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IMPACT study: Impact of adherence to anti-VEGF intravitreal injections for macular disease during COVID 19-related confinement in France.
Hurand, V, Ducloyer, JB, Baudin, F, Aho, S, Weber, M, Kodjikian, L, Devin, F, Gabrielle, PH, Creuzot-Garcher, C, Massin, P, et al
Acta ophthalmologica. 2023;(1):91-99
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Abstract
PURPOSE The aim of this study was to evaluate the impact of adherence to French coronavirus disease 2019 (COVID 19)-related guidelines for intravitreal injection (IVI) practice on the visual outcomes of patients treated with anti-vascular endothelial growth factor (VEGF) agents for macular diseases during the first lockdown period. METHODS Observational multicentre study including all patients from 18 centres with an IVI initially planned during the lockdown. Visual acuity (VA, ETDRS) was recorded at 1 and 4 months after lockdown. French COVID 19-related guidelines recommended maintaining IVI practice. We defined three groups of patients: A, adherent to guidelines; NA+, non-adherent with delayed IVIs; and NA-, non-adherent without IVIs performed during the lockdown. Risk factors for non-adherence and visual loss were studied. RESULTS A total of 3020 eyes of 3020 patients, aged 77.8 ± 11.6 years, 59.8% women, were included. 59.3% were non-adherent(46.7% NA+, 12.6% NA-). A smaller decrease in VA at 4 months was observed in the A group than the NA+ and NA- group (-0.2 ± 6.7, -0.3 ± 6.9 and -1.5 ± 6.9, respectively [p < 0.001]). Factors associated with non-adherence were in multivariable analysis, older age, hospital practice, low-density population areas, high viral incidence areas, longer intervals between injection and treat and extent protocol. Factors associated with visual loss at 4 months in multivariable analysis were, being in the NA- group, older age, T&E and fixed regimens. CONCLUSION Strict adherence to guidelines was associated with better visual outcome, although most of our patients did not attend as planned. Identification of patients at risk could help in the future in case of a new pandemic lockdown.
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Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care.
Shah, PL, Orton, CM, Grinsztejn, B, Donaldson, GC, Crabtree Ramírez, B, Tonkin, J, Santos, BR, Cardoso, SW, Ritchie, AI, Conway, F, et al
The Lancet. Respiratory medicine. 2023;(5):415-424
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BACKGROUND COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. METHODS We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733. FINDINGS Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87). INTERPRETATION Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19. FUNDING LifeArc and CW+.
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Homeopathic Medicines in Second Wave of COVID-19: Prognostic Factor Research.
Manchanda, RK, Miglani, A, Chakraborty, M, Kalsi, A, Meena, BS, Kaur, P, Saini, B, Arora, A, Nagrath, C, Kannoth, JT, et al
Homeopathy : the journal of the Faculty of Homeopathy. 2023;(1):12-21
Abstract
BACKGROUND The clinical profile and course of COVID-19 evolved perilously in a second wave, leading to the use of various treatment modalities that included homeopathy. This prognostic factor research (PFR) study aimed to identify clinically useful homeopathic medicines in this second wave. METHODS This was a retrospective, multi-centred observational study performed from March 2021 to May 2021 on confirmed COVID-19 cases who were either in home isolation or at COVID Care Centres in Delhi, India. The data were collected from integrated COVID Care Centres where homeopathic medicines were prescribed along with conventional treatment. Only those cases that met a set of selection criteria were considered for analysis. The likelihood ratio (LR) was calculated for the frequently occurring symptoms of the prescribed medicines. An LR of 1.3 or greater was considered meaningful. RESULTS Out of 769 confirmed COVID-19 cases reported, 514 cases were selected for analysis, including 467 in home isolation. The most common complaints were cough, fever, myalgia, sore throat, loss of taste and/or smell, and anxiety. Most cases improved and there was no adverse reaction. Certain new symptoms, e.g., headache, dryness of mouth and conjunctivitis, were also seen. Thirty-nine medicines were prescribed, the most frequent being Bryonia alba followed by Arsenicum album, Pulsatilla nigricans, Belladonna, Gelsemium sempervirens, Hepar sulphuris, Phosphorus, Rhus toxicodendron and Mercurius solubilis. By calculating LR, the prescribing indications of these nine medicines were ascertained. CONCLUSION Add-on use of homeopathic medicines has shown encouraging results in the second wave of COVID-19 in integrated care facilities. Further COVID-related research is required to be undertaken on the most commonly prescribed medicines.
