The page that follows in the pandemic: why the future of the fight against COVID-19 is the fourth dose

After more than a month of declining cases globally, new COVID-19 infections began to increase worldwide last week. With strong blockades in Asia and exponential increases in Europe, for the World Health Organization (WHO) the cause is “a combination of factors, including the highly transmissible Omicron variant and the BA.2 subvariant, coupled with the lifting of social and public health measures”.

In this context, and in view of the start of the winter season in the southern hemisphere, the pharmaceutical companies Pfizer/Biontech and Moderna have already requested the US FDA to authorize the emergency use of a fourth dose of their mRNA vaccine against COVID-19 (second booster or recall), in the face of a possible increase in cases and “to the possibility of another wave of the pandemic”.

In some countries, such as Spain, the application of a fourth dose of the COVID-19 vaccine was approved, but exclusively for people who are immunosuppressed and five months after receiving the last dose.

The debate was not long in coming, especially considering what is happening in Argentina where many people are still missing without taking the third dose. According to the Public Vaccination Monitor, 15,493,064 people have the booster dose in Argentina.

The prominent infectiologist Hugo Pizzi (M.N. 54.101) considered that the implementation of a fourth dose should be imminent. “There are several countries that are applying the fourth dose and there are two things to keep in mind: we are in a period of transition, where it is necessary to continue with care and we are going to enter a climate that is not favorable for respiratory diseases,” he explained.

In Argentina, “the only people who would receive a fourth dose are those who, by indication, received an additional dose in November or December”, as the Undersecretary for Health Strategies of the Ministry of Health of the Nation, who was responsible for the national health plan, told Infobae last week. vaccination, Juan Manuel Castelli.

These are people who are immunocompromised, either due to illness or who are undergoing immunosuppressive treatment. In addition, after four months of the additional dose, people aged 50 years or older who had received a primary inactivated vaccine scheme, such as that developed by Sinopharm, will also receive a fourth dose in the country.

In addition, the national health portfolio last week enabled the fourth dose of COVID-19 vaccines for people who have received Sputnik V, and must travel to countries that do not accept, who may apply any of the inoculants authorized by WHO.

However, regarding the suitability or not of extending this second booster dose to the entire population, from the Spanish Vaccinology Association its co-founder, pediatrician, and vaccine expert, Dr. José Antonio Navarro Alonso, sees it “difficult” to answer this question because, as he said, “everything will depend on epidemiological and virological surveillance in the coming weeks”.

As he considered in an interview with Infosalus, “from the point of view of antibodies it seems that the peak of antibodies after the fourth dose is similar to those reached after the third dose, indicating that the maximum immunogenicity would be achieved after the third dose”.

Along the same lines, the president of the Spanish Society of Immunology (SEI), Marcos López, shared the need for the administration of a fourth dose against COVID-19, “only in very vulnerable subjects”, and expressed his favor of preferably using other types of vaccines if they are available, that is, to use in this case other vaccines that are not based on the SARS-CoV-2 protein S, on which current vaccines are based, and do so on others that affect other parts of the aforementioned coronavirus.

“It is true that a fourth dose may be useful in some very vulnerable subject, but we also have therapeutic tools such as antivirals or monoclonal antibodies,” he said.

When asked by Infobae, the infectiologist Eduardo López (MN 37586), to begin with, clarified that “the only data on fourth doses available correspond to the studies that Israel did with the Pfizer mRNA vaccine”. “In that country it was seen that it was useful to give a second booster dose (that is, four in total) because it caused them to fall is the number of cases,” said the specialist, for whom “compared to the Ómicron variant, three doses are inexorably required, with which to discuss the need for a fourth when in Argentina a large percentage of the population have not yet received the third is complex”.

According to the latest data available in the Public Vaccination Monitor, the online registry of the Ministry of Health that shows in real time the immunization operation throughout Argentina, of the 36,838,041 people who completed their scheme initial two-dose (it should be clarified that there are still 3,730,045 who did not receive the second dose) 18,520,752 received the third dose, and almost the same amount (18,317,289) received their second dose more than five months ago and is still without reinforcement.

“The fourth dose is a booster of the third, and what was seen in Israel is that the amount of antibodies does not increase much more, but the effectiveness of the vaccine does increase and people get sick less,” said López, who said that “some countries are giving a fourth dose in certain populations, such as immunosuppressed people, older than 70 years and health personnel”.

Along the same lines, the infectiologist and member of the Vaccine Commission of the Argentine Society of Infectious Diseases (Sadi) Francisco Nacinovich (75,823), added that “the application of a fourth dose is still a matter of debate”. “I think some populations would benefit, and in addition to those who were immunocompromised and those over 50 who received their initial regimens with Sinopharm, it seems to me that, considering how long they have been given the third dose, whether they have had COVID or not, a group that I would consider to give a fourth dose is people over 60 years of age and health personnel”, said the specialist to this medium, who emphasized that “he would not apply it in a generalized way to everyone”.

In the opinion of the professor of Immunology Africa González, and former president of the Spanish Society of Immunology, “a second dose of memory could be indicated for some elderly people, who live in nursing homes, or are immunosuppressed.” “For now it is too early to say, if as we have been seeing, the vaccine does not prevent infections, it would not make sense to give it to the general population because even people with three doses have become infected, and in this sense Israel also commented: it does not make sense to give it to everyone”, added the expert.

For epidemiologist Elena Vanessa Martínez, president of the Spanish Society of Epidemiology (SEE), the need to apply a second dose of recall could be indicated in vulnerable people. “It would be something to think about but always based on showing that these people are more infected because the protection of the vaccine has dropped over time. If it does not go down over time, it would not be necessary, but the experts should analyze it,” he insisted.

The Spanish professor of Immunology Alfredo Corell went further, and said that, in his opinion, “the third dose of the vaccine against COVID-19 would not have been necessary massively, and it was only necessary for people with low defenses due to different treatments”. “And therefore, with less reason, the fourth is necessary,” he said.

In this sense, his recommendation to extend it also to the general population is that before putting it “at least the level of antibodies in the blood” should be measured in each person, and if they have enough they are exempted from this fourth dose because, he considered, “a repeated injection of the same product in such a short time can in the long run be harmful and not beneficial”.

Turning to the Israel case, according to López, “what was seen is that if three doses are given, mild forms of the disease are probably not avoided, but hospitalization is, while with a fourth dose even mild cases are prevented.”

“The problem we have with all the vaccines available is that we need to know how long immunity lasts,” said the infectiologist. It is generally considered to last six to eight months, although some authors consider that cellular immunity is greater and lasts for at least one year.”

For him, in Argentina “we must prioritize that almost 50% who are missing the third dose”, since “although infections are decreasing, it is possible that there will be a regrowth in the face of winter”.

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