ABSTRACT
Accurate and rapid evaluation of SARS-CoV-2 half-maximal neutralizing antibody (nAb) titer (NT50) is an important research tool for measuring nAb responses after prophylaxis or therapeutics for COVID-19 prevention and management. Compared with ACE2-competitive enzyme immunoassays for nAb detection, pseudovirus assays remain low-throughput and labor intensive. A novel application of the Bio-Rad Bio-Plex Pro Human SARS-CoV-2 D614G S1 Variant nAb Assay was used to determine NT50 from COVID-19-vaccinated individuals and showed strong correlation to a laboratory-developed SARS-CoV-2 pseudovirus nAb assay. The Bio-Plex nAb assay could provide a rapid, high-throughput, culture-free method for NT50 determination in sera.
Subject(s)
COVID-19 , RNA Viruses , Humans , SARS-CoV-2 , COVID-19/diagnosis , Antibodies, Viral , Antibodies, Neutralizing , Angiotensin-Converting Enzyme 2ABSTRACT
Rationale Many patient with end-stage fibrotic lung disease die in the hospital due to dependence on High Flow Nasal Cannula (HFNC), not available at home. Despite available technical maturity, HFNC is not sufficiently available due to size and portability, energy requirement and oxygen (O2) capacity. This has become particularly problematic during the current Covid-19 pandemic, when many had to die alone in hospital due to these constraints. ObjectiveThe objective of this investigation was to appreciate the number of patients who die in hospital on comfort care, who could benefit from HFNC at home to support person-centered care (self-determination, family involvement, comforts of home) at end of life (EOL). MethodsWe collected data from a convenience sampling of patients who received care at a 449-bed acute-care community hospital in Southern California between June 2020 and June 2021. Data from this retrospective review of the electronic health record included demographics (age, gender, BMI and ethnicity). Other variables collected were length of stay (LOS), Covid status (+/-), comfort care orders, and HFNC requirement. Data were analyzed for frequencies, means and percentages. Chi square (categorical) and t- tests (continuous) were performed to determine statistical significance and Pearson r (categorical) and eta (continuous) were performed to test strength of association.ResultsOf the sample (n = 91), mean age was 78 years (+/- 10.6) and mostly female (38.8%, n = 42). Mean LOS was 13.7 days (+/- 12.1). Most (71.4%) patients in the sample were Hispanic (n = 65). 63 patients had orders for comfort care (69.2%), and 61 patients were Covid positive (67%). There was a statistically significant difference in mean flow rate (p = 0.022, η = 0.564) and fi02 (p < 0.001, η = 0.688) for patients discharged to hospice vs. those who died in hospital. For patients who died in hospital, mean fi02 was 0.94 (12.2) and mean flow rate (in liters) was 48.6 (16.4). ConclusionsThe pandemic has highlighted many healthcare disparities in the United States, and made apparent the needs of persons with fibrotic lung disease at EOL. This investigation revealed that most patients in hospital opting for comfort care died in hospital as their needs for increased flow rates and fi02 far exceeds what is currently available for outpatient use of HFNC. Investments should be made into developing technologies to support these individuals with the benefits of decreased need for hospitalization and promoting self-determination at EOL.
