The Coronavirus pandemic – 2022: Viruses,variants & vaccines

Since the beginning of the COVID-19 pandemic in 2019–2020, Cytokine & Growth Factor Reviews has published several Special Issues focused on the biology, pathogenesis and therapeutic options in the treatment of COVID-19 infection, including articles on the involvement of the chemokine system in the cytokine storm in COVID-19, intervention in the early stages of COVID-19 pneumonia, the therapeutic value of corticosteroid treatment, early clinical intervention with type 1 interferons, progress in vaccine development, and organ specific complications of COVID-19. By 2022, multiple highly efficacious vaccines are available and are being administered in countries around the world, therapeutic options have been clinically evaluated and approved, and SARS-CoV-2 has arguably become the most thoroughly studied virus in history. But, with progress has also come unanticipated problems – misinformation, anti-vaxxers, opposition to protective masks, and politically motivated interference disguised as knowledge. With this issue of CGFR, we continue to document the global coronavirus pandemic and provide an update on the emergence of viral variants, the global effort to administer vaccines and the impediments to progress posed by misinformation and anti-vaccine sentiment.     

COVID-19疫苗研究现状*

2019年底于中国武汉暴发的新型冠状病毒肺炎疫情来势凶猛,迅速蔓延全球,并被世界卫生组织列为“国际关注的突发公共卫生事件”,给全人类的健康及经济发展造成难以估量的损害。新型冠状病毒对人群普遍易感且传染性强,在无特效药物及治疗手段的情况下,疫苗接种是防控COVID-19疫情最有效且最经济的途径。目前全球疫苗研发正在加速进行,各国之间通力合作,共同应对此次疫情。主要对目前正在研发的针对SARS-CoV-2的灭活疫苗、病毒载体疫苗、基因工程重组亚单位疫苗、核酸疫苗的研究进展进行综述。     

Beta-Adrenergic Blockers as a Potential Treatment for COVID-19 Patients

More than 15 million people have been affected by coronavirus disease 2019 (COVID-19) and it has caused 640 016 deaths as of July 26, 2020. Currently, no effective treatment option is available for COVID-19 patients. Though many drugs have been proposed, none of them has shown particular efficacy in clinical trials. In this article, the relationship between the Adrenergic system and the renin-angiotensin-aldosterone system (RAAS) is focused in COVID-19 and a vicious circle consisting of the Adrenergic system-RAAS-Angiotensin converting enzyme 2 (ACE2)-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (which is referred to as the “ARAS loop”) is proposed. Hyperactivation of the ARAS loop may be the underlying pathophysiological mechanism in COVID-19, and beta-adrenergic blockers are proposed as a potential treatment option. Beta-adrenergic blockers may decrease the SARS-CoV-2 cellular entry by decreasing ACE2 receptors expression and cluster of differentiation 147 (CD147) in various cells in the body. Beta-adrenergic blockers may decrease the morbidity and mortality in COVID-19 patients by preventing or reducing acute respiratory distress syndrome (ARDS) and other complications. Retrospective and prospective clinical trials should be conducted to check the validity of the hypothesis. Also see the video abstract here https://youtu.be/uLoy7do5ROo .     

Melatonin for the Early Treatment of COVID-19: A Narrative Review of Current Evidence and Possible Efficacy

ObjectiveTo discuss the use of melatonin as an early treatment option on the first day of diagnosis for COVID-19.MethodsMedical Subject Headings terms “COVID-19” and “viral diseases” were manually searched on PubMed, and relevant articles were included.ResultsThe results showed that melatonin acts to reduce reactive oxygen species–mediated damage, cytokine-induced inflammation, and lymphopenia in viral diseases similar to COVID-19.ConclusionThese conclusions provide evidence for potential benefits in melatonin use for COVID-19 treatment as early as the day of diagnosis.     

