Correction to: Is diet partly responsible for differences in COVID-19 death rates between and within countries?

[This corrects the article DOI: 10.1186/s13601-020-00323-0.].

Bridging Learning in Medicine and Citizenship During the COVID-19 Pandemic: A Telehealth-Based Case Study.

BACKGROUND: COVID-19 presented great challenges for not only those in the field of health care but also those undergoing medical training. The burden on health care services worldwide has limited the educational opportunities available for medical students due to social distancing requirements. OBJECTIVE: In this paper, we describe a strategy that combines telehealth and medical training to mitigate the adverse effects of the COVID-19 pandemic. METHODS: A toll-free telescreening service, Telecoronavirus, began operations in March 2020. This service was operated remotely by supervised medical students and was offered across all 417 municipalities (14.8 million inhabitants) in the Brazilian state of Bahia. Students recorded clinical and sociodemographic data by using a web-based application that was simultaneously accessed by medical volunteers for supervision purposes, as well as by state health authorities who conducted epidemiological surveillance and health management efforts. In parallel, students received up-to-date scientific information about COVID-19 via short educational videos prepared by professors. A continuously updated triage algorithm was conceived to provide consistent service. RESULTS: The program operated for approximately 4 months, engaging 1396 medical students and 133 physicians. In total, 111,965 individuals residing in 343 municipalities used this service. Almost 70,000 individuals were advised to stay at home, and they received guidance to avoid disease transmission, potentially contributing to localized reductions in the spread of COVID-19. Additionally, the program promoted citizenship education for medical students, who were engaged in a real-life opportunity to fight the pandemic within their own communities. The objectives of the education, organization, and assistance domains of the Telecoronavirus program were successfully achieved according to the results of a web-based post-project survey that assessed physicians' and students' perceptions. CONCLUSIONS: In a prolonged pandemic scenario, a combination of remote tools and medical supervision via telehealth services may constitute a useful strategy for maintaining social distancing measures while preserving some practical aspects of medical education. A low-cost tool such as the Telecoronavirus program could be especially valuable in resource-limited health care scenarios, in addition to offering support for epidemiological surveillance actions.

Prospective study of factors associated with asthma attack recurrence (ATTACK) in children from three Ecuadorian cities during COVID-19: a study protocol.

INTRODUCTION: Asthma is a growing health problem in children in marginalised urban settings in low-income and middle-income countries. Asthma attacks are an important cause of emergency care attendance and long-term morbidity. We designed a prospective study, the Asthma Attacks study, to identify factors associated with recurrence of asthma attacks (or exacerbations) among children and adolescents attending emergency care in three Ecuadorian cities. METHODS AND ANALYSIS: Prospective cohort study designed to identify risk factors associated with recurrence of asthma attacks in 450 children and adolescents aged 5-17 years attending emergency care in public hospitals in three Ecuadorian cities (Quito, Cuenca and Portoviejo). The primary outcome will be rate of asthma attack recurrence during up to 12 months of follow-up. Data are being collected at baseline and during follow-up by questionnaire: sociodemographic data, asthma history and management (baseline only); recurrence of asthma symptoms and attacks (monthly); economic costs of asthma to family; Asthma Control Test; Pediatric Asthma Quality of life Questionnaire; and Newcastle Asthma Knowledge Questionnaire (baseline only). In addition, the following are being measured at baseline and during follow-up: lung function and reversibility by spirometry before and after salbutamol; fractional exhaled nitric oxide (FeNO); and presence of IgG antibodies to SARS-CoV-2 in blood. Recruitment started in 2019 but because of severe disruption to emergency services caused by the COVID-19 pandemic, eligibility criteria were modified to include asthmatic children with uncontrolled symptoms and registered with collaborating hospitals. Data will be analysed using logistic regression and survival analyses. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Hospital General Docente de Calderon (CEISH-HGDC 2019-001) and Ecuadorian Ministry of Public Health (MSP-CGDES-2021-0041-O N° 096-2021). The study results will be disseminated through presentations at conferences and to key stakeholder groups including policy-makers, postgraduate theses, peer-review publications and a study website. Participants gave informed consent to participate in the study before taking part.

Available and affordable complementary treatments for COVID-19: From hypothesis to pilot studies and the need for implementation.

Vaccination is a highly effective preventive measure against COVID-19. However, complementary treatments are needed to better control the disease. Fermented vegetables and spices, agonists of the antioxidant transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and TRPA1/V1 channels (Transient Receptor Potential Ankyrin 1 and Vanillin 1), may help in the control of COVID-19. Some preliminary clinical trials suggest that curcumin (spice) can prevent some of the COVID-19 symptoms. Before any conclusion can be drawn and these treatments recommended for COVID-19, the data warrant confirmation. In particular, the benefits of the foods need to be assessed in more patients, through research studies and large trials employing a double-blind, placebo-controlled design.