ABSTRACT
Background: There have been few estimates of SARS-CoV-2 seroprevalence in rigorously sampled and geographically broad populations that include children, who have accounted for fewer diagnosed COVID-19 cases compared to adults. The COMPASS study assessed cross-sectional, population-based SARS-CoV-2 seroprevalence and PCR positivity among adults and children in 15 US communities. Methods: Time-location sampling was used to recruit adults and children >2 months of age from randomly selected venues in communities near participating research sites. Demographics, history of COVID-19 and willingness (likely, very likely or already received) to receive an approved COVID-19 vaccine were captured via an interviewer-administered questionnaire. Serologic analysis was performed using a SARS-CoV-2 IgG nucleocapsid antibody (Ab) assay (Abbott Diagnostics, Abbott Park, IL). PCR testing was performed on a mid-turbinate swab using an assay approved by the HPTN Laboratory Center. Prevalence estimates were constructed, overall and by age group (<18 y, 18-39 y, 40-59 y, 60+ y), for each community using survey weights that accounted for the sampling design. Results: A total of 22,732 persons were enrolled (median per community 1,246, range 511 to 2,925) from Jan 2021 to Aug 2021;of these, 2,151 (9.5%) were <18 y. Overall, SARS-CoV-2 seroprevalence (Ab+) ranged from 3.8 to 17.3% (median 12.5%) and SARS-CoV-2 PCR positivity ranged from 0 to 1.9% (median 0.7%). About half of Ab+ and half of PCR+ persons reported no prior or recent (within 14 days) COVID-19 symptoms, respectively [median by community 49.7% (IQR 45.8, 63.9) and 53.6% (IQR 44.3, 58.3)]. Most adults (18+ y) (median 77.3% [69.6 to 92.7%]) reported willingness to get a COVID-19 vaccination;willingness was higher among persons aged 60 y+ [median 88.1%, IQR 83.5, 90.6] compared to those aged 18-39 [median 72.5%, IQR 64.1, 79.8] and 40-59 [median 75.6%, IQR 72.5, 78.4]. The combined prevalence of prior (Ab+) or active (PCR+) SARS-CoV-2 infection across all communities ranged from 4.4 to 17.6% (median 12.7%), and was similar for children (median 12.7%, range 4.4 to 19.7%) and adults (median 12.5%, range 4.4% to 17.8%) among communities enrolling > 25 children (Figure). Conclusion: In this population-based survey, evidence of prior and active SARS-CoV-2 infection varied widely by community but, contrasting with earlier reports, not by age. These findings suggest that acquisition of SARS-CoV-2 is similar across all ages.
ABSTRACT
Background. Severe coronavirus disease 2019 (COVID-19) often results from the immune-mediated cytokine storm, triggered by granulocyte macrophage-colony stimulating factor (GM-CSF), potentially leading to respiratory failure and death. Lenzilumab, a novel anti-human GM-CSF monoclonal antibody, neutralizes GM-CSF and demonstrated potential to improve clinical outcomes in a matched case-cohort study of patients with severe COVID-19 pneumonia. This Phase 3 randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of lenzilumab to improve the likelihood of survival without invasive mechanical ventilation (SWOV), beyond available treatments. Methods. Hypoxic patients, hospitalized with COVID-19 (n=520), requiring supplemental oxygen, but not invasive mechanical ventilation, were randomized on Day 0 to receive lenzilumab (1800mg, n=261) or placebo (n=259), and available treatments, including remdesivir and/or corticosteroids;and were followed through Day 28. Results. Baseline demographics were comparable between groups: male, 64.7%;mean age, 60.5 years;median CRP, 79.0 mg/L. Patients across both groups received steroids (93.7%), remdesivir (72.4%), or both (69.1%). Lenzilumab improved the primary endpoint, likelihood of SWOV in the mITT population, by 1.54-fold (HR: 1.54;95%CI: 1.02-2.32, p=0.0403). Lenzilumab improved SWOV by 1.91-fold (nominal p=0.0073) and 1.92-fold (nominal p=0.0067) in patients receiving remdesivir or remdesivir and corticosteroids, respectively. A key secondary endpoint of incidence of IMV, ECMO or death was also improved in patients receiving remdesivir (p=0.020) or remdesivir and corticosteroids (p=0.0180). Treatment-emergent serious adverse events were similar across both groups. Conclusion. Lenzilumab significantly improved SWOV in hypoxic COVID-19 patients upon hospitalization, with the greatest benefit observed in patients receiving treatment with remdesivir and corticosteroids. NCT04351152.
ABSTRACT
[Figure: see text].
