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Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial.
Bravo, L, Smolenov, I, Han, HH, Li, P, Hosain, R, Rockhold, F, Clemens, SAC, Roa, C, Borja-Tabora, C, Quinsaat, A, et al
Lancet (London, England). 2022;(10323):461-472
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BACKGROUND A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019. METHODS This ongoing phase 2 and 3 double-blind, placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition, at 31 sites in five countries (Belgium, Brazil, Colombia, Philippines, and South Africa). The participants were randomly assigned 1:1 using a centralised internet randomisation system to receive two 0·5 mL intramuscular doses of SCB-2019 (30 μg, adjuvanted with 1·50 mg CpG-1018 and 0·75 mg alum) or placebo (0·9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart. All study staff and participants were masked, but vaccine administrators were not. Primary endpoints were vaccine efficacy, measured by RT-PCR-confirmed COVID-19 of any severity with onset from 14 days after the second dose in baseline SARS-CoV-2 seronegative participants (the per-protocol population), and the safety and solicited local and systemic adverse events in the phase 2 subset. This study is registered on EudraCT (2020-004272-17) and ClinicalTrials.gov (NCT04672395). FINDINGS 30 174 participants were enrolled from March 24, 2021, until the cutoff date of Aug 10, 2021, of whom 30 128 received their first assigned vaccine (n=15 064) or a placebo injection (n=15 064). The per-protocol population consisted of 12 355 baseline SARS-CoV-2-naive participants (6251 vaccinees and 6104 placebo recipients). Most exclusions (13 389 [44·4%]) were because of seropositivity at baseline. There were 207 confirmed per-protocol cases of COVID-19 at 14 days after the second dose, 52 vaccinees versus 155 placebo recipients, and an overall vaccine efficacy against any severity COVID-19 of 67·2% (95·72% CI 54·3-76·8), 83·7% (97·86% CI 55·9-95·4) against moderate-to-severe COVID-19, and 100% (97·86% CI 25·3-100·0) against severe COVID-19. All COVID-19 cases were due to virus variants; vaccine efficacy against any severity COVID-19 due to the three predominant variants was 78·7% (95% CI 57·3-90·4) for delta, 91·8% (44·9-99·8) for gamma, and 58·6% (13·3-81·5) for mu. No safety issues emerged in the follow-up period for the efficacy analysis (median of 82 days [IQR 63-103]). The vaccine elicited higher rates of mainly mild-to-moderate injection site pain than the placebo after the first (35·7% [287 of 803] vs 10·3% [81 of 786]) and second (26·9% [189 of 702] vs 7·4% [52 of 699]) doses, but the rates of other solicited local and systemic adverse events were similar between the groups. INTERPRETATION Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant. FUNDING Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations.
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The impact of Movement Control Order during the COVID-19 pandemic on lifestyle behaviours and body weight changes: Findings from the MyNutriLifeCOVID-19 online survey.
Chin, YS, Woon, FC, Chan, YM
PloS one. 2022;(1):e0262332
Abstract
BACKGROUND The COVID-19 pandemic lockdowns have affected daily lives of the communities worldwide. This study aims to determine the lifestyle behaviours and their associations with body weight changes among Malaysian adults during the Movement Control Order (MCO) due to COVID-19 pandemic. METHODS A total of 1319 Malaysian adults participated in this cross-sectional online survey. Information on anthropometric data including body weight and height, and lifestyle behaviours including eating pattern, physical activity, and sleep pattern were self-reported by the respondents. A multivariable generalised linear mixed model was used to assess the associations between lifestyle behaviours and body weight changes with adjustment of confounding factors; namely, age, sex, ethnicity, and body weight status before MCO. RESULTS During MCO, 41.2% of the respondents perceived that their eating patterns were healthier, but 36.3% reduced their physical activities, and 25.7% had a poorer sleep quality. Further, the proportion of adults who reported having lose weight (32.2%) was almost similar to those who reported having gained weight (30.7%). Lifestyle behaviours including less frequent practice of healthy cooking methods and lunch skipping were associated with weight gain, while less frequent consumption of high fat foods, more frequent physical activity, and good sleep latency were associated with lower risk of weight gain. In contrast, practicing healthy eating concept, skipped lunch, and more frequent physical activity were significantly associated with weight loss. CONCLUSION Lifestyle behaviours were associated with body weight changes during MCO. While the COVID-19 pandemic lockdown is necessary to prevent further spread of the disease, promoting healthy lifestyle practices during lockdown should be implemented for a healthy weight and better health.
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Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial.
