Respiratory viral infections are a leading cause of disease worldwide. A variety of respiratory viruses produce infections in humans with effects ranging from asymptomatic to life-treathening. Standard surveillance systems typically only target severe infections (ED outpatients, hospitalisations, deaths) and fail to track asymptomatic or mild infections. Here we performed a large-scale community study across multiple age groups to assess the pathogenicity of 18 respiratory viruses. We enrolled 214 individuals at multiple New York City locations and tested weekly for respiratory viral pathogens, irrespective of symptom status, from fall 2016 to spring 2018. We combined these test results with participant-provided daily records of cold and flu symptoms and used this information to characterise symptom severity by virus and age category. Asymptomatic infection rates exceeded 70% for most viruses, excepting influenza and human metapneumovirus, which produced significantly more severe outcomes. Symptoms were negatively associated with infection frequency, with children displaying the lowest score among age groups. Upper respiratory manifestations were most common for all viruses, whereas systemic effects were less typical. These findings indicate a high burden of asymptomatic respiratory virus infection exists in the general population.

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Background: Respiratory viral infections are a leading cause of disease worldwide.However, the overall community prevalence of infections has not been properly assessed, as standard surveillance is typically acquired passively among individuals seeking clinical care. Methods:We conducted a prospective cohort study in which participants provided daily diaries and weekly nasopharyngeal specimens that were tested for respiratory viruses. These data were used to analyze healthcare seeking behavior, compared with cross-sectional ED data and NYC surveillance reports, and used to evaluate biases of medically attended ILI as signal for population respiratory disease and infection. Results:The likelihood of seeking medical attention was virus-dependent: higher for influenza and metapneumovirus (19%-20%), lower for coronavirus and RSV (4%), and 71% of individuals with self-reported ILI did not seek care and half of medically attended symptomatic manifestations did not meet the criteria for ILI. Only 5% of cohort respiratory virus infections and 21% of influenza infections were medically attended and classifiable as ILI. We estimated 1 ILI event per person/year but multiple respiratory infections per year. Conclusion:Standard, healthcare-based respiratory surveillance has multiple limitations. Specifically, ILI is an incomplete metric for quantifying respiratory disease, viral respiratory infection, and influenza infection. The prevalence of respiratory viruses, as reported by standard, healthcare-based surveillance, is skewed toward viruses producing more severe symptoms. Active, longitudinal studies are a helpful supplement to standard surveillance, can improve understanding of the overall circulation and burden of respiratory viruses, and can aid development of more robust measures for controlling the spread of these pathogens.

Lecithin cholesterol acyl transferase (LCAT) catalyzes the conversion of unesterified, or free cholesterol (FC), to cholesteryl ester (CE), which moves from the surface of HDL into the neutral lipid core. As this iterative process continues, nascent lipid-poor HDL is converted to a series of larger, spherical cholesterol ester enriched HDL particles that can be cleared by the liver in a process that has been termed reverse cholesterol transport (RCT). We conducted a randomized, placebo controlled, cross-over study in 5 volunteers with ASCVD, to examine the effects of an acute increase of recombinant human (rh) LCAT via intravenous administration on the in vivo metabolism of HDL apolipoprotein (APO)A1 and APOA2, and the APOB100-lipoproteins, very low density (VLDL), intermediate density (IDL), and low density (LDL) lipoproteins. As expected, rhLCAT treatment significantly increased HDL CE content. This change did not affect the fractional clearance or production rates of HDL-APOA1 and HDL-APOA2. The metabolism of APOB100-lipoproteins was likewise unaffected. Our results suggest that an acute increase in LCAT activity drives greater flux of CE through the RCT pathway without altering the clearance and production of the main HDL proteins and without affecting the metabolism of APOB100-lipoproteins. Long-term elevations of LCAT might, therefore, have beneficial effects on total body cholesterol balance and atherogenesis.

Introduction Lipoprotein [Lp)(a)] is composed of an apoB100 containing lipoprotein bound to a glycoprotein, apolipoprotein (a). Epidemiological, genome‐wide association, and Mendelian randomization studies show high Lp(a) plasma levels as causal in the development of atherosclerotic cardiovascular disease (ASCVD). Plasma Lp(a) levels are 70‐90% determined by the number of DNA‐base repeats coding a highly polymorphic sequence of the LPA gene called Kringle IV Type 2 (KIV‐2). Most individuals have two Lp(a) isoforms that differ in apo(a) size. The pathways regulating Lp(a) clearance and secretion in humans are not well understood and are currently being studied by our group using stable isotopes. The latter may be regulated by the different proteins carried by the Lp(a) particle. However, these studies have concentrated on small cohorts and subjects with high levels of plasma Lp(a). Our goal was to examine the effect of Lp(a) levels (low vs. high) on Lp(a) protein composition, and in addition examine if the proteins carried by large size apo(a) isoforms (associated with low Lp(a) levels) and low size apo(a) isoforms (associated with high Lp(a) levels) were similar. We hypothesize that the protein expression of isolated Lp(a) particles from subjects with high and low Lp(a) will be enriched with different proteins. Methods: We enrolled 13 healthy volunteers (7 male, 6 female), obtained fasting bloods and isolated plasma samples from EDTA‐containing tubes. We measured plasma Lp(a) levels via a validated and standardized ELISA assay. Isoform sizes were obtained via SDS‐page electrophoresis and standardized to a known KIV‐2 repeat in 9 of the 13 subjects. We compared the proteomic profiles of isolated Lp(a) in 6 subjects with high Lp(a) levels (>75nmol/L) to that of 7 subjects with low Lp(a) levels (<40nmol/L). Lp(a) was isolated from 500uL of plasma by immunoprecipitation. The proteome of eluent was obtained by gel‐based protein identification. The use of proteome software Scaffold4 enabled the detection of protein biomarkers that may be related to functional abnormalities involved in the pathophysiology of Lp(a).Results: We found similar protein expression in subjects with high and low levels of Lp(a), these proteins are listed in Table 1. Additionally, protein expression counts for apo(a) and apoB100 were higher in subjects with high Lp(a) levels when compared with subjects with low Lp(a) levels. Lp(a) levels are inversely correlated to isoform size, i.e. subjects with small isoforms have high levels and vice versa. We examined the protein composition of Lp(a) in a small sub‐cohort of subjects expressing >24 repeats (low Lp(a) levels), n=6 and <24 (high Lp(a) levels), n=3. We found that subjects with >24 repeats (Table 2‐A) presented with higher protein expression counts of apoE and Von W factor while subjects with <24 (Table 2 ‐B) presented with higher protein expression of complement C3. Conclusion: We did not find differences in the proteome of subjects with high and low levels of Lp(a). Although protein expressio...