Recent advances, approaches and challenges in targeting pathways for potential COVID-19 vaccines development.
Immunologic research. 2020;(6):315-324
During the COVID-19 pandemic in a modern era, there is a global consensus on the need for the rapid development of a vaccine against SARS-CoV-2 for effective and sustainable control. Developing these vaccines is fundamental to public health. This urgent need is supported by the scientific explosion in structural and genomic biology that facilitates the urgent development of an ideal COVID-19 vaccine, using new pathways to facilitate its large-scale development, testing, and manufacture. Here, we summarize the types of COVID-19 candidate vaccines, their current stage in early testing in human clinical trials, and the challenges for their implementation.
Antivirals for COVID-19 and Breastfeeding.
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2020;(10):605-607
Cardiac injury is associated with severe outcome and death in patients with Coronavirus disease 2019 (COVID-19) infection: A systematic review and meta-analysis of observational studies.
European heart journal. Acute cardiovascular care. 2020;(6):665-677
Coronavirus disease 2019 (COVID-19) is a global pandemic impacting 213 countries/territories and more than 5,934,936 patients worldwide. Cardiac injury has been reported to occur in severe and death cases. This meta-analysis was done to summarize available findings on the association between cardiac injury and severity of COVID-19 infection. Online databases including Scopus, PubMed, Web of Science, Cochrane Library and Google Scholar were searched to detect relevant publications up to 20 May 2020, using relevant keywords. To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies. In total, 22 studies with 3684 COVID-19 infected patients (severe cases=1095 and death cases=365) were included in this study. Higher serum levels of lactate dehydrogenase (weighted mean difference (WMD) =108.86 U/L, 95% confidence interval (CI)=75.93-141.79, p<0.001) and creatine kinase-MB (WMD=2.60 U/L, 95% CI=1.32-3.88, p<0.001) were associated with a significant increase in the severity of COVID-19 infection. Furthermore, higher serum levels of lactate dehydrogenase (WMD=213.44 U/L, 95% CI=129.97-296.92, p<0.001), cardiac troponin I (WMD=26.35 pg/mL, 95% CI=14.54-38.15, p<0.001), creatine kinase (WMD=48.10 U/L, 95% CI=0.27-95.94, p = 0.049) and myoglobin (WMD=159.77 ng/mL, 95% CI=99.54-220.01, p<0.001) were associated with a significant increase in the mortality of COVID-19 infection. Cardiac injury, as assessed by serum analysis (lactate dehydrogenase, cardiac troponin I, creatine kinase (-MB) and myoglobin), was associated with severe outcome and death from COVID-19 infection.
The Knowns and Unknowns of Contemporary Statin Therapy for Familial Hypercholesterolemia.
Current atherosclerosis reports. 2020;(11):64
PURPOSE OF REVIEW Statins are first-line therapy for lowering low-density lipoprotein (LDL) cholesterol in familial hypercholesterolemia (FH), particularly in heterozygous patients. We review advances and new questions on the use of statins in FH. RECENT FINDINGS Cumulative evidence from registry data and sub-analyses of clinical trials mandates the value of statin therapy for prevention of atherosclerotic cardiovascular disease (ASCVD) in FH. Statins are safe in children and adolescents with FH, with longer term cardiovascular benefits. The potentially toxic effects of statins in pregnancy need to be considered, but no association has been reported in prospective cohort studies with birth defects. There is no rationale for discontinuation of statins in elderly FH unless indicated by adverse events. FH is undertreated, with > 80% of statin-treated FH patients failing to attain LDL cholesterol treatment targets. This may relate to adherence, tolerability, and genetic differences in statin responsiveness. Statin treatment from childhood may reduce the need for stringent cholesterol targets. Combination of statins with ezetimibe and PCSK9 inhibitors significantly improves the efficacy of treatment. Whether statin use could improve the clinical course of FH patients with COVID-19 and other respiratory infections remains an unsolved issue for future research. Statins are the mainstay for primary and secondary prevention of ASCVD in FH. Sustained long-term optimal statin treatment from an early age can effectively prevent ASCVD over decades of life. Despite their widespread use, statins merit further investigation in FH.