Bruen, C, Al-Saadi, M, Michelson, EA, Tanios, M, Mendoza-Ayala, R, Miller, J, Zhang, J, Stauderman, K, Hebbar, S, Hou, PC
Critical care (London, England). 2022;(1):101
Abstract
BACKGROUND Calcium release-activated calcium (CRAC) channel inhibitors block proinflammatory cytokine release, preserve endothelial integrity and may effectively treat patients with severe COVID-19 pneumonia. METHODS CARDEA was a phase 2, randomized, double-blind, placebo-controlled trial evaluating the addition of Auxora, a CRAC channel inhibitor, to corticosteroids and standard of care in adults with severe COVID-19 pneumonia. Eligible patients were adults with ≥ 1 symptom consistent with COVID-19 infection, a diagnosis of COVID-19 confirmed by laboratory testing using polymerase chain reaction or other assay, and pneumonia documented by chest imaging. Patients were also required to be receiving oxygen therapy using either a high flow or low flow nasal cannula at the time of enrolment and have at the time of enrollment a baseline imputed PaO2/FiO2 ratio > 75 and ≤ 300. The PaO2/FiO2 was imputed from a SpO2/FiO2 determine by pulse oximetry using a non-linear equation. Patients could not be receiving either non-invasive or invasive mechanical ventilation at the time of enrolment. The primary endpoint was time to recovery through Day 60, with secondary endpoints of all-cause mortality at Day 60 and Day 30. Due to declining rates of COVID-19 hospitalizations and utilization of standard of care medications prohibited by regulatory guidance, the trial was stopped early. RESULTS The pre-specified efficacy set consisted of the 261 patients with a baseline imputed PaO2/FiO2≤ 200 with 130 and 131 in the Auxora and placebo groups, respectively. Time to recovery was 7 vs. 10 days (P = 0.0979) for patients who received Auxora vs. placebo, respectively. The all-cause mortality rate at Day 60 was 13.8% with Auxora vs. 20.6% with placebo (P = 0.1449); Day 30 all-cause mortality was 7.7% and 17.6%, respectively (P = 0.0165). Similar trends were noted in all randomized patients, patients on high flow nasal cannula at baseline or those with a baseline imputed PaO2/FiO2 ≤ 100. Serious adverse events (SAEs) were less frequent in patients treated with Auxora vs. placebo and occurred in 34 patients (24.1%) receiving Auxora and 49 (35.0%) receiving placebo (P = 0.0616). The most common SAEs were respiratory failure, acute respiratory distress syndrome, and pneumonia. CONCLUSIONS Auxora was safe and well tolerated with strong signals in both time to recovery and all-cause mortality through Day 60 in patients with severe COVID-19 pneumonia. Further studies of Auxora in patients with severe COVID-19 pneumonia are warranted. Trial registration NCT04345614.
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COVID-19: Clinical Presentation and Prognostic Factors of Severe Disease and Mortality in the Oldest-Old Population: A Cohort Study.
Gálvez-Barrón, C, Arroyo-Huidobro, M, Miňarro, A, Añaños, G, Chamero, A, Martín, M, Gris, C, Avalos, JL, Capielo, AM, Ventosa, E, et al
Gerontology. 2022;(1):30-43
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INTRODUCTION The oldest-old population (80 years or older) has the highest lethality from COVID-19. There is little information on the clinical presentation and specific prognostic factors for this group. This trial evaluated the clinical presentation and prognostic factors of severe disease and mortality in the oldest-old population. METHODS This is an ambispective cohort study of oldest-old patients hospitalized for respiratory infection associated with COVID-19 and with a positive test by RT-PCR. The clinical presentation and the factors associated with severe disease and mortality were evaluated (logistic regression). All patients were followed up until discharge or death. RESULTS A total of 103 patients (59.2% female) were included. The most frequent symptoms were fever (68.9%), dyspnoea (60.2%), and cough (39.8%), and 11.7% presented confusion. Fifty-nine patients (57.3%) presented severe disease, and 59 died, with 43 patients (41.7%) presenting both of these. In the multivariate analysis, female sex (odds ratio [OR] 0.31, 95% confidence interval [95% CI] 0.13-0.73, p 0.0074) and serum lactate dehydrogenase (LDH) (OR 2.55, 95% CI 1.21-5.37, p 0.0139) were associated with severe disease, and serum sodium was associated with mortality (OR 3.12, 95% CI 1.18-8.26, p 0.0222). No chronic disease or pharmacological treatment was associated with worse outcomes. CONCLUSIONS The typical presenting symptoms of respiratory infection in COVID-19 are less frequent in the oldest-old population. Male sex and LDH level are associated with severe disease, and the serum sodium level is associated with mortality in this population.
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Impact on aerosol generation during upper endoscopy of mouthpiece designed to reduce COVID-19 droplet spread: single-center randomized controlled trial.
