We discuss the suitability of innate immune stimulation in acute respiratory infection post-exposure prophylaxis. The induction of innate immunity can be used to reduce susceptibility to immune-evasive pathogens (coronavirus, influenza virus, respiratory syncytial virus and rhinovirus). After the emergence of multiple SARS-CoV-2 variants, scientists are debating whether new variants could affect vaccine efficacy and how antigens could be redesigned to compensate. In addition, there is insufficient vaccine production to cover universal demand, and equitable vaccine distribution is a global challenge. Given these factors, non-specific immune stimulators may be suitable for a quick first response in the case of a suspected or early respiratory infection. Our group completed several HeberNasvac studies in healthy volunteers and patients with respiratory infections, and is currently starting large clinical trials in patients with early SARS-CoV-2 infections. This nasal formulation of hepatitis B vaccine has demonstrated its capacity to stimulate innate immunity markers (TLR3, TLR7 and TLR8 in tonsils) at the virus’ entry site, in systemic compartments (HLA class II in monocytes and lymphocytes) and in the activation of dendritic cells, lymphocytes and other cell lines in vitro and ex vivo. In addition, research generated by the current pandemic may obtain results useful for treating other acute respiratory infections, which have long been main drivers of mortality among older adults and in early childhood.

KEYWORDS Immunity, innate; toll-like-receptors; SARS-CoV-2; COVID-19; respiratory tract infections; Cuba

The call came from Calixto García University Hospital: Alfredo shattered his leg in a head-on collision driving from Havana to the beach. After emergency surgery and several weeks of intensive physical rehabilitation, Alfredo is back on two feet. Messages flooded in, my phone vibrating off the table: Manolo and his son were being examined at […]

At the time of this writing, more than 10 million Cubans (nearly 90% of the country’s population), had received at least their first dose of Soberana 02 or Abdala, two of five vaccine candidates for SARS-CoV-2 developed and produced on the island. Late-phase clinical trial data revealed that Abdala is 92.28% effective after the full, […]

INTRODUCTION Improved recovery protocols were implemented in surgical specialties over the last decade, which decreased anesthetic and surgical stress and the incidence of perioperative complications. However, these recovery protocols were introduced more slowly for cardiac surgeries. The most frequent complications in cardiac surgery are related to patient clinical status and the characteristics of the surgical procedures involved, which are becoming more varied and complex every day. The first version of the enhanced recovery program for cardiac surgery was published in 2019, but its recommendations were based on only a few studies, and scant research has evaluated its implementation. Randomized and controlled clinical trials for these protocols are scarce, so research that summarizes the results of studies with other methodological designs are useful in demonstrating their benefits in cardiovascular surgery services in Cuba and in other limited-resource settings.

OBJECTIVE Estimate the effectiveness of improved recovery protocols in the perioperative evolution of patients undergoing cardiac surgery.

METHODS We performed a systematic review and meta-analysis according to the guidelines of manual 5.1.0 for reviews of the Cochrane library. We included observational and quasi-experimental studies published from January 2015 through May 2020 that compared enhanced recovery protocols with conventional treatments in patients older than 18 years, and used a quality score to evaluate them. We used the following sources: the Cochrane Library, PubMed, LILACS, SciELO, EBSCO, Google Scholar, Web of Science, Clinical Key, ResearchGate and HINARI. The following keywords were used for the database searches in English: ERAS, protocols and cardiac surgery, enhanced recovery after cardiac surgery, ERACS, clinical pathway recovery and cardiac surgery, perioperative care and cardiac surgery. We used the following search terms for databases in Spanish: protocolos de recuperación precoz and cirugía cardiaca, protocolos de recuperación mejorada and cirugía cardiaca, cuidados perioperatorios and cirugía cardiaca, programas de recuperación precoz and cirugía cardiovascular. Methodological quality of included investigations was evaluated using the surgical research methodology scale. Meta-analyses were performed for perioperative complications, intensive care unit and hospital stays, and hospital readmission within 30 days of surgery. We calculated effect sizes of the interventions and the corresponding 95% confidence intervals. We used mean differences and confidence intervals for continuous variables, and for qualitative variables we calculated relative risk (RR). Random effects analysis was used. Heterogeneity of the studies was assessed using the Q statistic and the I2 statistic.

