People who were infected with Covid-19 at least once have a 88 per cent lower risk of hospitalisation or death due to the disease for at least 10 months, compared to those who had not been infected previously, according to a systematic review and meta-analysis published in The Lancet. This is the largest review and meta-analysis assessing the extent of protection following Covid-19 infection on the basis of the variant, and how that protection is against different variants. The review and meta-analysis included 65 studies from 19 countries.
According to the authors, this is the most comprehensive study to date that provides evidence on natural immunity protection by a Covid-19 variant and how the protection fades over time.
Natural immunity against severe disease for people previously infected with Covid
According to the review, the natural immunity against severe disease for people who have been infected with Covid-19 at least once was strong and long-lasting for all variants. Severe disease refers to the risk of hospitalisation or death. The natural immunity was 88 per cent or greater at 10 months post infection.
Natural immunity against reinfection for people infected with pre-Omicron variants
People who had earlier been infected with pre-Omicron variants had substantially reduced natural immunity protection against reinfection with Omicron BA.1. Their natural immunity against severe disease was 36 per cent at 10 months after infection.
While it is important to recognise the natural immunity in people who have been infected with Covid-19, the findings of the review should not discourage vaccination because it is the safest way to acquire immunity, the authors have warned.
The level and duration of protection against reinfection, symptomatic disease and severe illness is at least on par with that provided by two doses of the mRNA vaccines Moderna or Pfizer-BioNtech, the analysis suggested. This is true for the ancestral or wild strain of SARS-CoV-2, and the Alpha, Delta and Omicron BA.1 variants. The authors did not include data on infection from Omicron subvariant XBB and its sublineages.
In a statement released by The Lancet, Dr Stephen Lim, the lead author on the paper, said vaccination is the safest way to acquire immunity, whereas acquiring natural immunity must be weighed against the risks of severe illness and death associated with the initial infection.
Dr Caroline Stein, a co-author on the paper, said vaccines continue to be important for everyone in order to protect high-risk populations such as those who are over 60 years of age and those with comorbidities. She added that this also includes populations that have not previously been infected and unvaccinated groups, as well as those who were infected or received their last vaccine dose more than six months ago.
Stein said that decision makers should take both natural immunity and vaccination status into consideration to obtain a full picture of an individual’s immunity profile.
Several studies and reviews conducted since 2021 have reported the effectiveness of past Covid-19 infection in reducing the risk of re-infection and how immunity wanes over time. However, none of the studies had comprehensively assessed how long the protection after natural infection will last and how durable that protection will be against different variants.
How the study was conducted
The researchers conducted a review and meta-analysis of all previous studies that compared the reduction in risk of SARS-CoV-2 reinfection among unvaccinated individuals to the risk of Covid-19 in unvaccinated individuals without a previous infection up to September 2022.
The researchers evaluated the effectiveness of past infection by outcome, which included factors such as when the infection occurred, whether it was symptomatic or severe, and also considered parameters such as the type of variant, and the time since infection. The studies which examined individuals with natural immunity in combination with vaccination, which resulted in hybrid immunity, were excluded from the analysis.
Protection against reinfection from pre-Omicron variant 85% at one month
The researchers analysed the data of 21 studies which reported on the time since infection from a pre-Omicron variant. The analysis estimated that protection against reinfection from a pre-Omicron variant was about 85 per cent at one month, and this fell to about 79 per cent at 10 months.
Protection from pre-Omicron variant against reinfection with Omicron variant BA.1 low
However, protection from a pre-Omicron variant infection against reinfection with the Omicron variant BA.1 was lower. It was 74 per cent at one month, and declined more swiftly to 36 per cent at around 10 months.
Protection against severe disease universally high for specific individuals
The authors analysed five studies reporting on severe disease, which refers to hospitalisation and death. The analysis found that protection remained universally high for 10 months. For those infected with the ancestral strain of SARS-CoV-2, and the Alpha and Delta variants, the natural immunity against severe disease was 90 per cent for 10 months. The natural immunity against severe disease for people previously infected with Omicron BA.1 was 88 per cent.
Protection against Omicron sub-lineages BA.2 and BA.4/BA.5
Six studies specifically evaluated protection against Omicron sub-lineages BA.2 and BA.4/BA.5. The studies suggested that a person had significantly reduced protection when the prior infection was a pre-Omicron variant. But if the person was previously infected with an Omicron variant, their protection was maintained at a higher level.
Dr Hasan Nassereldine, one of the co-authors on the paper, said the weaker cross-variant immunity with the Omicron variant and its sub-lineages reflects the mutations they have that make them escape built-up immunity more easily than other variants.
He added that the limited data the researchers have on natural immunity protection from the Omicron variant and its sublineages underscores the importance of continued assessment, particularly since the variant and its sublineages are estimated to have infected 46 per cent of the global population between November 2021 and June 2022. In order to assess the natural immunity of emerging variants and to examine the protection provided by combinations of vaccination and natural infection, further research is needed, he said.
Limitations on the paper
One of the limitations the authors noted in the paper includes the fact that the number of studies examining the Omicron BA.1 variant and its sublineages and the number from Africa was generally limited. Another limitation, the authors noted, is that only limited data were available beyond 10 months after initial infection.
Also, some information, such as past infection status and hospital admissions, was measured differently or incomplete, and hence, could jeopardise the estimate of protection, the authors stated.
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