI 0.25-0.81, p = 0.008, and OR 0.25, 95% CI 0.12-0.50, p < 0.001, respectively). In multivariable analysis including age, race, insurance status, non-English primary language, county Social Vulnerability Index, illness severity, and total number of comorbidities, associations between receiving treatment and Hispanic/Latinx or Black race were no longer statistically significant (AOR 1.32, 95% CI 0.69-2.53, p = 0.400, and AOR 1.34, 95% CI 0.64-2.80, p = 0.439, respectively). However, patients who were uninsured or whose primary language was not English were less likely to receive treatment (AOR 0.16, 95% CI 0.03-0.88, p = 0.035, and AOR 0.37, 95% CI 0.15-0.90, p = 0.028, respectively). Spatial analysis suggested decreased monoclonal antibody delivery to Cook County patients residing in socially vulnerable communities., Conclusions: High-risk ambulatory patients with COVID-19 who identified as Hispanic/Latinx or Black were less likely to receive monoclonal antibody therapy in univariate analysis, a finding not explained by patient refusal. Multivariable and spatial analyses suggested insurance status, language, and social vulnerability contributed to racial disparities., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objectives: We assessed the incidence of extrahepatic cancer among people with HIV/HCV coinfection and the potential impact of direct-acting antivirals (DAAs) on extrahepatic cancer risk among people with HIV/HCV coinfection., Design: Our study cohort included adults who initiated HIV care at a CNICS site in the US during 1995-2017, excluding those with previous cancer and without HCV testing., Methods: We used Cox regression to estimate hazard ratios for extrahepatic cancer incidence among patients with HIV/HCV coinfection compared with those with HIV monoinfection. Standardized morbidity ratio (SMR) weights were used to create a 'pseudopopulation' in which all patients were treated with antiretroviral therapy (ART), and to compare extrahepatic cancer incidence among patients with untreated HIV/HCV coinfection with the incidence that would have been observed if they had been successfully treated for HCV., Results: Of 18 422 adults, 1775 (10%) had HCV RNA and 10 899 (59%) were on ART at baseline. Incidence rates of any extrahepatic cancer among patients with HIV/HCV coinfection and HIV monoinfection were 1027 and 771 per 100 000 person-years, respectively. In SMR-weighted analyses, the risk of any extrahepatic cancer among patients with untreated HCV coinfection at baseline was similar to the risk if they had been successfully treated for HCV. Patients with untreated HCV coinfection at baseline had higher incidence of kidney, lung and inflammation-related cancers than if their HCV had been successfully treated, but these associations were not statistically significant., Conclusions: We did not find evidence that treating HCV coinfection with DAAs would reduce the incidence of extrahepatic cancers among people with HIV receiving ART., (© 2021 British HIV Association.)

Background: An ideal test for COVID-19 would combine the sensitivity of laboratory-based PCR with the speed and ease of use of point-of-care (POC) or home-based rapid antigen testing. We evaluated clinical performance of the Diagnostic Analyzer for Selective Hybridization (DASH) SARS-CoV-2 POC rapid PCR test., Methods: We conducted a cross-sectional study of adults with and without symptoms of COVID-19 at four clinical sites where we collected two bilateral anterior nasal swabs and information on COVID-19 symptoms, vaccination, and exposure. One swab was tested with the DASH SARS-CoV-2 POC PCR and the second in a central laboratory using Cepheid Xpert Xpress SARS-CoV-2 PCR. We assessed test concordance and calculated sensitivity, specificity, negative and positive predictive values using Xpert as the "gold standard"., Results: We enrolled 315 and analyzed 313 participants with median age 42 years; 65% were female, 62% symptomatic, 75% had received ≥2 doses of mRNA COVID-19 vaccine, and 16% currently SARS-CoV-2 positive. There were concordant results for 307 tests indicating an overall agreement for DASH of 0.98 [95% CI 0.96, 0.99] compared to Xpert. DASH performed at 0.96 [95% CI 0.86, 1.00] sensitivity and 0.98 [95% CI 0.96, 1.00] specificity, with a positive predictive value of 0.85 [95% CI 0.73, 0.96] and negative predictive value of 0.996 [95% CI 0.99, 1.00]. The six discordant tests between DASH and Xpert all had high Ct values (>30) on the respective positive assay. DASH and Xpert Ct values were highly correlated (R = 0.89 [95% CI 0.81, 0.94])., Conclusions: DASH POC SARS-CoV-2 PCR was accurate, easy to use, and provided fast results (approximately 15 minutes) in real-life clinical settings with an overall performance similar to an EUA-approved laboratory-based PCR., Competing Interests: The authors have declared that no competing interests exist.

Men and women often respond differently to infectious diseases and their treatments. Tuberculosis (TB) is a life-threatening communicable disease that affects more men than women globally. Whether male sex is an independent risk factor for unfavorable TB outcomes, however, has not been rigorously investigated in an African context, where individuals are likely exposed to different microbial and environmental factors. We analyzed data collected from a cohort study in Mali by focusing on newly diagnosed active pulmonary TB individuals who were treatment naive. We gathered baseline demographic, clinical, and microbiologic characteristics before treatment initiation and also at three time points during treatment. More males than females were affected with TB, as evidenced by a male-to-female ratio of 2.4:1. In addition, at baseline, males had a significantly higher bacterial count and shorter time to culture positivity as compared with females. Male sex was associated with lower smear negativity rate after 2 months of treatment also known as the intensive phase of treatment, but not at later time points. There was no relationship between patients' sex and mortality from any cause during treatment. This study suggests that sex-based differences in TB outcomes exist, with sex-specific effects on disease outcomes being more pronounced before treatment initiation and during the intensive phase of treatment rather than at later phases of treatment.

