Undiagnosed Infection Research Articles

90. Deimplementation: Use of Electronic Clinical Decision Support to Reduce Unnecessary Erythrocyte Sedimentation Rate (ESR) Ordering

Abstract Background In recent years, several de-implementation initiatives have focused on diagnostic testing. One such initiative, the Choosing Wisely campaign, recommends against routine use of erythrocyte sedimentation rate (ESR) for assessment of acute undiagnosed inflammation or infection. With the development of newer biomarkers of inflammation, particularly C-reactive protein (CRP), there is a decreasing role for ESR in screening for acute-onset conditions; however, ESR continues to be commonly ordered. Methods We examined ESR and CRP ordering practices at the Children’s Hospital of Philadelphia (CHOP) from July 2019 to July 2020 and found that 80% of ESR orders were placed concurrently with an order for CRP. We aimed to reduce ESR ordering by 20% at CHOP by using electronic clinical decision support in the form of embedded order guidance for ESR orders placed in the Emergency Department (ED) and inpatient setting. We examined the effect of the clinical decision support by assessing ESR ordering rate, defined by ESR orders per monthly patient days for the inpatient setting and ESR orders per monthly ED visits for the ED setting. We then examined differences in ordering rates using a quasi-experimental model with a concurrent control (basic metabolic panel). ESR Electronic Clinical Decision Support Intervention Inpatient and ED versions of the embedded electronic clinical decision support for ESR orders. Results Prior to implementation of the electronic decision support intervention, the median monthly rate of ESR orders was 13.6 per 1000 patient days and 70.3 per 1000 ED visits. During the initial month after implementation, we found that ESR ordering was 12.5 in inpatient and 46.4 in ED, reflecting decreased rates of ordering. The median monthly rate of basic metabolic panel orders (concurrent control) was 194.5 per 1000 patient days and 110.0 per 1000 ED visits. This was unchanged after intervention. Conclusion We conclude that electronic clinical decision support is a potentially effective deimplementation method for improving diagnostic test utilization, even with non-disease specific testing such as inflammatory markers. However, continued post-implementation data monitoring and analysis is needed to determine if this is a true difference and sustainable trend. Disclosures All Authors: No reported disclosures

Vital Signs: HIV Infection, Diagnosis, Treatment, and Prevention Among Gay, Bisexual, and Other Men Who Have Sex with Men - United States, 2010-2019.

BackgroundMen who have sex with men (MSM) accounted for two thirds of new HIV infections in the United States in 2019 despite representing approximately 2% of the adult population.MethodsCDC analyzed surveillance data to determine trends in estimated new HIV infections and to assess measures of undiagnosed infection and HIV prevention and treatment services including HIV testing, preexposure prophylaxis (PrEP) use, antiretroviral therapy (ART) adherence, and viral suppression, as well as HIV-related stigma.ResultsThe estimated number of new HIV infections among MSM was 25,100 in 2010 and 23,100 in 2019. New infections decreased significantly among White MSM but did not decrease among Black or African American (Black) MSM and Hispanic/Latino MSM. New infections increased among MSM aged 25–34 years. During 2019, approximately 83% of Black MSM and 80% of Hispanic/Latino MSM compared with 90% of White MSM with HIV had received an HIV diagnosis. The lowest percentage of diagnosed infection was among MSM aged 13–24 years (55%). Among MSM with a likely PrEP indication, discussions about PrEP with a provider and PrEP use were lower among Black MSM (47% and 27%, respectively) and Hispanic/Latino MSM (45% and 31%) than among White MSM (59% and 42%). Among MSM with an HIV diagnosis, adherence to ART and viral suppression were lower among Black MSM (48% and 62%, respectively) and Hispanic/Latino MSM (59% and 67%) compared with White MSM (64% and 74%). Experiences of HIV-related stigma among those with an HIV diagnosis were higher among Black MSM (median = 33; scale = 0–100) and Hispanic/Latino MSM (32) compared with White MSM (26). MSM aged 18–24 years had the lowest adherence to ART (45%) and the highest median stigma score (39).ConclusionImproving access to and use of HIV services for MSM, especially Black MSM, Hispanic/Latino MSM, and younger MSM, and addressing social determinants of health, such as HIV-related stigma, that contribute to unequal outcomes will be essential to end the HIV epidemic in the United States.

