Cuban science in context of Covid-19

Dr Julio Cesar Aguilar Rubido, Dr Gerardo Enrique Guillen Nieto, Eduardo Pentón Árias, Dr Mamun Al Mahtab and Dr Sheikh Mohammad Fazle Akbar

The Cuban science in the context of COVID-19 has generated an important experience that need to be shared with developing countries. This article is an insight in the application of science in the fight against SARS-CoV-2.

Between May 15 and 21, Cuba had completed a week without regretting the death of any person due to SARS-CoV-2. Today's 4.2% case fatality rate is below the average for the Americas region (5.9%) and reported worldwide (6.6%). Of 1916 cases diagnosed to this day since the epidemic began, 85% of the patients have already recovered.

A brief approach to the use of science in Cuba reveals a group of elements that explain the mentioned results. Treatments begin in isolation centers -where contacts of positive cases are hosted- even prior to knowing their final diagnosis. 

From this early stage several treatments are administered to stimulate innate immune system of symptomatic and even asymptomatic persons. These treatments are reinforced with psychological attention, blood pressure and blood sugar checkups. If SARS CoV-2 penetrates the body, a strong immune response is the ideal scenario for the patient.

The Cuban strategy has not implied mandatory confinement for the entire population at any time. Instead, potential carriers are removed from circulation, this is a distinctive element can be verified with respect to many other countries. Entire neighborhoods have been temporarily isolated, for a total of 44 at present; however, this has been associated with the detection of local transmission of the virus.

Thousands of medical students have taken to the streets to look door-to-door for the virus. The direct detection of people with symptoms of respiratory disease is supplemented with a program for automatic self-examination developed by local scientists and programmers. 

This application allows a quick connection between patients with respiratory symptoms and the health system just by completing an online form. These patients are hosted in specialized centers where they begin treatment, free of charge and with all the guaranteed material conditions. 

Not all countries have isolation centers. Some countries leave suspects and contacts of confirmed cases in their homes. Mandatory isolation in centers on the outskirts of cities was applied to repatriated travelers on flights arriving in Cuba since the borders were closed.

As a developing country, a large number of persons crowd outside stores due to shortages. Presumably, in many developing countries the patients and their contacts will have to go out and earn a living on the streets and seek their own food, increasing the risk of transmission. A strong state is needed to take care of patients and contacts adequately.

Like many other countries, Cuba is also investigating a vaccine against SARS-CoV-2 with several vaccine approaches. One of the early developing vaccines is known by the code CIGB2020. This is a recently patented product generated by the Center for Genetic Engineering and Biotechnology in collaboration with researchers from Germany, Japan and Bangladesh. 

This product stimulates the immune system in a non-specific way. The expression of viral RNA receptors known as toll-like receptors (TLR3, TLR7and TLR8) is stimulated by CIGB2020. CIGB2020 has shown an increase in nonspecific antiviral properties as a result of in vitro pharmacology studies as well as after in vivo treatment of patients. 

In addition, innate immunity training pursues to ensure that this effect persists over time. This type of compound can induce a shorter immunological memory compared to adaptive vaccines, -up to 1 year. However, said period of time may be able to cover the gap until the appearance of a preventive vaccine based on specific antigens. 

Cuban and foreign scientists work to obtain the sanitary registration of a product of this nature and subsequent preventive and specific vaccines.

Since the SARS-CoV-2 was first detected in Cuba, clinical management has evolved to reach 20 drugs, most produced in Cuba. According to Dr. Durán, national director of epidemiology, the medical focus of the Cuban strategy has been on prevention, with "measures to improve innate immunity." This was done despite the blockade that prevents the arrival of drugs and raw materials for the production of medicine. Unfortunately this measure has not been relaxed even under pandemic time.

Among the first treatments indicated to Cuban patients is the Recombinant Interferon Alpha 2B, which is produced in Cuba, -a new anniversary of its first production in the 80’s of the last century is celebrated this May 28th. This product is administered three times a week intramuscularly, both to confirmed patients and symptomatic patients. 

In this way it is possible to reinforce the evolution of the disease towards a satisfactory outcome. More recently, an interferon-based nasal product was developed and started to be supplied as nasal drops to medical workers in Cuba and abroad, in order to reinforce their immune system when working in difficult areas from different countries.

The Cuban meningococcal vaccine is also used to boost the immune system in people from quarantined communities. Another preventive medicine that is being administered to the population at risk is Biomodulin-T, defined as a natural biological immune-modulator used in Cuba to treat patients with immune dysfunction. 

Specifically, it is used in people with gradual deterioration of the immune system caused by aging. This drug has been used to treat recurrent respiratory infections in Cuban elderly for more than two decades.

People in isolation centers are provided -in addition to Interferon- Oseltamivir, azithromycin and plasma from recovered patients who donate their plasma on a voluntary basis. 

Confirmed patients also receive Kaletra and chloroquine, and in serious and critical cases patients also receive Erythropoietin, Surfacen (a product of animal origin created in Cuba and used in the treatment of acute respiratory distress) and CIGB-258, another product of the CIGB under investigation as a treatment for rheumatoid arthritis, and it constitutes one of the most promising for treating the severe and severe patient of COVID-19.

The CIGB-258 peptide was designed to activate the mechanisms that control and reduce inflammatory processes; it has shown a 78.2% recovery in critically ill patients and 92% in critically ill patients. These are encouraging data taking into account the low survival of critically ill patients, which is 30% worldwide.

Another drug developed in Cuba, the humanized monoclonal antibody Itolizumab, is also used to stop the so-called "cytokine storm", an uncontrolled reaction of the immune system that can have fatal consequences. Itolizumab is commonly used to treat other conditions such as psoriasis and rheumatoid arthritis and has been used in 70 patients at nine hospitals with a high risk of aggravation.

The sum of critical and serious cases barely reached thirty beds in April, when the peak of the pandemic was detected on the island. Mathematicians, also appointed for studying the stages of the pandemic on the island, consider that the Cuban Health System managed to control the epidemic, did not collapse and is on the way to eradicating the SARS-CoV-2 in few weeks. A group of predictive models have been developed that confirm that the country will remain in a favorable scenario.

Given the exacerbated selfishness that has existed in the management of resources by the most developed countries, the management of this infection throughout the line at home has allowed Cuba to assist dozens of countries in need with their doctors and nurses, as did the more than one hundred health workers who attended Italy at the height of the epidemic in Italy and who are already returning home while writing these lines. 

We consider it is important to study the example and experiences from Cuba, especially developing countries, and to assimilate dialectically every aspect that allows saving lives and resources. 

South-South collaboration is desirable also in front of the present situation. In the joint development of clinical studies of many of these drugs developed in Cuba as well as the implementation of the above mentioned treatments may impact in saving lives.

Dr. Julio Cesar Aguilar Rubido, Dr. Gerardo Enrique Guillen Nieto and Eduardo Pentón Árias work at Centre for Genetic Engineering and Biotechnology, Cuba. 

Dr. Mamun Al Mahtab works at Bangabandhu Sheikh Mujib Medical University, Bangladesh and Dr Sheikh Mohammad Fazle Akbar works at Ehime University, Japan