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COVID-19 reinfection: a rapid systematic review of case reports and case series
  1. Jingzhou Wang1,
  2. Christopher Kaperak1,
  3. Toshiro Sato2,3,
  4. Atsushi Sakuraba4
  1. 1 Department of Medicine, University of Chicago, Chicago, Illinois, USA
  2. 2 Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan
  3. 3 Coronavirus Task Force, Keio Univeristy, Tokyo, Japan
  4. 4 Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, Chicago, Illinois, USA
  1. Correspondence to Dr Atsushi Sakuraba, Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, Chicago, IL 60637, USA; asakurab{at}


The COVID-19 pandemic has infected millions of people worldwide and many countries have been suffering from a large number of deaths. Acknowledging the ability of SARS-CoV-2 to mutate into distinct strains as an RNA virus and investigating its potential to cause reinfection is important for future health policy guidelines. It was thought that individuals who recovered from COVID-19 generate a robust immune response and develop protective immunity; however, since the first case of documented reinfection of COVID-19 in August 2020, there have been a number of cases with reinfection. Many cases are lacking genomic data of the two infections, and it remains unclear whether they were caused by different strains. In the present study, we undertook a rapid systematic review to identify cases infected with different genetic strains of SARS-CoV-2 confirmed by PCR and viral genome sequencing. A total of 17 cases of genetically confirmed COVID-19 reinfection were found. One immunocompromised patient had mild symptoms with the first infection but developed severe symptoms resulting in death with the second infection. Overall, 68.8% (11/16) had similar severity; 18.8% (3/16) had worse symptoms; and 12.5% (2/16) had milder symptoms with the second episode. Our case series shows that reinfection with different strains is possible, and some cases may experience more severe infections with the second episode. The findings also suggest that COVID-19 may continue to circulate even after achieving herd immunity through natural infection or vaccination, suggesting the need for longer-term transmission mitigation efforts.

  • COVID-19

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  • Contributors JW: methodology (equal) and writing of the original draft. CK: methodology (equal) and writing of original draft (equal). TS: editing and approval of the final draft. AS: conceptualization, methodology, writing, and review and editing.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.