Molecular Aspects Concerning the Use of the SARS-CoV-2 Receptor Binding Domain as a Target for Preventive Vaccines. Valdes-Balbin Y, Santana-Mederos D, Paquet F, Fernandez S, Climent Y, Chiodo F, Rodríguez L, Sanchez-Ramirez B, Leon K, Hernandez T, Castellanos-Serra L, et al. ACS Cent. Sci., 2021 April 19 https://doi.org/10.1021/acscentsci.1c00216
The development of recombinant COVID-19 vaccines has resulted from scientific progress made at an unprecedented speed during 2020. The recombinant spike glycoprotein monomer, its trimer, and its recombinant receptor-binding domain (RBD) induce a potent anti-RBD neutralizing antibody response in animals. In COVID-19 convalescent sera, there is a good correlation between the antibody response and potent neutralization. In this review, we summarize with a critical view the molecular aspects associated with the interaction of SARS-CoV-2 RBD with its receptor in human cells, the angiotensin-converting enzyme 2 (ACE2), the epitopes involved in the neutralizing activity, and the impact of virus mutations thereof. Recent trends in RBD-based vaccines are analyzed, providing detailed insights into the role of antigen display and multivalence in the immune response of vaccines under development.
COVID-19: Long-term support for biotech yields vaccine promise in Cuba. Larsen J. UNIDO. 2021 Feb 8.
Cuba hopes to inoculate its entire population against COVID-19 with a home-grown vaccine this year. The country has four potential vaccines in development, the most advanced of which – Soberana II – is due to start Phase III trials in March with 150,000 volunteers. If it clears this final clinical hurdle, the Cuban vaccine will be the first to be developed in Latin America. According to the Havana-based Finlay Vaccine Institute (IFV), 100 million doses could be supplied in 2021 for both domestic use and export. Cuba has signed a deal to carry out clinical trials in Iran in collaboration with the country’s Pasteur Institute, while Jamaica, Viet Nam and Venezuela, among others, have expressed interest in obtaining the vaccine once it passes the necessary safety and efficacy tests. As international squabbles over fair distribution grow, amid charges that rich countries are hoarding supplies, a successful roll-out of Soberana II could provide a potential lifeline to developing countries seeking to immunize their populations against COVID-19.
Cuba’s response to COVID-19: lessons for the future. Wylie LL. J Tourism Futures. 2021 Mar 11. Online ahead of print.
Purpose The purpose of this paper is to examine the relevance of Cuba’s medical system, its health tourism and related diplomacy in the context of the recent COVID-19 pandemic for the global response to disease outbreaks. In addition to Cuba being a destination for leisure tourists in the Caribbean, the renowned Cuban medical system attracts thousands of health tourists seeking low-cost but high-quality treatment. This paper demonstrates how Cuba’s unique response to the pandemic, which included sending thousands of medical staff abroad, can inform structural and global issues and contribute to a more sustainable future. Design/methodology/approach The research in this study is primarily drawn from published academic and media sources that address Cuba’s medical system, its health tourism and the government’s response to the recent pandemic. The author, a political scientist and an author of many publications on Cuba, and the PI of a study focused on Cuban tourism, will also draw on her expertise. Findings This paper addresses the Cuban Government’s ongoing response to the COVID-19 pandemic and places this response in the context of Cuba’s medical system, its health tourism and related diplomacy. It reveals key lessons from Cuba’s response for other tourist destination states and, more broadly, for the worldwide response to global outbreaks and the management of health systems. The findings will further research in diplomacy and tourism as well as inform policy and practice. Research limitations/implications This paper explores an ongoing topic and thus further research will be required following the pandemic. Practical implications This research note offers important implications for practice including providing accurate, research-based information that challenges misinformation about Cuba’s health system, its medical diplomacy program, health tourism and its response to COVID-19. It offers valuable lessons for public health authorities including the importance of preventative health measures, community medicine and the benefits of working globally to combat outbreaks through the sharing of medical staff and resources. Social implications This research note reveals the health, political and social implications of Cuba’s response in this time of crisis. It shows the benefits of a robust but low-cost community-based medicine program, medical diplomacy and how a state’s response during crisis can moderate the global inequities and injustices such as unequal access to care that often accompany disease outbreaks such as COVID-19. Originality/value This research note is an early analysis of a response by an important tourist destination country to the pandemic. The author anticipates that the information provided to the international community via this open access journal will offer practical implications for the ongoing global efforts to manage this crisis and contribute to the research on tourism, diplomacy, justice and health policy.