Background: Independent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada., Methods: We examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness., Results: Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P < .05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values., Conclusions: A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The Omicron variant of SARS-CoV-2 is more transmissible than prior variants of concern (VOCs). It has caused the largest outbreaks in the pandemic, with increases in mortality and hospitalizations. Early data on the spread of Omicron were captured in countries with relatively low case counts, so it was unclear how the arrival of Omicron would impact the trajectory of the pandemic in countries already experiencing high levels of community transmission of Delta., Objective: The objective of this study is to quantify and explain the impact of Omicron on pandemic trajectories and how they differ between countries that were or were not in a Delta outbreak at the time Omicron occurred., Methods: We used SARS-CoV-2 surveillance and genetic sequence data to classify countries into 2 groups: those that were in a Delta outbreak (defined by at least 10 novel daily transmissions per 100,000 population) when Omicron was first sequenced in the country and those that were not. We used trend analysis, survival curves, and dynamic panel regression models to compare outbreaks in the 2 groups over the period from November 1, 2021, to February 11, 2022. We summarized the outbreaks in terms of their peak rate of SARS-CoV-2 infections and the duration of time the outbreaks took to reach the peak rate., Results: Countries that were already in an outbreak with predominantly Delta lineages when Omicron arrived took longer to reach their peak rate and saw greater than a twofold increase (2.04) in the average apex of the Omicron outbreak compared to countries that were not yet in an outbreak., Conclusions: These results suggest that high community transmission of Delta at the time of the first detection of Omicron was not protective, but rather preluded larger outbreaks in those countries. Outbreak status may reflect a generally susceptible population, due to overlapping factors, including climate, policy, and individual behavior. In the absence of strong mitigation measures, arrival of a new, more transmissible variant in these countries is therefore more likely to lead to larger outbreaks. Alternately, countries with enhanced surveillance programs and incentives may be more likely to both exist in an outbreak status and detect more cases during an outbreak, resulting in a spurious relationship. Either way, these data argue against herd immunity mitigating future outbreaks with variants that have undergone significant antigenic shifts., (©Alexander L Lundberg, Ramon Lorenzo-Redondo, Judd F Hultquist, Claudia A Hawkins, Egon A Ozer, Sarah B Welch, P V Vara Prasad, Chad J Achenbach, Janine I White, James F Oehmke, Robert L Murphy, Robert J Havey, Lori A Post. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 03.06.2022.)

Background: Invasive cervical cancer (ICC) is a serious public health burden in Nigeria, where human immunodeficiency virus (HIV) remains highly prevalent. Previous research suggested that epigenetic age acceleration (EAA) could play a role in detection of HIV-associated ICC. However, little research has been conducted on this topic in Africa where the population is most severely affected by HIV-associated ICC. Here, we investigated the association between ICC and EAA using cervical tissues of ICC-diagnosed Nigerian women living with HIV., Methods: We included 116 cervical tissue samples from three groups of Nigerian women in this study: (1) HIV+/ICC+ ( n = 39); (2) HIV+/ICC- ( n = 53); and (3) HIV-/ICC + ( n = 24). We utilized four DNA methylation-based EAA estimators; IEAA, EEAA, GrimAA, and PhenoAA. We compared EAA measurements across the 3 HIV/ICC groups using multiple linear regression models. We also compared EAA between 26 tumor tissues and their surrounding normal tissues using paired t -tests. We additionally performed a receiver operating characteristics (ROC) curve analysis to illustrate the area under the curve (AUC) of EAA in ICC., Results: We found the most striking associations between HIV/ICC status and PhenoAge acceleration (PhenoAA). Among HIV-positive women, PhenoAA was on average 13.4 years higher in women with ICC compared to cancer-free women ( P = 0.005). PhenoAA was 20.7 and 7.1 years higher in tumor tissues compared to surrounding normal tissues among HIV-positive women ( P = 0.009) and HIV-negative women ( P = 0.284), respectively. We did not find substantial differences in PhenoAA between HIV-positive and HIV-negative women with ICC., Conclusion: PhenoAA is associated with ICC in HIV-infected women in our study. Our findings suggest that PhenoAA may serve as a potential biomarker for further risk stratification of HIV-associated ICC in Nigeria and similar resource-constrained settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Musa, Kim, Zheng, Qu, Joyce, Wang, Nannini, Gursel, Silas, Abdulkareem, Imade, Akanmu, Wei, Kocherginsky, Kim, Wehbe, Achenbach, Anorlu, Simon, Sagay, Ogunsola, Murphy and Hou.)

