Position Statement No. 22: A third dose – is the third time indeed the charm?

“There is no doubt that over time humanity will win the battle against SARS-CoV-2, but we must all do our best to do so at the lowest possible cost. Therefore, we should protect the lives of seniors by offering them third doses of the vaccine,” scientists from the interdisciplinary COVID-19 Advisory Team to the PAS President write in their newest position statement.

The virus and its variants

The SARS-CoV-2 pandemic has been with us for nearly two years now. Over this time, it has had several unexpected turning points. Even the initial phase of the epidemic appeared frightening to us and took a deadly toll in many countries. However, the virus keeps mutating. In the winter of 2020–2021, the world faced a pandemic wave caused by the Alpha variant. In the late spring and early summer, however, a new and more contagious variant (B1.617.2, called Delta) became responsible for nearly 100% of cases. In 2020, an infected person transmitted the virus to an average of 2–4 people; a person infected with the Delta variant infects 4–8 people. For this reason, a much higher threshold of herd immunity is required to extinguish the disease, namely 80–90% (up from 60–70%) of the population with immunity acquired after receiving a vaccine or after recovering from a previous infection. A similar phenomenon of increased transmissibility was witnessed during the Spanish flu pandemic back in 1918.

It is now well documented that virus pathogenicity and the immune response to an infection largely depend on the patient’s age. We may be witnessing the birth of a new member in the category of “infectious diseases associated with childhood,” one that is highly contagious, but a primary infection in children or adolescents is typically associated with a relatively mild course.


As the pandemic was taking its toll, scientists were able to develop innovative, highly effective, and safe vaccines against COVID-19. However, the premature hopes that vaccinations would provide full, long-term protection against SARS-CoV-2 infections have not been borne out. As with other respiratory pathogens (tuberculosis, influenza, pertussis) COVID-19 vaccines are effective in preventing the development of a severe form of the disease, hospitalization, and death, but they do not offer full protection against mild or asymptomatic “breakthrough” infections.

When exposed to the Delta variant of SARS-CoV-2, individuals over the age of 18 who have received two doses according to the basic vaccination schedule are five times less likely to become infected with SARS-CoV-2 (and to later transmit it to others) and, on average, more than 10 times less likely to become severely ill and die due to COVID-19. This protection is particularly visible in individuals under the age of 65.

Unfortunately, it has also been observed that the protection offered by vaccines wanes over time. After only a few months, we can notice a drop in antibody levels in the blood and more frequent infections. Although protection against severe illness and death remains very good in younger people, it drops in older people, and severe cases of the disease become increasingly frequent. These observations became a point of departure for research into the efficacy and safety of a third dose of the vaccine. An analysis conducted in Israel showed that people over the age of 60 who received their third doses of the vaccine were 11 times less likely to become infected with SARS-CoV-2, and the risk of severe disease and hospitalization was almost 20 times lower compared to patients who received only two doses more than six months earlier. Adverse vaccine reactions did not differ significantly from those observed after the first two doses. This makes a strong case for offering seniors booster doses. This will not protect them completely from a mild infection, but it will restore protection against severe disease.

Administering third doses to immunocompromised patients is a somewhat different issue. Studies show that such individuals do not develop a complete response after the classical vaccination regimen. Such patients require a stronger stimulation of the immune system to achieve comparable antibody levels, so it is recommended that they receive their third doses after only a few weeks. This differs from the administration of third doses as booster doses more than six months after the primary vaccination.

Current knowledge about combining of different vaccines remains limited, but available information suggests that the type of the vaccine used as a booster dose has no significant effect on the efficacy and safety of the third dose.

Prospects for the future

The most likely scenario envisages further waves of infections and deaths. With the highly contagious Delta variant, the number of infections could be as high in the fall of 2021 as it was a year previously. Thanks to vaccines, however, some of these infections will be milder and less likely to result in death. This should translate into less strain on the healthcare system. However, the vaccination rates among the highest-risk groups remain poor, so it is hard to expect the coming winter to be peaceful. For this reason, we should encourage our relatives and friends and those under our care who are in high-risk groups to take third doses. Further (ever milder) infection waves will probably continue until almost all those who have not been vaccinated gain immunity after recovering from the disease.

In the long term, however, the immunity gained after recovering from COVID-19 or after receiving a vaccine will slowly wane, and reinfections and the need for booster doses are to be expected, at least in high-risk groups. We must also consider the real risk of SARS-CoV-2 mutating into further variants, in the pessimistic scenario even completely circumventing the immune system because virions will not bind to existing antibodies. We can already observe variants that relatively successfully hide from being recognized by antibodies, such as the Mu variant.

Simultaneously, the development of an effective, safe, and inexpensive drug that patients could take by mouth at home to treat and prevent SARS-CoV-2 infections appears to be a realistic prospect. A dozen or so potential drugs are already at the stage of being tested in patients. The development of an effective drug will bring us closer to the moment when SARS-CoV-2 becomes endemic and stops paralyzing the world.

There is no doubt that over time humanity will win the battle against SARS-CoV-2, but we must all do our best to do so at the lowest possible cost. Therefore, we should protect the lives of seniors by offering them third doses of the vaccine. 

About the team

The Interdisciplinary COVID-19 Advisory Team to the President of the Polish Academy of Sciences was set up on 30 June 2020. The team is chaired by Prof. Jerzy Duszyński, President of the PAS, with Prof. Krzysztof Pyrć (Jagiellonian University) as deputy chair and Dr. Anna Plater-Zyberk (Polish Academy of Sciences) as its secretary. Other members of the team are: 

• Dr. Aneta Afelt (University of Warsaw)
• Prof. Małgorzata Kossowska (Jagiellonian University)
• Prof. Radosław Owczuk, MD (Medical University of Gdańsk)
• Dr. Anna Ochab-Marcinek (PAS Institute of Physical Chemistry)
• Dr. Wojciech Paczos (PAS Institute of Economics, Cardiff University)
• Dr. Magdalena Rosińska, MD (National Institute for Public Health – National Hygiene Institute, Warsaw)
• Prof. Andrzej Rychard (Institute of Philosophy and Sociology PAN),
• Dr. Tomasz Smiatacz, MD (Medical University of Gdańsk)