Covid-19: will we be able to make the virus disappear or will we have to live with it?

Judith Mueller, professor of epidemiology at the School of Advanced Studies in Public Health (EHESP), analyzes in this article what can be envisaged in the long term thanks to vaccination: could we make Covid-19 and its virus disappear? or will we just have to live with it?

Vaccine coverage against Covid-19 has increased rapidly in France in recent months. In France, 93% of adults have received a first dose and 80% now have a complete vaccination schedule. In Europe, 78% of those over 18 and 66% of the total population received at least one dose by September 10, 2021. These figures contrast with the international situation, with many countries showing a proportion of the population having received at least one much lower dose: Brazil 62%, India 36% or Nigeria 2%…

Coverage, in France and in Europe, is particularly high in the age groups at increased risk of severe form of Covid-19 (which lead to hospitalization, possibly going to intensive care and potentially death), i.e. from 40-50 years old. . This explains the decoupling observed between the infection and death curves. Thus, despite the dominance of the Delta variant, two to three times more infectious than the initial strain of SARS-CoV-2, the last wave observed this summer in France did not lead to a saturation of hospitals comparable to the previous ones.

These observations raise questions about what can be envisaged in the long term thanks to vaccination: could we make Covid-19 and its virus disappear? Or will we just have to end the epidemic and then continue to live with the virus? In either case, which vaccine strategy to consider? Here are the answers we have.

Natural immunity and theory

The Delta variant displays a “basic R0” (biological constant specific to each pathogen) of almost 6, in other words an infected person theoretically infects 6 unimmunized people. With such infectivity, an unvaccinated population would be almost entirely infected at term: more than 85% of individuals would have to be completely protected against infection in order to stop viral transmission (according to the collective immunity threshold formula = 1 / 1-R). The application of this theory is more complex …

Because the protection obtained by a first infection is not perfect: it reduces the risk of a new infection “only” by 73% during the following three months, a percentage which probably decreases over time. It is therefore very unlikely that viral transmission will stop on its own, even if the entire population has been infected.

The natural immunity that we develop after infection with a respiratory virus (coronavirus or influenza type) is, in fact, only partial and of limited duration: we have all already had colds or even the flu, and we know that we have them. will still have… These viruses are distinguished in this from those of childhood diseases (measles and others), which we only catch (if we have not been vaccinated) once.

However, imperfect though it is, this natural immunity is enough to reduce our vulnerability to respiratory viruses “cousins” of the one who infects us – we speak of cross-immunity, for example between strains of influenza. By transposition, it can be expected that people repeatedly infected with a variant of SARS-CoV-2 will develop protection against a possible severe form of Covid-19.

The effectiveness of vaccination against infection

What level of protection would vaccination achieve? The most reliable estimates come from cross-sectional studies with systematic testing of participants (regardless of the severity of symptoms, etc.). Thus, such a study carried out in English households revealed that a complete vaccination schedule (with Pfizer-BioNTech) had an effectiveness of 80% against the infection by the variant Delta.

In addition, this work showed that protection against infection persisted over time, but declined faster in those over 35 – by around 10 percentage points within three months of vaccination. Vaccination of previously infected persons gave them comparable protection, with better persistence over time. A similar observation was made in American caregivers: the vaccine efficacy against the infection increased from 85% to 73% respectively four and five months after the double injection.

It has also been shown that, when vaccinated, the risk of transmitting the virus in the event of infection seems to be reduced … but estimates vary and this effect could be less with the Delta variant. Taken together, this evidence suggests that vaccination achieves strong, but imperfect, protection against infection and transmission.

As a result, nearly 100% of the population would need to be vaccinated to stop viral circulation. To prevent the creation of viral circulation niches, it would be necessary at the same time to ensure that the entire territory is covered in a homogeneous manner – with boosters if necessary to maintain the level of protection against the infection over time.

Protection also against severe forms

The main issue of Covid-19 vaccination is protection against severe forms. Some data is already available on this point.

In the extension (six months) of the Pfizer-BioNTech clinical trials, it was observed that the vaccine efficacy against Covid-19 decreased only slightly – up to four months after vaccination, it was still around 90% , then rose to nearly 84% between four months and six months (end of data collection for this work). A study conducted in the United States showed that the protection provided by the vaccine against the risk of hospitalization remained above 80% in all age groups, despite the presence of the Delta variant and a time interval more than five months since vaccination.