Behind Cuba’s successful pandemic response. Burki T. Lancet Infec Dis. 2021 Apr 1;21(4):465-6.
Cuba’s long-standing commitment to health has led to a successful COVID-19 pandemic response, but it is threatened by financial and supplier issues. As The Lancet Infectious Diseases went to press, Cuba was due to launch a phase 3 trial of its subunit conjugate vaccine against COVID-19. Soberana-2 is one of four candidate COVID-19 vaccines in development in Cuba. It is produced by the Finlay Institute in Havana. On the basis of as-yet-unpublished results from early-stage clinical trials, Vicente Verez-Bencomo, director-general of the Finlay Institute, expects the vaccine to show an efficacy in the region of 80–95%. “We are very optimistic”, he said. If everything goes according to plan, Cuba could start a mass vaccination programme for its 11·2 million citizens sometime in the summer.
SARS-CoV-2 RBD-Tetanus toxoid conjugate vaccine induces a strong neutralizing immunity in preclinical studies. Valdes-Balbin Y, Santana-Mederos D, Quintero L, Fernández S, Rodríguez L, Sánchez-Ramírez B, et al. bioRxiv. 2021 Feb 9. Preprint.
The development of prophylactic vaccines at unprecedented speed is necessary to control the global pandemic due to SARS CoV 2 infection. Vaccines approved for use and those under development intend to block viral sites binding to the hosts cellular receptors by means of neutralizing antibodies. Virus infection is mediated by the spike glycoprotein trimer on the virion surface via its receptor binding domain (RBD). Antibody response against this domain is an important outcome of the immunization and correlates well with viral neutralization. Here we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid induce a potent immune response in laboratory animals. Some advantages of the immunization with the viral antigen coupled to tetanus toxoid have become evident such as predominantly IgG immune response due to affinity maturation and long term specific B memory cells. This work demonstrates that subunit conjugate vaccines can be an alternative for COVID19 paving the way for other viral conjugate vaccines based on the use of small viral proteins involved in the infection process.
Strategic perspective in the management of COVID-19 in Cuba. Arias Rivera ML. CLACSO.
Crisis management is one of the most complex, dynamic and creative processes managers face. For this reason, the analysis of the experiences of managing the health crisis caused by COVID-19 is especially important and topical. This work aims to analyze the Cuban experience, explain the peculiarities of the management model used by the government and point out the barriers that must be overcome to guarantee the results that are needed. Its content addresses theoretical elements on crisis management and provides the elements that allow us to understand the actions carried out and the results achieved in very adverse conditions. This systematization is focused on the March-July 2020 period, and should be monitored and expanded.
The scene from Cuba: How it’s getting so much right on COVID-19. Hosek JR. The Conversation. 2021 Mar 16.
As the COVID-19 pandemic disproportionately harms underprivileged people globally, Cuba’s “people over profit” approach has been saving many lives — both on the island and abroad. From the onset, Cuba’s approach has been holistic and integrated. Its response is among the most respected in the world. Widespread confidence in the Cuban government’s science-based policies, public service media messaging and volunteerism are key reasons as to why Cuba has been able to control the viral reproduction rate until mass vaccination begins.
CIGB-258, a peptide derived from human heat-shock protein 60, decreases hyperinflammation in COVID-19 patients. Hernández-Cedeño, Venegas-Rodríguez R, Peña-Ruiz R, Bequet-Romero M, Santana-Sánchez R, Pentón-Arias E, et al. Cell Stress Chaperones. 2021 Feb 24. DOI: 10.1007/s12192-021-01197-2. Online ahead of print.