RESULTS We selected 15 studies (a total of 5059 patients: study group, n = 1706; control group, n = 3353). The average quality score for the 15 articles included was 18.9 (out of a maximum of 36 according to the scale) and 66.6% had a score ≥18. With improved recovery protocols in cardiac surgery, the incidence of perioperative complications decreased (RR = 0.73; 95% CI 0.52–0.98) as did hospital readmission within 30 days after surgery (RR = 0.51; 95% CI 95% CI: 0.31–0.86). Differences in extubation time, hospital stay and length of stay in intensive care units were less marked, but always favored the group in which the enhanced protocols were implemented.

CONCLUSIONS Improved recovery protocols in cardiac surgery increase quality of care evidenced by reductions in perioperative complications and decreased incidence of hospital readmission in the month following surgery.

KEYWORDS Enhanced recovery after surgery, rehabilitation, perioperative care, thoracic surgery, cardiac surgical procedures, systematic review, meta-analysis, Cuba

INTRODUCTION Racotumomab is a therapeutic vaccine based on a monoclonal anti-idiotypic antibody developed by the Molecular Immunology Center in Havana, Cuba, that is registered in Cuba and Argentina for treatment of non-small cell lung cancer. It induces a specific humoral and cellular immune response against the N-glycolyl GM3 (NeuGcGM3) ganglioside present in tumor cells, thereby provoking the death of these cells.
OBJECTIVE Evaluate racotumomab vaccine use as switch maintenance and second-line therapy for patients with inoperable non-small cell lung cancer in routine clinical practice, outside the framework of clinical studies, and assess the overall survival, stage-specific survival and safety in these patients.
METHODS A descriptive, retrospective study was carried out in patients diagnosed with non-small cell lung cancer not suitable for surgical treatment, who received racotumomab as a part of switch maintenance or second-line treatments. Overall survival was defined from diagnosis and from the first immunization, until death.
RESULTS We included 71 patients treated with racotumomab, 57.7% (41/71) of whom were in stages IIIB and IV of non-small cell lung cancer. Of the patients, 84.5% (60/71) had no adverse events, and 15.5% (11/71) had mild adverse reactions. The median overall survival was 24.5 months, calculated from the first immunization, 17.2 months for those who received racotumomab as switch maintenance and 6.8 months for patients who had progressed after the first line of treatment.
CONCLUSIONS Racotumomab in routine clinical practice prolonged overall survival in patients with non-small cell lung cancer treated in switch maintenance, and in stage IV patients who received the treatment as second-line therapy. The vaccine was well tolerated.
KEY WORDS Racotumomab; carcinoma, non-small cell lung; lung neoplasms; Cuba

INTRODUCTION Anemia is a public health problem worldwide and is most prevalent in preschool children, for whom it is the most frequent cause of nutritional deficits. In turn, iron deficiency is the main cause of anemia, affecting 43% of children globally. Previous studies in Cuba show rates of iron deficiency in preschool children between 38.6% and 57.6%, higher in infants (71.2% to 81.1%). WHO recommends using serum ferritin as an indicator of iron deficiency accompanied by acute (C-reactive protein) and chronic (α1-acid glycoprotein) inflammation biomarkers.

OBJECTIVE Assess how inflammation affects measuring and reporting of iron-deficiency anemia rates in Cuban preschool children.

METHODS Data were obtained from serum samples contained in the National Anemia and Iron Deficiency Survey, and included presumably healthy preschool Cuban children (aged 6–59 months). Serum samples were collected from 1375 children from randomly selected provinces in 4 regions of the country from 2014 through 2018. We examined the association between ferritin and two inflammatory biomarkers: C-reactive protein and α1-acid glycoprotein. Individual inflammation-adjusted ferritin concentrations were calculated using four approaches: 1) a higher ferritin cut-off point (<30 g/L); 2) exclusion of subjects showing inflammation (C-reactive protein >5 mg/L or α1-acid glycoprotein >1 g/L); 3) mathematical correction factor based on C-reactive protein or α1-acid glycoprotein; and 4) correction by regression with the method proposed by the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia Group. We estimated confidence intervals of differences between unadjusted prevalence and prevalence adjusted for inflammation by each method.

