scholarly journals Baseline SARS-CoV-2 Viral Load is Associated With COVID-19 Disease Severity and Clinical Outcomes: Post-Hoc Analyses of a Phase 2/3 Trial

2021 ◽  
Author(s):  
Anita Boyapati ◽  
Matthew F Wipperman ◽  
Peter J Ehmann ◽  
Sara Hamon ◽  
David J Lederer ◽  
...  
Keyword(s):  
Viral Load ◽  
Clinical Outcomes ◽  
Disease Severity ◽  
Clinical Status ◽  
Supplemental Oxygen ◽  
Assisted Ventilation ◽  
Hospitalized Patients ◽  
Baseline Viral Load ◽  
Phase 2 ◽  
Post Hoc

Abstract Background Elucidating the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and clinical outcomes is critical for understanding COVID-19. Methods SARS-CoV-2 levels were analyzed by quantitative real-time polymerase chain reaction (RT-qPCR) of nasopharyngeal or oropharyngeal swab specimens collected at baseline and clinical outcomes were recorded over 60 days from 1362 COVID-19 hospitalized patients enrolled in a multicenter, randomized, placebo-controlled phase 2/3 trial of sarilumab for COVID-19 (NCT04315298). Results In post-hoc analyses, higher baseline viral load, measured by both RT-qPCR cycle threshold (Ct) and log10 copies/mL, was associated with greater supplemental oxygenation requirements and disease severity at study entry. Higher baseline viral load was associated with higher mortality, lower likelihood of improvement in clinical status and supplemental oxygenation requirements, and lower rates of hospital discharge. Viral load was not impacted by sarilumab treatment over time versus placebo. Conclusions These data support viral load as an important determinant of clinical outcomes in hospitalized patients with COVID-19 requiring supplemental oxygen or assisted ventilation.

scholarly journals REGEN-COV for the Treatment of Hospitalized Patients with Covid-19

2021 ◽  
Author(s):  
Selin Somersan-Karakaya ◽  
Eleftherios Mylonakis ◽  
Vidya P. Menon ◽  
Jason C. Wells ◽  
Shazia Ali ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Viral Load ◽  
Supplemental Oxygen ◽  
Hospitalized Patients ◽  
Low Flow ◽  
Baseline Viral Load ◽  
Post Exposure Prophylaxis ◽  
Positive Trend ◽  
Risk Of Death ◽  
All Cause Mortality

Background: Hospitalized patients with Covid-19 experience high mortality rates, ranging from 10-30%. Casirivimab and imdevimab (REGEN-COV) is authorized in various jurisdictions for use in outpatients with Covid-19 and in post-exposure prophylaxis. The UK-based platform RECOVERY study reported improved survival in hospitalized seronegative patients treated with REGEN-COV, but in most of the world, anti-spike monoclonal antibody therapy is currently not approved for use in hospitalized patients. Methods: In this phase 1/2/3 double-blind placebo-controlled trial, patients on low-flow or no supplemental oxygen hospitalized with Covid-19 were randomized (1:1:1) to 2.4 g or 8.0 g REGEN-COV or placebo and characterized at baseline for viral load and SARS-CoV-2 endogenous immune response. Results: 1336 patients on low-flow or no supplemental oxygen were treated. The primary endpoint was met: in seronegative patients, the LS mean difference (REGEN-COV vs. placebo) for TWA change from baseline viral load was -0.28 log10 copies/mL (95% CI: -0.51, -0.05; P=0.0172). The primary clinical analysis of death or mechanical ventilation from day 6-29 in patients with high-viral load had a strong positive trend but did not reach significance. REGEN-COV reduced all-cause mortality in seronegative patients through day 29 (RRR, 55.6%; 95% CI: 24.2%, 74%). No safety concerns were noted overall nor in seropositive patients. Conclusions: In hospitalized patients with Covid-19 on low-flow or no oxygen, REGEN-COV treatment reduced viral load and the risk of death or mechanical ventilation as well as all-cause mortality in the overall population, with the benefit driven by seronegative patients and no harm observed in seropositive patients. (ClinicalTrials.gov number, NCT04426695.)