Huang, IH, Sinonquel, P, Verbeure, W, Camps, C, Devriese, H, Holvoet, L, Verstockt, B, Willekens, H, Mori, H, Bisschops, R, et al
Endoscopy. 2022;(1):81-83
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Phase III, Randomized, Double-blind, Placebo controlled trial of Efficacy, Safety and Tolerability of Antiviral drug Umifenovir vs Standard care of therapy in non-severe COVID-19 patients.
Ramachandran, R, Bhosale, V, Reddy, H, Atam, V, Faridi, M, Fatima, J, Shukla, V, Khan, ZA, Khan, H, Singh, V, et al
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2022;:62-69
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OBJECTIVE To test efficacy, safety and tolerability of Umifenovir in non-severe COVID-19 adult patients. METHODS We carried out randomized, double-blind, placebo-controlled, multicenter, phase III trials involving adult (18-75 years), non-severe COVID19 patients, randomized 1:1 on placebo or Umifenovir (800 mg BID, maximum 14 days) respectively along with standard-of-care. The primary endpoint for Asymptotic-mild patients was time to nasopharyngeal swab RT-PCR test negativity. For Moderate patients, the average change in the ordinal scale from the baseline scores on the eight-point WHO ordinal scale was assessed. RESULTS 132 patients were recruited between 3rd October to 28th April 2021, of which 9 discontinued due to various reasons. In Mild-asymptomatic patients (n=82), we found that 73% patients in the Umifenovir arm were RT-PCR negative, while 40% patients in the placebo arm were negative (P=0.004) on day 5. However, in the moderate group (n=41), the WHO scores for the Umifenovir arm was not statistically significant (P=0.125 on day 3), while it was statistically significant in the Mild-asymptomatic group (P=0.019 on day 5). CONCLUSION Umifenovir meets the primary and secondary endpoint criteria and exhibits statistically significant efficacy for Mild-asymptomatic patients. It is efficacious, safe and well-tolerated at the tested dosage of 800mg BID, maximum 14 days.
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A Randomized Double-Blinded Placebo Controlled Trial of Clazakizumab for the Treatment of COVID-19 Pneumonia With Hyperinflammation.
Lonze, BE, Spiegler, P, Wesson, RN, Alachkar, N, Petkova, E, Weldon, EP, Dieter, RA, Li, Y, Quinn, M, Mattoo, A, et al
Critical care medicine. 2022;(9):1348-1359
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OBJECTIVES We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation. DESIGN Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial. SETTING Five U.S. medical centers. PATIENTS Adults inpatients with severe COVID-19 disease and hyperinflammation. INTERVENTIONS Eighty-one patients enrolled in phase II, randomized 1:1:1 to low-dose (12.5 mg) or high-dose (25 mg) clazakizumab or placebo. Ninety-seven patients enrolled in phase III, randomized 1:1 to high-dose clazakizumab or placebo. MEASUREMENTS AND MAIN RESULTS The primary outcome was 28-day ventilator-free survival. Secondary outcomes included overall survival, frequency and duration of intubation, and frequency and duration of ICU admission. Per Data Safety and Monitoring Board recommendations, additional secondary outcomes describing clinical status and status changes, as measured by an ordinal scale, were added. Bayesian cumulative proportional odds, logistic, and Poisson regression models were used. The low-dose arm was dropped when the phase II study suggested superiority of the high-dose arm. We report on 152 patients, 74 randomized to placebo and 78 to high-dose clazakizumab. Patients receiving clazakizumab had greater odds of 28-day ventilator-free survival (odds ratio [OR] = 3.84; p [OR > 1] 99.9%), as well as overall survival at 28 and 60 days (OR = 1.75; p [OR > 1] 86.5% and OR = 2.53; p [OR > 1] 97.7%). Clazakizumab was associated with lower odds of intubation (OR = 0.2; p [OR] < 1; 99.9%) and ICU admission (OR = 0.26; p [OR < 1] 99.6%); shorter durations of ventilation and ICU stay (risk ratio [RR] < 0.75; p [RR < 1] > 99% for both); and greater odds of improved clinical status at 14, 28, and 60 days (OR = 2.32, p [OR > 1] 98.1%; OR = 3.36, p [OR > 1] 99.6%; and OR = 3.52, p [OR > 1] 99.8%, respectively). CONCLUSIONS Clazakizumab significantly improved 28-day ventilator-free survival, 28- and 60-day overall survival, as well as clinical outcomes in hospitalized patients with COVID-19 and hyperinflammation.
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Pilot Social Network Weight Loss Intervention With Two Immigrant Populations During the COVID-19 Pandemic.