Background: The global effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during an ongoing pandemic has raised questions about how vaccine breakthrough infections compare with infections in immunologically naive individuals and the potential for vaccinated individuals to transmit the virus., Methods: We examined viral dynamics and infectious virus shedding through daily longitudinal sampling in 23 adults infected with SARS-CoV-2 at varying stages of vaccination, including 6 fully vaccinated individuals., Results: The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases., Conclusions: Vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To assess differences in anal cancer incidence between racial/ethnic groups among a clinical cohort of men with HIV who have sex with men., Design: Clinical cohort study., Methods: We studied men who have sex with men (MSM) in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who initiated antiretroviral therapy (ART) under HIV care in CNICS. We compared anal cancer incidence between Black and non-Black men and calculated hazard ratios controlling for demographic characteristics (age, CNICS site, year of ART initiation), HIV disease indicators (nadir CD4+, peak HIV RNA), and co-infection/behavioral factors including hepatitis B virus (HBV), hepatitis C virus (HCV), tobacco smoking and alcohol abuse., Results: We studied 7473 MSM with HIV who contributed 41 810 person-years of follow-up after initiating ART between 1996 and 2014 in CNICS. Forty-one individuals had an incident diagnosis of anal cancer under observation. Crude rates of anal cancer were 204 versus 61 per 100 000 person-years among Black versus non-Black MSM. The weighted hazard ratio for anal cancer in Black MSM (adjusting for demographics, HIV disease factors, and co-infection/behavioral factors) was 2.37 (95% confidence interval: 1.17, 4.82) compared to non-Black MSM., Conclusions: In this large multicenter cohort, Black MSM were at significantly increased risk for anal cancer compared to non-Black MSM. Further detailed studies evaluating factors impacting anal cancer incidence and outcomes in Black men with HIV are necessary. Inclusion of more diverse study cohorts may elucidate modifiable factors associated with increased anal cancer risk experienced by Black MSM., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Based on our recently reported associations between specific dietary behaviors and the risk of COVID-19 infection in the UK Biobank (UKB) cohort, we further investigate whether these associations are specific to COVID-19 or extend to other respiratory infections. Methods: Pneumonia and influenza diagnoses were retrieved from hospital and death record data linked to the UKB. Baseline, self-reported (2006−2010) dietary behaviors included being breastfed as a baby and intakes of coffee, tea, oily fish, processed meat, red meat (unprocessed), fruit, and vegetables. Logistic regression estimated the odds of pneumonia/influenza from baseline to 31 December 2019 with each dietary component, adjusting for baseline socio-demographic factors, medical history, and other lifestyle behaviors. We considered effect modification by sex and genetic factors related to pneumonia, COVID-19, and caffeine metabolism. Results: Of 470,853 UKB participants, 4.0% had pneumonia and 0.2% had influenza during follow up. Increased consumption of coffee, tea, oily fish, and fruit at baseline were significantly and independently associated with a lower risk of future pneumonia events. Increased consumption of red meat was associated with a significantly higher risk. After multivariable adjustment, the odds of pneumonia (p ≤ 0.001 for all) were lower by 6−9% when consuming 1−3 cups of coffee/day (vs. <1 cup/day), 8−11% when consuming 1+ cups of tea/day (vs. <1 cup/day), 10−12% when consuming oily fish in higher quartiles (vs. the lowest quartile—Q1), and 9−14% when consuming fruit in higher quartiles (vs. Q1); it was 9% higher when consuming red meat in the fourth quartile (vs. Q1). Similar patterns of associations were observed for influenza but only associations with tea and oily fish met statistical significance. The association between fruit and pneumonia risk was stronger in women than in men (p = 0.001 for interaction). Conclusions: In the UKB, consumption of coffee, tea, oily fish, and fruit were favorably associated with incident pneumonia/influenza and red meat was adversely associated. Findings for coffee parallel those we reported previously for COVID-19 infection, while other findings are specific to these more common respiratory infections.

Background: While several demographic and clinical correlates of coronavirus disease 2019 (COVID-19) outcome have been identified, their relationship to virological and immunological parameters remains poorly defined., Methods: To address this, we performed longitudinal collection of nasopharyngeal swabs and blood samples from a cohort of 58 hospitalized adults with COVID-19. Samples were assessed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load, viral genotype, viral diversity, and antibody titer. Demographic and clinical information, including patient blood tests and several composite measures of disease severity, was extracted from electronic health records., Results: Several factors, including male sex, higher age, higher body mass index, higher 4C Mortality score, and elevated lactate dehydrogenase levels, were associated with intensive care unit admission. Of all measured parameters, only the retrospectively calculated median Deterioration Index score was significantly associated with death. While quantitative polymerase chain reaction cycle threshold (Ct) values and genotype of SARS-CoV-2 were not significantly associated with outcome, Ct value did correlate positively with C-reactive protein levels and negatively with D-dimer, lymphocyte count, and antibody titer. Intrahost viral genetic diversity remained constant through the disease course and resulted in changes in viral genotype in some participants., Conclusions: Ultimately, these results suggest that worse outcomes are driven by immune dysfunction rather than by viral load and that SARS-CoV-2 evolution in hospital settings is relatively constant over time., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Variants of the SARS-CoV-2 virus carry differential risks to public health. The Omicron (B.1.1.529) variant, first identified in Botswana on November 11, 2021, has spread globally faster than any previous variant of concern. Understanding the transmissibility of Omicron is vital in the development of public health policy., Objective: The aim of this study is to compare SARS-CoV-2 outbreaks driven by Omicron to those driven by prior variants of concern in terms of both the speed and magnitude of an outbreak., Methods: We analyzed trends in outbreaks by variant of concern with validated surveillance metrics in several southern African countries. The region offers an ideal setting for a natural experiment given that most outbreaks thus far have been driven primarily by a single variant at a time. With a daily longitudinal data set of new infections, total vaccinations, and cumulative infections in countries in sub-Saharan Africa, we estimated how the emergence of Omicron has altered the trajectory of SARS-CoV-2 outbreaks. We used the Arellano-Bond method to estimate regression coefficients from a dynamic panel model, in which new infections are a function of infections yesterday and last week. We controlled for vaccinations and prior infections in the population. To test whether Omicron has changed the average trajectory of a SARS-CoV-2 outbreak, we included an interaction between an indicator variable for the emergence of Omicron and lagged infections., Results: The observed Omicron outbreaks in this study reach the outbreak threshold within 5-10 days after first detection, whereas other variants of concern have taken at least 14 days and up to as many as 35 days. The Omicron outbreaks also reach peak rates of new cases that are roughly 1.5-2 times those of prior variants of concern. Dynamic panel regression estimates confirm Omicron has created a statistically significant shift in viral spread., Conclusions: The transmissibility of Omicron is markedly higher than prior variants of concern. At the population level, the Omicron outbreaks occurred more quickly and with larger magnitude, despite substantial increases in vaccinations and prior infections, which should have otherwise reduced susceptibility to new infections. Unless public health policies are substantially altered, Omicron outbreaks in other countries are likely to occur with little warning., (©Alexander L Lundberg, Ramon Lorenzo-Redondo, Egon A Ozer, Claudia A Hawkins, Judd F Hultquist, Sarah B Welch, PV Vara Prasad, James F Oehmke, Chad J Achenbach, Robert L Murphy, Janine I White, Robert J Havey, Lori Ann Post. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 31.01.2022.)