Laboratory-based dried blood spot testing for hepatitis C: A protocol for systematic review and meta-analysis of diagnostic accuracy

Background: Diagnosis of chronic hepatitis C virus (HCV) infection typically involves collection of venous blood samples prior to serological investigation of an antibody response followed by a confirmatory viral load or antigen test to verify active HCV infection. This conventional pathway poses logistical challenges for the implementation of reflex testing, whereby the confirmatory test is performed on the same sample used for serological investigation. Dried blood spot (DBS) testing, in which capillary blood is deposited on filter paper, is a less invasive alternative that can enable reflex testing without the need for venepuncture, centrifugation and freezing of samples. Methods: This systematic review aims to assess the diagnostic accuracy of DBS compared with venous blood samples for diagnosis of chronic HCV infection. Observational studies which compare diagnostic tests using DBS with those using serum, plasma or whole blood in patients with chronic or resolved HCV infection will be included. Electronic searches will be conducted in PubMed, Embase, Scopus, Web of Science, Lilacs and the Cochrane library. Citation screening, data extraction and quality appraisal of included studies will be performed in duplicate using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A meta-analysis will be conducted to derive pooled estimates of sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and diagnostic odds ratios. Sensitivity analyses and meta-regression will also be performed. Quality of the evidence will be evaluated using the GRADE criteria. Discussion: Identifying and linking people with currently undiagnosed chronic HCV infection to care is pivotal to attaining global viral hepatitis elimination targets. The use of DBS could simplify diagnostic testing strategies by integrating reflex testing into the care pathway and reducing drop-off along the cascade of care. Registration: PROSPERO, CRD42020205204. Registered 19 th September 2020.

HIV Testing Strategies for Health Departments to End the Epidemic in the U.S.

An important goal of the Ending the HIV Epidemic in the U.S. initiative is the timely diagnosis of all people with HIV as early as possible after infection. To end the HIV epidemic, health departments were encouraged to propose new and innovative HIV testing strategies and improve the reach of existing programs. These activities were divided into 3 core strategies: expansion of routine screening in healthcare settings, locally tailored HIV testing initiatives in nonhealthcare settings, and specific efforts to increase the frequency of testing for individuals with increased potential for acquiring HIV. Because HIV testing is such a crucial part of the core activities of the Centers for Disease Control and Prevention's HIV prevention programs, there are many examples of evidence-based programs and best practices for HIV testing in both clinical and nonclinical settings. This article reviews the evidence base for these strategies and some of the activities proposed under the Diagnose pillar to achieve the goal of diagnosing all HIV infections as early as possible. All other Ending the HIV Epidemic in the U.S. activities start with an awareness of HIV status, which is actually the indicator for which most health departments are closest to the proposed targets. There are both proven and emerging approaches to increasing HIV screening and increasing the frequency of HIV screening available. The Ending the HIV Epidemic in the U.S. initiative provides the motivation, the resources, and a coordinated plan to bring them to scale.

HIV self-testing in Ottawa, Canada used by persons at risk for HIV: The GetaKit study.

The Public Health Agency of Canada estimates that about 87% of persons living with human immunodeficiency virus (HIV) in Canada have been diagnosed, which is well below the Joint United Nations Programme on HIV/AIDS target to have 95% of HIV-positive persons diagnosed. Research has shown that HIV self-testing may help increase such diagnoses, especially among the populations who are most affected by HIV. The objective of the study was to determine the uptake and diagnosis outcomes associated with free HIV self-testing. We developed the first online mailout free HIV self-testing program in Canada and implemented it in Ottawa. This project ran through the website, www.GetaKit.ca. We intended to recruit 150-400 participants over a 6-12-month period, estimating that this number would yield between 0-1 positive test results (expected positivity rate of 0.08%). Between July 20, 2020 and April 1, 2021, 1,268 people accessed the GetaKit website and verified their eligibility. In total, 600 persons were eligible and 405 ordered an HIV kit. Of those who ordered a kit, 399 completed a baseline survey. Overall, 71% of these participants were members of HIV priority groups. For test results, 228 persons reported test results, with one being positive, for a positivity rate of 0.24% overall and 0.44% of reported results. These rates exceed that normally observed in Ottawa. Self-testing of HIV can be effectively delivered through a website. Such an intervention will also be used by persons with undiagnosed infections and appears to do so at a rate higher than that observed by other means of testing. Self-testing of HIV may therefore help Canada achieve the United Nations 95-95-95 targets.

Estimating the population health burden of Lyme disease in Ontario, Canada: a microsimulation modelling approach.