Hyperinflammation distinguishes COVID-19 patients who develop a slight disease or none, from those progressing to severe and critical conditions. CIGB-258 is a therapeutic option for the latter group of patients. This drug is an altered peptide ligand (APL) derived from the cellular stress protein 60 (HSP60). In preclinical models, this peptide developed anti-inflammatory effects and increased regulatory T cell (Treg) activity. Results from a phase I clinical trial with rheumatoid arthritis (RA) patients indicated that CIGB-258 was safe and reduced inflammation. The aim of this study was to examine specific biomarkers associated with hyperinflammation, some cytokines linked to the cytokine storm granzyme B and perforin in a cohort of COVID-19 patients treated with this peptide. All critically ill patients were under invasive mechanical ventilation and received the intravenous administration of 1 or 2 mg of CIGB-258 every 12 h. Seriously ill patients were treated with oxygen therapy receiving 1 mg of CIGB-258 every 12 h and all patients recovered from their severe condition. Biomarker levels associated with hyperinflammation, such as interleukin (IL)-6, IL-10, tumor necrosis factor (TNF-α), granzyme B, and perforin, significantly decreased during treatment. Furthermore, we studied the ability of CIGB-258 to induce Tregs in COVID-19 patients and found that Tregs were induced in all patients studied. Altogether, these results support the therapeutic potential of CIGB-258 for diseases associated with hyperinflammation. Clinical trial registry: RPCEC00000313.
Clinical presentation, therapeutic approach, and outcome of young patients admitted for COVID-19, with respect to the elderly counterpart. Pepe M, Maroun-Eid C, Romero R, Arroyo-Espliguero R, Fernández-Rozas I, Aparisi A, et al. Clin Exp Med. 2021 Feb 8;1-20. DOI: 10.1007/s10238-021-00684-1. Online ahead of print.
There is limited information on the presenting characteristics, prognosis, and therapeutic approaches of young patients hospitalized for coronavirus disease 2019 (COVID-19). We sought to investigate the baseline characteristics, in-hospital treatment, and outcomes of a wide cohort < 65 years admitted for COVID-19. Using the international multicenter HOPE-COVID-19 registry, we evaluated the baseline characteristics, clinical presentation, therapeutic approach, and prognosis of patients < 65 years discharged (deceased or alive) after hospital admission for COVID-19, also compared with the elderly counterpart. Of the included 5746 patients, 2676 were < 65 and 3070 ≥ 65 years. All risk factors and several parameters suggestive of worse clinical presentation augmented through increasing age classes. In-hospital mortality rates were 6.8% and 32.1% in the younger and older cohort, respectively (p < 0.001). Among young patients, mortality, access to ICU and treatment with IMVwere positively correlated with age. Contrariwise, over 65 years of age this trend was broken so that only the association between age and mortality was persistent, while the rates of access to ICU and IMV started to decline. Younger patients also recognized specific predictors of case fatality, such as obesity and gender. Age negatively impacts on mortality, access to ICU and treatment with IMV in patients < 65 years. In elderly patients only case fatality rate keeps augmenting in a stepwise manner through increasing age categories, while therapeutic approaches become more conservative. Besides age, obesity, gender, history of cancer, and severe dyspnea, tachypnea, chest X-ray bilateral abnormalities, abnormal level of creatinine and leucocyte among admission parameters seem to play a central role in the outcome of patients younger than 65 years.
Current limitations to identify COVID-19 using artificial intelligence with chest X-ray imaging. López-Cabrera JA, Orozco-Morales R, Portal-Díaz JA, Lovelle-Enríquez O, Pérez-Díaz M. Health Technol (Berl). 2021 Feb 5;1-14.
DOI: 10.1007/s12553-021-00520-2. Online ahead of print.
The scientific community has joined forces to mitigate the scope of the current COVID-19 pandemic. The early identification of the disease, as well as the evaluation of its evolution is a primary task for the timely application of medical protocols. The use of medical images of the chest provides valuable information to specialists. Specifically, chest X-ray images have been the focus of many investigations that apply artificial intelligence techniques for the automatic classification of this disease. The results achieved to date on the subject are promising. However, some results of these investigations contain errors that must be corrected to obtain appropriate models for clinical use. This research discusses some of the problems found in the current scientific literature on the application of artificial intelligence techniques in the automatic classification of COVID-19. It is evident that in most of the reviewed works an incorrect evaluation protocol is applied, which leads to overestimating the results.
