Longitudinal SARS-CoV-2 Testing among the Unvaccinated Is Punctuated by Intermittent Positivity and Variable Rates of Increasing Cycle Threshold Values.

The coronavirus disease 2019 (COVID-19) pandemic is complicated by cases of vaccine breakthrough and reinfection and widespread transmission of variants of concern (VOCs). Consequently, the need to interpret longitudinal positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests is crucial in guiding clinical decisions regarding infection control precautions and treatment. Although diagnostic real-time reverse transcription (RT)-PCR tests yield CT values that are inversely correlated with RNA quantity, these tests are only approved for qualitative interpretation. In this study, we performed a retrospective review of 72,217 SARS-CoV-2 positive tests and identified 264 patients with longitudinal positivity prior to vaccination and VOC circulation. Patients with longitudinal positivity fell into two categories: short-term (207, 78%) or prolonged (57, 22%) positivity, defined as ≤28 (range, 1 to 28; median, 16) days and >28 (range, 29 to 152; median, 41) days, respectively. In general, CT values increased over time in both groups; however, 11 short-term-positive patients had greater amounts of RNA detected at their terminal test than at the first positive test, and 6 patients had RNA detected at CT values of <35 at least 40 days after initial infection. Oscillating positive and negative results occurred in both groups, although oscillation was seen three times more frequently in prolonged-positive patients. Patients with prolonged positivity had diverse clinical characteristics but were often critically ill and were discharged to high-level care or deceased (22%). Overall, this study demonstrates that caution must be emphasized when interpreting CT values as a proxy for infectivity, a predictor of severity, or a guide for patient care decisions in the absence of additional clinical context, particularly among the unvaccinated population. IMPORTANCE We describe the duration of positivity and the COVID-19 treatment and outcome characteristics of an unvaccinated population of patients with prolonged SARS-CoV-2 positivity. This investigation serves to highlight challenges in using CT values to guide clinical decisions among unvaccinated individuals.

Optimal Lung Cancer Screening Criteria Among Persons Living With HIV.

BACKGROUND: The US Preventive Services Task Force (USPSTF) 2021 updated recommendations on lung cancer screening with chest computed tomography to apply to individuals 50-80 years of age (previously 55-80 years), with a ≥20 pack-year history (previously ≥30), whether currently smoking or quit ≤15 years ago. Despite being at higher risk for lung cancer, persons with HIV (PWH) were not well-represented in the National Lung Screening Trial, which informed the USPSTF 2013 recommendations. It is unknown or unclear how PWH are affected by the 2021 recommendations. SETTING: This study was a retrospective analysis of PWH with and without lung cancer in the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. METHODS: We identified PWH, ages 40-80 years, who currently or previously smoked, with (cases) and without lung cancer (noncases). The sensitivity and specificity of the old, new, and alternative screening criteria were evaluated in each cohort. RESULTS: We identified 52 women and 19 men with lung cancer and 1950 women and 1599 men without lung cancer. Only 11 women (22%) and 6 men (32%) with lung cancer met 2013 screening criteria; however, more women (22; 44%) and men (12; 63%) met 2021 criteria. Decreased age and tobacco exposure thresholds in women further increased sensitivity of the 2021 criteria. CONCLUSIONS: The 2021 USPSTF lung cancer screening recommendations would have resulted in more PWH with lung cancer being eligible for screening at the time of their diagnosis. Further investigation is needed to determine optimal screening criteria for PWH, particularly in women.

SARS-CoV-2 Infection in Health Care Personnel and Their Household Contacts at a Tertiary Academic Medical Center: Protocol for a Longitudinal Cohort Study.

BACKGROUND: Health care personnel (HCP) are at high risk for exposure to the SARS-CoV-2 virus. While personal protective equipment (PPE) may mitigate this risk, prospective data collection on its use and other risk factors for seroconversion in this population is needed. OBJECTIVE: The primary objectives of this study are to (1) determine the incidence of, and risk factors for, SARS-CoV-2 infection among HCP at a tertiary care medical center and (2) actively monitor PPE use, interactions between study participants via electronic sensors, secondary cases in households, and participant mental health and well-being. METHODS: To achieve these objectives, we designed a prospective, observational study of SARS-CoV-2 infection among HCP and their household contacts at an academic tertiary care medical center in North Carolina, USA. Enrolled HCP completed frequent surveys on symptoms and work activities and provided serum and nasal samples for SARS-CoV-2 testing every 2 weeks. Additionally, interactions between participants and their movement within the clinical environment were captured with a smartphone app and Bluetooth sensors. Finally, a subset of participants' households was randomly selected every 2 weeks for further investigation, and enrolled households provided serum and nasal samples via at-home collection kits. RESULTS: As of December 31, 2020, 211 HCP and 53 household participants have been enrolled. Recruitment and follow-up are ongoing and expected to continue through September 2021. CONCLUSIONS: Much remains to be learned regarding the risk of SARS-CoV-2 infection among HCP and their household contacts. Through the use of a multifaceted prospective study design and a well-characterized cohort, we will collect critical information regarding SARS-CoV-2 transmission risks in the health care setting and its linkage to the community. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25410.

Pneumocystis and Severe Acute Respiratory Syndrome Coronavirus 2 Coinfection: A Case Report and Review of an Emerging Diagnostic Dilemma.

We present a case of a critically ill patient with coronavirus disease 2019 (COVID-19) found to have acquired immune deficiency syndrome and Pneumocystis jirovecii pneumonia (PCP). Coronavirus disease 2019 and PCP co-occurrence is increasingly reported and may complicate diagnostic and therapeutic strategies. Patients with severe COVID-19 should be screened for underlying immunocompromise and coinfections should be considered.

