The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4+ T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy

IntroductionTorque teno virus (TTV) is a non-pathogenic virus present in body fluids. Its titer in the circulation increases in association with immune suppression, such as in HIV-infected individuals. We evaluated if the TTV titer in saliva from HIV-positive individuals undergoing antiretroviral therapy (ART) was related to the circulating CD4+ T lymphocyte concentration and the HIV titer.MethodsSaliva was collected from 276 asymptomatic individuals undergoing ART, and an additional 48 individuals positive for AIDS-associated Kaposi's Sarcoma (AIDS-KS). The salivary TTV titer was measured by gene amplification analysis. The circulating CD4+ T lymphocyte and HIV levels were obtained by chart review.ResultsTTV was detectable in saliva from 80% of the asymptomatic subjects and 87% of those with AIDS-KS. In the asymptomatic group the median log10 TTV titer/ml was 3.3 in 200 males vs. 2.4 in 76 females (p < 0.0001). TTV titer/ml was 3.7 when HIV was acquired by intravenous drug usage, 3.2 when by sexual acquisition and 2.4 when blood transfusion acquired. The salivary TTV titer was inversely correlated with the circulating CD4+ T lymphocyte level (p < 0.0001) and positively correlated with the circulating HIV concentration (p = 0.0005). The median salivary TTV titer and circulating HIV titer were higher, and the CD4+ count was lower, in individuals positive for AIDS-KS than in the asymptomatic subjects (p < 0.0001).ConclusionThe TTV titer in saliva is a potential biomarker for monitoring immune status in individuals undergoing ART.

Screening for SARS-CoV-2 persistence in Long COVID patients using sniffer dogs and scents from axillary sweats samples

Objectives: Dogs can be trained to identify several substances not detected by humans, corresponding to specific volatile organic compounds (VOCs). The presence of VOCs, triggered by SARS-CoV-2 infection, was tested in sweat from Long COVID patients. Patients and methods: An axillary sweat sample of Long COVID patients and of COVID-19 negative, asymptomatic individuals was taken at home to avoid any hospital contact. Swabs were randomly placed in olfaction detection cones, and the material sniffed by at least 2 trained dogs. Results: Forty-five Long COVID patients, mean age 45 (6-71), 73.3% female, with prolonged symptoms evolving for a mean of 15.2 months (5-22) were tested. Dogs discriminated in a positive way 23/45 (51.1%) Long COVID patients versus 0/188 (0%) control individuals (p<.0001). Conclusion:This study suggests the persistence of a viral infection in some Long COVID patients and the possibility of providing a simple, highly sensitive, non-invasive test to detect viral presence, during acute and extended phases of COVID-19.

Early signatures of breast cancer up to seven years prior to clinical diagnosis in plasma cell-free DNA methylomes

Limited studies to date have investigated the detectability of cell-free DNA (cfDNA) markers in asymptomatic individuals prior to a cancer diagnosis. Here, we performed cfDNA methylation profiling in blood of individuals up to seven years prior to a breast cancer diagnosis in addition to matched cancer-free controls (n=150). We identified cfDNA differentially methylated signatures that discriminated cancer-free controls from pre-diagnosis breast cancer cases over five years prior to diagnosis and demonstrate that these markers were reflective of methylation profiles in breast cancer tissue. We report classification of a range of pre-diagnosis breast cancer cases detected at Stage I (area under the receiver operating characteristic curve (AUC) of 0.771), and in cases with a negative mammogram screening within a year of blood collection (AUC of 0.852). This study provides evidence that cfDNA methylation markers indicative of breast cancers can be detected in blood among asymptomatic individuals prior to clinical detection.

Epidemiologic characteristics, clinical management and Public Health Implications of Coronavirus Disease 2019 (COVID-19) in Pregnancy: A Systematic Review and meta-analysis

Background: The novel coronavirus disease 2019 (COVID-19) outbreak, caused by the pathogenic severe acute respiratory syndrome-2 (SARS-CoV-2) virus, is exponentially spreading across the globe. Methods: The current systematic review was performed utilizing electronic databases i.e. PubMed, MEDLINE and EMBASE. We searched for the keywords "COVID-19 AND "pregnancy" between January 1st, 2020 until December 31, 2020. Results: Out of 4005 records which were identified, 36 original studies were included in this systematic review. Pooled prevalence of vertical transmission was 10%, 95% CI: 4-17%. Pooled prevalence of neonatal mortality was 7%, 95% CI: 0-21%. Conclusion: The contemporary evidence suggests that the incubation period of COVID-19 is 2-14 days, and this infection could be transmitted even from the infected asymptomatic individuals. It is found that the clinical presentation of pregnant women with COVID-19 infection is comparable with the infected non-pregnant females, and the frequent symptoms were fever, cough, myalgia, sore throat and malaise. There are some cases with severe maternal morbidity and perinatal deaths secondary to COVID-19 infection. Under these circumstances, the pregnant women should focus on maintaining personal hygiene, proper nutrition and extreme social distancing to reduce the risk of COVID-19. Therefore, a systematic data reporting for evidence base clinical assessment, management and pregnancy outcomes is essential for prevention of COVID-19 infection among pregnant women.

