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CUBAN RESEARCH ON COVID-19

COVID-19, external migration and territorial displacement in Cuba, a deferential look at the population residing in the country’s capital Aja, A.; Rodríguez, A.;  Orbea, M. Novedades en Población, Centro de Estudios Demográficos, Universidad de La Habana, Cuba; Vol. 16, Núm. 32 (2020)
The pandemic caused by COVID-19 has had an unprecedented impact on all areas of human life, including migration and mobility. Starting from the fact that, if the epidemic is contained in one place and in others it is not very likely that it will constantly re-emerge, without a doubt, an important aspect for the gradual and effective recovery of society will be the effectiveness with the that population mobility is contained and subsequently restarted. Based on this scenario and taking into account that human mobility constitutes the main risk of importation and dissemination of the SARS-CoV-2 infection, it has been decided to carry out an analysis of the epidemiological situation and of international mobility and migration in Cuba -with emphasis on Havana- since this province is the capital of the country and the epicenter of the epidemic in the national territory. The fundamental sources of information come from the National Statistical Information System; the Ministry of Public Health; the Ministry of Labor and Social Security; the Ministry of Transport; of the Directorate of Identification, Immigration and Aliens and of information published on the website Our World in Data.

La ciencia cubana en el enfrentamiento a la COVID-19. Velázquez-Pérez L. Anales de la Academia de Ciencias de Cuba [revista en Internet].  11(1):[aprox. 0 p.]. Editorial https://orcid.org/0000-0003-1628-2703

Science, technology and innovation strategy of the National Center for Biological Products against COVID-19 Lobaina-Rodríguez T, De-Armas-Rodríguez J, Rodríguez-Cabrera T, González-García G, Labrada-Rosado A, Rojas-Gattorno I, Espinosa-López O, Cruz-Bayo A, Mieres-Díaz N, Reyes-Morgado M, López-Martínez Y, Fernández-Durand A, Lorenzo-Jaime H. Anales de la Academia de Ciencias de Cuba [revista en Internet]. 2020; 10(3)
The National Center of Biological Products, a Science and Technology entity integrated into the actions of the State to update the economic model, takes on new challenges facing COVID-19 in its science and innovation activity. In just 10 weeks, a transport medium for SARS-CoV-2 was developed and registered; the application of Biomodulin T® was also introduced into the prevention protocols with more than 10 000 older adults treated, without any subject having acquired the disease. Two new drugs derived from the research were introduced and 2,8 millions of units of other eight products were produced. The main dynamic elements leading into the generation of innovative products were adapted to the new conditions, especially the management of highly qualified and motivated human capital, the most intensive use of productive and analytical capacities, complying with the high regulatory standards, the business structure, the logistics system, and commercial management.

Estimating undocumented Covid-19 infections in Cuba by means of a hybrid mechanistic-statistical approach Gil G, Lage Castellanos A. Ciencias Matemáticas, Vol. 34, No. 1, 2020, Pag. 49-54
We adapt the hybrid mechanistic-statistical approach of Ref. [1] to estimate the total number of undocumented Covid-19 infections in Cuba. This scheme is based on the maximum likelihood estimation of aSIR-like model parameters for the infected population, assuming that the detection process matches a Bernoullitrial. Our estimations show that (a) 60% of the infections were undocumented, (b) the real epidemics behind the data peaked ten days before the reports suggested, and (c) the reproduction number swiftly vanishes after 80th epidemic days.

PREPRINT Phase II randomized controlled trial to evaluate the efficacy and safety of HeberFERON versus Heberon alpha R in symptomatic or asymptomatic patients infected with the SARS-CoV-2 (Study ESPERANZA/HOPE). Iraldo B, Hernandez-Bernal F, Nodarse-Cuni H, et al. Research Square; 2020. DOI: 10.21203/rs.3.rs-28958/v2
Background: As the outbreak of COVID-19 has accelerated, an urgent need for finding strategies to combat the virus is growing. Results from in vitro studies suggest that a combination of IFN type I and Type II may be effective against SARS-CoV. The aim of this study is to investigate the efficacy of treatment with a recombinant IFN alpha 2b and gamma, provided with standard protocol (Kaletra (lopinavir-ritonavir 200/50 mg; 200/100 mg every 12 hour for 30 days; Chloroquine (250 mg) every 12 hours for 10 days) for COVID-19 patients, compared to standard protocol (IFN alpha 2b/Kaletra/Chloroquine) for COVID-19 hospitalized patients, positive diagnosed for SARS-Cov-2. Methods: Hospitalized adult patients with qPCR confirmed SARS-Cov-2 will be enrolled in this open-labeled, single center, prospective, randomized and controlled clinical trial. One hundred and twenty eligible patients with confirmed SARS-CoV-2 positivity by qPCR amplification in oropharyngeal/nasopharyngeal swab samples will be enrolled at “Luis Diaz Soto” Hospital, Havana, Cuba. The primary outcomes are the time to 2019-nCoV RNA negativity in patients and the time until progression to severe COVID-19. Discussion: This will be the first randomized controlled trial of a potential treatment for SARC-Cov-2 using the combinations of IFNs. Trial registration: The study is sponsored by Center for Genetic and Biotechnology and Ministry of Health of Cuba and was duly registered April 2020 at http://registroclinico.sld.cu/en/trials/RPCEC00000307-En. Enrolment for this study began in April 11, 2020, and has enrolled one hundred patients as of May-26-2020.

