Even though the epidemiological indicator has turned green in several entities of the country and there is an intense social activity, cultural and sports activities have resumed, and partially academic activities, it is essential to maintain the sanitary measures to continue with low transmission and minimum risk, warned Samuel Ponce de León Rosales, coordinator of the University Program for Health Research (PUIS) of the UNAM and head of the University Commission for the Attention of the Coronavirus Emergency.

"It is necessary to get vaccinated, use a mouth cover, wash hands, keep social distance and avoid family and social gatherings, as the pandemic continues," he warned.

Ponce de Leon warned: "the scenario for the following weeks, and hopefully, at least two or three months is that the transmission decreased drastically, but the message is that we are not returning to a situation where this is over, by no means. We have to maintain precautions, maintain care, there are still people who get infected, but the scenario is much better because we have a very high number of patients who have been naturally immunized: they got sick, survived, and have defenses".

During the program "Hipócrates 2.0", of Radio UNAM, hosted by Mauricio Rodríguez Álvarez, academic of the Faculty of Medicine (FM), he considered that it is likely that we are close to 100 million people who could have been infected naturally; additionally, more than 110 million doses have been applied in the country, with almost 60 million people with two reagents.

"The sum of these numbers gives a high number of the population that has defenses, and where the disease is not going to manifest itself so seriously and the possibilities of viral replication decrease significantly," he said. Although it depends on several circumstances whether the epidemiological traffic light stays green, Ponce de León emphasized what must be done to keep us safe: what we can control is the transmission, which is avoided by the use of masks, distance, vaccination, and avoiding meetings.

The specialist emphasized that "the government has carried out a good vaccination campaign, well-coordinated and with good results. At some point we are going to have to have boosters, although we do not know when". The third dose, which has been applied in countries such as the United States, Colombia, and Uruguay, is influenced by the expiration of the vaccines and the freezing they require, but this is a scenario that has not been discussed in Mexico, he pointed out.

In turn, Mauricio Rodriguez Alvarez emphasized that not getting vaccinated puts others at risk, which is why this decision requires a social commitment that has been well accepted in our country. Both physicians agreed that medical personnel and public workers such as policemen, firemen, and other support personnel should be inoculated as a matter of obligation.

Latest Mexican COVID-19 Epidemic Risk Semaphore

Last Friday, the Ministry of Health announced that during the next two weeks, 20 Mexican states, including Mexico City and the State of Mexico, will be in green on the Covid-19 epidemiological traffic light. Eleven states will be in yellow, while Baja California will be the only state in orange.

COVID-19 semaphore in Mexico.
Epidemic Risk Semaphore from October 18 to 31 by the state. Red indicates maximum risk, orange - high, yellow - medium, and green means a low-risk area. Image: SSA

What are the recommendations according to the stoplight?

According to information from the Ministry of Health, unlike the first two epidemic waves in the country, the growth relationship of the curves of cases, hospitalizations, and deaths was modified and the speed of growth of the curves is different. In the new semaphore estimation, the ranges of each risk level were reassigned, so that now the total score is "homogeneously distributed".

Half of the score covers the lower risk levels (low and moderate) and the other half covers the higher risk levels (high and extreme). Thus, together with the changes in the cut-off points of the indicators, it is expected that, under conditions of potentially endemic viral activity, the entities will transit between low and moderate risk levels most of the time, and that moving to the high and maximum epidemic risk levels will be understood as a true health alert.


Epidemiological and Clinical Impact of COVID-19

In December 2019, a series of cases of pneumonia of unknown cause emerged in Wuhan, Hubei, China, with clinical presentations closely resembling viral pneumonia. On January 7, 2020, the etiologic agent responsible for this picture was identified as a new betacoronavirus (SARS-CoV-2), distinct from SARS-CoV (2003) and MERS-CoV (2012), the disease is referred to as COVID-19; undoubtedly this new virus is the first pandemic of the 21st century that has come to permanently alter and transform the daily, economic, political and social life of the world. The disease spread to the countries of the region: Thailand, Hong Kong, South Korea, Japan and later to Iran, Italy, Spain, and the rest of Europe; in America, it appeared initially in the state of Washington and with greater intensity in New York and the rest of the American Union.

The virus

Coronaviruses are enveloped viruses with a positive polarity RNA genome belonging to the coronaviridae family and the order Nidovirales. These viruses are widely distributed in humans and other mammals. SARS-CoV-2 has a genome of about 30,000 nucleotides and consists of four genes for the characteristic structural proteins of coronaviruses that are designated by the letters S (glycoprotein homotrimer whose distal widening of its folds forms the tips of the surface), E (small envelope protein), M (matrix protein linking the envelope to the viral core) and N (nucleocapsid phosphoprotein), in addition to ORFs (open reading frames), which encode nonstructural proteins, including enzymes that appear during its intrahospital reproductive cycle. The size of SARS-CoV-2 virions is approximately 50-200 nm in diameter. The complete genomic sequence of this new agent is available and different qualitative and quantitative detection protocols have been developed to understand the pathophysiology of the disease.

Although most human infections are mild, epidemics of the two beta coronaviruses, severe acute respiratory syndrome (SARS-CoV) and the Middle East respiratory syndrome (MERS-CoV), caused more than 10,000 cumulative cases in the past two decades, with the lethality of 10% for SARS-CoV and 37% for MERS-CoV. The coronaviruses that have been identified to date may represent only the tip of the iceberg, with potential new and severe zoonotic events yet to occur.

Pathophysiology

The immune response with which the human being defends himself is both humoral, forming antibodies, and cellular, mediated by lymphocytes. In patients with advanced disease with respiratory failure and multiple organ failure, it has been found that they are suffering from a cytosine storm, and in fact, some treatments in these advanced cases are based on using monoclonal antibodies against cytosines.