COVID-19 and food and nutritional (in)security: action by the Brazilian Federal Government during the pandemic, with budget cuts and institutional dismantlement.
Cadernos de saude publica. 2020;(8):e00161320
The COVID-19 pandemic poses one of this century's greatest public health challenges, with impacts on the health and living conditions of populations worldwide. The literature has reported that the pandemic affects the hegemonic food system in various ways. In Brazil, the pandemic amplifies existing social, racial, and gender inequalities, further jeopardizing the Human Right to Adequate Food (HRAF) and the attainment of food and nutritional security, especially among more vulnerable groups. In this context, the article aims to analyze the first measures by the Brazilian Federal Government to mitigate the pandemic's effects and that may have repercussions on food and nutritional security, considering the recent institutional changes in policies and programs. A narrative literature review was performed, and the information sources were the bulletins of the Center for Coordination of Operations by the Crisis Committee for Supervising and Monitoring the Impacts of COVID-19 and homepages of various government ministries, from March to May 2020. The actions were systematized according to the guidelines of the National Policy for Food and Nutritional Security. The analysis identified the creation of institutional crisis management arrangements. The proposed actions feature those involving access to income, emergency aid, and food, such as authorization for food distribution outside schools with federal funds from the National School Feeding Program. However, the setbacks and dismantlement in food and nutritional security may undermine the Federal Government's capacity to respond to COVID-19.
Safety and efficacy of lopinavir/ritonavir combination in COVID-19: A systematic review, meta-analysis, and meta-regression analysis.
Indian journal of pharmacology. 2020;(4):313-323
BACKGROUND Being protease inhibitors and owing to their efficacy in SARS-CoV, lopinavir + ritonavir (L/R) combination is being used in the management of COVID-19. In this systematic review and meta-analysis, we have evaluated the comparative safety and efficacy of L/R combination. MATERIALS AND METHODS Comparative, observational studies and controlled clinical trials comparing L/R combination to standard of care (SOC)/control or any other antiviral agent/combinations were included. A total of 10 databases were searched to identify 13 studies that fulfilled the predefined inclusion/exclusion criteria. RESULTS No discernible beneficial effect was seen in the L/R group in comparison to SOC/control in terms of "progression to more severe state" (4 studies, odds ratio [OR]: 1.446 [0.722-2.895]), "mortality" (3 studies, OR: 1.208 [0.563-2.592]), and "virological cure on days 7-10" (3 studies, OR: 0.777 [0.371-1.630]), while the L/R combination arm performed better than the SOC/control arm in terms of "duration of hospital stay" (3 studies, mean difference (MD): -1.466 [-2.403 to - 0.529]) and "time to virological cure" (3 studies, MD: -3.272 [-6.090 to - 0.454]). No difference in efficacy was found between L/R versus hydroxychloroquine (HCQ) and L/R versus arbidol. However, in a single randomized controlled trail (open label), chloroquine (CQ) performed better than L/R. The combination L/R with arbidol may be beneficial (in terms of virological clearance and radiological improvement); however, we need more dedicated studies. Single studies report efficacy of L/R + interferon (IFN, either alpha or 1-beta) combination. We need more studies to delineate the proper effect size. Regarding adverse effects, except occurrence of diarrhea (higher in the L/R group), safety was comparable to SOC. CONCLUSION In our study, no difference was seen between the L/R combination and the SOC arm in terms of "progression to more severe state," "mortality," and virological cure on days 7-10;" however, some benefits in terms of "duration of hospital stay" and "time to virological cure" were seen. No significant difference in efficacy was seen when L/R was compared to arbidol and HCQ monotherapy. Except for the occurrence of diarrhea, which was higher in the L/R group, safety profile of L/R is comparable to SOC. Compared to L/R combination, CQ, L/R + arbidol, L/R + IFN-α, and L/R + IFN-1β showed better efficacy, but the external validity of these findings is limited by limited number of studies (1 study each).