ABSTRACT
BackgroundThe hyperinflammatory cytokine storm (CS) of COVID-19 is mediated by GM-CSF leading to release of downstream inflammatory chemokines, cytokines, and markers of systemic inflammation (C-reactive protein, CRP). The LIVE-AIR study demonstrated that lenzilumab, an anti-GM-CSF monoclonal antibody in patients hospitalized with COVID-19, safely improved the likelihood of achieving the primary endpoint, survival without ventilation (SWOV) by 1.54-fold (HR: 1.54;95%CI: 1.02–2.32, p=0.0403) compared with placebo. An exploratory analysis in patients with CRP<150 mg/L and age<85 years was conducted to determine lenzilumab efficacy when administered prior to advanced inflammation.MethodsLIVE-AIR was a phase 3 randomized, double-blind, placebo-controlled trial. Patients with COVID-19 (n=520), >18 years, and ≤94% oxygen saturation on room air and/or requiring supplemental oxygen, but not invasive mechanical ventilation (IMV), were randomized to receive lenzilumab (600 mg, n=261) or placebo (n=259) via three intravenous infusions administered 8 hours apart. Participants were followed through Day 28 following treatment.ResultsOverall, baseline demographics were comparable between treatment groups: male, 64.7%;mean age, 60.5 years;mean BMI, 32.5 kg/m2;median CRP, 79 mg/L;CRP was <150 mg/L in 78% of participants. Participants received steroids (93.7%), remdesivir (72.4%), or both (69.1%). Lenzilumab (n=159) improved the likelihood of SWOV by 3.04-fold in participants with CRP<150 mg/L and age<85 years (3.04;1.68–5.51, nominal p=0.0003) compared with placebo (n=178). Response to lenzilumab was observed in the first through third quartiles of baseline CRP (<41 mg/L, HR:8.33;41<79 mg/L, HR:1.60;79<137 mg/L, HR: 2.12;>137 mg/L, HR: 1.17). The incidence of IMV, ECMO, or death was reduced (OR: 0.31;95%CI: 0.15–0.63, p=0.002) and mortality was improved by 2.22-fold (OR: 2.22;95%CI: 1.07–4.67, p=0.034). In these participants, lenzilumab decreased CRP as early as Day 2 following treatment, compared with placebo which was further decreased by 38% on Day 28 compared with placebo (24.4±3.4 mg/L vs 39.1±4.9 mg/L).ConclusionLenzilumab significantly improved SWOV in hospitalized, hypoxic participants with COVID-19 pneumonia with the greatest benefits in SWOV and survival in patients with CRP<150 mg/L and age <85 years. Inhibition of GM-CSF, an orchestrator of CS, early in the hyperinflammatory response improved outcomes in COVID-19. NCT04351152
ABSTRACT
Background: The contributions of non-AIDS comorbidities and HIV-related factors to coronavirus disease 2019 (COVID-19) outcomes among persons with HIV (PWH) remain unclear. We aimed to identify risk factors for COVID-19 hospitalization among PWH. Methods: We evaluated all adult (≥18 years) PWH with a positive SARS-CoV-2 PCR evaluated in a public safety-net hospital system, a Ryan White-funded HIV clinic and a Veterans Affairs medical center in Atlanta, GA between March 1, 2020 and November 15, 2020. Demographic and clinical characteristics and COVID-19 disease outcomes were ascertained by medical record abstraction. We performed multivariable logistic regression to determine associations with COVID-19 hospitalization. Results: 180 patients (mean age 49 years, 78% male, 78% Black, 14% Latinx) were included. 97% were on antiretroviral therapy (ART), 91% had HIV-1 RNA <200 copies/ml, and mean CD4 count was 527 cells/mm3. 60 patients (33%) were hospitalized, 28 (47%) required supplemental oxygen. Overall mortality rate among PWH was 1.63%;mortality among hospitalized PWH was 5%. 130 patients (72%) had at least 1 non-AIDS comorbidity;22% had >4 comorbidities (hypertension, dyslipidemia, obesity and diabetes were most prevalent). In univariable models, age, hypertension, dyslipidemia, diabetes, heart disease, and chronic kidney disease were associated with hospitalization. HIV characteristics including CD4 count, viral load, and ART use were not associated with hospitalization. After adjusting for those baseline characteristicsassociated with hospitalization, only age [aOR(95%CI) 1.073 (1.036-1.110), p<0.0001] and diabetes mellitus [aOR(95%CI) 2.653 (1.027-6.853), p=0.0439] were associated with hospitalization. In a multivariable model adjusting only for age, comorbidity count was associated with a 25% increased risk for hospitalization [aOR(95% CI) 1.245 (1.013-1.531), p=0.0375];and having ≥4 comorbidities was associated with a 2.8-fold increased risk of hospitalization compared with 0-1 comorbidities [aOR(95% CI) 2.848 (1.174-6.910), p=0.0240] (Figure). In age-adjusted analyses restricted to CD4 <200 cells/mm3 or HIV-1 RNA >200 copies/mL, HIV-related factors were not associated with hospitalization. Conclusion: In a cohort of PWH with well-controlled HIV and COVID-19, age and non-AIDS comorbidities, but not HIV-related factors, were associated with hospitalization for COVID-19. Further research into causes of severe COVID-19 among PWH is warranted. (Figure Presented).
