Relationship Between Rhabdomyolysis and SARS-CoV-2 Disease Severity.

Background Rhabdomyolysis has historically been associated with viral infections, of which influenza A is the most common. A literature review suggests that up to 1/3 of patients hospitalized with COVID-19 develop acute kidney injury (AKI), and of those, nearly half are admitted to the ICU. AKI complicating COVID-19 infection is attributed to several pathogeneses, including sepsis, direct cytopathic effects on the kidneys, and rhabdomyolysis. Objective We aimed to link COVID-19 infection to the development of rhabdomyolysis via creatine kinase (CK) measurement to assess whether this association increases ICU admission, length of stay (LOS), and mortality. Design and setting In this single-center, retrospective cohort study, we enrolled 984 adult patients with confirmed COVID-19 infection requiring admission to a community hospital between March 2020 and May 2021. Measurements Demographic data, laboratory values, and clinical outcomes were collected. The primary outcome measured was the development of rhabdomyolysis and/or AKI. Secondary outcomes included associations of rhabdomyolysis with ICU admission, length of hospital stay, and mortality, utilizing multivariable logistic regression methods. Results Out of the 984 patients included, 39 met the clinical criteria for rhabdomyolysis (4%). The incidence of rhabdomyolysis was higher in patients with AKI (38.3%) and in those who required ICU admission (53.8%) (p<0.001). There was an insignificant difference in death in this cohort (11 patients, 52.4%, p=0.996). However, the mean LOS in patients who had rhabdomyolysis was 18.2 days versus 9.8 days in patients who did not develop rhabdomyolysis (p<0.001). Conclusion Objectively tracking CK levels in COVID-19-infected patients can assist in diagnosing rhabdomyolysis, identifying AKI etiology, and accordingly making a preliminary prognosis for COVID-19 infection, which could direct physicians to initiate more intensive treatment earlier.

Smartphone Biosensor With App Meets FDA/ISO Standards for Clinical Pulse Oximetry and Can Be Reliably Used by a Wide Range of Patients.

BACKGROUND: Millions of smartphones contain a photoplethysmography (PPG) biosensor (Maxim Integrated) that accurately measures pulse oximetry. No clinical use of these embedded sensors is currently being made, despite the relevance of remote clinical pulse oximetry to the management of chronic cardiopulmonary disease, and the triage, initial management, and remote monitoring of people affected by respiratory viral pandemics, such as severe acute respiratory syndrome coronavirus 2 or influenza. To be used for clinical pulse oximetry the embedded PPG system must be paired with an application (app) and meet US Food and Drug Administration (FDA) and International Organization for Standardization (ISO) requirements. RESEARCH QUESTION: Does this smartphone sensor with app meet FDA/ISO requirements? Are measurements obtained using this system comparable to those of hospital reference devices, across a wide range of people? STUDY DESIGN AND METHODS: We performed laboratory testing addressing ISO and FDA requirements in 10 participants using the smartphone sensor with app. Subsequently, we performed an open-label clinical study on 320 participants with widely varying characteristics, to compare the accuracy and precision of readings obtained by patients with those of hospital reference devices, using rigorous statistical methodology. RESULTS: "Breathe down" testing in the laboratory showed that the total root-mean-square deviation of oxygen saturation (Spo2) measurement was 2.2%, meeting FDA/ISO standards. Clinical comparison of the smartphone sensor with app vs hospital reference devices determined that Spo2 and heart rate accuracy were 0.48% points (95% CI, 0.38-0.58; P < .001) and 0.73 bpm (95% CI, 0.33-1.14; P < .001), respectively; Spo2 and heart rate precision were 1.25 vs reference 0.95% points (P < .001) and 5.99 vs reference 3.80 bpm (P < .001), respectively. These small differences were similar to the variation found between two FDA-approved reference instruments for Spo2: accuracy, 0.52% points (95% CI, 0.41-0.64; P < .001) and precision, 1.01 vs 0.86% points (P < .001). INTERPRETATION: Our findings support the application for full FDA/ISO approval of the smartphone sensor with app tested for use in clinical pulse oximetry. Given the immense and immediate practical medical importance of remote intermittent clinical pulse oximetry to both chronic disease management and the global ability to respond to respiratory viral pandemics, the smartphone sensor with app should be prioritized and fast-tracked for FDA/ISO approval to allow clinical use. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04233827; URL: www.clinicaltrials.gov.