Background: Chronic inflammatory diseases (CIDs) are considered risk enhancing factors for coronary heart disease (CHD). However, sparse data exist regarding relative CHD risks across CIDs. Objective: Determine relative differences in CHD risk across multiple CIDs: psoriasis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), systemic sclerosis (SSc), and inflammatory bowel disease (IBD). Methods: The cohort included patients with CIDs and controls without CID in an urban medical system from 2000 to 2019. Patients with CIDs were frequency-matched with non-CID controls on demographics, hypertension, and diabetes. CHD was defined as myocardial infarction (MI), ischemic heart disease, and/or coronary revascularization based on validated administrative codes. Multivariable-adjusted Cox models were used to determine the risk of incident CHD and MI for each CID relative to non-CID controls. In secondary analyses, we compared CHD risk by disease severity within each CID. Results: Of 17,049 patients included for analysis, 619 had incident CHD (202 MI) over an average of 4.4 years of follow-up. The multivariable-adjusted risk of CHD was significantly higher for SLE [hazard ratio (HR) 1.9, 95% confidence interval (CI) 1.2, 3.2] and SSc (HR 2.1, 95% CI 1.2, 3.9). Patients with SLE also had a significantly higher risk of MI (HR 3.6, 95% CI 1.9, 6.8). When CIDs were categorized by markers of disease severity (C-reactive protein for all CIDs except HIV, for which CD4 T cell count was used), greater disease severity was associated with higher CHD risk across CIDs. Conclusions: Patients with SLE and SSc have a higher risk of CHD. CHD risk with HIV, RA, psoriasis, and IBD may only be elevated in those with greater disease severity. Clinicians should personalize CHD risk and treatment based on type and severity of CID., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sinha, Rivera, Chadha, Prasada, Pawlowski, Thorp, DeBerge, Ramsey-Goldman, Lee, Achenbach, Lloyd-Jones and Feinstein.)

Background: The prevalence of non-tuberculous mycobacteria (NTM) has been increasing worldwide in both developed and developing countries. NTM infection is clinically indistinguishable from tuberculosis and therefore poses significant challenges in patient management, especially in patients chronically treated for pulmonary TB. In this study, we evaluated a new highly sensitive Multiplex MTB/NTM assay that can differentiate M. tuberculosis complex (MTBC) from all NTM, including the treatable and most common NTM, M. avium complex (MAC)., Methods: We developed and optimized a new open- Multiplex MTB/NTM assay with two gene-targets for MTBC (IS6110/senX3-regX3) and two targets for MAC (IS1311/DT1) with samples spiked with stored strains and testing 20 replicates. Patients with presumptive TB and NTM were enrolled at the Respiratory Disease Department of The University Teaching Hospital of Point G, in Mali., Findings: In the development stage, the new assay showed a high analytic performance with 100% detections of MTBC and MAC at only 5 colony forming units (CFUs). Overall, without the treatment failure cases, the Multiplex assay and the Xpert showed a sensitivity, specificity, PPV and NPV of 83·3% [66·4-92·6], 96·6% [88·6-99·0], 92·5% [82·3-96·5] and 92·2% [82·7-96·5] and the Xpert had values of 96·7% [83·3-99·4], 80·0% [68·2-88·1], 70·7 [55·5-82·3] and 97·9% [89·3-99·6], respectively. The Multiplex assay successfully detected all (5/5) the MAC cases., Interpretation: Our new Multiplex assay demonstrates better specificity than Xpert for all group studied, in addition to detecting potential NTM cases. The assay could therefore complement the widely used Xpert assay and enhance discrimination of TB and NTM infections., Funding: This work was supported by the National Institutes of Health (R03AI137674, U54EB027049, D43TW010350 and UM1AI069471) and Northwestern University's Institute for Global Health Catalyzer Fund., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to report., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Nutritional status influences immunity but its specific association with susceptibility to COVID-19 remains unclear. We examined the association of specific dietary data and incident COVID-19 in the UK Biobank (UKB)., Methods: We considered UKB participants in England with self-reported baseline (2006-2010) data and linked them to Public Health England COVID-19 test results-performed on samples from combined nose/throat swabs, using real time polymerase chain reaction (RT-PCR)-between March and November 2020. Baseline diet factors included breastfed as baby and specific consumption of coffee, tea, oily fish, processed meat, red meat, fruit, and vegetables. Individual COVID-19 exposure was estimated using the UK's average monthly positive case rate per specific geo-populations. Logistic regression estimated the odds of COVID-19 positivity by diet status adjusting for baseline socio-demographic factors, medical history, and other lifestyle factors. Another model was further adjusted for COVID-19 exposure., Results: Eligible UKB participants ( n = 37,988) were 40 to 70 years of age at baseline; 17% tested positive for COVID-19 by SAR-CoV-2 PCR. After multivariable adjustment, the odds (95% CI) of COVID-19 positivity was 0.90 (0.83, 0.96) when consuming 2-3 cups of coffee/day (vs. <1 cup/day), 0.88 (0.80, 0.98) when consuming vegetables in the third quartile of servings/day (vs. lowest quartile), 1.14 (1.01, 1.29) when consuming fourth quartile servings of processed meats (vs. lowest quartile), and 0.91 (0.85, 0.98) when having been breastfed (vs. not breastfed). Associations were attenuated when further adjusted for COVID-19 exposure, but patterns of associations remained., Conclusions: In the UK Biobank, consumption of coffee, vegetables, and being breastfed as a baby were favorably associated with incident COVID-19; intake of processed meat was adversely associated. Although these findings warrant independent confirmation, adherence to certain dietary behaviors may be an additional tool to existing COVID-19 protection guidelines to limit the spread of this virus.