Attitudes toward COVID-19 vaccines in Chinese college students

Background: Vaccination is an important preventative measure against the coronavirus disease 19 (COVID-19) pandemic. To implement vaccination and immunization programs effectively, it is essential to investigate public attitudes toward COVID-19 vaccines. This study examined the attitudes of Chinese college students toward COVID-19 vaccines and their associated factors. Methods: A cross-sectional study was conducted in college students nationwide from December 27, 2020 to January 18, 2021. Attitudes toward COVID-19 vaccines and acceptance of future vaccination programs were assessed. Results: Totally, 2,881 college students participated in this survey; of them, 76.3% (95% CI: 74.8% - 77.9%) were willing to accept a COVID-19 vaccine in the future. Multiple logistic analysis revealed that students living in urban (OR=1.409, 95% CI: 1.152 - 1.724, p=0.001) and those studying health-related courses (OR=1.581, 95% CI: 1.291 - 1.935, p<0.001) were more likely to have a positive attitude toward COVID-19 vaccines. In addition, those who were worried about being infected with COVID-19 (very much vs no, OR=1.690, 95% CI: 1.212-2.356, p=0.002), heard previously about COVID-19 vaccines (OR=1.659, 95% CI: 1.268-2.170, p<0.001), believed that vaccines are safe (Yes vs No, OR=3.570, 95% CI: 1.825-6.980), thought that vaccines can protect people from being infected with COVID-19 (Yes vs No, OR=1.957, 95% CI: 1.286-2.979, p=0.002), and had encouraged their family and friends to have a vaccine (Yes vs No, OR=17.745, 95% CI: 12.271-25.660, p<0.001) had higher acceptance of COVID-19 vaccination. Conclusions: A high rate of acceptance of COVID-19 vaccines was found among Chinese college students. However, vaccine uptake may be reduced by concerns about vaccine safety and efficacy. Alleviating these concerns and enhancing public confidence in vaccines are crucial for future immunization programs against the COVID-19 pandemic.     

Coronavirus Disease 2019 (COVID-19) Diagnostic Tools: A Focus on Detection Technologies and Limitations

The ongoing coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a severe threat to human health and the global economy and has resulted in overwhelming stress on health care systems worldwide. Despite the global health catastrophe, especially in the number of infections and fatalities, the COVID-19 pandemic has also revolutionized research and discovery with remarkable success in diagnostics, treatments, and vaccine development. The use of many diagnostic methods has helped establish public health guidelines to mitigate the spread of COVID-19. However, limited information has been shared about these methods, and there is a need for the scientific community to learn about these technologies, in addition to their sensitivity, specificity, and limitations. This review article is focused on providing insights into the major methods used for SARS-CoV-2 detection. We describe in detail the core principle of each method, including molecular and serological approaches, along with reported claims about the rates of false negatives and false positives, the types of specimens needed, and the level of technology and the time required to perform each test. Although this study will not rank or prioritize these methods, the information will help in the development of guidelines and diagnostic protocols in clinical settings and reference laboratories.     

COVID-ONE-hi: The One-stop Database for COVID-19-specific Humoral Immunity and Clinical Parameters

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (named COVID-ONE-hi). COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients. In addition, 96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database. Furthermore, COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the “START” button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-hi is freely available at www.COVID-ONE.cn.     

Glucocorticoid-Induced Hyperglycemia Including Dexamethasone-Associated Hyperglycemia in COVID-19 Infection: A Systematic Review

ObjectiveOptimal glucocorticoid-induced hyperglycemia (GCIH) management is unclear. The COVID-19 pandemic has made this issue more prominent because dexamethasone became the standard of care in patients needing respiratory support. This systematic review aimed to describe the management of GCIH and summarize available management strategies for dexamethasone-associated hyperglycemia in patients with COVID-19.MethodsA systematic review was conducted using the PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science databases with results from 2011 through January 2022. Keywords included synonyms for “steroid-induced diabetes” or “steroid-induced hyperglycemia.” Randomized controlled trials (RCTs) were included for review of GCIH management. All studies focusing on dexamethasone-associated hyperglycemia in COVID-19 were included regardless of study quality.ResultsInitial search for non-COVID GCIH identified 1230 references. After screening and review, 33 articles were included in the non-COVID section of this systematic review. Initial search for COVID-19–related management of dexamethasone-associated hyperglycemia in COVID-19 identified 63 references, whereas 7 of these were included in the COVID-19 section. RCTs of management strategies were scarce, did not use standard definitions for hyperglycemia, evaluated a variety of treatment strategies with varying primary end points, and were generally not found to be effective except for Neutral Protamine Hagedorn insulin added to basal-bolus regimens.ConclusionFew RCTs are available evaluating GCIH management. Further studies are needed to support the formulation of clinical guidelines for GCIH especially given the widespread use of dexamethasone during the COVID-19 pandemic.     