Background:If untreated, Lyme disease can lead to long-term sequelae and post-treatment Lyme disease syndrome (PTLDS), resulting in reduced health-related quality of life. The objective of this study was to develop a microsimulation model to estimate the population-level health burden of Lyme disease in Ontario, Canada.Methods:We developed a Lyme disease history model using microsimulation, simulating 100 000 people (mean age 37.6 yr, 51% female) from 2017 in Ontario over a lifetime risk of infection and time horizon. We extracted the sensitivity and specificity of the 2-tier testing recommended by the Canadian Public Health Laboratory Network, probabilities and health state utility values from the published literature and health administrative data. Our reported outcomes from our stochastic analysis include diagnosed cases of Lyme disease (stratified by stage), undiagnosed infections, sequelae, individuals with PTLDS and quality-adjusted life-years (QALYs) lost.Results:Our model estimated 333 (95% confidence interval [CI] 329–337) infections over the lifetime of 100 000 simulated people (mean age 37.6 yr, 51% female), with 92% (95% CI 91%–93%) of infections diagnosed. Of those 308 people with Lyme Disease diagnoses, 67 (95% CI 65–69) developed sequelae (e.g., arthritic, cardiac, neurologic sequelae), and 34 (95% CI 33–35) developed PTLDS. Lyme disease resulted in a loss of 84.5 QALYs (95% CI 82.9–86.2) over the lifetime of the simulated cohort. Sensitivity and scenario analysis showed that increasing incidence rates of Lyme disease, potential underreporting, duration of PTLDS and quality of life (health state utility) associated with PTLDS had the greatest impact on health burden.Interpretation:Lyme disease contributes considerable health burden in terms of QALYs lost. Our analysis provides evidence to understand the disease burden and lays the foundation to assess the cost-effectiveness of pharmaceutical and nonpharmaceutical interventions.

Trends in undiagnosed HIV prevalence in England and implications for eliminating HIV transmission by 2030: an evidence synthesis model

SummaryBackgroundA target to eliminate HIV transmission in England by 2030 was set in early 2019. This study aimed to estimate trends from 2013 to 2019 in HIV prevalence, particularly the number of people living with undiagnosed HIV, by exposure group, ethnicity, gender, age group, and region. These estimates are essential to monitor progress towards elimination.MethodsA Bayesian synthesis of evidence from multiple surveillance, demographic, and survey datasets relevant to HIV in England was used to estimate trends in the number of people living with HIV, the proportion of people unaware of their HIV infection, and the corresponding prevalence of undiagnosed HIV. All estimates were stratified by exposure group, ethnicity, gender, age group (15–34, 35–44, 45–59, or 60–74 years), region (London, or outside of London) and year (2013–19).FindingsThe total number of people living with HIV aged 15–74 years in England increased from 83 500 (95% credible interval 80 200–89 600) in 2013 to 92 800 (91 000–95 600) in 2019. The proportion diagnosed steadily increased from 86% (80–90%) to 94% (91–95%) during the same time period, corresponding to a halving in the number of undiagnosed infections from 11 600 (8300–17 700) to 5900 (4400–8700) and in undiagnosed prevalence from 0·29 (0·21–0·44) to 0·14 (0·11–0·21) per 1000 population. Similar steep declines were estimated in all subgroups of gay, bisexual, and other men who have sex with men and in most subgroups of Black African heterosexuals. The pace of reduction was less pronounced for heterosexuals in other ethnic groups and people who inject drugs, particularly outside London; however, undiagnosed prevalence in these groups has remained very low.InterpretationThe UNAIDS target of diagnosing 90% of people living with HIV by 2020 was reached by 2016 in England, with the country on track to achieve the new target of 95% diagnosed by 2025. Reductions in transmission and undiagnosed prevalence have corresponded to large scale-up of testing in key populations and early diagnosis and treatment. Additional and intensified prevention measures are required to eliminate transmission of HIV among the communities that have experienced slower declines than other subgroups, despite having very low prevalences of HIV.FundingUK Medical Research Council and Public Health England.

SARS-CoV-2 infection hospitalization, severity, criticality, and fatality rates in Qatar

The SARS-CoV-2 pandemic resulted in considerable morbidity and mortality as well as severe economic and societal disruptions. Despite scientific progress, true infection severity, factoring both diagnosed and undiagnosed infections, remains poorly understood. This study aimed to estimate SARS-CoV-2 age-stratified and overall morbidity and mortality rates based on analysis of extensive epidemiological data for the pervasive epidemic in Qatar, a country where < 9% of the population are ≥ 50 years. We show that SARS-CoV-2 severity and fatality demonstrate a striking age dependence with low values for those aged < 50 years, but rapidly growing rates for those ≥ 50 years. Age dependence was particularly pronounced for infection criticality rate and infection fatality rate. With Qatar’s young population, overall SARS-CoV-2 severity and fatality were not high with < 4 infections in every 1000 being severe or critical and < 2 in every 10,000 being fatal. Only 13 infections in every 1000 received any hospitalization in acute-care-unit beds and < 2 in every 1000 were hospitalized in intensive-care-unit beds. However, we show that these rates would have been much higher if Qatar’s population had the demographic structure of Europe or the United States. Epidemic expansion in nations with young populations may lead to considerably lower disease burden than currently believed.

