Sep 02, 2021

"This study demonstrated that natural immunity confers longer lasting and stronger protection against infection"

https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v...

Aug 27, 2021

Agreed, the original paper title is more appropriate: https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v...

Aug 27, 2021

It's important to be aware of the tremendous amount of evidence from a wide body of peer-reviewed literature which supports the fact that immunity acquired through natural infection provides protection against reinfection that is at least equally effective as vaccination. This fact has been repeatedly demonstrated in multiple large scale and long term serological studies [1][2][3][4][5].

It's still an open question whether natural infection confers better protection than vaccine-induced immunity, or if some combination of the two is even better. That's why the primary pre-print cited in OP is so important [6]. It is one of the first and largest scale studies to evaluate the risk of reinfection - in the context of the delta variant which is currently dominant in many countries around the world - by directly comparing naturally acquired immunity to vaccine-induced immunity.

The other cited papers in OP give some reasoning why natural infection might confer more robust protection, particularly when challenged by variants of concern [7][8][9]. The gist is that the immune response acquired through natural infection evolves in such a way that broader and more diverse antibodies can be developed. Another major difference is that natural infection induces antibodies against the nucleocapsid (N) protein, whereas vaccination with the current mRNA based spike protein focused formulations do not [10][11].

All of these findings have major implications for public health policy. In particular, optimal vaccination strategy should likely be targeted towards immunologically naive individuals, or individuals more vulnerable due to age and poor health [12].

- A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. [1] (N=25,661)

- Reinfection is rare in the young and international population of Qatar. Natural infection appears to elicit strong protection against reinfection with an efficacy ~95% for at least seven months. [4] (N=192,967)

- The degree of protection (10-fold) associated with seropositivity appears to be comparable to that observed in the initial reports of the efficacy of mRNA vaccines in large clinical trials. [5] (N=3,257,478)

> those vaccinated are still at a 5.96-fold increased risk for breakthrough infection and at a 7.13-fold increased risk for symptomatic disease compared to those previously infected. [6]

> SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalization compared to those who were previously infected. [6]

[1] SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN) https://pubmed.ncbi.nlm.nih.gov/33844963/

[2] Risk of Reinfection After Seroconversion to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Population-based Propensity-score Matched Cohort Study https://academic.oup.com/cid/advance-article/doi/10.1093/cid...

[3] Assessment of SARS-CoV-2 Reinfection 1 Year After Primary Infection in a Population in Lombardy, Italy https://jamanetwork.com/journals/jamainternalmedicine/fullar...

[4] SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy https://www.sciencedirect.com/science/article/pii/S258953702...

[5] Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection https://jamanetwork.com/journals/jamainternalmedicine/fullar...

[6] Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v...

[7] Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection https://www.nature.com/articles/s41586-021-03696-9

[8] Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations https://pubmed.ncbi.nlm.nih.gov/34331873/

[9] High genetic barrier to escape from human polyclonal SARS-CoV-2 neutralizing antibodies https://www.biorxiv.org/content/10.1101/2021.08.06.455491v1

[10] Combining spike- and nucleocapsid-based vaccines improves distal control of SARS-CoV-2 https://www.cell.com/cell-reports/pdf/S2211-1247(21)01108-6....

[11] Immunogenicity and crossreactivity of antibodies to the nucleocapsid protein of SARS-CoV-2: utility and limitations in seroprevalence and immunity studies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879156/

[12] Model-informed COVID-19 vaccine prioritization strategies by age and serostatus https://science.sciencemag.org/content/sci/371/6532/916.full...