scholarly journals Impact of Tenofovir/Lamivudine/Dolutegravir (Tld) on the Health-Related Quality of Life and Clinical Outcomes of HIV/AIDS Patients at a Tertiary Health Facility in Niger State

2020 ◽  
Author(s):  
Danjuma Umar ◽  
Bala Waziri ◽  
Umar Ndagi ◽  
Shafiu Mohammed ◽  
Ndagi Usman ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Regression Analysis ◽  
Viral Load ◽  
Clinical Outcomes ◽  
Viral Suppression ◽  
Baseline Viral Load ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related

Abstract Background: Human Immuno-deficiency Virus (HIV) remains a major global public health issue. However, it is now considered a chronic infection which can be managed with new, well-tolerated and efficacious ARVs. The aim of the study was to evaluate the effect of Tenofovir/Lamivudine/Dolutrgravir (TLD) on the HRQoL and viral suppression over a short period.Method: The study was prospective, with a time frame of three (3) months. HRQoL was measured using a disease specific HIV/AID Targeted Quality of Life (HAT-QoL) tool and the clinical outcomes focused on viral load using structured data collection tool.Results: Most of the participants were female (62.1%), currently married 63.2% and no co-morbidity, mean age 43±SD (range 21-77years). There was a statistically significant improvement in HRQoL scores across all domain after 3months of transitioning to TLD. While 8 of the 9 domains namely; overall functions, life satisfaction, health worries, financial worries, medication worries, HIV mastery, Disclosure worries, Provider trust, (p <0.001) sexual function (p =0.015). Improvement was also seen in viral suppression (p <0.001).Using multiple linear regression analysis, predictors for overall HRQol scores include female gender (ᵝ= 3.59, 95%CI 1.30-5.78, p=0.002), older age, >65years (ᵝ= 4.12, 95%CI -1.42,9.67 p=0.08), living with family (ᵝ= -5.80, 95%CI -9.60,-2.00, p=0.003), higher family income, >N100,000 (ᵝ= 6.09, 95%CI 1.75,10.44, p=0.006) and duration on ART (ᵝ=0.52, 95%CI 0.12, 0.91, p=0.01). While determinants of viral suppression using multi-variant logistic regression analysis revealed living with family (AOR=18.03, 95%CI 3.32-97.85, p<0.001), Primary education (AOR= 0.16, 965%CI 0.029,0.93, P=0.041), being employed (AOR=0.16, 95%CI 0.028,0.91, P=0.008), income and baseline viral load (AOR= 0.53, 95%CI 0.44,0.69, p<0.001). However, living with family is major determinant of viral suppression.Conclusion: TLD help improved health related quality of life among HIV infected individual and essential in rapid viral suppression.

Multicenter Trial of Single-Dose Modified Bovine Surfactant Extract (Survanta) for Prevention of Respiratory Distress Syndrome

PEDIATRICS ◽  
1990 ◽  
Vol 85 (6) ◽  
pp. 1092-1102
Author(s):  
Roger F. Soll ◽  
Ronald E. Hoekstra ◽  
John J. Fangman ◽  
Anthony J. Corbet ◽  
James M. Adams ◽  
...  
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Airway Pressure ◽  
Distress Syndrome ◽  
Clinical Status ◽  
Supplemental Oxygen ◽  
Assisted Ventilation ◽  
Fraction Of Inspired Oxygen ◽  
Alveolar Oxygen ◽  
Inspired Oxygen