Background: COVID-19 transmission rates in South Asia initially were under control when governments implemented health policies aimed at controlling the pandemic such as quarantines, travel bans, and border, business, and school closures. Governments have since relaxed public health restrictions, which resulted in significant outbreaks, shifting the global epicenter of COVID-19 to India. Ongoing systematic public health surveillance of the COVID-19 pandemic is needed to inform disease prevention policy to re-establish control over the pandemic within South Asia., Objective: This study aimed to inform public health leaders about the state of the COVID-19 pandemic, how South Asia displays differences within and among countries and other global regions, and where immediate action is needed to control the outbreaks., Methods: We extracted COVID-19 data spanning 62 days from public health registries and calculated traditional and enhanced surveillance metrics. We use an empirical difference equation to measure the daily number of cases in South Asia as a function of the prior number of cases, the level of testing, and weekly shifts in variables with a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R., Results: Traditional surveillance metrics indicate that South Asian countries have an alarming outbreak, with India leading the region with 310,310 new daily cases in accordance with the 7-day moving average. Enhanced surveillance indicates that while Pakistan and Bangladesh still have a high daily number of new COVID-19 cases (n=4819 and n=3878, respectively), their speed of new infections declined from April 12-25, 2021, from 2.28 to 2.18 and 3.15 to 2.35 daily new infections per 100,000 population, respectively, which suggests that their outbreaks are decreasing and that these countries are headed in the right direction. In contrast, India's speed of new infections per 100,000 population increased by 52% during the same period from 14.79 to 22.49 new cases per day per 100,000 population, which constitutes an increased outbreak., Conclusions: Relaxation of public health restrictions and the spread of novel variants fueled the second wave of the COVID-19 pandemic in South Asia. Public health surveillance indicates that shifts in policy and the spread of new variants correlate with a drastic expansion in the pandemic, requiring immediate action to mitigate the spread of COVID-19. Surveillance is needed to inform leaders whether policies help control the pandemic., (©Sarah B Welch, Dinushi Amanda Kulasekere, P V Vara Prasad, Charles B Moss, Robert Leo Murphy, Chad J Achenbach, Michael G Ison, Danielle Resnick, Lauren Singh, Janine White, Tariq Z Issa, Kasen Culler, Michael J Boctor, Maryann Mason, James Francis Oehmke, Joshua Marco Mitchell Faber, Lori Ann Post. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 17.06.2021.)

Background: Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART)., Methods: We evaluated AIDS-free, ART-naive PLWH during 1996-2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350-500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject's age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses., Results: Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37-.86), AIDS-defining cancers (HR 0.23; 95% CI, .11-.49), any virus-related cancer (HR 0.30; 95% CI, .16-.54), Kaposi sarcoma (HR 0.25; 95% CI, .10-.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06-.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference -1.6; 95% CI, -2.8, -.5)., Conclusions: Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

[Figure: see text].

Background: The COVID-19 global pandemic has disrupted structures and communities across the globe. Numerous regions of the world have had varying responses in their attempts to contain the spread of the virus. Factors such as public health policies, governance, and sociopolitical climate have led to differential levels of success at controlling the spread of SARS-CoV-2. Ultimately, a more advanced surveillance metric for COVID-19 transmission is necessary to help government systems and national leaders understand which responses have been effective and gauge where outbreaks occur., Objective: The goal of this study is to provide advanced COVID-19 surveillance metrics for Canada at the country, province, and territory level that account for shifts in the pandemic including speed, acceleration, jerk, and persistence. Enhanced surveillance identifies risks for explosive growth and regions that have controlled outbreaks successfully., Methods: Using a longitudinal trend analysis study design, we extracted 62 days of COVID-19 data from Canadian public health registries for 13 provinces and territories. We used an empirical difference equation to measure the daily number of cases in Canada as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R., Results: We compare the week of February 7-13, 2021, with the week of February 14-20, 2021. Canada, as a whole, had a decrease in speed from 8.4 daily new cases per 100,000 population to 7.5 daily new cases per 100,000 population. The persistence of new cases during the week of February 14-20 reported 7.5 cases that are a result of COVID-19 transmissions 7 days earlier. The two most populous provinces of Ontario and Quebec both experienced decreases in speed from 7.9 and 11.5 daily new cases per 100,000 population for the week of February 7-13 to speeds of 6.9 and 9.3 for the week of February 14-20, respectively. Nunavut experienced a significant increase in speed during this time, from 3.3 daily new cases per 100,000 population to 10.9 daily new cases per 100,000 population., Conclusions: Canada excelled at COVID-19 control early on in the pandemic, especially during the first COVID-19 shutdown. The second wave at the end of 2020 resulted in a resurgence of the outbreak, which has since been controlled. Enhanced surveillance identifies outbreaks and where there is the potential for explosive growth, which informs proactive health policy., (©Lori Post, Michael J Boctor, Tariq Z Issa, Charles B Moss, Robert Leo Murphy, Chad J Achenbach, Michael G Ison, Danielle Resnick, Lauren Singh, Janine White, Sarah B Welch, James F Oehmke. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 10.05.2021.)