Clinical evaluation of the SD Biosensor SARS-CoV-2 saliva antigen rapid test with symptomatic and asymptomatic, non-hospitalized patients

Background Performance of the SD Biosensor saliva antigen rapid test was evaluated at a large designated testing site in non-hospitalized patients, with or without symptoms. Method All eligible people over 18 years of age presenting for a booked appointment at the designated SARS-CoV-2 testing site were approached for inclusion and enrolled following verbal informed consent. One nasopharyngeal swab was taken to carry out the default antigen rapid test from which the results were reported back to the patient and one saliva sample was self-taken according to verbal instruction on site. This was used for the saliva antigen rapid test, the RT-PCR and for virus culture. Sensitivity of the saliva antigen rapid test was analyzed in two ways: i, compared to saliva RT-PCR; and ii, compared to virus culture of the saliva samples. Study participants were also asked to fill in a short questionnaire stating age, sex, date of symptom onset. Recommended time of ≥30mins since last meal, drink or cigarette if applicable was also recorded. The study was carried out in February-March 2021 for 4 weeks. Results We could include 789 people with complete records and results. Compared to saliva RT-PCR, overall sensitivity and specificity of the saliva antigen rapid test was 66.1% and 99.6% which increased to 88.6% with Ct ≤30 cutoff. Analysis by days post onset did not result in higher sensitivities because the large majority of people were in the very early phase of disease ie <3 days post onset. When breaking down the data for symptomatic and asymptomatic individuals, sensitivity ranged from 69.2% to 50% respectively, however the total number of RT-PCR positive asymptomatic participants was very low (n = 5). Importantly, almost all culture positive samples were detected by the rapid test. Conclusion Overall, the potential benefits of saliva antigen rapid test, could outweigh the lower sensitivity compared to nasopharyngeal antigen rapid test in a comprehensive testing strategy, especially for home/self-testing and in vulnerable populations like elderly, disabled or children where in intrusive testing is either not possible or causes unnecessary stress.

Detection and Monitoring of Viral Infections via Wearable Devices and Biometric Data

Mounting clinical evidence suggests that viral infections can lead to detectable changes in an individual's normal physiologic and behavioral metrics, including heart and respiration rates, heart rate variability, temperature, activity, and sleep prior to symptom onset, potentially even in asymptomatic individuals. While the ability of wearable devices to detect viral infections in a real-world setting has yet to be proven, multiple recent studies have established that individual, continuous data from a range of biometric monitoring technologies can be easily acquired and that through the use of machine learning techniques, physiological signals and warning signs can be identified. In this review, we highlight the existing knowledge base supporting the potential for widespread implementation of biometric data to address existing gaps in the diagnosis and treatment of viral illnesses, with a particular focus on the many important lessons learned from the coronavirus disease 2019 pandemic. Expected final online publication date for the Annual Review of Biomedical Engineeing, Volume 24 is June 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The lower limit for FEV1/FVC in dive medical assessments: a retrospective study

Introduction: Interpreting pulmonary function test (PFT) results requires a valid reference set and a cut-off differentiating pathological from physiological pulmonary function; the lower limit of normal (LLN). However, in diving medicine it is unclear whether an LLN of 2.5% (LLN-2.5) or 5% (LLN-5) in healthy subjects constitutes an appropriate cut-off. Methods: All PFTs performed at the Royal Netherlands Navy Diving Medical Centre between 1 January 2015 and 1 January 2021 resulting in a forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and/or FEV1/FVC with a Z-score between -1.64 (LLN-5) and -1.96 (LLN-2.5) were included. Records were screened for additional tests, referral to a pulmonary specialist, results of radiological imaging, and fitness to dive. Results: Analysis of 2,108 assessments in 814 subjects showed that 83 subjects, 74 men and nine women, mean age 32.4 (SD 8.2) years and height 182 (7.0) cm, had an FVC, FEV1 and/or FEV1/FVC with Z-scores between -1.64 and -1.96. Of these 83 subjects, 35 (42%) underwent additional tests, 77 (93%) were referred to a pulmonary specialist and 31 (37%) underwent high-resolution CT-imaging. Ten subjects (12%) were declared ‘unfit to dive’ for various reasons. Information from their medical history could have identified these individuals. Conclusions: Use of LLN-2.5 rather than LLN-5 for FEV1/FVC in asymptomatic individuals reduces additional investigations and referrals to a pulmonary specialist without missing important diagnoses, provided a thorough medical history is taken. Adoption of LLN-2.5 could save resources spent on diving medical assessments and protect subjects from harmful side effects associated with additional investigations, while maintaining an equal level of safety.