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Short-term complications and post-acute sequelae in hospitalized paediatric patients with COVID-19 and obesity: A multicenter cohort study.
Valenzuela, G, Alarcón-Andrade, G, Schulze-Schiapacasse, C, Rodríguez, R, García-Salum, T, Pardo-Roa, C, Levican, J, Serrano, E, Avendaño, MJ, Gutiérrez, M, et al
Pediatric obesity. 2023;(2):e12980
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BACKGROUND Obesity increases the severity of coronavirus disease 2019 illness in adults. The role of obesity in short-term complications and post-acute sequelae in children is not well defined. OBJECTIVE To evaluate the relationship between obesity and short-term complications and post-acute sequelae of SARS-CoV-2 infection in hospitalized paediatric patients. METHODS An observational study was conducted in three tertiary hospitals, including paediatric hospitalized patients with a confirmatory SARS-CoV-2 RT-PCR from March 2020 to December 2021. Obesity was defined according to WHO 2006 (0-2 years) and CDC 2000 (2-20 years) growth references. Short-term outcomes were intensive care unit admission, ventilatory support, superinfections, acute kidney injury, and mortality. Neurological, respiratory, and cardiological symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms were considered as post-acute sequalae. Adjusted linear, logistic regression and generalized estimating equations models were performed. RESULTS A total of 216 individuals were included, and 67 (31.02%) of them had obesity. Obesity was associated with intensive care unit admission (aOR = 5.63, CI95% 2.90-10.94), oxygen requirement (aOR = 2.77, CI95% 1.36-5.63), non-invasive ventilatory support (aOR = 6.81, CI95% 2.11-22.04), overall superinfections (aOR = 3.02 CI95% 1.45-6.31), and suspected bacterial pneumonia (aOR = 3.00 CI95% 1.44-6.23). For post-acute sequalae, obesity was associated with dyspnea (aOR = 9.91 CI95% 1.92-51.10) and muscle weakness (aOR = 20.04 CI95% 2.50-160.65). CONCLUSIONS In paediatric hospitalized patients with COVID-19, severe short-term outcomes and post-acute sequelae are associated with obesity. Recognizing obesity as a key comorbidity is essential to develop targeted strategies for prevention of COVID-19 complications in children.
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Impact of Bias in Data Collection of COVID-19 Cases.
Manchanda, RK, Miglani, A, Chakraborty, M, Meena, BS, Sharma, K, Gupta, M, Sharma, A, Chadha, V, Rani, P, Singh, RK, et al
Homeopathy : the journal of the Faculty of Homeopathy. 2022;(1):57-65
Abstract
BACKGROUND Prognostic factor research (PFR), prevalence of symptoms and likelihood ratio (LR) play an important role in identifying prescribing indications of useful homeopathic remedies. It involves meticulous unbiased collection and analysis of data collected during clinical practice. This paper is an attempt to identify causes of bias and suggests ways to mitigate them for improving the accuracy in prescribing for better clinical outcomes and execution of randomized controlled studies. METHODS A prospective, open label, observational study was performed from April 2020 to December 2020 at two COVID Health Centers. A custom-made Excel spreadsheet containing 71 fields covering a spectrum of COVID-19 symptoms was shared with doctors for regular reporting. Cases suitable for PFR were selected. LR was calculated for commonly occurring symptoms. Outlier values with LR ≥5 were identified and variance of LRs was calculated. RESULTS Out of 1,889 treated cases of confirmed COVID-19, 1,445 cases were selected for pre-specified reasons. Nine medicines, Arsenicum album, Bryonia alba, Gelsemium sempervirens, Pulsatilla nigricans, Hepar sulphuricus, Magnesia muriaticum, Phosphorus, Nux vomica and Belladonna, were most frequently prescribed. Outlier values and large variance for Hepar sulphuricus and Magnesia muriaticum were noticed as indication of bias. Confirmation bias leading to lowering of symptom threshold, keynote prescribing, and deficiency in checking of all symptoms in each case were identified as the most important sources of bias. CONCLUSION Careful identification of biases and remedial steps such as training of doctors, regular monitoring of data, checking of all pre-defined symptoms, and multicenter data collection are important steps to mitigate biases.