Background: The COVID-19 pandemic has severely impacted Europe, resulting in a high caseload and deaths that varied by country. The second wave of the COVID-19 pandemic has breached the borders of Europe. Public health surveillance is necessary to inform policy and guide leaders., Objective: This study aimed to provide advanced surveillance metrics for COVID-19 transmission that account for weekly shifts in the pandemic, speed, acceleration, jerk, and persistence, to better understand countries at risk for explosive growth and those that are managing the pandemic effectively., Methods: We performed a longitudinal trend analysis and extracted 62 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in Europe as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R., Results: New COVID-19 cases slightly decreased from 158,741 (week 1, January 4-10, 2021) to 152,064 (week 2, January 11-17, 2021), and cumulative cases increased from 22,507,271 (week 1) to 23,890,761 (week 2), with a weekly increase of 1,383,490 between January 10 and January 17. France, Germany, Italy, Spain, and the United Kingdom had the largest 7-day moving averages for new cases during week 1. During week 2, the 7-day moving average for France and Spain increased. From week 1 to week 2, the speed decreased (37.72 to 33.02 per 100,000), acceleration decreased (0.39 to -0.16 per 100,000), and jerk increased (-1.30 to 1.37 per 100,000)., Conclusions: The United Kingdom, Spain, and Portugal, in particular, are at risk for a rapid expansion in COVID-19 transmission. An examination of the European region suggests that there was a decrease in the COVID-19 caseload between January 4 and January 17, 2021. Unfortunately, the rates of jerk, which were negative for Europe at the beginning of the month, reversed course and became positive, despite decreases in speed and acceleration. Finally, the 7-day persistence rate was higher during week 2 than during week 1. These measures indicate that the second wave of the pandemic may be subsiding, but some countries remain at risk for new outbreaks and increased transmission in the absence of rapid policy responses., (©Lori Post, Kasen Culler, Charles B Moss, Robert L Murphy, Chad J Achenbach, Michael G Ison, Danielle Resnick, Lauren Nadya Singh, Janine White, Michael J Boctor, Sarah B Welch, James Francis Oehmke. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 28.04.2021.)

Background: The COVID-19 pandemic has placed unprecedented stress on economies, food systems, and health care resources in Latin America and the Caribbean (LAC). Existing surveillance provides a proxy of the COVID-19 caseload and mortalities; however, these measures make it difficult to identify the dynamics of the pandemic and places where outbreaks are likely to occur. Moreover, existing surveillance techniques have failed to measure the dynamics of the pandemic., Objective: This study aimed to provide additional surveillance metrics for COVID-19 transmission to track changes in the speed, acceleration, jerk, and persistence in the transmission of the pandemic more accurately than existing metrics., Methods: Through a longitudinal trend analysis, we extracted COVID-19 data over 45 days from public health registries. We used an empirical difference equation to monitor the daily number of cases in the LAC as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. COVID-19 transmission rates were tracked for the LAC between September 30 and October 6, 2020, and between October 7 and 13, 2020., Results: The LAC saw a reduction in the speed, acceleration, and jerk for the week of October 13, 2020, compared to the week of October 6, 2020, accompanied by reductions in new cases and the 7-day moving average. For the week of October 6, 2020, Belize reported the highest acceleration and jerk, at 1.7 and 1.8, respectively, which is particularly concerning, given its high mortality rate. The Bahamas also had a high acceleration at 1.5. In total, 11 countries had a positive acceleration during the week of October 6, 2020, whereas only 6 countries had a positive acceleration for the week of October 13, 2020. The TAC displayed an overall positive trend, with a speed of 10.40, acceleration of 0.27, and jerk of -0.31, all of which decreased in the subsequent week to 9.04, -0.81, and -0.03, respectively., Conclusions: Metrics such as new cases, cumulative cases, deaths, and 7-day moving averages provide a static view of the pandemic but fail to identify where and the speed at which SARS-CoV-2 infects new individuals, the rate of acceleration or deceleration of the pandemic, and weekly comparison of the rate of acceleration of the pandemic indicate impending explosive growth or control of the pandemic. Enhanced surveillance will inform policymakers and leaders in the LAC about COVID-19 outbreaks., (©Lori Post, Ramael O Ohiomoba, Ashley Maras, Sean J Watts, Charles B Moss, Robert Leo Murphy, Michael G Ison, Chad J Achenbach, Danielle Resnick, Lauren Nadya Singh, Janine White, Azraa S Chaudhury, Michael J Boctor, Sarah B Welch, James Francis Oehmke. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 27.04.2021.)

Background: SARS-CoV-2, the virus that caused the global COVID-19 pandemic, has severely impacted Central Asia; in spring 2020, high numbers of cases and deaths were reported in this region. The second wave of the COVID-19 pandemic is currently breaching the borders of Central Asia. Public health surveillance is necessary to inform policy and guide leaders; however, existing surveillance explains past transmissions while obscuring shifts in the pandemic, increases in infection rates, and the persistence of the transmission of COVID-19., Objective: The goal of this study is to provide enhanced surveillance metrics for SARS-CoV-2 transmission that account for weekly shifts in the pandemic, including speed, acceleration, jerk, and persistence, to better understand the risk of explosive growth in each country and which countries are managing the pandemic successfully., Methods: Using a longitudinal trend analysis study design, we extracted 60 days of COVID-19-related data from public health registries. We used an empirical difference equation to measure the daily number of cases in the Central Asia region as a function of the prior number of cases, level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R., Results: COVID-19 transmission rates were tracked for the weeks of September 30 to October 6 and October 7-13, 2020, in Central Asia. The region averaged 11,730 new cases per day for the first week and 14,514 for the second week. Infection rates increased across the region from 4.74 per 100,000 persons to 5.66. Russia and Turkey had the highest 7-day moving averages in the region, with 9836 and 1469, respectively, for the week of October 6 and 12,501 and 1603, respectively, for the week of October 13. Russia has the fourth highest speed in the region and continues to have positive acceleration, driving the negative trend for the entire region as the largest country by population. Armenia is experiencing explosive growth of COVID-19; its infection rate of 13.73 for the week of October 6 quickly jumped to 25.19, the highest in the region, the following week. The region overall is experiencing increases in its 7-day moving average of new cases, infection, rate, and speed, with continued positive acceleration and no sign of a reversal in sight., Conclusions: The rapidly evolving COVID-19 pandemic requires novel dynamic surveillance metrics in addition to static metrics to effectively analyze the pandemic trajectory and control spread. Policy makers need to know the magnitude of transmission rates, how quickly they are accelerating, and how previous cases are impacting current caseload due to a lag effect. These metrics applied to Central Asia suggest that the region is trending negatively, primarily due to minimal restrictions in Russia., (©Lori Ann Post, Elana T Benishay, Charles B Moss, Robert Leo Murphy, Chad J Achenbach, Michael G Ison, Danielle Resnick, Lauren Nadya Singh, Janine White, Azraa S Chaudhury, Michael J Boctor, Sarah B Welch, James Francis Oehmke. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 03.02.2021.)

