COVID-19 – The way to immunity: what happened and what is next?

By Domenico Gangemi, Giuseppe Scarlata, Antonino Napoleone | January 23, 2021.

Although almost a month has passed since the first vaccinations against SARS-CoV-2 started, there are still many questions to be answered by the worldwide population. Will the vaccine really provide lasting protection against the coronavirus? And if so, will it be able to achieve the much sought-after herd immunity? In order to decipher these questions, numerous research groups are working and trials are still in progress ready to be evaluated by regulatory agencies in due course.
In the meantime, let us try to answer another important question concerning the duration of the vaccination campaign: by when will the whole population have access to the vaccine?

Availability and distribution of the next vaccine doses

To date, there are no clinical trial data that have proven the efficacy of specific drugs against SARS-CoV-2. Scientists around the world have focused their efforts on possible approaches that could guarantee solutions in the shortest possible time: testing drugs that are already commercially available and in use for other therapeutic purposes, identifying specific neutralising antibodies against the virus and using them to fight the infection, or focusing on prevention rather than treatment, i.e. vaccine development. As of 25 December 2020, there were 13 vaccines in the final stages of clinical trials (including Pfizer/BioNTech and Moderna mRNA vaccines, read more: Covid-19 – What is the secret ingredient in Pfizer and Moderna vaccines?), 52 vaccines in the early stages of clinical trials and 162 vaccines in pre-clinical studies¹.
The regulatory agencies Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved Pfizer/BioNTech and Moderna’s vaccines under an emergency access mechanism (EUA) that is not based on standard drug approval practices. This type of authorisation is only issued when the emergency conditions exist to justify the use of available medicines and/or biotechnology products, but only if certain criteria are met and there are no other valid alternatives approved and available. Furthermore, this extraordinary decision is based solely on scientific evidence and data showing that the product can be effective and safe and that the known benefits outweigh the known and potential risks.
Once this was established, given the need to speed up the time required to make available the doses of Pfitzer/BioNTech and Moderna vaccines, as an extraordinary operation, in parallel with the completion of the clinical trials, preparation for their production on an industrial scale was planned and started, with a view to their worldwide distribution.
Italy has received 13.46% of the 1.3 billion doses that the European Union has secured from the various manufacturing companies. The doses received by Italy will be distributed as follows (Table 1)².

Who will be vaccinated first? Priority groups

Within the population, there are categories that are more at risk of contracting and therefore transmitting the virus and categories in which COVID-19 has a high lethality rate. In the initial distribution phase, these categories have been and will be given priority in the administration of the vaccine:

1. Health and social care workers: they are not only the most exposed individuals to the virus, but are also those who are in closest contact with people who are immunocompromised.
2. Residents and staff of nursing homes for the elderly (RSAs): in the first pandemic wave, the highest mortality rate was recorded among the elderly in RSAs. Patients in nursing homes require continuous care, so contact with nursing staff is more frequent than in other settings, increasing the risk of infection. The vaccine, by preventing infection or the development of severe symptoms, in this context more than in others has the aim of lowering the lethality rate.
3. Elderly people over 80 years of age.
4. Subjects aged between 60 and 79 years.
5. Subjects with at least one chronic disease.

Numerous studies have shown that mortality due to COVID-19 is higher in elderly people with multiple diseases³. This explains the inclusion of these individuals in the last three priority categories.
As the number of available vaccine doses increases, people working in closed communities such as schools (teachers and school staff), prisons and, finally, people with moderate comorbidities of all ages will be vaccinated. In this way, vaccination phases (marked with the letter T in Figure 1) will emerge, which over a longer or shorter period of time (depending on the time taken by the regulatory agencies to authorise the marketing of the vaccines) will lead to the achievement of the ( long-awaited) vaccination coverage of 90% of the entire population, thus limiting the circulation of the virus to a minimum and achieving the much sought-after herd immunity.

