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Genomic Evidence for Reinfection With SARS-CoV-2
TAKE-HOME MESSAGE
- This article discusses the case of a Nevada man who is believed to have been re-infected with SARS-CoV-2. The case study reports an initial infection in April followed by two negative tests in May. This period was then followed by a positive test in May. The two SARS-CoV-2 infections were recorded as symptomatically different in terms of severity as well as genetically different.
- There have now been a few cases of reinfection reported worldwide, raising concerns for how long immunity is conferred following SARS-CoV-2 infection.
– Andrea Dotson, MD, MSPH
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
The degree of protective immunity conferred by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently unknown. As such, the possibility of reinfection with SARS-CoV-2 is not well understood. We describe an investigation of two instances of SARS-CoV-2 infection in the same individual.
METHODS
A 25-year-old man who was a resident of Washoe County in the US state of Nevada presented to health authorities on two occasions with symptoms of viral infection, once at a community testing event in April, 2020, and a second time to primary care then hospital at the end of May and beginning of June, 2020. Nasopharyngeal swabs were obtained from the patient at each presentation and twice during follow-up. Nucleic acid amplification testing was done to confirm SARS-CoV-2 infection. We did next-generation sequencing of SARS-CoV-2 extracted from nasopharyngeal swabs. Sequence data were assessed by two different bioinformatic methodologies. A short tandem repeat marker was used for fragment analysis to confirm that samples from both infections came from the same individual.
FINDINGS
The patient had two positive tests for SARS-CoV-2, the first on April 18, 2020, and the second on June 5, 2020, separated by two negative tests done during follow-up in May, 2020. Genomic analysis of SARS-CoV-2 showed genetically significant differences between each variant associated with each instance of infection. The second infection was symptomatically more severe than the first.
INTERPRETATION
Genetic discordance of the two SARS-CoV-2 specimens was greater than could be accounted for by short-term in vivo evolution. These findings suggest that the patient was infected by SARS-CoV-2 on two separate occasions by a genetically distinct virus. Thus, previous exposure to SARS-CoV-2 might not guarantee total immunity in all cases. All individuals, whether previously diagnosed with COVID-19 or not, should take identical precautions to avoid infection with SARS-CoV-2. The implications of reinfections could be relevant for vaccine development and application.
Additional Info
Disclosure statements are available on the authors' profiles:
Genomic Evidence for Reinfection With SARS-CoV-2: A Case Study
Lancet Infect Dis 2020 Oct 12;[EPub Ahead of Print], RL Tillett, JR Sevinsky, PD Hartley, H Kerwin, N Crawford, A Gorzalski, C Laverdure, SC Verma, CC Rossetto, D Jackson, MJ Farrell, S Van Hooser, M PandoriFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
SARS-CoV-2 Reinfection
Case presentations inform us on what is possible. Case series let us know that events can occur more than once. Cross-sectional studies can fill in the details on how often or how much—but the starting point is possibility. In a detailed case report, Tillett and colleagues present a well-documented and supported case of reinfection with SARS-CoV-2; the first reported for North America.
A 25-year-old male in Nevada developed symptoms of an acute respiratory infection on March 25, 2020. SARS-CoV-2 was detected by PCR on April 18, and he was placed into isolation. He reported symptom resolution on April 27. Two subsequent laboratory assessments for SARS-CoV-2 were negative on May 9 and May 26. He again developed respiratory symptoms on May 28, this time with greater severity. By June 5, he had developed hypoxemia and shortness of breath and was admitted for inpatient care and oxygen support. A chest radiograph demonstrated patchy, bilateral interstitial opacities. PCR at this time was again positive. IgG and IgM were positive for SARS-CoV-2 on June 6.
In my mind, this is fairly good evidence for the possibility of reinfection by SARS-CoV-2, but the case is made even stronger through next-generation sequencing of the genomes of the viruses captured during the first and second episodes. Sequencing demonstrated distinctly different virus variants. This is a very similar situation, approach, and argument that my research team made recently for a case of reinfection with influenza A(H3N2), 36 days following the initial infection, in a healthy 9-year-old.1
This case report adds to others from across the world. Accordingly, reinfection is possible and has happened repeatedly. We do not know, however, the frequency of this phenomenon. Reinfection in this case produced a more significant clinical course, unlike three other published cases. The worsened symptoms could have been due to differences in infectious dose, genomic differences between the two viruses, or antibody-dependent enhancement of disease.
The take-home message for clinicians is that exposure to, infection by, and recovery from SARS-CoV-2 does not necessarily result in long-term immunity. This message needs to be conveyed to our patients:
We need more assessments to better understand the frequency of reinfection, and a much more in-depth appreciation of the immunology of SARS-CoV-2 in terms of overall protection and durability of protection.
Reference