Sequence Proven Reinfections with SARS-CoV-2 at a Large Academic Center

  1. C. Paul Morris
  2. Raghda E. Eldesouki
  3. Amary Fall
  4. David C. Gaston
  5. Julie M. Norton
  6. Nicholas Gallagher
  7. Chun Huai Luo
  8. Omar Abdullah
  9. Eili Y. Klein
  10. Heba H. Mostafa

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Abstract

Background

Increased reinfection rates with SARS-CoV-2 have recently been reported, with some locations basing reinfection on a second positive PCR test at least 90 days after initial infection.

Methods

We identified cases where patients had two positive tests for SARS-CoV-2 and evaluated which of these had been sequenced as part of our surveillance efforts, and evaluated sequencing and clinical data.

Results

750 patients (920 samples) had a positive test at least 90 days after the initial test. The median time between tests was 377 days, and 724 (79%) of the post 90-day positives were collected after the emergence of the Omicron variant in November 2021. Sequencing was attempted on 231 samples and successful in 127. Successful sequencing spiked during the Omicron surge and showed higher median days from initial infection compared to failed sequences (median 398 days compared to 276 days, p<0.0005). A total of 122 (98%) patients showed evidence of reinfection, 45 of which had sequence proven reinfection and 77 had inferred reinfections (later sequence showed a clade that was not circulating when the patient was initially infected). Children accounted for only 4% of reinfections. 43 (96%) of 45 infections with sequence proven reinfection were caused by the Omicron variant, 41 (91%) were symptomatic, 32 (71%), were vaccinated prior to the second infection, and 6 (13%) were Immunosuppressed. Only 2 (4%) were hospitalized, and both had underlying conditions.

Conclusion

Sequence proven reinfections increased with the Omicron variant but generally caused mild infections.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.17.22275210: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsField Sample Permit: Sequencing: Specimens were extracted as previously described [16, 17].
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Oxford Nanopore Technology GridION was used for sequencing, and reads were basecalled with MinKNOW.
    MinKNOW
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are some limitations to this study. First, there is still a large proportion of genomes that failed sequencing. The reason for this is not always clear, however, successful sequencing is highly dependent on viral RNA load, and thus the failed sequences may be due to lower viral load. However, there is not sufficient evidence to determine the rate at which the failed sequences in the post 90-day positives may be due to reinfections with low viral load or a low-level persistence. It has been shown that residual slowly wanes over approximately a year after an infection [19], which is about the time that sequence proven reinfections spiked after the initial infection. Second, the vast majority of reinfections happened over a small period of time with the Omicron variant. It is clear that the circulating variants have a large impact on the likelihood of reinfection. The Omicron variant is immunologically distinct from prior variants that resulted in incomplete cross protection to Omicron [5]. Thus, as we surveil for reinfections, the likelihood at any given time will likely be dependent on similarity of circulating variants to prior variants. Similarly, although persistence of the initial genome is rare in the post 90-day positives currently, future variants may show a different propensity towards persistence. Continued sequencing is necessary to determine new trends that may arise. Lastly, we cannot obtain a true rate of reinfection compared to total cases with these data, ...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2022.05.17.22275210v1 on medRxiv