A multicenter, prospective randomized controlled trial was performed comparing the efficacy of a single intratracheal dose of modified bovine surfactant extract (Survanta, 100 mg/kg, Abbott Laboratory, North Chicago, IL) with air placebo in preventing respiratory distress syndrome. Infants were enrolled if they were estimated to be between 24 and 30 weeks' gestation, weighed between 750 and 1250 g, and were intubated and stabilized within 15 minutes after birth. A total of 160 infants were treated (79 with surfactant, 81 with air placebo) between 4 and 37 minutes after birth (median time 12 minutes). Of these, 5 infants were excluded from the final analysis. The 72-hour average values for the arterial-alveolar oxygen ratio, fraction of inspired oxygen, and mean airway pressure were calculated from the area under the curve of scheduled values measured throughout 72 hours. Clinical status was classified using five ordered categories (no supplemental oxygen or assisted ventilation, supplemental oxygen only, continuous positive airway pressure or assisted ventilation with intermittent mandatory ventilation ≤6 breaths/min, assisted ventilation with intermittent mandatory ventilation &gt;6 breaths/min, death). Chest radiographs at 24 hours were graded for severity of respiratory distress syndrome. Infants receiving Survanta had less severe radiographic changes at 24 hours of age and decreased average fraction of inspired oxygen (31% vs 42%, P = .002) compared with control infants. No differences were noted in the average arterial-alveolar oxygen ratio, mean airway pressure, or clinical status on days 7 and 28. A beneficial effect was noted in the incidence of pneumothorax (P = .057) and an increase was noted in the incidence of necrotizing enterocolitis (P = .052). No differences in incidence of patent ductus arteriosus, intraventricular hemorrhage, sepsis, or bronchopulmonary dysplasia were seen. According to results of a secondary analysis, there was improvement in the fraction of inspired oxygen and a greater number of survivors without bronchopulmonary dysplasia in the subgroup of infants weighing &lt;1000 g who were treated with surfactant. It was concluded that a single dose of Survanta given shortly after birth resulted in decreased severity of chest radiographic findings 24 hours after treatment and improved oxygenation during 72 hours after treatment, but did not improve other acute measures of disease severity or clinical status later in the neonatal period. The group at highest risk for respiratory distress syndrome (infants with birth weights between 750 and 999 g) may benefit the most from preventive therapy.

scholarly journals Assessment and Modeling of COVID-19 Outcomes in a Longitudinal Cohort of Hospitalized Adults

2021 ◽  
Author(s):  
Lacy M Simons ◽  
Ramon Lorenzo-Redondo ◽  
Meg Gibson ◽  
Sarah L Kinch ◽  
Jacob P Vandervaart ◽  
...  
Keyword(s):  
Viral Load ◽  
Disease Severity ◽  
Antibody Titer ◽  
Neutrophil Count ◽  
Clinical Management ◽  
Lymphocyte Count ◽  
Hospitalized Patients ◽  
Viral Genotype ◽  
Icu Admission ◽  
Over Time

Background: While several demographic and clinical correlates of Coronavirus Disease 2019 (COVID-19) outcome have been identified, they remain imprecise tools for clinical management of disease. Furthermore, there are limited data on how these factors are associated with virological and immunological parameters over time. Methods and Findings: Nasopharyngeal swabs and blood samples were longitudinally collected from a cohort of 58 hospitalized adults with COVID-19 in Chicago, Illinois between March 27 and June 9, 2020. Samples were assessed for SARS-CoV-2 viral load, viral genotype, viral diversity, and antibody titer. Demographic and clinical information, including patient blood tests and several composite measures of disease severity, were extracted from electronic health records. All parameters were assessed for association with three patient outcome groups: discharge without intensive care unit (ICU) admission (n = 23), discharge with ICU admission (n = 29), and COVID-19 related death (n = 6). Higher age, male sex, and higher body mass index (BMI) were significantly associated with ICU admission. At hospital admission, higher 4C Mortality scores and lactate dehydrogenase (LDH) levels were likewise associated with ICU admission. Longitudinal trends in Deterioration Index (DI) score, Modified Early Warning Score (MEWS), and serum neutrophil count were also associated with ICU admission, though only the retrospectively calculated median DI score was predictive of death. While viral load and genotype were not significantly associated with outcome in this study, viral load did correlate positively with C-reactive protein levels and negatively with D-dimer, lymphocyte count, and antibody titer. Intra-host viral genetic diversity resulted in changes in viral genotype in some participants over time, though intra-host evolution was not associated with outcome. A stepwise-generated multivariable model including BMI, lymphocyte count at admission, and neutrophil count at admission was sufficient to predict outcome with a 0.82 accuracy rate in this cohort. Conclusions: These studies suggest that COVID-19 disease severity and poor outcomes among hospitalized patients are likely driven by dysfunctional host responses to infection and underlying co-morbid conditions rather than SARS-CoV-2 viral loads. Several parameters, including 4C mortality score, LDH levels, and DI score, were ultimately predictive of participant outcome and warrant further exploration in larger cohort studies for use in clinical management and risk assessment. Finally, the prevalence of intra-host diversity and viral evolution in hospitalized patients suggests a mechanism for population-level change, further emphasizing the need for effective antivirals to suppress viral replication and to avoid the emergence of new variants.