Strategies in its Management and Updating of the Autoimmune-rheumatic Diseases in the SARSCoV-2 Pandemic and COVID-19 Cuban Rheumatology Society and its National Group. REYES LLERENA, Gil Alberto et al. Rev Cuba Reumatol [online]. 2020, vol.22, n.3
The outbreak of the infection by the new coronavirus SARSCoV-2, COVID-19, in December in Wuhan Province of China, has become a pandemic and health emergency given the deficiency of antiviral therapy for the acute respiratory syndrome that generates danger to life. The debut of the epidemic was in China, then the epicenter developed in Europe, northern Italy that suffered a severe blow. Worldwide, more than 10 million people are infected with the virus that has impacted on health systems until it practically collapsed, resulting in thousands of deaths. Today the epicenter of the pandemic has shifted to the Americas. Alarming figures highlight the United States of North America with some 2,737,600 infected and more than 128,471 deaths, followed by the South American giant Brazil with 1.3 million infections and 57,659 deaths. The Caribbean has a better setting. In Cuba, by the end of June, 2,340 cases of patients infected with deaths from COVID-19 were reported. We conducted a review, analysis and evaluation study of more than 150 articles from international journals, update bulletins of the WEB sites, health pages of the MINSAP of Cuba, and summaries selected for their methodological quality, and reviews, on the subject COVID-19 and autoimmune-rheumatic diseases by MEDLINE: database prepared by the National Library of Medicine of The USA contains bibliographic references and abstracts from more than 4,000 biomedical journals published in the United States and in 70 other countries, We also use Latin American and Caribbean Center for Information on Health Sciences: System, in Latin America and the Caribbean, since 1982. Our objective and results achieved have been to develop the theoretical-practical bases in an updated scientific document that allow access in an essential and summarized way to current knowledge about the infection by SACOV-2, COVID-19, and its repercussion and impact on patients suffering from rheumatic autoimmune diseases, and thus outline a coping and action strategy with recommendations for the Cuban rheumatologists in their health care work, and for patients as a guideline, given their well-founded concerns and fears given their underlying condition and the immunosuppressive drugs prescribed in an unfavorable context of a pandemic. The information is based on international experiences with the most published scientific evidence and those treasured national experiences in the face of similar situations of epidemics, faced by the vast health system and achievements of Cuban science.

Psychology, addictions and COVID-19: Lessons learned for recovery and coping with other critical situations Fabelo-Roche J, Iglesias-Moré S, Gómez-García A. Anales de la Academia de Ciencias de Cuba [revista en Internet]. 2020; 11(1):[aprox. 0 p.].
People with addictions are vulnerable to critical situations. During these events there are frequent setbacks and relapses that determine the restart or increase of drug use and addictive disorders. A narrative review of publications that address the impact of critical situations on these individuals was carried out. Articles, reports and other documents published between 2018 and 2020 were considered. The objectives were to characterize the impact of critical situations on people with addictive behaviors and describe the particularities of the recovery and preparation process to face new contingencies. Obstacles were specified for the successful coping with these circumstances based on individual and family problems and behavioral, cognitive and affective difficulties. The recovery process is complex and variable, but the inclusion of these topics and certain therapeutic resources in the psychological preparation of these people facilitates both recovery and coping with other critical situations.

Therapeutic effectiveness of Interferon-α2b Against COVID-19: The Cuban Experience. Pereda R, González D, Blas Rivero H, Rivero JC, Pérez A, López LR, et al. J Interferon Cytokine Res. 2020 Sep;40(9):438–42.