Containment and curfew have slowed the progression of the epidemic – and access restrictions, wearing a mask and maintaining barrier gestures still allow it. The aim is to save time and avoid saturation of health services as much as possible, until all people at increased risk of developing severe forms have been fully immunized.

This is all the more important since people who have not yet been vaccinated will most likely be infected in the coming months. However, they are not immune to complications, since the risk of hospitalization is 1% for 40-50 years, as is the risk of death in the 60-70 age group.

As regards the youngest, their aim is not so much to protect them against a serious form (they are less at risk) as to slow down the progression of the epidemic in the unvaccinated or unimmunized population. Their involvement in the vaccination campaign makes it possible to envisage an alternative to the restrictions which impact on social life – what is more, with more lasting effects.

Control or eliminate: what long-term strategy?

Two distinct objectives can be considered: to control Covid-19, or to eliminate it. Each involves different strategies.

Controlling the disease requires reducing the number of severe forms below an acceptable threshold (bearing in mind that this threshold remains to be defined), avoiding epidemic outbreaks… or reacting with a vaccine response if such a wave occurs despite everything. With the desire to establish a stable situation in the long term.

This strategy involves targeting those most at risk for severe disease and designing a vaccination schedule to maintain good protection – possibly with boosters or regular vaccination to respond to changing strains. The choice is made according to the vaccine efficacy against severe forms and its evolution over time. While vaccination reduces the risk of transmission, it can be extended to those around vulnerable people (family, caregivers).

This is the approach that is used against the so-called seasonal flu, for example. The vaccination strategy implemented is aimed primarily at people over 65 years of age or suffering from comorbidity, and can be extended to those around them. And since the viruses responsible are constantly mutating, vaccines must be “updated” every year – with varying degrees of success. Another example is pertussis vaccination (vaccination of infants by targeting those around the newborns).

This strategy would be entirely applicable to Covid-19 in France, given the excellent vaccine efficacy against severe forms including in the elderly, over a period of at least six months, even in the presence of new variants. . The annual influenza vaccination campaigns would constitute a good logistical basis.

The interval between the boosters should be determined according to the duration of protection, the circulating strains and the available vaccines. The main indicator for establishing such a program would be the number of hospitalizations and intensive care admissions.

Eliminate the virus, a less obvious strategy

The second possible goal is to eliminate the disease. This time, it would involve avoiding any new cases and stopping the circulation of the SARS-CoV-2 virus. This strategy was chosen for smallpox (target achieved worldwide), poliomyelitis (target achieved in Europe and on most continents) or measles (target not achieved in France). The ultimate goal is to eradicate the virus on a global level, and thus be able to stop vaccination.

In addition to political will, its theoretical feasibility is based on three criteria: the absence of an animal reservoir in which the virus can “fall back”; a low proportion of asymptomatic infections (because they make it difficult to monitor the circulation of the virus); and the existence of effective vaccines.

For SARS-CoV-2, the first two conditions are not met. The most likely hypothesis as to its origin is that it is a “zoonotic” virus, possibly originating from a bat population. In addition, it causes about 25% of asymptomatic infections. Regarding vaccines, the situation is more favorable, even if their current performance required repeated vaccination of the entire population.

As for a national or European elimination objective only, it would run up against imports of the SARS-CoV-2 virus from other regions of the world.

What strategy tomorrow?

The status of several factors to be taken into account in establishing a long-term vaccine strategy remains uncertain: appearance of new more transmissible variants or more serious forms of disease and / or beyond vaccine immunity; capacity of laboratories to adapt their vaccines to emerging strains and to develop new formulations that are more effective against infection in the long term (a vaccine in development by Novax opens up new perspectives); quality of immunity after initial vaccination followed by sporadic infections; capacity of the international community to provide access to vaccination to people at risk or to a major part of the world population.

It is therefore unrealistic to consider eliminating SARS-CoV-2 today. This observation should not distract from the fact that the strategy of also vaccinating the age groups with lower risk of serious Covid-19 makes it possible to slow the progression of the epidemic and thus to reduce the burden on healthcare services and to save money. time for vaccination of people at increased risk of severe forms. Defining when this strategy can be withdrawn to focus on controlling the disease and its severe forms is a matter of policy – particularly important in times of epidemic.

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