scholarly journals A Randomized Placebo-Controlled Trial of Sarilumab in Hospitalized Patients with Covid-19

2021 ◽  
Author(s):  
Sumathi Sivapalasingam ◽  
David Lederer ◽  
Rafia Bhore ◽  
Negin Hajizadeh ◽  
Gerard Criner ◽  
...  
Keyword(s):  
Relative Risk ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Clinical Status ◽  
Hospitalized Patients ◽  
Phase 2 ◽  
Primary Analysis ◽  
Phase 3 ◽  
Double Blind ◽  
Critical Patients

BACKGROUND Sarilumab (anti-interleukin-6 receptor-alpha; monoclonal antibody) may attenuate the inflammatory response in Covid-19. METHODS We performed an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial of intravenous sarilumab 200 mg or 400 mg in adults hospitalized with Covid-19. The phase 3 primary analysis population (cohort 1) was patients with critical Covid-19 receiving mechanical ventilation (MV) randomized to sarilumab 400 mg or placebo. The primary end point for phase 3 was the proportion of patients with ≥1-point improvement in clinical status from baseline to day 22. RESULTS Four-hundred fifty-seven (457) and 1365 patients were randomized and treated in phases 2 and 3, respectively. Among phase 3 critical patients receiving MV (n=289; 34.3% on corticosteroids), the proportion with ≥1-point improvement in clinical status (alive not receiving MV) at day 22 was 43.2% in sarilumab 400 mg and 35.5% in placebo (risk difference [RD] +7.5%; 95% confidence interval [CI], − 7.4 to 21.3; P=0.3261), representing a relative risk improvement of 21.7%. Day 29 all-cause mortality was 36.4% in sarilumab 400 mg versus 41.9% in placebo (RD − 5.5%; 95% CI, −20.2 to 8.7; relative risk reduction 13.3%). In post hoc analyses pooling phase 2 and 3 critical patients receiving MV, the hazard ratio (HR) for death in sarilumab 400 mg compared with placebo was 0.76 (95% CI, 0.51 to 1.13) overall, improving to 0.49 (95% CI, 0.25 to 0.94) in patients receiving corticosteroids at baseline. CONCLUSION In hospitalized patients with Covid-19 receiving MV, numerical benefits with sarilumab did not achieve statistical significance, but benefit may be greater in patients receiving corticosteroids. A larger study is required to confirm this observed numerical benefit.

scholarly journals Disease Severity and Prognosis of SARS-CoV-2 Infection in Hospitalized Patients Is Not Associated With Viral Load in Nasopharyngeal Swab

2021 ◽  
Vol 8 ◽  
Author(s):  
Elisabetta Cocconcelli ◽  
Gioele Castelli ◽  
Francesco Onelia ◽  
Enrico Lavezzo ◽  
Chiara Giraudo ◽  
...  
Keyword(s):  
Viral Load ◽  
Medical Care ◽  
Disease Severity ◽  
High Intensity ◽  
Hospitalized Patients ◽  
Nasopharyngeal Swab ◽  
Asymptomatic Individuals ◽  
The Right ◽  
Asymptomatic Subjects ◽  
The Impact