A prospective observational study was conducted for assessing the therapeutic efficacy of interferon (IFN)-α2b in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first month after the coronavirus disease 2019 (COVID-19) outbreak began in Cuba. From March 11th to April 14th, 814 patients were confirmed SARS-CoV-2 positive in Cuba. Seven hundred sixty-one (93.4%) were treated with a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular administration of IFN-α2b (Heberon®Alpha R, Center for Genetic Engineering and Biotechnology, Havana, Cuba), 3 times per week, for 2 weeks. Fifty-three patients received the approved COVID protocol without IFN treatment. The proportion of patients discharged from hospital (without clinical and radiological symptoms and nondetectable virus by real-time polymerase chain reaction) was higher in the IFN-treated compared with the non-IFN treated group (95.4% vs. 26.1%, P< 0.01). The case fatality rate (CFR) for all patients was 2.95%, and for those patients who received IFN-α2b the CFR was reduced to 0.92. Intensive care was required for 82 patients (10.1%), 42 (5.5%) had been treated with IFN. This report provides preliminary evidence for the therapeutic effectiveness of IFN-α2b for COVID-19 and suggests that the use of Heberon Alpha R may contribute to complete recovery of patients.

Therapeutic Effectiveness of Interferon Alpha 2b Treatment for COVID-19 Patient Recovery. Pereda R, González D, Blas Rivero H, Rivero JC, Pérez A, Del Rosario López L, et al. J Interferon Cytokine Res. 2020 Dec;40(12):578–88.

A previous report on 814 patients who were coronavirus disease 2019 (COVID-19) positive provided preliminary therapeutic efficacy evidence with interferon-α2b (IFN-α2b) in Cuba, from March 11 to April 14, 2020. This study re-evaluates the effectiveness of IFN-α2b during the period from March 11 to June 17, 2020. Patients received a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular or subcutaneous administration of IFN-α2b. The primary endpoint was the proportion of patients discharged from the hospital; the secondary endpoint was the case fatality rate, and several outcomes related to time variables were also evaluated. From March 11 to June 17, 2,295 patients had been confirmed to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive in Cuba, 2,165 were treated with Heberon® Alpha R, and 130 received the approved protocol without IFN. The proportion of fully recovered patients was higher in the IFN-treated compared with the non-IFN-treated group. Prior IFN treatment decreases the likelihood of intensive care and increases the survival after severe or critical diseases. Benefits of IFN were significantly supported by time variables analyzed. This second report confirmed our preliminary evidence about the therapeutic effectiveness of IFN-α2b in SARS-CoV-2 infection and postulated Heberon Alpha R as the main component within antiviral drugs used in the Cuban protocol COVID-19.

Underlying heart diseases and acute COVID-19 outcomes. Núñez-Gil IJJ, Fernández-Ortiz A, Maroud Eid C, huang J, Romero R, Becerra-Muñoz VM, et al. Cardiol J. 2020 Dec 21. DOI: 10.5603/CJ.a2020.0183. Online ahead of print.

Background The presence of any underlying heart condition could influence outcomes during the coronavirus disease 2019 (COVID-19). Methods The registry HOPE-COVID-19 (Health Outcome Predictive Evaluation for COVID-19, NCT04334291) is an international ambispective study, enrolling COVID-19 patients discharged from hospital, dead or alive. Results HOPE enrolled 2798 patients from 35 centers in 7 countries. Median age was 67 years (IQR: 53.0-78.0), and most were male (59.5%). A relevant heart disease was present in 682 (24%) cases. These were older, more frequently male, with higher overall burden of cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, smoking habit, obesity) and other comorbidities such renal failure, lung, cerebrovascular disease and oncologic antecedents (p < 0.01, for all). The heart cohort received more corticoids (28.9% vs. 20.4%, p < 0.001), antibiotics, but less hydroxychloroquine, antivirals or tocilizumab. Considering the epidemiologic profile, a previous heart condition was independently related with short-term mortality in the COX multivariate analysis (1.62; 95% CI 1.29-2.03; p < 0.001). Moreover, heart patients needed more respiratory, circulatory support, and presented more in-hospital events, such heart failure, renal failure, respiratory insufficiency, sepsis, SIRS and clinically relevant bleedings (all, p < 0.001), and mortality (39.7% vs. 15.5%; p < 0.001). Conclusions An underlying heart disease is an adverse prognostic factor for patients suffering COVID-19. Its presence could be related with different clinical drug management and would benefit from maintaining treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers during in-hospital stay. Trial Numbers: NCT04334291/ EUPAS34399.

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