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Prior infection plus vaccination provides the strongest protection against Covid variants

Prior infection plus vaccination provides the strongest protection against Covid variants
A student applies pressure to the site of their Covid-19 vaccine during a rural vaccination drive by Broadreach NGO at Duduzile Secondary School in Mpumalanga, South Africa, on Wednesday, March 9, 2022. (Photo: Waldo Swiegers/Bloomberg via Getty Images)

Research suggests hybrid immunity (prior infection plus vaccination) provides the strongest protection against a wide range of variants, possibly for an extended time period. We thus strongly recommend that whether you have had Covid-19 or not, you vaccinate.

Since the outbreak of the global Covid-19 pandemic in 2020, scientists have been working tirelessly to answer a myriad questions that relate to the virus, such as severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) and the disease Covid-19.

As we reflected on this, we were prompted to ask: did researchers study coronaviruses prior to 2020? Absolutely! But did they specifically and scientifically investigate Sars-CoV-2, the virus causing Covid-19 disease? No, they did not.

While Sars-CoV-2 is genetically related to the coronavirus responsible for the severe acute respiratory syndrome (Sars) outbreak of 2003, it is a novel coronavirus. The Sars-CoV-2 virus is thus a new coronavirus that was first detected at the end of 2019 in the Hubei Province of China. It is, however, crucial that the following information be stressed – Sars-CoV-2 was new; research into vaccine development for coronaviruses was not.

The outbreak of Sars (2003), the Middle East respiratory syndrome (MERS, 2012), and the fact that there are hundreds of coronaviruses, four of which cause the common cold, compelled researchers to investigate the development of vaccines against coronaviruses.

In fact, scientists have been studying coronaviruses for more than 50 years. As mentioned, given that Sars-CoV-2 is genetically related to these other coronaviruses, researchers were not starting from scratch when they developed the Covid-19 vaccine. They could use the knowledge gained through past research to assist and speed up the initial development of Covid-19 vaccines.

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Crucially, this existing vaccine development knowledge, as well as global collaboration (scientists around the world worked together and shared knowledge – which allowed for accelerated research findings) and the availability of funding (contributions were received from governments and the private sector) – meant that effective vaccine technology was available within a year, for a novel coronavirus.

Nonetheless, there are still misconceptions and concerns – as well as misunderstandings – related to the Covid-19 vaccines. We will attempt to address three major questions:

  • Why do vaccinated individuals get Covid-19?
  • Why use vaccines as opposed to antibiotics? and
  • Is natural immunity more/as effective as the vaccine?

Why do vaccinated individuals get Covid-19?

Historically, the primary goal of vaccines has been to prevent disease severity; it has never been to prevent infections or onward transmissions. Similarly, the primary goal of Covid-19 vaccinations is to prevent severe disease so that infected individuals experience milder symptoms.

Fully vaccinated individuals are less likely to develop severe disease, experience complications, long-term health problems, long-term hospitalisation, get admitted to an intensive care unit or die from Covid-19 complications (WHO, 2022).

Moreover, it has been found that vaccinated people aged 65+ years who received both doses of the Pfizer vaccine had a 94% reduced risk of Covid-19 related disease outcomes and hospitalisations (CDC, 2021).

The effectiveness against severe illness increased up to 95% with the administration of the Pfizer booster vaccine (Hart et al, 2022). Meanwhile, unvaccinated individuals were found to be at 11 times greater risk of severe disease or death from Covid-19 than vaccinated individuals (CDC, 2021).  

Being vaccinated against Covid-19 is thus a known effective and safer way to reduce disease severity. Overall, Covid-19 vaccines are an effective protective mechanism against severe illness.

However, the misconception that the primary focus of vaccines is to prevent infection can lead to vaccine hesitancy, especially when vaccinated individuals contract Sars-CoV-2; and ongoing vaccine education is therefore required. South Africa still needs to achieve higher vaccination and booster rates as the Covid-19 waves evolve in order to prevent disease severity and save lives.

An example here is when one of the authors contracted Sars-CoV-2 in July 2021, with moderate symptoms (while she would argue it felt severe, she was not hospitalised). She then contracted the virus again in March 2022 (after a double dose-Pfizer and booster), and other than fatigue and a persistent cough, she exhibited no other symptoms.

While she cannot eliminate that variant type (the variants were not genetically characterised) or other factors may have played a role in the manifestation of less severe symptoms (the second time she contracted the virus), she does believe that her vaccination status assisted in protecting her against serious disease onset.

Why use vaccines as opposed to antibiotics?