Cognitive and Microbiome Impacts of Experimental Ancylostoma ceylanicum Hookworm Infections in Hamsters.

Hookworms are one of the most prevalent and important parasites, infecting ~500 million people worldwide. Hookworm disease is among the leading causes of iron-deficiency anemia in the developing world and is associated with significant growth stunting and malnutrition. In humans, hookworms appear to impair memory and other forms of cognition, although definitive data are hard to come by. Here we study the impact of a human hookworm parasite, Ancylostoma ceylanicum, on cognition in hamsters in a controlled laboratory setting. We developed tests that measure long-term memory in hamsters. We find that hookworm-infected hamsters were fully capable of detecting a novel object. However, hookworm-infected hamsters were impaired in detecting a displaced object. Defects could be discerned at even at low levels of infection, whereas at higher levels of infection, hamsters were statistically unable to distinguish between displaced and non-displaced objects. These spatial memory deficiencies could not be attributed to defects in infected hamster mobility or to lack of interest. We also found that hookworm infection resulted in reproducible reductions in diversity and changes in specific taxanomic groups in the hamster gut microbiome. These data demonstrate that human hookworm infection in a laboratory mammal results in a specific, rapid, acute, and measurable deficit in spatial memory, and we speculate that gut alterations could play some role in these cognitive deficits. Our findings highlight the importance of hookworm elimination and suggest that finer tuned spatial memory studies be carried out in humans.

Plasmacytoid and myeloid dendritic cells with a partial activation phenotype accumulate in lymphoid tissue during asymptomatic chronic HIV-1 infection.

Dendritic cells (DCs) from HIV-1-infected individuals display numeric and functional defects, and recent evidence suggests that HIV-1 can directly and indirectly activate DCs in vitro. The in vivo activation state and compartmentalization of DC subsets during HIV-1 infection remain poorly understood, however. We evaluated phenotypic and functional characteristics of myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) directly ex vivo in peripheral blood and lymphoid tissue from HIV-1-infected and HIV-seronegative individuals. Analysis of a wide range of chemokine receptors and activation/maturation markers on circulating DCs from viremic HIV-1-infected donors revealed a phenotype indicative of partial activation. Yet, blood DCs from viremic subjects still achieved full maturation when stimulated in vitro. In addition, blood pDCs from viremic individuals had a reduced capacity to migrate to CXCL12 in vitro. Total numbers of both DC subsets were increased in lymph nodes of asymptomatic untreated HIV-1-infected subjects, consistent with DC accumulation in the lymphoid compartment. Lymph node DCs also expressed high levels of CD40 in the absence of increases of other typical activation/maturation markers. Activation and depletion of DCs in blood with accumulation in lymphoid tissue may contribute to HIV-associated chronic immune activation and T-cell dysfunction.

Human dendritic cell interactions with whole recombinant yeast: implications for HIV-1 vaccine development.

Defects in number and function of dendritic cells (DCs) have been observed during HIV-1 infection, so therapeutic HIV-1 vaccine approaches that target or activate DCs may improve vaccine immunogenicity. To determine the potential of recombinant Saccharomyces cerevisiae yeast as an HIV-1 vaccine, we investigated interactions between yeast and human DCs. Yeast induced direct phenotypic maturation of monocyte-derived DCs (MDDCs) and enriched blood myeloid DCs (mDCs), but only indirectly matured blood plasmacytoid DCs (pDCs). Yeast-pulsed MDDCs and blood mDCs produced inflammatory cytokines and stimulated strong allo-reactive T cell proliferation. Both blood DC subsets internalized yeast, and when pulsed with yeast recombinant for HIV-1 Gag protein, both stimulated in vitro expansion of Gag-specific CD8+ memory T cells. These results suggest that S. cerevisiae yeast have potent adjuvant effects on human DCs. Furthermore, recombinant yeast-derived antigens are processed by human blood DCs for MHC class-I cross-presentation. These DC-targeting characteristics of yeast suggest that it may be an effective vaccine vector for induction of HIV-1-specific cellular immune responses.