Global Initiative for Asthma Strategy 2021: Executive Summary and Rationale for Key Changes.

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes. GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting ß2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS-formoterol reduces severe exacerbations by ≥60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA. Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS-formoterol as the reliever at all steps: as needed only in Steps 1-2 (mild asthma), and with daily maintenance ICS-formoterol (maintenance-and-reliever therapy, "MART") in Steps 3-5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS-long-acting ß2-agonist (Steps 3-5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6-11 years, new treatment options are added at Steps 3-4. Across all age groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment, and review remain essential to optimize asthma outcomes.

Health workers' perspectives on asthma care coordination between primary and specialised healthcare in the COVID-19 pandemic: a protocol for a qualitative study in Ecuador and Brazil.

INTRODUCTION: Asthma is a common long-term disorder and strategies to improve asthma control are still a challenge. Integrated delivery of health systems is critical for effective asthma care: there is limited information on experiences of care coordination for asthma from Latin America, especially on perspectives of health personnel and in the context of the COVID-19 pandemic. METHODS AND ANALYSIS: This protocol details a qualitative approach to analyse health workers' perspectives of healthcare coordination for asthma control during COVID-19 pandemic in Ecuador and Brazil, at primary and specialised levels, through in-depth semistructured interviews using a video communications platform. The analysis will identify knowledge and perspectives based on coordination of clinical information, clinical management and administrative coordination. Theoretical sampling will be used to obtain approximately equal numbers of women and men within each level of healthcare; data saturation will be used to determine sample size. Transcripts will be analysed using content-coding procedures to mark quotations related to major topics and subthemes included in the interview guide, and narrative analysis will be based on a theoretical framework for healthcare coordination to identify new themes and subthemes. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethics committees of Hospital General Docente Calderón, Quito, Ecuador; and Universidade Federal da Bahia, Salvador, Brazil. The findings of this study will be disseminated through peer-reviewed articles, conference presentations and condensed summaries for key stakeholders and partners.

Impact of COVID-19 pandemic on asthma symptoms and management: A prospective analysis of asthmatic children in Ecuador.

BACKGROUND: Asthma affects up to 33% of children in Latin American settings. The ongoing COVID-19 pandemic has had a significant impact on access to and use of health services. We aimed to evaluate the impact of the COVID-19 lockdown on asthma exacerbations, medical facility visits, and use of asthma medications in children. METHODS: We used data from a prospective cohort of 213 children aged 5-17 years in 3 Ecuadorian cities and analysed the impact of the COVID-19 lockdown on asthma. Outcomes (asthma exacerbations, emergency room [ER] visits, planned and unplanned outpatient visits, and use of inhaled corticosteroids and Beta-2 agonists) were analysed using repeated Poisson counts (ie, number of events per participant before and during the COVID-19 lockdown). RESULTS: During compared to before lockdown: a) the number of asthma exacerbations remained constant (IRR, 0.87; 95% CI: 0.72-1.05; p = 0.152); b) outpatient visits (IRR 0.26, 95% CI 0.14-0.47, p < 0.001) declined 74% while ER visits declined 89% (IRR 0.11, 95% CI 0.04-0.32, p < 0.001); and c) there was no change in inhaled corticosteroids use (IRR 1.03, 95% CI 0.90-1.16, P = 0.699) while Beta-2 agonist use increased (IRR 1.32, 95% CI 1.10-1.58, P = 0.003). CONCLUSIONS: In a cohort of Ecuadorian children with asthma, health services attendance decreased dramatically after COVID-19 lockdown, but asthma exacerbations and use of inhaled corticosteroids were unchanged. Future analyses will address the question of the effect of SARS-CoV-2 infection on asthma exacerbations and control in this paediatric population.

Management of anaphylaxis due to COVID-19 vaccines in the elderly.

Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.

Potential Interplay between Nrf2, TRPA1, and TRPV1 in Nutrients for the Control of COVID-19.

In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1 and TRPV1 induce inflammation and play a key role in the physiology of almost all organs. They may augment sensory or vagal nerve discharges to evoke pain and several symptoms of COVID-19, including cough, nasal obstruction, vomiting, diarrhea, and, at least partly, sudden and severe loss of smell and taste. TRPA1 can be activated by reactive oxygen species and may therefore be up-regulated in COVID-19. TRPA1 and TRPV1 channels can be activated by pungent compounds including many nuclear factor (erythroid-derived 2) (Nrf2)-interacting foods leading to channel desensitization. Interactions between Nrf2-associated nutrients and TRPA1/TRPV1 may be partly responsible for the severity of some of the COVID-19 symptoms. The regulation by Nrf2 of TRPA1/TRPV1 is still unclear, but suggested from very limited clinical evidence. In COVID-19, it is proposed that rapid desensitization of TRAP1/TRPV1 by some ingredients in foods could reduce symptom severity and provide new therapeutic strategies.

Is asthma a risk factor for coronavirus disease-2019 worse outcomes? The answer is no, but .