RESULTS The proportion of children with inflammation according to C-reactive protein concentrations >5 mg/L was lower (11.1%, 153/1375) than the proportion measured according to the concentrations of α1-acid glycoprotein, at >1 g/L (30.8%, 424/1375). The percentage of children with high concentrations of at least one of the aforementioned biomarkers was 32.7% (450/1375). Thus, each correction method increased the observed prevalence of iron deficiency compared to unadjusted estimates (23%, 316/1375). This increase was more pronounced when using the internal regression correction method (based only on C-reactive protein) or the method based on a higher cut-off point. Adjustment using all four methods changed estimated iron deficiency prevalence, increasing it from 0.1% to 8.8%, compared to unadjusted values.

CONCLUSION One-third of preschool children had biomarkers indicating elevated inflammation levels. Without adjusting for inflammation, iron deficiency prevalence was underestimated. The significant disparity between unadjusted and inflammation-adjusted ferritin when using some approaches highlights the importance of selecting the right approach for accurate, corrected measurement. The internal regression correction approach is appropriate for epidemiological studies because it takes into account inflammation severity. However, other models should be explored that account for inflammation and also provide better adjusted ferritin concentrations.

KEYWORDS Anemia, iron deficiency; child, preschool; inflammation; Cuba

One of the most dreadful complications that can occur during the course of COVID-19 is the cytokine storm—also known as cytokine release syndrome—a form of systemic inflammatory response syndrome triggered by SARS-CoV-2 infection.

The cytokine storm is an activation cascade of auto-amplifying cytokines, which leads to excessive activation of immune cells and generation of pro-inflammatory cytokines. It occurs when large numbers of white blood cells are activated and release inflammatory cytokines, in turn activating even more white blood cells, finally resulting in an exaggerated pro-inflammatory–mediated response and ineffective anti-inflammatory control, leading to tissue damage, multiorgan failure, acute respiratory distress syndrome and death. Although cytokine storm pathogenesis is multifactorial, we hypothesize there is a close association between hypoxemia and cytokine storms in COVID-19, although it is difficult to establish the direction of this relationship. Most probably they coexist and, given enough time, one triggers the other in a chain reaction. Careful analysis of the day-to-day clinical evolution of COVID-19 indicates that there are short and slight periods of hypoxemia (confirmed by pulse oximetry and arterial gasometry), even on the day of the onset of persistent cough and/or shortness of breath.

We propose the use of continuous positive airway pressure in early stages of COVID-19, at the onset of respiratory symptoms. This non-invasive ventilation method may be useful in individualized treatments to prevent early hypoxemia in COVID-19 patients and thus avoid triggering a cytokine storm.

We believe such an approach is relevant everywhere, and in Cuba in particular, since the country has initiated national production of mechanical ventilation systems, including non-invasive ventilators. Moreover, as Cuba’s COVID-19 protocols ensure early patient admission to isolation centers or hospitals, clinicians can prescribe the early use of continuous positive airway pressure as soon as respiratory symptoms begin, averting early hypoxemia and its triggering effect on cytokine storm development, and consequently, avoiding acute respiratory distress syndrome, multi-organ failure, and death.

KEYWORDS COVID-19, SARS-CoV-2, cytokine release syndrome, respiratory distress syndrome, noninvasive ventilation, continuous positive airway pressure, Cuba

The results are in and deeply troubling: in the absence of rapid, comprehensive vaccination rollouts, SARS-CoV-2 runs amok, mutates into more contagious variants and, for the unvaccinated, kills at a breakneck pace. Witness the Delta variant that research suggests is more than twice as contagious as the original strain that ripped the world asunder in […]

INTRODUCTION Unlike most high-income countries where subtype B viruses predominate, the Cuban HIV-1 epidemic is characterized by a great diversity of subtypes and circulating recombinant forms. Some studies have shown that HIV variants exhibiting a preference for the CXCR4 co-receptor (X4-tropic) could have impacts on disease pathogenesis, with clinical implications for antiviral treatment plans. Determination of HIV co-receptor tropism is crucial for clinicians in deciding whether maraviroc is an appropriate antiviral.