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Mortality among hospitalized COVID-19 patients during surges of SARS-CoV-2 alpha (B.1.1.7) and delta (B.1.617.2) variants.
Zali, A, Khodadoost, M, Gholamzadeh, S, Janbazi, S, Piri, H, Taraghikhah, N, Hannani, K, Looha, MA, Mohammadi, G
Scientific reports. 2022;(1):18918
Abstract
The aim of this study was to evaluate the death proportion and death risk of COVID-19 hospitalized patients over time and in different surges of COVID-19. This multi-center observational study was conducted from March 21, 2021 to October 3, 2021 which included the alpha and delta SARS-CoV-2 surges occurred in April and August in Tehran, respectively. The risk of COVID-19 death was compared in different months of admission. A total of 270,624 patients with COVID-19, of whom 6.9% died, were admitted to hospitals in Tehran province. Compared to patients admitted in March, a higher risk of COVID-19 death was observed among patients admitted to the hospital in July (HR 1.28; 95% CI 1.17, 1.40), August (HR 1.40; 95% CI 1.28, 1.52), September (HR 1.37; 95% CI 1.25, 1.50) and October (HR 4.63; 95% CI 2.77, 7.74). The ICU death proportion was 36.8% (95% CI: 35.5, 38.1) in alpha surge and increased significantly to 39.8 (95% CI 38.6, 41.1) in delta surge. The risk of COVID-19 death was significantly higher in delta surge compared to alpha surge (HR 1.22; 95% CI 1.17, 1.27). Delta surge was associated with a higher risk of death compared to alpha surge. High number of hospitalizations, a shortage of hospital beds, ICU spaces and medical supplies, poor nutritional status of hospitalized patients, and lack of the intensivist physicians or specialized nurses in the ICU were factors that contributed to the high mortality rate in the delta surge in Iran.
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Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.
Fernandes, AL, Murai, IH, Reis, BZ, Sales, LP, Santos, MD, Pinto, AJ, Goessler, KF, Duran, CSC, Silva, CBR, Franco, AS, et al
The American journal of clinical nutrition. 2022;(3):790-798
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BACKGROUND The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1β, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1β (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.
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Novel Strategies for the Treatment of COVID-19.
McCarthy, MW
Drugs in R&D. 2022;(4):257-262
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On 4 September, 2020, the US National Institutes of Health launched a new clinical trial, "A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic and Additional Strategies in Hospitalized Adults with COVID-19." This open-label, placebo-controlled, multicenter, adaptive platform study was designed to evaluate therapeutic options for patients hospitalized with mild, moderate, or severe COVID-19. A variety of drugs and drug classes were selected, including heparin, the monoclonal antibody crizanlizumab, sodium-glucose cotransporter-2 inhibitors, and purinergic signaling receptor Y12 inhibitors. These medications have been widely used in the treatment of other conditions, from sick cell disease to type 2 diabetes mellitus and some forms of cardiovascular disease, but their inclusion in a study of COVID-19 was somewhat unexpected. This article examines the rationale behind the use of these disparate agents in the treatment and prevention of adverse outcomes in patients with COVID-19 and explores how these strategies may be utilized in the future to address the severe acute respiratory syndrome coronavirus 2 pandemic.
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Cardiopulmonary Imaging Utilization and Findings among Hospitalized COVID-19 Patients in Latin America: (From "RIMAC: Registry IMAging Cardiopulmonary among Hospitalized COVID-19 Patients in LATAM").