Duration of immune memory after contact with the virus

It has been repeatedly pointed out that SARS-CoV-2, due to its single-stranded RNA nature, is more prone to developing mutations in its genome, which can lead to changes in the structure of the virus itself, and can even give rise to new strains over time (for more information: Covid-19 – No alarmism for the new English variant: what is there to know?). There is a possibility, therefore, that the immune system, having come into contact with the virus or following the administration of the vaccine, does not have ‘memory’ of the first encounter for a prolonged period of time because it has to deal with a host with new, sufficiently different characteristics. Another hypothesis is that the immune system does not develop such efficacy as to prolong its response against the same virus. There are few data in the literature on the exact duration of vaccination coverage. However, a study recently published in the well-known journal Nature4 raises many questions in this regard. In this study, 231 COVID-19 patients from three different groups were examined, including individuals who developed severe symptoms, individuals with mild symptoms and asymptomatic individuals. Virus positivity and viral loads were quantified by molecular testing, and the level of neutralising antibodies developed in these individuals was analysed in relation to the time elapsed since the start of the infection. The results were very interesting, showing that specific neutralising antibodies against Coronavirus are developed by patients over a level and duration of time since the start of the infection, depending on the severity of the symptoms developed. These results showed that the category of patients with severe symptoms had higher antibody titres than the other two categories, but took longer to peak (approximately 90 days) than patients with mild symptoms (approximately 60 days) and asymptomatic patients (approximately 30 days). To give an estimation of the duration of immunity to Coronavirus, it was calculated that it takes 372, 416 and 133 days for neutralising antibody titres to fall below the detection limit, for severe, mild and asymptomatic patients respectively. These results show that in asymptomatic individuals the neutralising antibody level starts to decline a few weeks after confirmation of the infection, whereas for patients who have developed severe or mild symptoms, the duration of immunisation can exceed one year with higher antibody titres (Figure 2).

Updated data on vaccinations carried out in Italy

At this link http://www.aifa.gov.it/-/report-vaccini-anti-covid-19, it is possible to find the number of doses delivered throughout Italy and to each region, with the relative rates of administration, the percentage of vaccinated subjects by age group and risk category, and the regional points of administration. Since 27 December, more than a million vaccines have been administered in Italy. The particularly virtuous regions (with high percentages of administration out of the total number of doses delivered) are Campania, Veneto and Emilia-Romagna.
There is no shortage of evidence of the effectiveness of the anti-SARS-CoV-2 vaccination, and preliminary data have been made public from clinical trials carried out on tens of thousands of volunteers, although there are still no definite answers on the duration of immune coverage. The studies are still ongoing, and at the moment the vaccine is the only weapon to counteract the infection, the spread of the virus and the onset of serious symptoms.
Never before have new scientific discoveries and the individual people’s sense of responsibility to progress at the same pace. Promoting vaccination means trusting science and offering a chance to safeguard the health and well-being of the worldwide population for the near future. Therefore, let’s do the vaccine, and trust the biomedical sciences rather than the media, to find a way out of the pandemic as soon as possible.

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References

1. Li Q, Lu H. Latest updates on COVID-19 vaccines. Biosci Trends. Published online 2020. doi:10.5582/bst.2020.03445.
2. Piano strategico per la vaccinazione anti-SARS-CoV-2/COVID-19 (salute.gov.it);
3. Imam Z, Odish F, Gill I, et al. Older age and comorbidity are independent mortality predictors in a large cohort of 1305 COVID-19 patients in Michigan, United States. J Intern Med. 2020;288(4):469-476. doi:10.1111/joim.13119Lau, E.H.Y., Tsang, O.T.Y., Hui, D.S.C. et al. Neutralizing antibody titres in SARS-CoV-2 infections. Nat Commun 12, 63 (2021). https://doi.org/10.1038/s41467-020-20247-4.
4. www.aifa.gov.it/-/report-vaccini-anti-covid-19
5. https://www.dw.com/en/covid-19-vaccine-development-whats-the-progress/a-55648707