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

From 1991 to 1993, an epidemic of optic and peripheral neuropathy—the largest of the century—broke out in Cuba, affecting more than 50,000 people. Initially the main clinical features were decreased visual acuity, central and cecocentral scotomas, impaired color vision and absence of the papillomacular bundle. Later, peripheral and mixed optic–peripheral forms began to appear. Due to the magnitude of the epidemic, the Cuban government requested help from the international community at the 46th World Health Assembly in 1993. PAHO and WHO immediately responded by sending a mission of international experts. Several hypotheses regarding the pathogenesis of Cuban epidemic neuropathy were put forward including: toxic, nutritional, genetic and infectious. The authors refer to extensive studies by researchers sponsored by the Cuban government and PAHO/WHO, joined by scientists from several other countries, including the USA. This paper describes their multidisciplinary work, particularly devoted to investigating the hypothesis of a primary toxic–nutritional cause of the epidemic. Clinical aspects, such as case definition and clinical description, were vital issues from the start. Cuban physicians who first examined patients received a clear impression of its toxic–nutritional origin, later confirmed by international experts. Research then focused on the mechanisms contributing to damage under the toxic–nutritional hypothesis. These included injuries to the mitochondrial oxidative phosphorylation pathway, nutritional deficiencies, excitotoxicity, formate toxicity and dysfunction of the blood–brain barrier. It was expected that the results of such international collaboration into this major health problem would also shed more light on mechanisms underlying other nutritional or tropical myeloneuropathies.

KEYWORDS Optic neuritis, optic neuropathy, peripheral neuropathy, neurotoxicity syndromes, disease outbreaks, international cooperation, Cuba

Erratum:
Page 30, first complete paragraph, line 7, “Two models were developed independently by Cuban researchers” should read “Two models were developed independently by AAS and AGQ.”

La hipertensión arterial es la enfermedad no trasmisible con mayor prevalencia en el mundo, reconocida desde hace mucho tiempo como el principal factor de riesgo para las enfermedades cardiovasculares
y cerebrovasculares. La elevada presión sanguínea tiene consecuencias negativas en los principales órganos diana (corazón, riñón y cerebro) y en varios estudios se ha visto que es más frecuente el daño al cerebro que al corazón y al riñón. Las lesiones silentes pueden conducir subsecuentemente a la declinación cognitiva, la demencia o el ictus.
No obstante, raramente se realiza una pesquisa para el deterioro subclínico del cerebro ya que las escasas y costosas técnicas de imagenología requeridas no permiten su uso habitual por los médicos en el nivel primario de atención de salud. En consecuencia, el desafío consiste en la detección temprana de lesiones cerebrales asintomáticas con técnicas rentables que permita estudiar a miles de pacientes en la comunidad. En esta revisión presentamos una actualización del estado de biomarcadores investigados como alternativa para la detección temprana del daño cerebral en la hipertensión arterial, potencialmente útiles para identifi car a los pacientes que necesiten ser estudiados mediante una RMN cerebral: monitoreo ambulatorio de la presión arterial, evaluación cuantitativa microvascular de la retina, electroencefalografía cuantitativa, ultrasonografía carotidea, estudios neurocognitivos y biomarcadores sanguíneos. Se hace especial énfasis en los biomarcadores sanguíneos ya que nuestro grupo publicó la primera demostración preliminar de una asociación entre la enolasa sérica neuroespecífi ca y la gravedad de las lesiones de la sustancia blanca en pacientes con hipertensión esencial. En consecuencia, esta revisión examina el potencial de los biomarcadores sanguíneos como vía para una detección temprana más rápida, económica y accesible, lo cual es particularmente benefi cioso en lugares con recursos limitados como es el caso de Cuba.
PALABRAS CLAVE Hipertensión arterial, enfermedad de los vasos pequeños, daño cerebral, biomarcadores, enfermedades de la sustancia blanca, leucoaraiosis, infarto lacunar, subunidad beta de la proteína S100 enlazadora de calcio, proteína S100B, proteína S100 enlazadora de calcio G, enolasa neuroespecífica, receptores NMDA, receptores, N-metil-D-aspartato, pesquisa masiva, Cuba

Arterial hypertension is the most prevalent non-communicable disease worldwide, and has long been recognized as a major risk factor for cardiovascular and cerebrovascular diseases. High blood pressure has deleterious consequences on the main target organs (heart, kidney, brain), and several studies have shown that brain damage is more frequent than heart and kidney involvement. Silent lesions can subsequently lead to cognitive decline, dementia or stroke.

Nevertheless, screening for subclinical brain deterioration is rarely performed because it requires imaging techniques whose scarcity and high cost rule out routine use by primary care physicians. The challenge is thus early detection of asymptomatic brain lesions with cost-effective techniques to test thousands of patients in the community. In this review we present an update on the status of biomarkers explored as alternatives for early detection of brain damage in arterial hypertension, potentially useful to identify patients needing referrals for brain MRI: ambulatory blood pressure monitoring, quantitative retinal microvascular assessment, quantitative electroencephalography, carotid ultrasonography, neurocognitive studies and blood-based biomarkers. We place special emphasis on blood-based biomarkers, for which our group reported the first preliminary evidence of an association between serum neuron-specific enolase and severity of white matter lesions in patients with essential hypertension. This review consequently explores the potential for blood-based biomarkers to provide a faster, cheaper and more accessible early-detection solution, particularly beneficial in resource-limited settings such as Cuba’s.

KEYWORDS Arterial hypertension,small vessel disease, brain damage, biomarkers, white matter diseases, leukoaraiosis, lacunar infarct, S100 calcium binding protein beta subunit, S100B protein, S100 calcium binding protein G, neuron specific enolase, NMDA receptors, receptors, N-methyl-D-aspartate, mass screening, Cuba

Introduction Many studies to date on the link between blood lipid levels and cerebrovascular disease have been hampered by conceptual and methodological limitations, especially failure to separate different types of stroke.

Objective Determine the relationship between serum lipid levels and the occurrence of different types of stroke.

Methods Two case and control studies were undertaken. The first consisted of three groups: subjects with cerebral infarction (CI), subjects with cerebral hemorrhage (CH) and a control group of healthy individuals with no history of cerebrovascular disease. The second study included three groups: those with atheromatous CI, those with CI of other etiology, and the healthy control group. The influence of variables such as age, sex, and presence of risk factors was also assessed.

Results CI patients were found to have higher total cholesterol levels (p<0.01), low-density lipoprotein (LDL) cholesterol (p<0.01), and triglycerides (p<0.01) than those in the control group. CH patients had lower total cholesterol levels (p<0.05), and higher triglycerides levels (p<0.05) than the control group. The second study revealed a link between blood lipid levels and CI only in cases of atheromatous stroke. This association was prevalent in women, and was independent of other risk factors.

Conclusions The type of stroke (ischemic or hemorrhagic) and the etiopathogenic subtype of CI must be considered when studying association between blood lipids and occurrence of stroke. Elevated levels of total cholesterol, LDL and triglycerides are associated with occurrence of atheromatous CI, while low total cholesterol levels and high triglycerides levels are associated with the CH occurrence.

Keywords cholesterol, HDL, LDL, triglycerides, cerebral hemorrhage, cerebral infarction, atherosclerosis, vascular diseases, cerebrovascular disorders, stroke, cerebrovascular accident, CVA, ischemia, hyperlipidemias

The following erratum has been corrected in all versions of this article.

Page 28, full paragraph 8, second sentence should read: “Serum was stored at -20ºC for no longer than 20 days.”