Spina, SV, Campos Vieira, ML, Herrera, CJ, Munera Echeverri, AG, Rojo, P, Arrioja Salazar, AS, Vázquez Ortiz, ZY, Arellano, RB, Reyes, G, Millán, RA, et al
Global heart. 2022;(1):49
Abstract
OBJECTIVES Describe the use and findings of cardiopulmonary imaging-chest X-ray (cX-ray), echocardiography (cEcho), chest CT (cCT), lung ultrasound (LUS), and/or cardiac magnetic resonance imaging (cMRI)-in COVID-19 hospitalizations in Latin America (LATAM). BACKGROUND There is a lack of information on the images used and their findings during the SARS-CoV-2 pandemic in LATAM. METHODS Multicenter, prospective, observational study of COVID-19 inpatients, conducted from March to December 2020, from 12 high-complexity centers, in nine LATAM countries. Adults (>18 years) with at least one imaging modality performed, followed from admission until discharge and/or in-hospital death, were included. RESULTS We studied 1,435 hospitalized patients (64% males) with a median age of 58 years classified into three regions: Mexico (Mx), 262; Central America and Caribbean (CAC), 428; and South America (SAm), 745. More frequent comorbidities were overweight/obesity, hypertension, and diabetes. During hospitalization, 58% were admitted to the ICU. The in-hospital mortality was 28%, and it was highest in Mx (37%).The most frequent images performed were cCT (61%), mostly in Mx and SAm, and cX-ray (46%), significant in CAC. The cEcho was carried out in 18%, similarly among regions, and LUS was carried out in 7%, with a higher frequently in Mx. Abnormal findings on the cX-ray were peripheral or basal infiltrates, and in cCT abnormal findings were the ground glass infiltrates, more commonly in Mx. In LUS, interstitial syndrome was the most abnormal finding, predominantly in Mx and CAC.Renal failure was the most prevalent complication (20%), predominant in Mx and SAm. Heart failure developed in 13%, predominant in Mx and CAC. Lung thromboembolism was higher in Mx while myocardial infarction was in CAC.Logistic regression showed associations of abnormal imaging findings and their severity, with comorbidities, complications, and evolution. CONCLUSIONS The use and findings of cardiopulmonary imaging in LATAM varied between regions and had a great impact on diagnosis and prognosis.
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Dendrimer nanotherapy for severe COVID-19 attenuates inflammation and neurological injury markers and improves outcomes in a phase2a clinical trial.
Gusdon, AM, Faraday, N, Aita, JS, Kumar, S, Mehta, I, Choi, HA, Cleland, JL, Robinson, K, McCullough, LD, Ng, DK, et al
Science translational medicine. 2022;(654):eabo2652
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Hyperinflammation triggered by SARS-CoV-2 is a major cause of disease severity, with activated macrophages implicated in this response. OP-101, a hydroxyl-polyamidoamine dendrimer-N-acetylcysteine conjugate that specifically targets activated macrophages, improves outcomes in preclinical models of systemic inflammation and neuroinflammation. In this multicenter, randomized, double-blind, placebo-controlled, adaptive phase 2a trial, we evaluated safety and preliminary efficacy of OP-101 in patients with severe COVID-19. Twenty-four patients classified as having severe COVID-19 with a baseline World Health Organization seven-point ordinal scale of ≥5 were randomized to receive a single intravenous dose of placebo (n = 7 patients) or OP-101 at 2 (n = 6), 4 (n = 6), or 8 mg/kg (n = 5 patients). All study participants received standard of care, including corticosteroids. OP-101 at 4 mg/kg was better than placebo at decreasing inflammatory markers; OP-101 at 4 and 8 mg/kg was better than placebo at reducing neurological injury markers, (neurofilament light chain and glial fibrillary acidic protein). Risk for the composite outcome of mechanical ventilation or death at 30 and 60 days after treatment was 71% (95% CI: 29%, 96%) for placebo and 18% (95% CI: 4%, 43%; P = 0.021) for the pooled OP-101 treatment arms. At 60 days, 3 of 7 patients given placebo and 14 of 17 OP-101-treated patients were surviving. No drug-related adverse events were reported. These data show that OP-101 was well tolerated and may have potential to treat systemic inflammation and neuronal injury, reducing morbidity and mortality in hospitalized patients with severe COVID-19.