Fear of COVID-19 Scale (FCV-19S) across countries: Measurement invariance issues. Lin CY, Hou WL, Mamun MA, da Silva, JA, Broche-Pérez Y, Ullah I, et al. Nurs Open. 2021 Mar 21. DOI: 10.1002/nop2.855. Online ahead of print
Aim The threats of novel coronavirus disease 2019 (COVID-19) have caused fears worldwide. The Fear of COVID-19 Scale (FCV-19S) was recently developed to assess the fear of COVID-19. Although many studies found that the FCV-19S is psychometrically sound, it is unclear whether the FCV-19S is invariant across countries. The present study aimed to examine the measurement invariance of the FCV-19S across eleven countries. Design Cross-sectional study. Methods Using data collected from prior research on Bangladesh (N = 8,550), United Kingdom (N = 344), Brazil (N = 1,843), Taiwan (N = 539), Italy (N = 249), New Zealand (N = 317), Iran (N = 717), Cuba (N = 772), Pakistan (N = 937), Japan (N = 1,079) and France (N = 316), comprising a total 15,663 participants, the present study used the multigroup confirmatory factor analysis (CFA) and Rasch differential item functioning (DIF) to examine the measurement invariance of the FCV-19S across country, gender and age (children aged below 18 years, young to middle-aged adults aged between 18 and 60 years, and older people aged above 60 years). Results The unidimensional structure of the FCV-19S was confirmed. Multigroup CFA showed that FCV-19S was partially invariant across country and fully invariant across gender and age. DIF findings were consistent with the findings from multigroup CFA. Many DIF items were displayed for country, few DIF items were displayed for age, and no DIF items were displayed for gender. Conclusion Based on the results of the present study, the FCV-19S is a good psychometric instrument to assess fear of COVID-19 during the pandemic period. Moreover, the use of FCV-19S is supported in at least ten countries with satisfactory psychometric properties.
Non-invasive ventilation for SARS-CoV-2 acute respiratory failure: a subanalysis from the HOPE COVID-19 registry. Bertaina M, Núñez-Gil IJ, FranchinL, Fernández Rozas I, Arroyo-Espliguero R, Viana-Llamas MC, et al. Emerg Med J. 2021 Mar 16;emermed-2020-210411. DOI: 10.1136/emermed-2020-210411. Online ahead of print
Background The COVID-19 pandemic has seriously challenged worldwide healthcare systems and limited intensive care facilities, leading to physicians considering the use of non-invasive ventilation (NIV) for managing SARS-CoV-2-related acute respiratory failure (ARF). Methods We conducted an interim analysis of the international, multicentre HOPE COVID-19 registry including patients admitted for a confirmed or highly suspected SARS-CoV-2 infection until 18 April 2020. Those treated with NIV were considered. The primary endpoint was a composite of death or need for intubation. The components of the composite endpoint were the secondary outcomes. Unadjusted and adjusted predictors of the primary endpoint within those initially treated with NIV were investigated. Results 1933 patients who were included in the registry during the study period had data on oxygen support type. Among them, 390 patients (20%) were treated with NIV. Compared with those receiving other non-invasive oxygen strategy, patients receiving NIV showed significantly worse clinical and laboratory signs of ARF at presentation. Of the 390 patients treated with NIV, 173 patients (44.4%) met the composite endpoint. In-hospital death was the main determinant (147, 37.7%), while 62 patients (15.9%) needed invasive ventilation. Those requiring invasive ventilation had the lowest survival rate (41.9%). After adjustment, age (adjusted OR (adj(OR)) for 5-year increase: 1.37, 95% CI 1.15 to 1.63, p<0.001), hypertension (adj(OR) 2.95, 95% CI 1.14 to 7.61, p=0.03), room air O2 saturation <92% at presentation (adj(OR) 3.05, 95% CI 1.28 to 7.28, p=0.01), lymphocytopenia (adj(OR) 3.55, 95% CI 1.16 to 10.85, p=0.03) and in-hospital use of antibiotic therapy (adj(OR) 4.91, 95% CI 1.69 to 14.26, p=0.003) were independently associated with the composite endpoint. Conclusion NIV was used in a significant proportion of patients within our cohort, and more than half of these patients survived without the need for intubation. NIV may represent a viable strategy particularly in case of overcrowded and limited intensive care resources, but prompt identification of failure is mandatory to avoid harm. Further studies are required to better clarify our hypothesis.