Using test positivity and reported case rates to estimate state-level COVID-19 prevalence and seroprevalence in the United States.

Accurate estimates of infection prevalence and seroprevalence are essential for evaluating and informing public health responses and vaccination coverage needed to address the ongoing spread of COVID-19 in each United States (U.S.) state. However, reliable, timely data based on representative population sampling are unavailable, and reported case and test positivity rates are highly biased. A simple data-driven Bayesian semi-empirical modeling framework was developed and used to evaluate state-level prevalence and seroprevalence of COVID-19 using daily reported cases and test positivity ratios. The model was calibrated to and validated using published state-wide seroprevalence data, and further compared against two independent data-driven mathematical models. The prevalence of undiagnosed COVID-19 infections is found to be well-approximated by a geometrically weighted average of the positivity rate and the reported case rate. Our model accurately fits state-level seroprevalence data from across the U.S. Prevalence estimates of our semi-empirical model compare favorably to those from two data-driven epidemiological models. As of December 31, 2020, we estimate nation-wide a prevalence of 1.4% [Credible Interval (CrI): 1.0%-1.9%] and a seroprevalence of 13.2% [CrI: 12.3%-14.2%], with state-level prevalence ranging from 0.2% [CrI: 0.1%-0.3%] in Hawaii to 2.8% [CrI: 1.8%-4.1%] in Tennessee, and seroprevalence from 1.5% [CrI: 1.2%-2.0%] in Vermont to 23% [CrI: 20%-28%] in New York. Cumulatively, reported cases correspond to only one third of actual infections. The use of this simple and easy-to-communicate approach to estimating COVID-19 prevalence and seroprevalence will improve the ability to make public health decisions that effectively respond to the ongoing COVID-19 pandemic.

SARS-CoV-2 RNA concentrations in wastewater foreshadow dynamics and clinical presentation of new COVID-19 cases

Current estimates of COVID-19 prevalence are largely based on symptomatic, clinically diagnosed cases. The existence of a large number of undiagnosed infections hampers population-wide investigation of viral circulation. Here, we quantify the SARS-CoV-2 concentration and track its dynamics in wastewater at a major urban wastewater treatment facility in Massachusetts, between early January and May 2020. SARS-CoV-2 was first detected in wastewater on March 3. SARS-CoV-2 RNA concentrations in wastewater correlated with clinically diagnosed new COVID-19 cases, with the trends appearing 4–10 days earlier in wastewater than in clinical data. We inferred viral shedding dynamics by modeling wastewater viral load as a convolution of back-dated new clinical cases with the average population-level viral shedding function. The inferred viral shedding function showed an early peak, likely before symptom onset and clinical diagnosis, consistent with emerging clinical and experimental evidence. This finding suggests that SARS-CoV-2 concentrations in wastewater may be primarily driven by viral shedding early in infection. This work shows that longitudinal wastewater analysis can be used to identify trends in disease transmission in advance of clinical case reporting, and infer early viral shedding dynamics for newly infected individuals, which are difficult to capture in clinical investigations.

Lemierre’s Syndrome in an Elderly Female Patient with Polycythemia Vera: Does Polycythemia Vera Predispose to Lemierre’s Syndrome?

Patient: Female, 66-year-old Final Diagnosis: Lemierre’s syndrome Symptoms: Chills • neck pain • odynophagia • rigors • trismus Medication: — Clinical Procedure: Computed tomography Specialty: Cardiology • Hematology • Infectious Diseases • General and Internal Medicine Objective: Unusual clinical course Background:Lemierre’s syndrome (LS), a potentially fatal condition, is characterized by thrombophlebitis of a head or neck vein secondary to a head or neck infection, most commonly involving Fusobacterium necrophorum. Its association with polycythemia vera (PV) is not well reported despite the predisposition to thrombogenesis.Case Report:We present the case of a 66-year-old woman with a known history of polycythemia vera (PV) who presented with 4 days of worsening right-sided neck pain and odynophagia. The physical examination revealed poor oral dentition, mild erythema of the posterior pharyngeal mucosa, and non-erythematous tonsils without exudate. A computed tomography with i.v. contrast of the neck revealed complete thrombosis of the right internal jugular vein (IJV). Treatment was initiated with i.v. antibiotics and anticoagulation, with symptoms improving rapidly within 24 h. She was eventually discharged on apixaban and clindamycin and was encouraged to follow up with her hematologist.Conclusions:PV predisposes patients to a hyper-viscous and prothrombotic state, which may warrant a stronger suspicion of Lemierre’s syndrome. In addition, lack of aspirin use for prophylaxis of thrombosis and undiagnosed oral infection are factors to consider when assessing risk factors for Lemierre’s syndrome in PV patients.