Importance: People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era., Objective: To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era., Design, Setting, and Participants: This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020., Exposures: HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation., Main Outcomes and Measures: HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage., Results: Of 109 283 PWH with 723 441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93 017 (85.1%) were male, 44 752 (40.9%) were White, 44 322 (40.6%) were Black, 21 343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/μL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection., Conclusions and Relevance: HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk.

Background: The COVID-19 pandemic has had a profound global impact on governments, health care systems, economies, and populations around the world. Within the East Asia and Pacific region, some countries have mitigated the spread of the novel coronavirus effectively and largely avoided severe negative consequences, while others still struggle with containment. As the second wave reaches East Asia and the Pacific, it becomes more evident that additional SARS-CoV-2 surveillance is needed to track recent shifts, rates of increase, and persistence associated with the pandemic., Objective: The goal of this study is to provide advanced surveillance metrics for COVID-19 transmission that account for speed, acceleration, jerk, persistence, and weekly shifts, to better understand country risk for explosive growth and those countries who are managing the pandemic successfully. Existing surveillance coupled with our dynamic metrics of transmission will inform health policy to control the COVID-19 pandemic until an effective vaccine is developed. We provide novel indicators to measure disease transmission., Methods: Using a longitudinal trend analysis study design, we extracted 330 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in East Asia and the Pacific as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R., Results: The standard surveillance metrics for Indonesia, the Philippines, and Myanmar were concerning as they had the largest new caseloads at 4301, 2588, and 1387, respectively. When looking at the acceleration of new COVID-19 infections, we found that French Polynesia, Malaysia, and the Philippines had rates at 3.17, 0.22, and 0.06 per 100,000. These three countries also ranked highest in terms of jerk at 15.45, 0.10, and 0.04, respectively., Conclusions: Two of the most populous countries in East Asia and the Pacific, Indonesia and the Philippines, have alarming surveillance metrics. These two countries rank highest in new infections in the region. The highest rates of speed, acceleration, and positive upwards jerk belong to French Polynesia, Malaysia, and the Philippines, and may result in explosive growth. While all countries in East Asia and the Pacific need to be cautious about reopening their countries since outbreaks are likely to occur in the second wave of COVID-19, the country of greatest concern is the Philippines. Based on standard and enhanced surveillance, the Philippines has not gained control of the COVID-19 epidemic, which is particularly troubling because the country ranks 4th in population in the region. Without extreme and rigid social distancing, quarantines, hygiene, and masking to reverse trends, the Philippines will remain on the global top 5 list of worst COVID-19 outbreaks resulting in high morbidity and mortality. The second wave will only exacerbate existing conditions and increase COVID-19 transmissions., (©Lori Ann Post, Jasmine S Lin, Charles B Moss, Robert Leo Murphy, Michael G Ison, Chad J Achenbach, Danielle Resnick, Lauren Nadya Singh, Janine White, Michael J Boctor, Sarah B Welch, James Francis Oehmke. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 01.02.2021.)

Background: The COVID-19 pandemic has disrupted the lives of millions and forced countries to devise public health policies to reduce the pace of transmission. In the Middle East and North Africa (MENA), falling oil prices, disparities in wealth and public health infrastructure, and large refugee populations have significantly increased the disease burden of COVID-19. In light of these exacerbating factors, public health surveillance is particularly necessary to help leaders understand and implement effective disease control policies to reduce SARS-CoV-2 persistence and transmission., Objective: The goal of this study is to provide advanced surveillance metrics, in combination with traditional surveillance, for COVID-19 transmission that account for weekly shifts in the pandemic speed, acceleration, jerk, and persistence to better understand a country's risk for explosive growth and to better inform those who are managing the pandemic. Existing surveillance coupled with our dynamic metrics of transmission will inform health policy to control the COVID-19 pandemic until an effective vaccine is developed., Methods: Using a longitudinal trend analysis study design, we extracted 30 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in MENA as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel data model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R., Results: The regression Wald statistic was significant (χ 2 5 =859.5, P<.001). The Sargan test was not significant, failing to reject the validity of overidentifying restrictions (χ 2 294 =16, P=.99). Countries with the highest cumulative caseload of the novel coronavirus include Iran, Iraq, Saudi Arabia, and Israel with 530,380, 426,634, 342,202, and 303,109 cases, respectively. Many of the smaller countries in MENA have higher infection rates than those countries with the highest caseloads. Oman has 33.3 new infections per 100,000 population while Bahrain has 12.1, Libya has 14, and Lebanon has 14.6 per 100,000 people. In order of largest to smallest number of cumulative deaths since January 2020, Iran, Iraq, Egypt, and Saudi Arabia have 30,375, 10,254, 6120, and 5185, respectively. Israel, Bahrain, Lebanon, and Oman had the highest rates of COVID-19 persistence, which is the number of new infections statistically related to new infections in the prior week. Bahrain had positive speed, acceleration, and jerk, signaling the potential for explosive growth., Conclusions: Static and dynamic public health surveillance metrics provide a more complete picture of pandemic progression across countries in MENA. Static measures capture data at a given point in time such as infection rates and death rates. By including speed, acceleration, jerk, and 7-day persistence, public health officials may design policies with an eye to the future. Iran, Iraq, Saudi Arabia, and Israel all demonstrated the highest rate of infections, acceleration, jerk, and 7-day persistence, prompting public health leaders to increase prevention efforts., (©Lori Post, Emily Marogi, Charles B Moss, Robert Leo Murphy, Michael G Ison, Chad J Achenbach, Danielle Resnick, Lauren Singh, Janine White, Sarah B Welch, James Francis Oehmke. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 15.01.2021.)