An unethical trial and the politicization of the COVID-19 pandemic in Brazil: The case of Prevent Senior

The Brazilian Federal Senate created a Parliamentary Inquiry Commission (CPI) to investigate the Bolsonaro government's irregularities in the management of the COVID-19 pandemic. One of the cases that drew attention was the research conducted by Prevent Senior, a private health insurance company, on the early treatment of COVID-19. The article analyzes the scientific validity of the research and the ethical problems related to its implementation. It is based on analysis of Prevent Senior's report of the clinical study, the Brazilian and USA clinical trial registries, the Senate's CPI report, and on the information reported by the media. This case of scientific fraud and political-ideological bias exemplifies how Prevent Senior, using a questionable protocol to enhance its reputation and gain government support, was instrumental in building the “early treatment” narrative for COVID-19, and shows how it served as a basis for a government public policy that promoted the use of ineffective drugs.     

Considerations for Gut Microbiota and Probiotics in Patients with Diabetes Amidst the Covid-19 Pandemic: A Narrative Review

Objective: To review data implicating microbiota influences on Coronavirus Disease 2019 (COVID-19) in patients with diabetes.Methods: Primary literature review included topics: “COVID-19,” “SARS,” “MERS,” “gut micro-biota,” “probiotics,” “immune system,” “ACE2,” and “metformin.”Results: Diabetes was prevalent (~11%) among COVID-19 patients and associated with increased mortality (about 3-fold) compared to patients without diabetes. COVID-19 could be associated with worsening diabetes control and new diabetes diagnosis that could be linked to high expression of angiotensin-converting enzyme 2 (ACE2) receptors (coronavirus point of entry into the host) in the endocrine pancreas. A pre-existing gut microbiota imbalance (dysbiosis) could contribute to COVID-19–related complications in patients with diabetes. The COVID-19 virus was found in fecal samples (~55%), persisted for about 5 weeks, and could be associated with diarrhea, suggesting a role for gut dysbiosis. ACE2 expressed on enterocytes and colonocytes could serve as an alternative route for acquiring COVID-19. Experimental models proposed some probiotics, including Lactobacillus casei, L. plantarum, and L. salivarius, as vectors for delivering or enhancing efficacy of anti-coronavirus vaccines. These Lactobacillus probiotics were also beneficial for diabetes. The potential mechanisms for interconnections between coronavirus, diabetes, and gut microbiota could be related to the immune system, ACE2 pathway, and metformin treatment. There were suggestions but no proof supporting probiotics benefits for COVID-19 infection.Conclusion: The data suggested that the host environment including the gut microbiota could play a role for COVID-19 in patients with diabetes. It is a challenge to the scientific community to investigate the beneficial potential of the gut microbiota for strengthening host defense against coronavirus in patients with diabetes.     

新型冠状病毒疫苗接种与疫情进展

新型冠状病毒肺炎(简称新冠)疫情仍在发展,新型冠状病毒变异株的出现致使其传染性和致病性增强,部分国家的政府和民众防控措施松懈导致某些地区疫情加剧。新型冠状病毒疫苗广泛使用后,接种情况会影响疫情发展。本文主要阐述新冠疫情与疫苗接种、病毒变异的关联性,接种疫苗存在的问题及其应对措施,并建议在加快疫苗接种的同时应做好各项新冠防控工作。     

The cytokine storm in COVID-19: Further advances in our understanding the role of specific chemokines involved

SARS-COV-2 infection represents the greatest pandemic of the world, counting daily increasing number of subjects positive to the virus and, sadly, increasing number of deaths. Current studies reported that the cytokine/chemokine network is crucial in the onset and maintenance of the “cytokine storm”, the event occurring in those patients in whom the progression of COVID-19 will progress, in most cases, to a very severe and potentially threatening disease. Detecting a possible “immune signature” in patients, as assessed by chemokines status in patients with COVID-19, could be helpful for individual risk stratification for developing a more or less severe clinical course of the disease. The present review is specifically aimed at overviewing current evidences provided by in vitro and in vivo studies addressing the issue of which chemokines seems to be involved, at least at present, in COVID-19. Currently available experimental and clinical studies regarding those chemokines more deeply studied in COVID-19, with a specific focus on their role in the cytokine storm and ultimately with their ability to predict the clinical course of the disease, will be taken into account. Moreover, similarities and differences between chemokines and cytokines, which both contribute to the onset of the pro-inflammatory loop characterizing SARS-COV-2 infection, will be briefly discussed. Future studies will rapidly accumulate in the next months and their results will hopefully provide more insights as to the complex physiopathology of COVID-19-related cytokine storm. This will likely make the present review somehow “dated” in a short time, but still the present review provides an overview of the scenario of the current knowledge on this topic.     

