To the editor:
Qatar had a first wave of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March to June 2020, after which approximately 40% of the population had detectable antibodies to SARS-CoV-2. The country subsequently had two back-to-back waves from January to May 2021, triggered by the introduction of B.1.1.7 (or alpha) and B.1.351 (or beta) variants.1 This created an epidemiological opportunity to assess reinfections.
Using national, federated databases that have captured all SARS-CoV-2 related data since the beginning of the pandemic (Section S1 of the Supplementary Appendix, available in full text of this letter on NEJM.org), we investigated the risk of serious illness (leading to acute hospitalization), critical illness (leading to intensive care unit admission [ICU]), and fatal disease caused by reinfections compared to primary infections in the national cohort of 353,326 people with polymerase chain reaction (PCR) -confirmed infection between 28 February 2020 and 28 April 2021 after excluding 87,547 people with a vaccination record. Primary infection was defined as the first PCR-positive inoculation. Gene infection was defined as the first PCR-positive inoculation obtained at least 90 days after the primary infection. Individuals with re-infection were matched with those with primary infection in the ratio 1: 5 by sex, 5-year age group, nationality, and calendar week of the PCR test date (Fig. S1 and Table S1 in the supplementary supplement). Classification of severe, critical, and fatal Covid-19 followed the guidelines of the World Health Organization, and assessments were performed by trained medical personnel through individual chart reviews.
Of the 1304 reinfections identified, 413 (31.7%) were caused by the B.1.351 variant, 57 (4.4%) by the B.1.1.7 variant, 213 (16.3%) by “wild-type” virus and 621 (47.6)%) were of unknown status (section S1 of the Supplementary Appendix). For reinfected individuals, the median time between first infection and re-infection was 277 days (interquartile range, 179 to 315). The chances of serious illness by re-infection were 0.12 times (95% confidence interval [CI], 0.03 to 0.31) that of primary infection (table 1). There were no cases of critical illness in re-infection and 28 cases in primary infection (Table S3) with an odds ratio of 0.00 (95% CI, 0.00 to 0.64). There were no cases of death from Covid-19 in re-infection and 7 cases in primary infection, resulting in an odds ratio of 0.00 (95% CI, 0.00 to 2.57). The odds of the complex outcome of serious, critical or fatal disease in re-infection were 0.10 times (95% CI, 0.03 to 0.25) higher than in primary infection. Sensitivity analyzes were consistent with these results (Table S2).
Reinfections had 90% lower odds of resulting in hospitalization or death than primary infections. Four reinfections were severe enough to lead to acute hospitalization. No one led to hospitalization in an intensive care unit, and no one ended in death. Reinfections were rare and were generally mild, perhaps due to the primed immune system after primary infection.
In previous studies, we evaluated the efficacy of previous natural infection as protection against re-infection with SARS-CoV-22.3 as being 85% or more. Consequently, for a person who has already had a primary infection, the risk of getting a serious reinfection is only about 1% of the risk of a previously uninfected person having a serious primary infection. It must be determined whether such protection against serious disease by re-infection lasts for a longer period, analogous to the immunity developed against other seasonal “common cold” viruses,4 which elicits short-term immunity to mild re-infection, but long-term immunity to more serious disease with re-infection. If this were the case with SARS-CoV-2, the virus (or at least the variants studied to date) could assume a more benign infection pattern when it becomes endemic.4
Laith J. Abu-Raddad, Ph.D.
Hiam Chemaitelly, M.Sc.
Weill Cornell Medicine – Qatar, Doha, Qatar
Roberto Bertollini, MD, MPH
Ministry of Public Health, Doha, Qatar
for the National Research Group on COVID-19 Epidemiology
Supported by the Biomedical Research Program and the Research Core for Biostatistics, Epidemiology and Biomathematics at
Information forms provided by the authors are available with the full text of this letter at NEJM.org.
This letter was published on November 24, 2021 on NEJM.org.
Members of the National Study Group for COVID-19 Epidemiology are listed in the Supplementary Appendix, which is available in full text of this letter at NEJM.org.
1. Abu-Raddad LJ, Chemaitelly H, Bagdel AA. The efficacy of the BNT162b2 Covid-19 vaccine against the B.1.1.7 and B.1.351 variants. N Engl J Med 2021; 385:187–189.
2. Abu-Raddad LJ, Chemaitelly H, Coyle Pet al. SARS-CoV-2 antibody positivity protects against re-infection for at least seven months with 95% efficacy. EClinical Medicine 2021; 35:100861–100861.
3. Abu-Raddad LJ, Chemaitelly H, Malek JAet al. Assessment of the risk of re-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an intense gene exposure setting. Clin Infect Dis 202173 (7):e1830–and 1840.
4. Avalanche JS, Bjørnstad ON, Antia R. Immunological properties control the transition of COVID-19 to endemic. Science 2021; 371:741–745.
10.1056 / NEJMc2108120-t1
|Disease outcome *||Reinfection †||Primary infection †||Odds ratio (95% CI)|
|none. of persons with outcome / no. of persons with infection that was not serious, critical, or fatal|
|Serious disease||4/1300||158/6095||0.12 (0.03-0.31)|
|Critical illness||0/1300||28/6095||0.00 (0.00-0.64)|
|Deadly disease||0/1300||7/6095||0.00 (0.00-2.57)|
|Serious, critical or fatal disease||4/1300||193/6095||0.10 (0.03-0.25)|