Wieland, ML, Njeru, JW, Asiedu, GB, Zeratsky, KA, Clark, MM, Goetze, R, Patten, CA, Kelpin, SS, Novotny, P, Lantz, K, et al
American journal of health promotion : AJHP. 2022;(3):458-471
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PURPOSE To examine the feasibility and acceptability of a social network weight loss intervention delivered by lay health promoters (HPs) to immigrant populations. DESIGN Single-arm, non-randomized, pilot study of a social network weight loss intervention developed by a community-based participatory research partnership and delivered by HPs. SETTING Community-based setting in Southeastern Minnesota, United States. SAMPLE Somali and Hispanic immigrants to the United States: 4 social networks of adults (2 Hispanic and 2 Somali) with 39 network participants. INTERVENTION Twelve-week behavioral weight loss intervention delivered by HPs (4 weeks in-person and then 8 weeks virtual). MEASURES Feasibility was assessed by recruitment and retention rates. Acceptability was assessed by surveys and focus groups with HPs and participants. Behavioral measures included servings of fruits and vegetables, drinking soda, and physical activity. Physiologic measures included weight, blood pressure, glucose, cholesterol, and triglycerides. ANALYSIS Paired t-tests of pre- to post-intervention changes at the end of 12 weeks of treatment. RESULTS Recruitment was feasible and post-intervention was 100%. Participants highly rated the intervention on satisfaction, motivation, and confidence to eat a healthy diet, be physically active, and lose weight. Participants were motivated by group social support and cohesion of their social networks. On average, participants lost weight (91.6 ± 15.9 to 89.7 ± 16.6 kg, P < .0001), lowered their systolic blood pressure (133.9±16.9 to 127.2 ± 15.8 mm Hg; P < .001), lowered their diastolic blood pressure (81 ± 9.5 to 75.8 ± 9.6 mm Hg; P < .0001), had more servings of vegetables per day (1.9 ± 1.2 to 2.6 ± 1.4; P < .001), and increased their physical activity (2690 ± 3231 to 6595 ± 7322 MET-minutes per week; P = .02). CONCLUSION This pilot study of 2 immigrant communities who participated in a peer-led weight loss social network intervention delivered during the COVID-19 pandemic demonstrated high feasibility and acceptability. Participants lost weight, improved their health status, and improved their health behaviors.
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Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial.
Crombie, N, Doughty, HA, Bishop, JRB, Desai, A, Dixon, EF, Hancox, JM, Herbert, MJ, Leech, C, Lewis, SJ, Nash, MR, et al
The Lancet. Haematology. 2022;(4):e250-e261
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BACKGROUND Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock. METHODS Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938. FINDINGS From Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths. INTERPRETATION The trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders. FUNDING National Institute for Health Research Efficacy and Mechanism Evaluation.
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Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo- Controlled Clinical Trial.
Di Stadio, A, D'Ascanio, L, Vaira, LA, Cantone, E, De Luca, P, Cingolani, C, Motta, G, De Riu, G, Vitelli, F, Spriano, G, et al
Current neuropharmacology. 2022;(10):2001-2012
Abstract
BACKGROUND Olfactory training is the only evidence-based treatment for post-viral olfactory dysfunction. Smell disorders after SARS-CoV-2 infection have been attributed to neuroinflammatory events within the olfactory bulb and the central nervous system. Therefore, targeting neuroinflammation is one potential strategy for promoting recovery from post-COVID-19 chronic olfactory dysfunction. Palmitoylethanolamide and luteolin (PEA-LUT) are candidate antiinflammatory/ neuroprotective agents. OBJECTIVE To investigate recovery of olfactory function in patients treated with PEA-LUT oral supplements plus olfactory training versus olfactory training plus placebo. METHODS Multicenter double-blinded randomized placebo-controlled clinical trial was held. Eligible subjects had prior COVID-19 and persistent olfactory impairment >6 months after follow-up SARS-CoV-2 negative testing, without prior history of olfactory dysfunction or other sinonasal disorders. Participants were randomized to daily oral supplementation with ultramicronized PEA-LUT 770 mg plus olfactory training (intervention group) or olfactory training with placebo (control). Sniffin' Sticks assessments were used to test the patients at baseline and 90 days. RESULTS A total of 185 patients, including intervention (130) and control (55) were enrolled. The intervention group showed significantly greater improvement in olfactory threshold, discrimination, and identification scores compared to controls (p=0.0001). Overall, 92% of patients in the intervention group improved versus 42% of controls. Magnitude of recovery was significantly greater in the intervention group versus control (12.8 + 8.2 versus mean 3.2 + 3), with >10-fold higher prevalence of anosmia in control versus intervention groups at the 90-day endpoint. CONCLUSION Among individuals with olfactory dysfunction post-COVID-19, combining PEA-LUT with olfactory training resulted in greater recovery of smell than olfactory training alone.