Keeping people with epilepsy safe during the COVID-19 pandemic.
OBJECTIVES To provide information on the effect of the coronavirus disease of 2019 (COVID-19) pandemic on people with epilepsy and provide consensus recommendations on how to provide the best possible care for people with epilepsy while avoiding visits to urgent care facilities and hospitalizations during the novel coronavirus pandemic. METHODS The authors developed consensus statements in 2 sections. The first was "How should we/clinicians modify our clinical care pathway for people with epilepsy during the COVID-19 pandemic?" The second was "What general advice should we give to people with epilepsy during this crisis? The authors individually scored statements on a scale of -10 (strongly disagree) to +10 (strongly agree). Five of 11 recommendations for physicians and 3/5 recommendations for individuals/families were rated by all the authors as 7 or above (strongly agree) on the first round of rating. Subsequently, a teleconference was held where statements for which there was a lack of strong consensus were revised. RESULTS After revision, all consensus recommendations received a score of 7 or above. The recommendations focus on administration of as much care as possible at home to keep people with epilepsy out of health care facilities, where they are likely to encounter COVID-19 (including strategies for rescue therapy), as well as minimization of risk of seizure exacerbation through adherence, and through ensuring a regular supply of medication. We also provide helpful links to additional helpful information for people with epilepsy and health providers. CONCLUSION These recommendations may help health care professionals provide optimal care to people with epilepsy during the coronavirus pandemic.
Containing COVID-19 by Matching Messages on Social Distancing to Emergent Mindsets-The Case of North America.
International journal of environmental research and public health. 2020;(21)
Public compliance with social distancing is key to containing COVID-19, yet there is a lack of knowledge on which communication 'messages' drive compliance. Respondents (224 Canadians and Americans) rated combinations of messages about compliance, systematically varied by an experimental design. Independent variables were perceived risk; the agent communicating the policy; specific social distancing practices; and methods to enforce compliance. Response patterns to each message suggest three mindset segments in each country reflecting how a person thinks. Two mindsets, the same in Canada and the US, were 'tell me exactly what to do,' and 'pandemic onlookers.' The third was 'bow to authority' in Canada, and 'tell me how' in the US. Each mindset showed different messages strongly driving compliance. To effectively use messaging about compliance, policy makers may assign any person or group in the population to the appropriate mindset segment by using a Personal Viewpoint Identifier that we developed.
Effect of hydroxychloroquine on COVID-19 prevention in cancer patients undergoing treatment: a structured summary of a study protocol for a randomised controlled trial.
OBJECTIVES In this study, we investigate the effect of hydroxychloroquine on the prevention of Novel Coronavirus Disease (COVID-19) in cancer patients being treated. TRIAL DESIGN This is a multi-centre, two-arm, parallel-group, triple-blind, phase 2-3 randomised controlled trial. PARTICIPANTS All patients over the age of 15 from 5 types of cancer are included in the study. Patients with acute lymphoid and myeloid leukemias in the first line treated with curative intent, patients with high-grade non-Hodgkin's lymphoma treated with leukemia protocols and patients with non-metastatic breast and colon cancer in the first line of treatment will enter the study. The exclusion criteria will include known sensitivity to Hydroxychloroquine, weight below 35 kilograms, history of retinopathy, history of any cardiac disease, acute respiratory tract infection in the last 2 months, having COVID-19 in the first two weeks of entering the trial, having Diabetes Mellitus, having an immuno-suppressive disease other than cancer, having chronic pulmonary disease and taking immuno-suppressant drug other than chemotherapeutic agents for current cancer. This study is performed in five academic centres affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. INTERVENTION AND COMPARATOR Patients are randomly assigned to two groups; one being given hydroxychloroquine and the other is given placebo. During two months of