Why we must fight ignorance about COVID-19 vaccines and menstrual cycles

The COVID-19 pandemic has revealed a critical gap in female health science, fueling anxiety, polarized views, and vaccine hesitancy. Although menstrual cycles feel like a niche topic for some, efforts to augment knowledge on the ‘fifth vital sign’ experienced by more than 300 million people on any given day worldwide are crucial to promote gender equity in health.     

COVID-19 therapy: What weapons do we bring into battle?

Urgent treatments, in any modality, to fight SARS-CoV-2 infections are desired by society in general, by health professionals, by Estate-leaders and, mainly, by the scientific community, because one thing is certain amidst the numerous uncertainties regarding COVID-19: knowledge is the means to discover or to produce an effective treatment against this global disease. Scientists from several areas in the world are still committed to this mission, as shown by the accelerated scientific production in the first half of 2020 with over 25,000 published articles related to the new coronavirus. Three great lines of publications related to COVID-19 were identified for building this article: The first refers to knowledge production concerning the virus and pathophysiology of COVID-19; the second regards efforts to produce vaccines against SARS-CoV-2 at a speed without precedent in the history of science; the third comprehends the attempts to find a marketed drug that can be used to treat COVID-19 by drug repurposing. In this review, the drugs that have been repurposed so far are grouped according to their chemical class. Their structures will be presented to provide better understanding of their structural similarities and possible correlations with mechanisms of actions. This can help identifying anti-SARS-CoV-2 promising therapeutic agents.     

Social determinants of mortality from COVID-19: A simulation study using NHANES

BackgroundThe COVID-19 epidemic in the United States is widespread, with more than 200,000 deaths reported as of September 23, 2020. While ecological studies show higher burdens of COVID-19 mortality in areas with higher rates of poverty, little is known about social determinants of COVID-19 mortality at the individual level.Methods and findingsWe estimated the proportions of COVID-19 deaths by age, sex, race/ethnicity, and comorbid conditions using their reported univariate proportions among COVID-19 deaths and correlations among these variables in the general population from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). We used these proportions to randomly sample individuals from NHANES. We analyzed the distributions of COVID-19 deaths by race/ethnicity, income, education level, and veteran status. We analyzed the association of these characteristics with mortality by logistic regression. Summary demographics of deaths include mean age 71.6 years, 45.9% female, and 45.1% non-Hispanic white. We found that disproportionate deaths occurred among individuals with nonwhite race/ethnicity (54.8% of deaths, 95% CI 49.0%–59.6%, p < 0.001), individuals with income below the median (67.5%, 95% CI 63.4%–71.5%, p < 0.001), individuals with less than a high school level of education (25.6%, 95% CI 23.4% –27.9%, p < 0.001), and veterans (19.5%, 95% CI 15.8%–23.4%, p < 0.001). Except for veteran status, these characteristics are significantly associated with COVID-19 mortality in multiple logistic regression. Limitations include the lack of institutionalized people in the sample (e.g., nursing home residents and incarcerated persons), the need to use comorbidity data collected from outside the US, and the assumption of the same correlations among variables for the noninstitutionalized population and COVID-19 decedents.ConclusionsSubstantial inequalities in COVID-19 mortality are likely, with disproportionate burdens falling on those who are of racial/ethnic minorities, are poor, have less education, and are veterans. Healthcare systems must ensure adequate access to these groups. Public health measures should specifically reach these groups, and data on social determinants should be systematically collected from people with COVID-19.

In this simulation study, Benjamin Seligman and colleagues explore socio-demographic factors associated with COVID-19 deaths in the US.     