Screening Tests in the Era of COVID-19: Implications for the Plastic Surgeon.

The novel coronavirus, severe acute respiratory syndrome coronavirus 2, responsible for the coronavirus disease of 2019 (COVID-19) pandemic, has claimed over 2 million lives to date and brought the global economy to a halt, including elective surgery. As the authors emerge from lockdown, new protocols must be implemented to minimize risk by means of appropriate screening of their patients, surgical adjustments to reduce viral transmission in case of undiagnosed infection, and the development of accurate severe acute respiratory syndrome coronavirus 2 tests while awaiting the distribution of an effective vaccine. Many serology and molecular tests have received emergency use authorization from the U.S. Food and Drug Administration, but they have not yet been independently verified. There are three main types of diagnostic tests available: (1) imaging studies, (2) molecular tests, and (3) serology tests. Imaging studies reveal bilateral lower lobe pneumonia and ground-glass opacities that are suggestive of disease. Quantitative reverse transcription polymerase chain reaction identifies specific segments of viral RNA, indicating the active presence of the virus in the test subject, which is most useful for elective surgery screening. Finally, serology studies detect the presence of immunoglobulin M and immunoglobulin G antibodies to the virus, indicating a current or past infection. Each test offers its own benefits and limitations.

Antigenic and immunogenic evaluation of permutations of soluble hepatitis C virus envelope protein E2 and E1 antigens.

Yearly, about 1.5 million people become chronically infected with hepatitis C virus (HCV) and for the 71 million with chronic HCV infection about 400,000 die from related morbidities, including liver cirrhosis and cancer. Effective treatments exist, but challenges including cost-of-treatment and wide-spread undiagnosed infection, necessitates the development of vaccines. Vaccines should induce neutralizing antibodies (NAbs) against the HCV envelope (E) transmembrane glycoprotein 2, E2, which partly depends on its interaction partner, E1, for folding. Here, we generated three soluble HCV envelope protein antigens with the transmembrane regions deleted (i.e., fused peptide backbones), termed sE1E2 (E1 followed by E2), sE2E1 (E2 followed by E1), and sE21E (E2 followed by inverted E1). The E1 inversion for sE21E positions C-terminal residues of E1 near C-terminal residues of E2, which is in analogy to how they likely interact in native E1/E2 complexes. Probing conformational E2 epitope binding using HCV patient-derived human monoclonal antibodies, we show that sE21E was superior to sE2E1, which was consistently superior to sE1E2. This correlated with improved induction of NAbs by sE21E compared with sE2E1 and especially compared with sE1E2 in female BALB/c mouse immunizations. The deletion of the 27 N-terminal amino acids of E2, termed hypervariable region 1 (HVR1), conferred slight increases in antigenicity for sE2E1 and sE21E, but severely impaired induction of antibodies able to neutralize in vitro viruses retaining HVR1. Finally, comparing sE21E with sE2 in mouse immunizations, we show similar induction of heterologous NAbs. In summary, we find that C-terminal E2 fusion of E1 or 1E is superior to N-terminal fusion, both in terms of antigenicity and the induction of heterologous NAbs. This has relevance when designing HCV E1E2 vaccine antigens.

Does Every Patient with a Positive SARS-CoV-2 RT-PCR Test Require Isolation? A Prospective Analysis