treatment, the two groups are treated with either hydroxychloroquine (Amin® Pharmaceutical Company, Isfahan, Iran) or placebo (identical in terms of shape, colour, smell) as a single 200 mg tablet every other day. Patients will be monitored for COVID-19 symptoms during the follow-up period. If signs or symptoms occur (fever, cough, shortness of breath), they will be examined and investigated with a high-resolution computed tomography (CT) scan of the lungs, COVID-19 specific IgM, IgG antibody assay and a nucleic acid amplification test (NAT) for the SARS-CoV-2 virus. MAIN OUTCOMES The primary end point of this study is to investigate the incidence of COVID-19 in patients being treated for their cancer over a 2-month period. RANDOMISATION Randomisation will be performed using randomly permuted blocks. By using an online website (www.randomization.com) the randomization sequence will be produced by quadruple blocks. The allocation ratio in intervention and control groups is 1:1. BLINDING (MASKING): Participants and caregivers do not know whether the patient is in the intervention or the control group. The outcome assessor and the data analyst are also blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The calculated total sample size is 60 patients, with 30 patients in each group. TRIAL STATUS The trial began on April 14, 2020 and recruitment is ongoing. Recruitment is anticipated to be completed by June 14, 2020 There has been no change in study protocol since approval, protocol version 1 was approved April 12, 2020. TRIAL REGISTRATION This trial has been registered by the title of "Effect of Hydroxychloroquine on Novel Coronavirus Disease (COVID-19) prevention in cancer patients under treatment" in Iranian Registry of Clinical Trials (IRCT) with code "IRCT20200405046958N1", https://www.irct.ir/trial/46946. Registration date is April 14, 2020. FULL PROTOCOL The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
Physical Distancing Measures and Walking Activity in Middle-aged and Older Residents in Changsha, China, During the COVID-19 Epidemic Period: Longitudinal Observational Study.
Journal of medical Internet research. 2020;(10):e21632
BACKGROUND Physical distancing measures taken to contain COVID-19 transmission may substantially reduce physical activity levels and cause individuals to adopt a more sedentary lifestyle. OBJECTIVE The objective of this study is to determine if there was any change in daily steps, an important component of daily physical activity, and examine risk factors for frequent low daily steps during the COVID-19 epidemic. METHODS We used data collected from the Step Study, a population-based longitudinal study of walking activity among residents aged ≥40 years in Changsha, China. Daily steps were collected via a smartphone linked to WeChat, a social networking platform. We plotted mean daily steps and the prevalence of low daily steps (≤1500 steps/day) 30 days before (reference period) and 30 days after (epidemic period) January 21, 2020 (date of the first COVID-19 case diagnosed in Changsha), and compared it with the same corresponding period from 2019. We examined the association of risk factors with the prevalence of frequent low daily steps (≤1500 steps/day for ≥14 days) using logistic regression. RESULTS Among 3544 participants (mean age 51.6 years; n=1226 females, 34.6%), mean daily steps dropped from 8097 to 5440 and the prevalence of low daily steps increased from 3% (2287/76,136 person-day) to 18.5% (12,951/70,183 person-day) during the reference and epidemic periods, respectively. No such phenomenon was observed during the corresponding period in 2019. Older age (P for interaction=.001) and female sex (P for interaction<.001) were both associated with a higher prevalence of frequent low daily steps and were more pronounced during the epidemic period. More education was associated with a lower prevalence of frequent low daily steps during the reference period but not the epidemic period (P for interaction=.34). Body mass index or comorbidity were not associated with frequent low daily steps during either period. CONCLUSIONS Daily steps of Changsha residents aged ≥40 years dropped significantly during the COVID-19 period, especially among older adults and females. Although successful physical distancing, measured by the rapid downward trend in daily step counts of residents, played a critical role in the containment of the COVID-19 epidemic, our findings of an increase in the prevalence of frequent low daily steps raise concerns about unintended effects on physical activity.