Background: The impact of viral burden on severity and prognosis of patients hospitalized for Coronavirus Disease 2019 (COVID-19) is still a matter of debate due to controversial results. Herein, we sought to assess viral load in the nasopharyngeal swab and its association with severity score indexes and prognostic parameters.Methods: We included 127 symptomatic patients and 21 asymptomatic subjects with a diagnosis of SARS-CoV-2 infection obtained by reverse transcription polymerase chain reaction and presence of cycle threshold. According to the level of care needed during hospitalization, the population was categorized as high-intensity (HIMC, n = 76) or low intensity medical care setting (LIMC, n = 51).Results: Viral load did not differ among asymptomatic, LIMC, and HIMC SARS-CoV-2 positive patients [4.4 (2.9–5.3) vs. 4.8 (3.6–6.1) vs. 4.6 (3.9–5.7) log10 copies/ml, respectively; p = 0.31]. Similar results were observed when asymptomatic individuals were compared to hospitalized patients [4.4 (2.9–5.3) vs. 4.68 (3.8–5.9) log10 copies/ml; p = 0.13]. When the study population was divided in High (HVL, n = 64) and Low Viral Load (LVL, n = 63) group no differences were observed in disease severity at diagnosis. Furthermore, LVL and HVL groups did not differ with regard to duration of hospital stay, number of bacterial co-infections, need for high-intensity medical care and number of deaths. The viral load was not an independent risk factor for HIMC in an adjusted multivariate regression model (OR: 1.59; 95% CI: 0.46–5.55, p = 0.46).Conclusions: Viral load at diagnosis is similar in asymptomatic and hospitalized patients and is not associated with either worse outcomes during hospitalization. SARS CoV-2 viral load might not be the right tool to assist clinicians in risk-stratifying hospitalized patients.

Long-term safety, tolerability and antiviral activity of rilpivirine in antiretroviral-naïve adolescents living with HIV-1, aged 12 to less than 18 years: Week 240 findings of a phase 2, open-label study, PAINT

2021 ◽  
Author(s):  
Johan Lombaard ◽  
Francis Ssali ◽  
Puthanakit Thanyawee ◽  
Jan Fourie ◽  
Simon Vanveggel ◽  
...  
Keyword(s):  
Viral Load ◽  
Virologic Failure ◽  
Virologic Response ◽  
Baseline Viral Load ◽  
Phase 2 ◽  
Adequate Treatment ◽  
Living With Hiv ◽  
Hiv 1 ◽  
Extension Period

Introduction: This Phase-2 study investigated long-term safety and efficacy of rilpivirine (RPV)+two investigator-selected nucleos(t)ide reverse-transcriptase inhibitors (NRTIs), in HIV-1-infected antiviral therapy-naïve adolescents. Methods: Participants (≥12to <18 years) were treated with RPV 25mg qd+2 NRTIs who entered treatment extension period for up to 240 weeks with visits every 3 months. Long-term safety (analysis of adverse events [AEs], laboratory results), efficacy (virologic-response and outcome for patients with viral load <50 and <400 by time to loss of virologic-response (TLOVR) and FDA Snapshot methods, and CD4+ cell count), and adherence (by pill-count) for up to 240 weeks are presented. Results: 24 of 36 entered treatment extension period and 21 completed week 240. At week 240, viral load <50 copies/mL was achieved by 14/32 (43.8%) participants; virologic-response by TLOVR was higher in participants with baseline viral load≤100,000 copies/mL (48.0%) versus viral load >100,000 copies/mL (28.6%). By FDA Snapshot, viral load < 50 copies/mL at week 240 was 53.1% (17/32) in participants with baseline viral load ≤100,000 copies/mL. Higher response was observed in participants with adherence >95% and baseline viral load ≤100,000 copies/mL. Through week 240, 16/32 participants (50.0%) experienced virologic-failure, including seven who developed treatment-emergent RPV resistance-associated mutations (RAMs; frequently E138K); all 7 had ≥1 treatment-emergent NRTI RAM. No serious AEs after week 48, no discontinuations due to AEs between week 48 and week 240 and no new safety signals were observed. RPV did not affect pubertal development/adolescent growth. Conclusions: At the 5-year follow-up, efficacy was low in adolescents, particularly those with poor adherence and/or high baseline viral load >100,000 copies/mL. To limit the risk of virologic failure, Edurant is restricted to patients with a baseline VL ≤100,000 copies/mL in most countries. In addition, adequate treatment adherence to RPV treatment is imperative for long-term viral suppression and should be emphasized in the management of adolescents living with HIV. RPV exhibited favorable long-term safety profile for adolescents living with HIV-1 with adequate adherence. Clinical Trial Number: NCT00799864

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