Sleep during COVID-19 lockdown: A cross-cultural study investigating job system relevance. Florea C, Topalidis P, Hauser T, Angerer M, Kurapov A, Beltrán León CA, et al. Biochem Pharmacol. 2021 Feb 10;114463. DOI: 10.1016/j.bcp.2021.114463. Online ahead of print.
Our study aimed to assess the change in the sleep patterns during the Coronavirus lockdown in five regions (Austria/Germany, Ukraine, Greece, Cuba and Brazil), using online surveys, translated in each language. Part of the cohort (age 25-65, well-educated) was collected directly during lockdown, to which retrospective cross-sectional data from and after lockdown (retrospective) questionnaires were added. We investigated sleep times and sleep quality changes from before to during lockdown and found that, during lockdown, participants had (i) worse perceived sleep quality if worried by COVID-19, (ii) a shift of bedtimes to later hours during workdays, and (iii) a sleep loss on free days (resulting from more overall sleep during workdays in non-system relevant jobs), leading to (iv) a marked reduction of social jetlag across all cultures. For further analyses we directly compared system relevant and system irrelevant jobs, because it was assumed that the nature of the lockdown’s consequences is dependent upon system relevance. System relevant jobs were found to have earlier wake-up times as well as shorter total sleep times on workdays, leading to higher social jetlag for people in system relevant jobs. Cultural differences revealed a general effect that participants from Greece and Ukraine had later bedtimes (on both work and free days) and wake-up times (on workdays) than Cuba, Brazil and Austria, irrespective of COVID-19 lockdown restrictions.
The Importance of Understanding the Stages of COVID-19 in Treatment and Trials. Griffin DO, Brennan-Rieder D, Ngo B, Kory P, Confalonieri M, Shapiro L, et al. AIDS Rev. 2021 Feb 8. DOI: 10.24875/AIDSRev.200001261. Online ahead of print.
COVID-19, caused by SARS-CoV-2, continues to be a major health problem since its first description in Wuhan, China, in December 2019. Multiple drugs have been tried to date in the treatment of COVID-19. Critical to treatment of COVID-19 and advancing therapeutics is an appreciation of the multiple stages of this disease and the importance of timing for investigation and use of various agents. We considered articles related to COVID-19 indexed on PubMed published January 1, 2020-November 15, 2020, and considered papers on the medRxiv preprint server. We identified relevant stages of COVID-19 including three periods: pre-exposure, incubation, and detectable viral replication; and five phases: the viral symptom phase, the early inflammatory phase, the secondary infection phase, the multisystem inflammatory phase, and the tail phase. This common terminology should serve as a framework to guide when COVID-19 therapeutics being studied or currently in use is likely to provide benefit rather than harm.
The Time to Offer Treatments for COVID-19. Ngo BT, Marik P, Kory P, Shapiro L, Thomadsen R, Iglesias J, et al. Expert Opin Investig Drugs. 2021 Mar 15. DOI: 10.1080/13543784.2021.1901883. Online ahead of print.
COVID-19 has several overlapping phases. Treatment has focused on the late stage of the disease in hospital. Yet, the continuation of the pandemic is by propagation of the disease in outpatients. The current public health strategy relies solely on vaccines to prevent disease. Areas Covered: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results with subject numbers of 100 or more on, and used a targeted search to find announcements of unpublished trial results. As of 2/15/2021, we found 111 publications reporting findings in human studies on 14 classes of agents, and on 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care, the rest all in hospitalized patients. Remdesivir and convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but the supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries.Expert Opinion: Worldwide vaccination is now underway. Vaccines and antibodies are highly antigen specific and new variants are appearing. There is a need for treatment of outpatients who contract the disease, in addition to mass immunization. We call on public health authorities to authorize treatments with known low risk and potential benefit for use in parallel with mass immunization.