OBJECTIVE Characterize V3 sequence variability and its relation to viral tropism across different subtypes circulating in Cuba and explore how this may affect treatment success with maraviroc.

METHODS We designed a cross-sectional study that included 72 plasma samples obtained at the Pedro Kourí Tropical Medicine Institute in Havana, Cuba. We sequenced the C2V3 env region and assessed subtype based both on env and pol sequences; tropism was predicted by Geno2pheno analysis. Additionally, 35 V3-loop Cuban sequences, obtained from a previous study, were incorporated into the analysis. Statistical associations among virological, clinical and epidemiological variables were assessed by a chi-square test.

RESULTS Tropism prediction for 72 variants revealed that CRF19_cpx was associated with dual-tropic R5X4 viruses (p = 0.034). Moreover, when 35 sequences from a former study were added, the association was significant not only for R5X4 (p = 0.019) but also for X4-tropic variants (p = 0.044). Alignment of 107 V3-loop sequences showed wide diversity among the different HIV-1 subtypes circulating in Cuba.

CONCLUSIONS In accordance with G2P, CRF19_cpx is a genetic variant with a high proportion of X4 and R5X4-tropic viruses. The results from the present study suggest that the Cuban recombinant could be a more pathogenic variant and that maraviroc may not be suitable for patients infected with CRF19_cpx.

KEYWORDS HIV, CCR5 receptor antagonists, maraviroc, HIV envelope glycoprotein gp120, Cuba

INTRODUCTION One year after WHO declared COVID-19 a pandemic, we found it useful to carry out a diagnosis of the situation in Latin America.

OBJECTIVES Examine the prevailing epidemiological panorama in mid-March 2021 in 16 countries in Latin America and the performance, over time, in the two countries with the best responses to their respective epidemics.

METHODS Using morbidity and mortality data, we compared the relative performance of each country under review and identified the two countries with the most successful responses to the pandemic. We used five indicators to analyze the course of each country’s performance during the pandemic throughout 2020: prevalence of active cases per million population; cumulative incidence rate in 7 days per 100,000 population; positivity rate over a 7-day period; percentage of recovered patients and crude mortality rate per 1,000,000 population.

RESULTS According to the performance indicators, Cuba was ranked highest, followed by Uruguay. Although figures remained within acceptable margins, both nations experienced notable setbacks in the first weeks of 2021, especially sharp in Uruguay.

CONCLUSIONS Any characterization of the situation is condemned to be short-lived due to the emergence of mutational variants; however, this analysis identified favorable sociodemographic characteristics in both nations, and in their health systems, which may offer possible explanations for the results we obtained.

KEYWORDS COVID-19, infodemic, Latin America, Uruguay, Cuba

Autoimmune diseases are not always recognized as urgent health issues, despite a worldwide prevalence of 4%–5%. Most estimates come from high-income countries, as low- and middle-income countries face more issues of under-reporting. Despite this and the lack of recognition under current reporting practices, the role these diseases play in mortality must be acknowledged. In particular, considering multiple causes of death as opposed to a single cause of death results in a 1.5–4.2-fold increase in deaths classified as relating to autoimmune diseases, evidence of their share in overall mortality burden, a factor important for patient care and healthcare policy decision making. However, formulating such policies and programs for timely, appropriate diagnoses and care is stymied in low- and middle-income countries by the shortage of methodologically sound studies on mor tality from systemic autoimmune diseases. This limitation exacerbates inequalities and health gaps among patients in different countries and localities. Multiple cause-of-death methodology has been validated for research on other diseases and demonstrates the mortality burden of these illnesses in countries where traditional methodological approaches, primarily based on prospective cohort studies, are not feasible. Studying mortality from systemic autoimmune diseases by analyzing multiple causes of death with data from national mortality registries is a low-cost alternative to traditional mortality analysis. The objective of this paper is to demonstrate and defend the usefulness of this approach to estimate mortality burden.

KEYWORDS Autoimmune diseases, mortality, cause of death, Cuba

Cuba has five COVID-19 vaccines in clinical trials and is on track to receive emergency use authorization from the country’s regulatory agency to begin mass vaccination with two of those candidates: Abdala and SOBERANA 02. Results from phase 1 and 2 trials of these vaccines, the first developed and produced in Latin America, have been […]