Ear Wax and its Impaction: Clinical Findings and Management

Cerumen, sometimes known as "earwax," is a natural material that cleans, coats, and smooths the external auditory canal. It is the most common cause of ear canal obstruction. While cerumen blockage of the ear canal is usually painless, it can result in a variety of implications, for example, loss of hearing, tinnitus, overflowing, itching, otalgia, discharge, odour, and cough. Ear wax becomes a concern only when it causes hearing loss or other ear-related ailments. Cerumen build-up can arise for various causes, including an inability to self-clear, overproduction or underproduction of its essential components due to delayed skin movement, or mechanical difficulties such as usage of cotton buds or hearing aids. Wax can obstruct the understanding and view of the tympanic membrane and must be gone for investigative purposes or to take imprints before installing hearing support or creating earplugs. Cerumen impaction is usually innocuous; however, it might be associated with more significant symptoms. The removal of affected cerumen is typically regarded safe. However, as eardrum tear, canal laceration, and unsuccessful ear wax elimination. These dangers can be reduced by recognizing risky individuals and customising care measures to their specific needs. All common cerumen removal strategies are Cerumenolytics (ear wax emollient agents), irrigation, and manual elimination. It is also prudent not to interfere if asymptomatic individuals and tympanic membrane visualization are not required.

Durability of Humoral Immune Responses to SARS-CoV-2 in Citizens of Ariano Irpino (Campania, Italy): A Longitudinal Observational Study With an 11.5-Month Follow-Up

As of November 17, 2021, SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2), the causative agent of COVID-19 (COronaVIrus Disease 19), has infected ~250 million people worldwide, causing around five million deaths. Titers of anti-SARS-CoV-2 neutralizing antibodies were relatively stable for at least 9 months in a population-based study conducted in Wuhan, China, both in symptomatic and in asymptomatic individuals. In the mass screening campaign conducted in the town of Ariano Irpino (Avellino, Italy) in May, 2020, 5.7% (95% CI: 5.3-6-1) of the 13,444 asymptomatic citizens screened were positive for anti-nucleocapsid antibodies against SARS-CoV-2. Among these, 422 citizens were re-tested for anti SARS-CoV-2 antibodies in January, 2021 and/or in April, 2021 and enrolled in this longitudinal observational study. Median (interquartile range) age of the study cohort was 46 years (29–59), with 47 (11.1%) participants of minor age, while 217 (51.4%) participants were females. There was no evidence of re-infection in any of the subjects included. Presence of anti-nuclear antibodies antibodies (Elecysis, Roche) was reported in 95.7 and 93.7% of evaluable participants in January and April, 2021. Multiple logistic regression analysis used to explore associations between age, sex and seroprevalence showed that adults vs. minors had significantly lower odds of having anti-S1 antibodies (Biorad) both in January, 2021 and in April, 2021. Our findings showed that antibodies remained detectable at least 11.5 months after infection in &gt;90% of never symptomatic cases. Further investigation is required to establish duration of immunity against SARS-CoV-2.

Diagnostic Performance of a Rapid Antigen Test Compared with the Reverse Transcription Polymerase Chain Reaction for SARS-CoV-2 Detection in Asymptomatic Individuals Referring to a Drive-in Testing Facility

Quick and reliable identification of severe acute respiratory syndrome coronavirus SARS-CoV-2 in the population is required to manage the COVID-19 pandemic. This is a prospective observational study of diagnostic accuracy. Paired swab samples from 317 asymptomatic individuals referring to a drive-in testing facility were tested in parallel by means of the rapid antigen test developed by Jiangsu Bioperfectus Technologies and routine nucleic acid detection. Overall specificity was 100% and sensitivity was 49% but reached 87% at higher viral loads (Ct < 25). In this study, the antigen detection test showed high specificity and good sensitivity in asymptomatic individuals carrying higher viral loads. The assay performance worsened with lower viral loads, making it useful when a rapidly deployable test is essential and to assess a potential risk of immediate transmission in the community, but not recommended for testing asymptomatic individuals.