Covid-19 is an infection caused by a virus. Antibiotics are medications that are used to treat bacterial infections and cannot be used for viral infections. Thus, antibiotics do not have a role in the treatment or prevention of Covid-19 infections. Antibiotic use in Covid-19-positive individuals should only be used in hospitalised patients who have a secondary or super infection with bacteria. A recent review reported that only 3.5% of Covid-19 patients presented with a bacterial co-infection on admission and 15% of patients developed a bacterial co-infection during their hospital stay (Sieswerda, 2020). 

Patients who are in intensive care units are usually more susceptible to a bacterial infection. Irrational and unnecessary use of antibiotics leads to antibiotic resistance and the resultant spread of antimicrobial resistant infections. This is a major public health challenge and the use of antibiotics for mild Covid-19 symptoms (eg, cough, rhinitis, diarrhoea) should be discouraged since these usually have a different aetiology.

Is natural immunity more/as effective as the vaccine?

Globally and within SA, many have proclaimed that since they had (at some stage) contracted the virus and recovered, their natural immunity will protect them moving forward, and use this argument to forego vaccines. In this regard it is worth critically considering the evidence before us. A 2021 study by Khan et al explored this idea and their article has been cited.

They investigated whether (natural) neutralising immunity (elimination or reduction of the virus’s ability to replicate) elicited by Omicron infection would similarly neutralise the Delta variant and the role of prior vaccination.

Within their study (23 participants), 10 participants were vaccinated and 13 were unvaccinated, and all 23 were infected with Omicron. They analysed neutralisation (in a lab setting) of the virus, using plasma from participants from the day of enrolment into the study (five days post-symptoms onset) to the last follow-up visit (a median of 23 days) post-symptom onset. In vaccinated participants, neutralisation of the Omicron variant increased 13.7-fold over baseline. This compared to a 4.4-fold increase in unvaccinated individuals.

Over the same period, Delta virus neutralisation was enhanced 6.6-fold in vaccinated participants but only 2.5-fold (non-statistically significant) in unvaccinated participants. Moreover, vaccinated participants were able to mount a stronger neutralisation response against Delta relative to the Omicron virus (neutralisation of Delta virus was 2.1-fold higher than Omicron). This was not the case in unvaccinated individuals, where neutralisation of Delta was 2.5-fold lower, relative to Omicron, although this was not statistically significant because of the high variability between participant values.

As indicated by the authors, the sample size was small and the researchers suggest some might have been previously infected with Covid-19: “Therefore, it is unclear if what we observe is effective cross-neutralisation of Delta virus by Omicron elicited antibodies, or activation of antibody immunity from previous infection and/or vaccination.”

What does this mean? As expected, Omicron infection can produce natural immunity to neutralise the Omicron variant and as shown, can produce immunity which is able to neutralise the Delta variant. Not surprisingly, this was seen more in vaccinated individuals than in unvaccinated participants. However, Delta infection provides only limited protection against the Omicron variant. Thus, Omicron may possibly reinfect individuals who were previously infected with the Delta variant.

Some studies have shown that natural immunity provided good immunisation. Having had Covid allows the body to develop the immune “memory” that helps with protection against future infections. However, natural immunity has its limits. What varies among us is the antibody level, the time of infection, the variant and the length of natural immunity. Age, our immunocompromised state, the level of disease during the original infection, and comorbidities, also play a role.

For vaccination, factors to be considered are the type of vaccine we received, whether we have been boosted and the overall strength of our immune system. Research suggests hybrid immunity (prior infection plus vaccination) provides the strongest protection against a wide range of variants, possibly for an extended time period. The SA study, a study in Israel (March 2022) and another in the UK (March 2022) corroborate this hypothesis.

We thus strongly recommend that whether you have had Covid-19 or not, you vaccinate.

What is evident, is that there is still so much to learn about infections and reinfections… especially with an evolving virus. What protection will vaccination and previous infections provide against new variants? As new variants are identified and studied, so more answers will be available. DM

Sehaam Khan is Professor (Microbiology & Molecular Virology) and Executive Dean: Faculty of Health Sciences, University of Johannesburg. Nisha Naicker is Professor (Public Health), Department of Environmental Health, Faculty of Health Sciences, University of Johannesburg. Refilwe Phaswana-Mafuya is Professor (Epidemiology and Public Health) and the Director of the South African Medical Research Council/University of Johannesburg Pan African Centre for Epidemics Research Extramural Unit, Faculty of Health Sciences, University of Johannesburg.


"Information pertaining to Covid-19, vaccines, how to control the spread of the virus and potential treatments is ever-changing. Under the South African Disaster Management Act Regulation 11(5)(c) it is prohibited to publish information through any medium with the intention to deceive people on government measures to address COVID-19. We are therefore disabling the comment section on this article in order to protect both the commenting member and ourselves from potential liability. Should you have additional information that you think we should know, please email [email protected]"

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