Diagnostics

Diagnostic methods are mainly molecular: PCR (polymerase Chain Reaction), which detects the genes of the virus E gene for screening and RdRp gene for confirmation, which is not only specific, it is also very sensitive if the sample is taken properly, and methods based on the detection of IgG (past infection) and IgM (active infection) antibodies, These are marketed as rapid tests, because of the duration of the procedure, but it does not mean an immediate diagnosis, since they will be positive until after a week after the onset of symptoms, which makes them insensitive, giving false negatives if taken in the first days of symptoms.

Clinical Presentation

From the clinical point of view, in the beginning, only respiratory symptoms, fever, and general malaise were mentioned, and it was erroneously thought that 1% were asymptomatic, when in fact 35 to 40% of people have no symptoms and these help the spread of the virus by not being detected if the corresponding studies are not carried out. Fortunately, in 80% of those who present symptoms, the disease is self-limiting, but 15% require hospitalization and 5 to 6% require intensive care units for mechanical ventilation and comprehensive management of critically ill patients.

The clinical spectrum also includes alterations in the nervous system, such as cerebral and heart infarcts, producing carditis and arrhythmias; in the skin, vesicular lesions in the extremities; in the kidneys, 15% of hospitalized patients develop kidney failure and in a fraction of these the damage is permanent, requiring hemodialysis; there is also loss of smell, disseminated intravascular coagulation and a whole clinical spectrum yet to be defined. In the pediatric population, which until recently was considered immune or with little impact, a syndrome similar to Kawasaki disease is now recognized, which is severe and requires hospitalization and has even caused some deaths.

Treatment

The treatment consists not only of an antiviral drug, but also of integral management of each case since it is necessary to hydrate with serum and electrolytes, medication with vasopressors for those with low blood pressure, anticoagulants, and mechanical ventilatory assistance for the subgroup that can no longer breathe on their own, that is why even if there is no effective antiviral, patients can survive if they receive adequate care, and the earlier the patient goes to the hospital, the better their prognosis. So far there is no effective and safe antiviral treatment.

One of the most promising, according to recently published studies, is remdesivir, and one of the most used initially, which studies have shown to be not only ineffective but also dangerous, due to side effects, is hydroxychloroquine, with or without azithromycin, therefore it is not recommended. The use of plasma from people who have overcome the disease has also been tried; the first studies did not show a decrease in mortality, apparently because it was administered in very advanced stages, but now attempts are being made to administer it in earlier stages.

Prevention

Among the measures that have proven to be effective in controlling the spread of the virus is social distancing, in which people are asked to stay at home so that the virus does not find susceptible people and does not massively saturate hospitals, as has already occurred in Italy, Spain and New York; also effective is the use of protective masks, frequent hand washing and avoiding sneezing or coughing in front of other people.

However, for social distancing to be effective, it must be implemented early, as its effectiveness diminishes considerably if it is deferred for one or two weeks. Unfortunately, what has been achieved is threatened by an early opening of isolation due to economic and political pressures, without taking adequate precautions such as having sufficient tests and personnel for contact tracing with the possibility of having outbreaks that would force new, stricter isolation, which would result in greater economic and social damage.

SARS-CoV-2 Vaccines

The purpose of a vaccine is to "train" a person's immune system to generate a response to fight the virus and prevent disease. All vaccines aim to expose the body to an antigen that will not cause disease but will elicit an immune response that can block or kill the virus if a person becomes infected. Conventional approaches used to do this usually focus on the use of live attenuated viruses or inactivated or fragmented viruses. At least eight types are being tested against coronavirus, which is based on different viruses or viral parts. Although multiple candidate vaccines are still in different stages of development.

Vaccine mRNA-1273-Moderna Therapeutics (United States): this vaccine involves molecular biology strategies. It is based on a messenger RNA that will produce an antibody response against the surface protein (S).

Vaccine INO-4800-Inovio Pharmaceuticals (United States): involves a design of direct injection of DNA through a plasmid (a small genetic structure) so that the patient's cells produce antibodies to fight infection.

AD5-nCoV vaccine-CanSino Biologics (China): This vaccine uses a non-replicating version of adenovirus as a vector. It carries the S protein gene (spike) from the surface of the coronavirus, which is intended to elicit the immune response to fight infection.

LV-SMENP-DC vaccine from the Geno-Immune Medical Institute in Shenzhen (China): an approach focused on the use of dendritic cells modified with lentiviral vectors.

Inactivated virus vaccine (China): this type of vaccine requires producing virus particles in reactors and then purifying them so that they lose their ability to cause disease. It uses common classical technology and is the most experienced production platform in vaccine production.

ChAdOx1 vaccine (United Kingdom): recombinant vaccine using as a vector an attenuated version of a chimpanzee adenovirus that has been modified so that it does not reproduce in humans.

Conclusion

We are facing a new highly transmissible virus, with a negative impact on social, economic, and educational aspects, as well as on the daily lives of people to a greater or lesser extent in different countries. Thousands of priceless lives have been lost, and although it is not yet under control, there are thousands of health workers attending the population with great intensity in this crisis. The scientific community is providing therapeutic options while searching for an effective vaccine; however, its control requires the collaboration of society in maintaining the social distance; for, without this participation, we will lose what has been gained through the efforts of thousands of people.

Sources: daily and weekly updates from Hugo Lopez-Gatell, Mexican Undersecretary of Prevention and Health Promotion, Ciencia UANL (102), by Javier Ramos Jiménez and Ana María Rivas Estilla