Repercussions of the COVID-19 pandemic on athletes: a cross-sectional study

The COVID-19 pandemic has presented significant challenges and implications for the sports community. Thus, this study aimed to describe the prevalence of COVID-19 in Brazilian athletes and identify the epidemiological, clinical, athletic, life and health factors associated with the disease in these individuals. A cross-sectional study was performed involving 414 athletes from 22 different sports using an online questionnaire from August to November 2020. The association between the athletes’ characteristics and COVID-19 was evaluated using a logistic regression model. The prevalence of COVID-19 was 8.5%, although only 40% of athletes reported having been tested. Being under 27 years of age (3-fold), having children (~5-fold), having a teammate test positive for COVID-19 (2.5-fold), and smoking (14-fold) were associated with a possible higher risk of disease. Almost 20% of athletes self-reported musculoskeletal injuries during the period of the pandemic that was studied. Athletes with a university education (P = 0.02), a profession other than sports (P < 0.001), those from a low-income family (P = 0.01), and public health system users (P = 0.04) were significantly less frequently tested for COVID-19, whereas international competitors, athletes who received a wage, and athletes who had a teammate who tested positive for COVID-19 were 2-, 3-, and 15-fold more likely to be tested for COVID-19, respectively. Approximately 26% of the athletes who tested negative or were untested reported more than three characteristic COVID-19 symptoms, and 11% of athletes who tested positive for COVID-19 were asymptomatic. The identification of modifiable (have children, smoking, and teammates positively tested) and non-modifiable (age under 27 years) factors related to COVID-19 in athletes can contribute to implementing surveillance programmes to decrease the incidence of COVID-19 in athletes and its negative impacts in sports.     

Molecular and pro-inflammatory aspects of COVID-19: The impact on cardiometabolic health

Obesity, type 2 diabetes (T2DM), hypertension (HTN), and Cardiovascular Disease (CVD) often cluster together as “Cardiometabolic Disease” (CMD). Just under 50% of patients with CMD increased the risk of morbidity and mortality right from the beginning of the COVID-19 pandemic as it has been reported in most countries affected by the SARS-CoV2 virus.One of the pathophysiological hallmarks of COVID-19 is the overactivation of the immune system with a prominent IL-6 response, resulting in severe and systemic damage involving also cytokines such as IL2, IL4, IL8, IL10, and interferon-gamma were considered strong predictors of COVID-19 severity. Thus, in this mini-review, we try to describe the inflammatory state, the alteration of the adipokine profile, and cytokine production in the obese state of infected and not infected patients by SARS-CoV2 with the final aim to find possible influences of COVID-19 on CMD and CVD.The immunological-based discussion of the molecular processes could inspire the study of promising targets for managing CMD patients and its complications during COVID-19.     

The evolving role of preprints in the dissemination of COVID-19 research and their impact on the science communication landscape

The world continues to face a life-threatening viral pandemic. The virus underlying the Coronavirus Disease 2019 (COVID-19), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has caused over 98 million confirmed cases and 2.2 million deaths since January 2020. Although the most recent respiratory viral pandemic swept the globe only a decade ago, the way science operates and responds to current events has experienced a cultural shift in the interim. The scientific community has responded rapidly to the COVID-19 pandemic, releasing over 125,000 COVID-19–related scientific articles within 10 months of the first confirmed case, of which more than 30,000 were hosted by preprint servers. We focused our analysis on bioRxiv and medRxiv, 2 growing preprint servers for biomedical research, investigating the attributes of COVID-19 preprints, their access and usage rates, as well as characteristics of their propagation on online platforms. Our data provide evidence for increased scientific and public engagement with preprints related to COVID-19 (COVID-19 preprints are accessed more, cited more, and shared more on various online platforms than non-COVID-19 preprints), as well as changes in the use of preprints by journalists and policymakers. We also find evidence for changes in preprinting and publishing behaviour: COVID-19 preprints are shorter and reviewed faster. Our results highlight the unprecedented role of preprints and preprint servers in the dissemination of COVID-19 science and the impact of the pandemic on the scientific communication landscape.

An analysis of bioRxiv and medRxiv during the first 10 months of the COVID-19 pandemic reveals that the pandemic has resulted in a cultural shift in the use of preprints for disseminating pandemic-related science.