ABSTRACT
Background: Social isolation and loneliness are risk factors for decline in functional status, frailty, and early mortality in older adults. The SARS-CoV-2 pandemic has necessitated physical distancing to prevent virus transmission, resulting in many older adults lacking interpersonal connection, particularly if they live alone. Methods: Clinicians at University of North Carolina Geriatrics Specialty Clinic identified older adult patients at risk of loneliness, and invited them to participate in phone calls with students. We then recruited health professions student volunteers via email listservs and word of mouth. We assigned each student volunteer 1-3 patients and advised them to call their patients once every 1-2 weeks for 20-50 minutes of non-clinical conversation on topics of the student-patient dyad's choosing. We assessed students' comfort level in speaking with older adults with cognitive or physical impairments, depression, anxiety, or loneliness before and after participation via online surveys. We assessed patients' experience of loneliness and reception to student calls via mailed surveys. Results: Eighteen students and 35 patients participated in student outreach calls between April and December 2020. Of the students who completed the post-volunteer survey (n = 17), 82% reported that their comfort level in speaking with older adults with cognitive impairment increased, and 88% reported that that their comfort level in speaking with older adults with physical impairments, anxiety, depression, or loneliness increased. Among patients returning surveys (n = 15), 73% felt they lacked companionship, 60% felt left out, and 67% felt isolated from others often or some of the time. In addition, 94% agreed that talking to the student volunteer was enjoyable, 88% agreed that the volunteer was a source of support, and 82% agreed that the length of the call was appropriate. Conclusions: Outreach calls by health professions students not only positively affected isolated older adults, but also increased students' level of comfort in speaking with older adults with cognitive and physical impairments, mood disorders, and loneliness.
ABSTRACT
The widespread and rapid social and economic changes from Covid-19 response might be expected to dramatically improve air quality. However, national monitoring data from the US Environmental Protection Agency for criteria pollutants (PM2.5, ozone, NO2, CO, PM10) provide inconsistent support for that expectation. Specifically, during stay-at-home orders, average PM2.5 levels were slightly higher (~10% of its multi-year interquartile range [IQR]) than expected; average ozone, NO2, CO, and PM10 levels were slightly lower (~30%, ~20%, ~27%, and ~1% of their IQR, respectively) than expected. The timing of peak anomaly, relative to the stay-at-home orders, varied by pollutant (ozone: 2 weeks before; NO2, CO: 3 weeks after; PM10: 2 weeks after); but, by 5-6 weeks after stay-at-home orders, the concentration anomalies appear to have ended. For PM2.5, ozone, CO, and PM10, no US state had lower-than-expected pollution levels for all weeks during stay-at-home-orders; for NO2, only Arizona had lower-than-expected levels for all weeks during stay-at-home orders. Our findings show that the enormous changes from the Covid-19 response have not lowered PM2.5 levels across the US beyond their normal range of variability; for ozone, NO2, CO, and PM10 concentrations were lowered but the reduction was modest and transient.