Highly dampened blood transcriptome response in HIV patients after influenza infection.

Respiratory viral (RV) infections represent a major threat for human health worldwide. Persons with HIV (PWH) have a compromised immune response and are thought to be at higher risk for severe RV disease. However, very little is known about the host immune response to RV infection in PWH. Here, we investigated gene expression changes in the peripheral blood of PWH co-infected with RV. Only very few differentially expressed genes could be detected between PWH with and without RV infection, suggesting that the immune response to RV in PWH is strongly dampened. Our data provides important insights into the host response to RV infections in HIV patients.

Burden of respiratory viral infection in persons with human immunodeficiency virus.

This study was conducted to determine the prevalence of respiratory viral infections (RVI) in persons living with HIV (PLH) admitted with a respiratory complaint using real-time reverse transcription polymerase chain reaction and primer-independent next-generation sequencing (NGS). Of 82 subjects, respiratory viruses were the most common pathogen identified in 27 (33%), followed by fungus and bacteria in 8 (10%) and 4 (5%) subjects, respectively. Among subjects with RVI, 11 (41%) required ICU admission and 16 (59%) required mechanical ventilation. The proportion of respiratory viruses identified, and the associated complicated hospital course highlights the significant role that RVIs play in the lung health of PLH.

Runaway Kaposi Sarcoma-associated herpesvirus replication correlates with systemic IL-10 levels.

KSHV-associated inflammatory cytokine syndrome (KICS) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV). KICS is associated with high-level, systemic replication of KSHV. This study characterized the clinical and virologic features of a KICS patient over time. Additionally, it compared the cytokine profiles of the KICS case to Kaposi's sarcoma (KS) (n = 11) and non-KS (n = 6) cases. This KICS case presented with elevated levels of KSHV and IL-10, as expected. Surprisingly, this case did not have elevated levels of IL-6 or human immunodeficiency virus 1 (HIV-1). Nevertheless, treatment with anti-IL6 receptor antibody (tocilizumab) reduced KSHV viral load and IL-10. The KSHV genome sequence showed no significant changes over time, except in ORF24. Phylogenetic analysis established this isolate as belonging to KSHV clade A and closely related to other US isolates. These findings suggest IL-10 as potential biomarker and therapy target for KICS.

Age-Associated Changes in the Respiratory Epithelial Response to Influenza Infection.

Older adults suffer a disproportionate burden of influenza-related morbidity and mortality typically attributed to defects in the aging immune system collectively known as immunosenescence. While the age-related decline in the adaptive immune system has been well characterized, little is known about how aging affects the principal site of influenza infection-the nasal epithelium. In human nasal epithelial cell cultures (hNECs) from older adults, we found similar or increased levels of cytokines during influenza infection compared with hNECs from younger individuals. However, hNECs from older individuals demonstrated decreased mRNA expression for several key proteins that affect clearance of infected cells, including MHC-I and transporter associated with antigen presentation (TAP). These findings were confirmed at the level of protein expression. In vivo studies corroborated the in vitro differences in MHC-I and TAP gene expression and also revealed important decreases in the expression of key influenza-specific antiviral mediators MX1 and IFITM1. Furthermore, epithelial cell-cytotoxic T lymphocyte co-cultures demonstrate that CTL cytotoxic activity is dose-dependent on MHC-I antigen presentation. Taken together, these results indicate that aging is associated with important changes in the nasal epithelium, including antigen presentation and antiviral pathways, which may contribute to increased severity of disease in older adults through impaired clearance of infected cells.

The hidden burden of influenza: A review of the extra-pulmonary complications of influenza infection.

Severe influenza infection represents a leading cause of global morbidity and mortality. Although influenza is primarily considered a viral infection that results in pathology limited to the respiratory system, clinical reports suggest that influenza infection is frequently associated with a number of clinical syndromes that involve organ systems outside the respiratory tract. A comprehensive MEDLINE literature review of articles pertaining to extra-pulmonary complications of influenza infection, using organ-specific search terms, yielded 218 articles including case reports, epidemiologic investigations, and autopsy studies that were reviewed to determine the clinical involvement of other organs. The most frequently described clinical entities were viral myocarditis and viral encephalitis. Recognition of these extra-pulmonary complications is critical to determining the true burden of influenza infection and initiating organ-specific supportive care.

ACE inhibitor-induced angioedema.

Angiotensin-converting enzyme inhibitors (ACEI) are commonly prescribed for blood pressure control and renal protection. ACEI angioedema is a common problem in patients who are taking ACEI, although, in most cases, the disorder is self-limited, and spontaneous episodes of apparently unprovoked angioedema stop with the discontinuation of the medication. In a subset of patients, hospitalization and even intubation are required for airway protection. The diagnosis is made clinically. There are no laboratory studies that establish the diagnosis. However, such investigations help exclude alternative diagnoses as the cause for the patient's presentation. Conventional treatment with regimens used to control allergic angioedema is ineffective in this condition. The mechanism of ACEI-induced angioedema is thought to be related to its effect on the kallikrein-kinin system. Kallikrein is a protease that converts high-molecular-weight kininogens into kinins, primarily bradykinin. Medications recently developed, primarily icatibant and ecallantide, to control hereditary angioedema, a disorder also associated with kallikrein-kinin activation, have been used to treat ACEI angioedema with some success. The efficacy of these agents and their optimal use remains to be established by randomized and placebo controlled trials.