Group Name: CDC Prevention Epicenters Program Background: Reverse-transcriptase polymerase chain reaction (RT-PCR) tests are the reference standard for diagnosing SARS-CoV-2 infection, but false positives can occur and viral RNA may persist for weeks-to-months following recovery. Isolating such patients increases pressure on limited hospital resources and may impede care. Therefore, we quantified the percentage of patients who tested positive by RT-PCR yet were unlikely to be infectious and could be released from isolation. Methods: We prospectively identified all adults hospitalized at Brigham and Women’s Hospital (Boston, MA) who tested positive for SARS-CoV-2 by RT-PCR (primarily Hologic Panther Fusion or Cepheid Xpert platforms) between December 24, 2020, and January 24, 2021. Each case was assessed by infection control staff for possible discontinuation of isolation using an algorithm that incorporated the patient’s prior history of COVID-19, current symptoms, RT-PCR cycle threshold (Ct) values, repeat RT-PCR testing at least 24 hours later, and SARS-CoV-2 serologies (Figure 1). Results: Overall, 246 hospitalized patients (median age, 66 years [interquartile range, 50–74]; 131 [53.3%] male) tested positive for SARS-CoV-2 by RT-PCR during the study period. Of these, 201 (81.7%) were deemed new diagnoses of active disease on the basis of low Ct values and/or progressive symptoms. Moreover, 44 patients (17.9%) were deemed noninfectious: 35 (14.2%) had prior known resolved infections (n = 21) or unknown prior infection but positive serology (n = 14), high Ct values on initial testing, and negative or stably high Ct values on repeat testing. Also, 5 (2.0%) had recent infection but &gt;10 days had passed since symptom onset and they were clinically improving. In addition, 4 (1.6%) results were deemed false positives based on lack of symptoms and at least 1 negative repeat RT-PCR test (Figure 2). One patient was asymptomatic with Ct value &lt;35 but was discharged before further testing could be obtained. Among the 44 noninfectious patients, isolation was discontinued a median of 3 days (IQR, 2–4) after the first positive test. We did not identify any healthcare worker infections attributable to early discontinuation of isolation in these patients. Conclusions: During the winter COVID-19 second surge in Massachusetts, nearly 1 in 5 hospitalized patients who tested positive for SARS-CoV-2 by RT-PCR were deemed noninfectious and eligible for discontinuation of precautions. Most of these cases were consistent with residual RNA from prior known or undiagnosed infections. Active assessments of SARS-CoV-2 RT-PCR tests by infection control practitioners using clinical data, Ct values, repeat tests, and serologies can safely validate the release many patients from isolation and thereby conserve resources and facilitate patient care.Funding: NoDisclosures: None

Prevalence of SARS-CoV-2 antibodies in Denmark: nationwide, population-based seroepidemiological study

Seroprevalence studies have proven an important tool to monitor the progression of the coronavirus disease 2019 (COVID-19) pandemic. We present results of consecutive population-based seroprevalence surveys performed in Denmark in 2020. In spring, late summer and autumn/winter of 2020, invitation letters including a questionnaire covering symptoms were sent to representative samples of the population above 12 years and to parents of children below 18 years in the sample. Blood samples were analysed for total Ig and seroprevalence estimates per population segment were calculated and compared to other surveillance parameters. Based on 34 081 participants (participation rate 33%), seroprevalence estimates increased from 1.2% (95%CI: 0.3–1.9%) in May to 4.1% (95%CI: 3.1–4.9%) in December 2020. Seroprevalence estimates were roughly three times higher in those aged 12–29 years compared to 65 + and higher in metropolitan municipalities. By December 2020, 1.5% of the population had tested positive by RT-PCR. Infected individuals in older age groups were hospitalised several fold more often than in younger. Amongst seropositives, loss of taste/smell were the more specific symptoms, 32–56% did not report any symptoms. In more than half of seroconverted families, we did not see evidence of transmission between generations. Seroprevalence increased during 2020; adolescents were primarily infected in the autumn/winter. Denmark has a high per capita test rate; roughly one undiagnosed infection of SARS-CoV-2 were estimated to occur for each diagnosed case. Approximately half were asymptomatically infected. The epidemic appears to have progressed relatively modestly during 2020 in Denmark.

Simultaneous arterial and venous thromboembolic events associated with COVID-19. A case report

Infections with COVID-19 can induce thrombophilia and increase the risk of thrombotic events. We describe a case of a 64- years-old male who presents with intermediate-risk pulmonary embolism and brachial artery thrombosis secondary to an undiagnosed patent foramen ovale and COVID-19 infection. The patient was successfully treated with thrombolysis and heparin infusions and was discharged home with long-term anticoagulation. Managing patients with multiple pathologies occurring concurrently requires effective inter-speciality working in order to take a holistic approach to managing the patient opposed to managing the conditions in isolation. This case report highlights how clinical guidelines can support decision making of the individual pathologies but working as a team will enable the best care.

