Heparan sulfates from bat and human lung and their binding to the spike protein of SARS-CoV-2 virus

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has resulted in a pandemic and continues to spread at an unprecedented rate around the world. Although a vaccine has recently been approved, there are currently few effective therapeutics to fight its associated disease in humans, COVID-19. SARS-CoV-2 and the related severe acute respiratory syndrome (SARS-CoV-1), and Middle East respiratory syndrome (MERS-CoV) result from zoonotic respiratory viruses that have bats as the primary host and an as yet unknown secondary host. While each of these viruses has different protein-based cell-surface receptors, each rely on the glycosaminoglycan, heparan sulfate as a co-receptor. In this study we compare, for the first time, differences and similarities in the structure of heparan sulfate in human and bat lungs. Furthermore, we show that the spike glycoprotein of COVID-19 binds 3.5 times stronger to human lung heparan sulfate than bat lung heparan sulfate.

Risk Factors Associated with Hospitalization among 0 to 21 Years Old Patients with Active Asthma/Active Airway Disease: Preliminary Findings from Multi-Center Study Across United States

Background. More data are needed to understand the risk for COVID-19 severity among pediatric asthma patients. We present findings from a national registry characterizing COVID-19 hospitalizations among pediatric asthma patients. Methods. Data were obtained from the Pediatric COVID-19 US Registry, which included medical records of COVID-19 cases < 21 years old between March 2020 and May 2021. Those with asthma were eligible while immunocompromised and transplant cases were excluded. Descriptive statistics and chi-square tests were performed. Results. Of the 1089 eligible asthma cases, half were 12 to 17 years old [Figure 1], the majority were male [Figure 2], a third Black African American [Figure 3], and most were Non-Hispanic/Latino 825 (76%). 242 (22%) reported a history of smoking. A fourth of cases (257 (23.6%) were hospitalized for COVID-19. More than half (54%) reported asthma as their only pre-existing condition. The majority (n=71, 28%) were taking regular inhaled corticosteroids. Almost half (n=120, 47%) had abnormal chest radiographic findings, 20 (7.8%) had abnormal CT findings, and 24 (9%) progressed to lower respiratory infection. About 10% (n=25) needed mechanical ventilation. A third (n=88, 34%) required ICU care with 33% of those receiving inhaled corticosteroids. A quarter needed mechanical ventilation [Figure 5]. Compared to asthma patients not hospitalized for COVID-19, those hospitalized were significantly (P< 0.05) more likely to be non-Hispanic, have multiple pre-existing conditions, and be obese [Figure 6]. Compared to those not admitted to ICU, ICU cases were significantly more likely to be obese and be diagnosed with MIS-C [Figure 7]. Demographics Conclusion. This is one of the first national studies examining COVID-19 among pediatric cases with asthma. Our data suggest that children with asthma who have multiple pre-existing conditions and/or are obese have a higher risk for hospitalization. These early data may aid clinicians in developing future prospective studies to understand COVID-19 risk among this vulnerable population. (Figure Presented).

IgG Antibody Response to the Pfizer BNT162b2 SARS-CoV-2 Vaccine in Healthcare Workers with Healthy Weight, Overweight, and Obesity.

Obesity is a significant factor for increased morbidity and mortality upon infection with SARS-CoV-2. Because of the higher potential for negative outcomes following infection of individuals with obesity, the impact of body mass index (BMI) on vaccine immunogenicity and efficacy is an important public health concern. Few studies have measured the magnitude and durability of the vaccine-specific response in relation to BMI. We measured the receptor binding domain (RBD)-specific serum IgG and surrogate neutralizing titers in a cohort of 126 vaccinated individuals with no clinical history or serological evidence of previous SARS-CoV-2 infection 50 and 200 days following vaccination. BMI had no significant impact on RBD-specific IgG titers and surrogate neutralizing titers 50 days following immunization, and leptin levels had no correlation with the response to immunization. Two hundred days following immunization, antibody titers in all groups had declined by approximately 90%. The responses were also similar between male and female participants and did not significantly vary across age groups. These results indicate that the magnitude and durability of the antibody response to mRNA-based vaccines are unaffected by BMI in this cohort.