Purpose of Review: The aim of this review was to compare and contrast the application of molecular epidemiology approaches for the improved management and understanding of the HIV versus SARS-CoV-2 epidemics., Recent Findings: Molecular biology approaches, including PCR and whole genome sequencing (WGS), have become powerful tools for epidemiological investigation. PCR approaches form the basis for many high-sensitivity diagnostic tests and can supplement traditional contact tracing and surveillance strategies to define risk networks and transmission patterns. WGS approaches can further define the causative agents of disease, trace the origins of the pathogen, and clarify routes of transmission. When coupled with clinical datasets, such as electronic medical record data, these approaches can investigate co-correlates of disease and pathogenesis. In the ongoing HIV epidemic, these approaches have been effectively deployed to identify treatment gaps, transmission clusters and risk factors, though significant barriers to rapid or real-time implementation remain critical to overcome. Likewise, these approaches have been successful in addressing some questions of SARS-CoV-2 transmission and pathogenesis, but the nature and rapid spread of the virus have posed additional challenges., Summary: Overall, molecular epidemiology approaches offer unique advantages and challenges that complement traditional epidemiological tools for the improved understanding and management of epidemics.

Background : Body mass index (BMI) measures overweight/obesity. It, however, especially in sub-Saharan Africa (SSA), misclassifies cardiometabolic risk. Central obesity measures are superior. We therefore sought to compare BMI, waist-to-hip ratio (WHR) and abdominal height (AH) in predicting cardiovascular disease risk in sub-Saharan Africa. Methods : Subjects had blood pressures, BMI, and WHR determined. Blood pressure was taken, weight and height measured to generate BMI, and AH measured with a new locally fabricated abdominometer. The ability of the anthropometric indices in identifying abnormal individuals needing intervention was assessed with sensitivity, specificity, and area under the receiver operator characteristic curve. Results : Adults totaling 1,508 (728 M/780 F) adults were studied. For BMI, 985 (65.3%) were normal, while 375 (24.9%), consisting of 233 males and 142 females, had normal WHR. Blood pressure was normal in 525 (34.8%) and 317 (21.0%) for systolic and diastolic blood pressures, respectively. Using BMI as gold standard, sensitivity, specificity, positive, and negative predictive values for WHR in males were 80.7, 37.5, 62.5, and 19.3%, respectively. For females and in the same order, they were 62.0, 34.3, 65.7, and 38.0%. For AH, it was equal in both genders at 82.6, 39.2, 60.8, and 17.4%. By receiver operating curves comparing AH, WHR, and BMI against blood pressure detection, the area under the curve was 0.745, 0.604, and 0.554 for AH, BMI, and WHR, respectively. Conclusion : Abdominometer-derived AH has a better sensitivity and greater area under the receiver operator curve compared with BMI and WHR in this sub-Sahara African population; implying superiority as a cardiovascular anthropometric index., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Agbo, Zoakah, Isichei, Sagay, Achenbach and Okeahialam.)

Background: The emergence of SARS-CoV-2, the virus that causes COVID-19, has led to a global pandemic. The United States has been severely affected, accounting for the most COVID-19 cases and deaths worldwide. Without a coordinated national public health plan informed by surveillance with actionable metrics, the United States has been ineffective at preventing and mitigating the escalating COVID-19 pandemic. Existing surveillance has incomplete ascertainment and is limited by the use of standard surveillance metrics. Although many COVID-19 data sources track infection rates, informing prevention requires capturing the relevant dynamics of the pandemic., Objective: The aim of this study is to develop dynamic metrics for public health surveillance that can inform worldwide COVID-19 prevention efforts. Advanced surveillance techniques are essential to inform public health decision making and to identify where and when corrective action is required to prevent outbreaks., Methods: Using a longitudinal trend analysis study design, we extracted COVID-19 data from global public health registries. We used an empirical difference equation to measure daily case numbers for our use case in 50 US states and the District of Colombia as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R., Results: Examination of the United States and state data demonstrated that most US states are experiencing outbreaks as measured by these new metrics of speed, acceleration, jerk, and persistence. Larger US states have high COVID-19 caseloads as a function of population size, density, and deficits in adherence to public health guidelines early in the epidemic, and other states have alarming rates of speed, acceleration, jerk, and 7-day persistence in novel infections. North and South Dakota have had the highest rates of COVID-19 transmission combined with positive acceleration, jerk, and 7-day persistence. Wisconsin and Illinois also have alarming indicators and already lead the nation in daily new COVID-19 infections. As the United States enters its third wave of COVID-19, all 50 states and the District of Colombia have positive rates of speed between 7.58 (Hawaii) and 175.01 (North Dakota), and persistence, ranging from 4.44 (Vermont) to 195.35 (North Dakota) new infections per 100,000 people., Conclusions: Standard surveillance techniques such as daily and cumulative infections and deaths are helpful but only provide a static view of what has already occurred in the pandemic and are less helpful in prevention. Public health policy that is informed by dynamic surveillance can shift the country from reacting to COVID-19 transmissions to being proactive and taking corrective action when indicators of speed, acceleration, jerk, and persistence remain positive week over week. Implicit within our dynamic surveillance is an early warning system that indicates when there is problematic growth in COVID-19 transmissions as well as signals when growth will become explosive without action. A public health approach that focuses on prevention can prevent major outbreaks in addition to endorsing effective public health policies. Moreover, subnational analyses on the dynamics of the pandemic allow us to zero in on where transmissions are increasing, meaning corrective action can be applied with precision in problematic areas. Dynamic public health surveillance can inform specific geographies where quarantines are necessary while preserving the economy in other US areas., (©Lori Ann Post, Tariq Ziad Issa, Michael J Boctor, Charles B Moss, Robert L Murphy, Michael G Ison, Chad J Achenbach, Danielle Resnick, Lauren Nadya Singh, Janine White, Joshua Marco Mitchell Faber, Kasen Culler, Cynthia A Brandt, James Francis Oehmke. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 03.12.2020.)