Estimating HIV incidence, prevalence, and percent of undiagnosed infections in Taiwan using CD4 data

Estimation of the human immunodeficiency virus (HIV) epidemic trend and percent of undiagnosed infections is an important measure for the assessment of HIV control programs. In this study, we aimed to investigate and estimate the HIV incidence, HIV prevalence, and percent of undiagnosed HIV infections in Taiwan using the CD4 depletion model. Data on newly reported HIV diagnoses during 2012-2019 were obtained from the National HIV/AIDS reporting and case management system. We used an Asian-adjusted CD4 depletion model to determine diagnosis delays and then used this distribution and HIV case surveillance data to estimate the incidence, prevalence and percent of undiagnosed infections. The estimated HIV incidence rate decreased after 2012, from 9.4 per 100,000 people (95% confidence interval [CI]: 8.7 to 10.2) to 7.1 per 100,000 people (95% CI: 5.7 to 8.5) in 2019. The prevalence rate increased from 111 per 100,000 people (95% CI: 107 to 116) in 2012 to 158 per 100,000 people (95% CI: 146 to 169) in 2019, whereas the undiagnosed rate decreased from 21.5% (95% CI: 18.2%-24.8%) in 2012 to 12.1% (95% CI: 8.9%-15.2%) in 2019. In addition, the undiagnosed percentage in the population of men who have sex with men (MSM) also decreased from 28.8% to 13.6% during this period. We found decreases in the HIV incidence and undiagnosed percentage from 2012 to 2019 in Taiwan. These findings highlight the importance of intensified HIV testing efforts to achieve the global 95-95-95 goals by 2030.

Universal Use of N95 Respirators in Healthcare Settings When Community Coronavirus Disease 2019 Rates Are High.

The Centers for Disease Control and Prevention recommends N95 respirators for all providers who see patients with possible or confirmed coronavirus disease 2019 (COVID-19). We suggest that N95 respirators may be just as important for the care of patients without suspected COVID-19 when community incidence rates are high. This is because severe acute respiratory syndrome coronavirus 2 is most contagious before symptom onset. Ironically, by the time patients are sick enough to be admitted to the hospital with COVID-19, they tend to be less contagious. The greatest threat of transmission in healthcare facilities may therefore be patients and healthcare workers with early occult infection. N95 respirators’ superior fit and filtration provide superior exposure protection for healthcare providers seeing patients with early undiagnosed infection and superior source control to protect patients from healthcare workers with early undiagnosed infection. The probability of occult infection in patients and healthcare workers is greatest when community incidence rates are high. Universal use of N95 respirators may help decrease nosocomial transmission at such times.

Tracking elimination of HIV transmission in men who have sex with men in England: a modelling study

SummaryBackgroundTo manage the HIV epidemic among men who have sex with men (MSM) in England, treatment as prevention strategies based on test and treat were strengthened between 2011 and 2015, and supplemented from 2015 by scale-up of pre-exposure prophylaxis (PrEP). We examined the effect of these interventions on HIV incidence and investigated whether internationally agreed targets for HIV control and elimination of HIV transmission by 2030 might be within reach among MSM in England.MethodsWe used a novel, age-stratified, CD4-staged Bayesian back-calculation model to estimate HIV incidence and undiagnosed infections among adult MSM (age ≥15 years) during the 10-year period between 2009 and 2018. The model used data on HIV and AIDS diagnoses routinely collected via the national HIV and AIDS Reporting System in England, and knowledge on the progression of HIV through CD4-defined disease stages. Estimated incidence trends were extrapolated, assuming a constant MSM population from 2018 onwards, to quantify the likelihood of achieving elimination of HIV transmission, defined as less than one newly aquired infection per 10 000 MSM per year, by 2030.FindingsThe peak in HIV incidence in MSM in England was estimated with 80% certainty to have occurred in 2012 or 2013, at least 1 year before the observed peak in new diagnoses in 2014. Results indicated a steep decrease in the annual number of new infections among MSM, from 2770 (95% credible interval 2490–3040) in 2013 to 1740 (1500–2010) in 2015, followed by a steadier decrease from 2016, down to 854 (441–1540) infections in 2018. A decline in new infections was consistently estimated in all age groups, and was particularly marked in MSM aged 25–34 years, and slowest in those aged 45 years or older. Similar trends were estimated in the number of undiagnosed infections, with the greatest decrease after 2013 in the 25–34 years age group. Under extrapolation assumptions, we calculated a 40% probability of achieving the defined target elimination threshold by 2030.InterpretationThe sharp decrease in HIV incidence, estimated to have begun before the scale up of PrEP, indicates the success of strengthening treatment as prevention measures among MSM in England. To achieve the 2030 elimination threshold, targeted policies might be required to reach those aged 45 years or older, in whom incidence is decreasing at the slowest rate.FundingUK Medical Research Council, UK National Institute of Health Research Health Protection Unit in Behavioural Science and Evaluation, and Public Health England.

Severe coronavirus disease 2019 in a patient with HIV-2 infection.