PURPOSE OF REVIEW: To search for evidence on whether having asthma increases the risk of poor outcomes of COVID-19 and report on recommendations on optimal asthma management in times of COVID-19. RECENT FINDINGS: Patients with asthma are neither at greater risk of becoming infected by SARS-CoV-2 nor they are at risk of complications of COVID-19 but those requiring frequent use of oral corticosteroid may be at greater risk. SUMMARY: In general, patients with asthma are not at risk of COVID-19 morbidity or mortality. On the contrary, patients with asthma may be at lower risk of hospitalizations during the COVID-19 pandemic. This may be related to asthma and its treatment, to patient's behavior, to the health system, and to collective changes in activities. It is likely that reduction in respiratory infections because of social distancing, face masks, and hand washing have a role in the reduction in asthma hospitalizations. Management of asthma in times of COVID-19 must be optimized, medication have to be used regularly and exacerbations detected early. Systemic corticosteroids may be used for control of severe asthma or severe exacerbations. Patient education on an action plan is crucial, as well as facilitating communications with the healthcare team.

Spices to Control COVID-19 Symptoms: Yes, but Not Only .

There are large country variations in COVID-19 death rates that may be partly explained by diet. Many countries with low COVID-19 death rates have a common feature of eating large quantities of fermented vegetables such as cabbage and, in some continents, various spices. Fermented vegetables and spices are agonists of the antioxidant transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and spices are transient receptor potential ankyrin 1 and vanillin 1 (TRPA1/V1) agonists. These mechanisms may explain many COVID-19 symptoms and severity. It appears that there is a synergy between Nrf2 and TRPA1/V1 foods that may explain the role of diet in COVID-19. One of the mechanisms of COVID-19 appears to be an oxygen species (ROS)-mediated process in synergy with TRP channels, modulated by Nrf2 pathways. Spicy foods are likely to desensitize TRP channels and act in synergy with exogenous antioxidants that activate the Nrf2 pathway.

Efficacy of broccoli and glucoraphanin in COVID-19: From hypothesis to proof-of-concept with three experimental clinical cases.

COVID-19 is described in a clinical case involving a patient who proposed the hypothesis that Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-interacting nutrients may help to prevent severe COVID-19 symptoms. Capsules of broccoli seeds containing glucoraphanin were being taken before the onset of SARS-CoV-2 infection and were continued daily for over a month after the first COVID-19 symptoms. They were found to reduce many of the symptoms rapidly and for a duration of 6-12 h by repeated dosing. When the patient was stable but still suffering from cough and nasal obstruction when not taking the broccoli capsules, a double-blind induced cough challenge confirmed the speed of onset of the capsules (less than 10 min). A second clinical case with lower broccoli doses carried out during the cytokine storm confirmed the clinical benefits already observed. A third clinical case showed similar effects at the onset of symptoms. In the first clinical trial, we used a dose of under 600 µmol per day of glucoraphanin. However, such a high dose may induce pharmacologic effects that require careful examination before the performance of any study. It is likely that the fast onset of action is mediated through the TRPA1 channel. These experimental clinical cases represent a proof-of-concept confirming the hypothesis that Nrf2-interacting nutrients are effective in COVID-19. However, this cannot be used in practice before the availability of further safety data, and confirmation is necessary through proper trials on efficacy and safety.

BCG vaccine protection from severe coronavirus disease 2019 (COVID-19).

A series of epidemiological explorations has suggested a negative association between national bacillus Calmette-Guérin (BCG) vaccination policy and the prevalence and mortality of coronavirus disease 2019 (COVID-19). However, these comparisons are difficult to validate due to broad differences between countries such as socioeconomic status, demographic structure, rural vs. urban settings, time of arrival of the pandemic, number of diagnostic tests and criteria for testing, and national control strategies to limit the spread of COVID-19. We review evidence for a potential biological basis of BCG cross-protection from severe COVID-19, and refine the epidemiological analysis to mitigate effects of potentially confounding factors (e.g., stage of the COVID-19 epidemic, development, rurality, population density, and age structure). A strong correlation between the BCG index, an estimation of the degree of universal BCG vaccination deployment in a country, and COVID-19 mortality in different socially similar European countries was observed (r2 = 0.88; P = 8 × 10-7), indicating that every 10% increase in the BCG index was associated with a 10.4% reduction in COVID-19 mortality. Results fail to confirm the null hypothesis of no association between BCG vaccination and COVID-19 mortality, and suggest that BCG could have a protective effect. Nevertheless, the analyses are restricted to coarse-scale signals and should be considered with caution. BCG vaccination clinical trials are required to corroborate the patterns detected here, and to establish causality between BCG vaccination and protection from severe COVID-19. Public health implications of a plausible BCG cross-protection from severe COVID-19 are discussed.

Is diet partly responsible for differences in COVID-19 death rates between and within countries?

Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.