Randomized controlled trial of an adherence intervention in youth living with HIV

Background: Youth living with HIV (YLWH) have low rates of viral suppression (VS). We evaluated the impact of a 12-week intervention using remote coaching, electronic dose monitoring (EDM) and tailored outreach (the Triggered Escalating Real-Time Adherence [TERA] intervention) compared to standard of care (SOC) on VS and electronic dose monitored adherence of antiretroviral therapy (ART), among viremic (HIV-1 RNA≥200 copies/ml) youth (ages 13-24 yrs) in the United States. Methods: 89 YLWH were randomized to TERA intervention versus SOC and followed for 48 weeks with study visits at weeks 0, 4, 12, 24, 36 and 48. Remote coaching sessions were delivered at Weeks 0, 4 and 12, with continuous EDM monitoring for delayed or missed ART doses and as needed outreach from coach by text and phone in the TERA arm. Primary outcome was VS at week 12 (HIV-1 RNA <200 cp/ml at 10-14 weeks). RNA ≥ 200 cp/ml (10-14 wks) or missing set to failure. Proportions with VS were compared by arm (Fisher's exact test and log binomial regression for adjusted comparisons). Secondary outcomes included EDM adherence summarized in 12-week intervals using percent days device was opened (PCT12) and incidence rates (IR) of number of ≥7-day gaps between openings (GAPIR), compared using Wilcoxon rank sum tests. Results are reported using data collected before the study paused due to COVID-19 in March 2020. Results: 88 YLWH completed study entry: 55% male, 85% Black/African American, median age 22 (range 13-24 yrs), 44% acquired HIV perinatally and 30% on ≥3rd ART regimen. VS was achieved in 15/43 (35%;95% CI: 21%, 51%) TERA arm and 16/45 (36%;95% CI: 22%, 51%) SOC arm participants;difference (TERA-SOC) was-1% (95% CI:-21%, 20%). No differences by arm were apparent at weeks 24, 36 or 48 or after adjusting for sex, age or mode of transmission. Of 54 participants with opportunity for follow-up to week 48, 14% (4/29) and 8% (2/25) in the TERA and SOC arms, respectively, achieved consistent VS (TERA-SOC: 6%;95% CI: 15%, 25%). Median (Q1, Q3) PCT12 over the first 12 weeks was 72% (47%, 89%) versus 41% (21%, 59%) in the TERA and SOC arms, respectively (p<0.001). GAPIRs were higher in the SOC arm than TERA arm with SOC/TERA IR ratio of 2.51 (95% CI: 1.90, 3.33). Conclusion: The 12-week TERA intervention improved adherence to ART but not VS among YLWH failing treatment. TERA will be further assessed for indication, timing, and outcome duration in YLWH.

Heparan sulfates from bat and human lung and their binding to the spike protein of SARS-CoV-2 virus.

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has resulted in a pandemic and continues to spread at an unprecedented rate around the world. Although a vaccine has recently been approved, there are currently few effective therapeutics to fight its associated disease in humans, COVID-19. SARS-CoV-2 and the related severe acute respiratory syndrome (SARS-CoV-1), and Middle East respiratory syndrome (MERS-CoV) result from zoonotic respiratory viruses that have bats as the primary host and an as yet unknown secondary host. While each of these viruses has different protein-based cell-surface receptors, each rely on the glycosaminoglycan, heparan sulfate as a co-receptor. In this study we compare, for the first time, differences and similarities in the structure of heparan sulfate in human and bat lungs. Furthermore, we show that the spike glycoprotein of COVID-19 binds 3.5 times stronger to human lung heparan sulfate than bat lung heparan sulfate.