Around the globe, millions of people living with HIV-1 face the challenges posed to them by the current coronavirus disease 2019 (COVID-19) pandemic [1,2]. Thriving on health disparity, COVID-19 can overwhelm the same communities where HIV-1 prevalence is highest [3,4]. Despite the threat of insufficient public health support, it is vital to ensure a continuous provision of a good quality of care and the avoidance of treatment discontinuation [5]. Alarmingly, people living with an HIV-1 infection also seem to be at increased risk of COVID-19 mortality [3]. However, to the best of our knowledge, no data are available for people infected with HIV-2 infection. Here, we describe a unique case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (the virus that causes COVID-19), infection in a patient who is being treated for HIV-2. In April 2020, a 66-year-old patient presented at the emergency room with a 5-day history of fever, dry cough and shortness of breath. The episode started with complaints of unsteadiness upon which he had fallen on the ground of his bedroom. A review of systems was negative for chest pain, rhinorrhoea, altered smell or taste, sore throat or any gastrointestinal symptoms. Born in Burkina Faso, he was living in the Netherlands since 15 years. He was known at our outpatient HIV clinic because of a well controlled asymptomatic HIV-2 monoinfection diagnosed in 2014 for which he received a fixed combination of darunavir/cobicistat/emtricitabine/tenofoviralafenamide. His plasma HIV-2 RNA load was less than 50 copies/ml with a CD4+ cell count of 760 × 106/l and a CD8+ cell count of 510 × 106/l. In addition, he was known with obesity (BMI 32.8 kg/m2) and moderately controlled hypertension treated with losartan and hydrochlorothiazide. On presentation, he was hypoxemic with a SpO2 of 90% on 5 l/min oxygen. His temperature was 38.0 °C and his respiratory rate was 30/min. Blood pressure and pulse were normal. On auscultation, bibasal crackles was heard. The patient's full blood count demonstrated a normal white cell count (8.5 × 109/l) with a diminished lymphocyte (1.42 × 109/l) and platelets count (104 × 109/l). Haemoglobin was 13.7 g/l and the d-dimer level was strongly elevated at 13.15 mg/l. Biochemical markers demonstrated raised levels of C-reactive protein (242.3 mg/l), aspartate aminotransferase (879 IU/l), alanine aminotransferase (134 IU/l), creatine (2.32 mg/dl) and creatine phosphokinase (40.724 U/l). Lactate (1.5 mmol/l) and bicarbonate (23.1 mmol/l) levels were normal. The patient underwent thoracic computed tomography (CT) which demonstrated widespread bilateral areas of patchy consolidations, findings consistent with severe COVID-19 infection (classified as CO-RADS 5 and CT severity score 7). An ultrasound for lower extremity deep venous thrombosis was negative. The nasopharyngeal SARS-CoV-2 PCR was positive. The patient was admitted to a COVID-19 ward and received treatment with oxygen and empiric broad-spectrum antibiotics according to the then current guidelines [1]. For the presumptive diagnosis of acute renal failure secondary to rhabdomyolysis fluid, resuscitation was started. After 6 days, he was discharged from the hospital in good health. All abnormal laboratory values continued to normalize. In addition to persistent but waning complaints of shortness of breath for a period of approximately 4 months, his recovery was otherwise uneventful. A follow-up CT-scan 4 months after his initial presentation showed a clear decline of COVID-19-related lung abnormalities. Total SARS-CoV-2 antibodies (including IgG and IgM) became positive (Wantai ELISA) and his plasma HIV-2 RNA load remains undetectable. Now, 8 months after his original presentation, he is in good spirits and does not experience any long-term COVID-19-related adverse health outcomes. In conclusion, we present a first case report of a SARS-CoV-2 and HIV-2 coinfection in a patient who needed hospital admission for severe COVID-19 and experienced long lasting but self-limiting symptoms after discharge. His disease course was complicated by acute renal failure secondary to rhabdomyolysis which has been associated with COVID-19 in both HIV-1 positive and negative patients [6,7]. Most probably, the kidney injury is caused by pneumonia-induced rhabdomyolysis and direct effects of SARS-CoV-2 on the renal parenchyma [6]. After its first recognition in 1985, HIV-2 is now seen throughout West Africa with an exceptionally high prevalence in Burkina Faso [8]. It is estimated that approximately 1–2 million people live with HIV-2 worldwide [9]. Reported numbers of HIV-2 infections, however, may be a significant underestimation of actual numbers due to unrecognized or undiagnosed infections [8,9]. Our current case report highlights the potential challenges associated with HIV-2 infection in the current COVID-19 pandemic. Acknowledgements W.J.W. is currently receiving a Vidi grant (#91716475) from the Netherlands Organization for Scientific Research (NWO). M.v.d.V. has received consultancy fees paid to his institution by Gilead, MSD, ViiV and research support from Gilead, MSD, ViiV, Abbvie. Conflicts of interest There are no conflicts of interest.