Wednesday, March 3, 2021
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Coronavirus Illness 2019 (COVID-19)


CDC is conscious of latest studies of suspected circumstances of SARS-CoV-2 reinfection amongst individuals who had been beforehand recognized with COVID-19 [1–3]. There may be presently no broadly accepted definition of what constitutes SARS-CoV-2 reinfection and the studies use completely different testing strategies, making reinfection diagnoses tough. To develop a standard understanding of what constitutes SARS-CoV-2 reinfection, CDC proposes utilizing each

1) investigative standards for figuring out circumstances with a better index of suspicion for reinfection and
2) genomic testing of paired specimens.

CDC examined applicable time durations following preliminary SARS-CoV-2 an infection or sickness to research reinfection. Since August 2020, CDC has really useful in opposition to the necessity for retesting individuals with asymptomatic an infection inside 90 days of first SARS-CoV-2 an infection or sickness as a result of proof to this point means that reinfection doesn’t happen inside this time window (CDC Steerage on Period of Isolation and Precautions for Adults with COVID-19).

Right now, we suggest two time home windows for investigation as listed beneath:

  1. For individuals with or with out COVID-19like signs ≥90 days after preliminary an infection/sickness; and
  2. For individuals with COVID-19like signs 45–89 days after preliminary an infection/sickness.

For individuals with detection of SARS-CoV-2 RNA from a respiratory specimen ≥90 days after their first laboratory-confirmed SARS-CoV-2 an infection/sickness, we apply a regular set of standards detailed beneath. Investigating extremely suspicious COVID-19–like circumstances within the 45–89-day window can be vital. Nevertheless, we suggest stricter standards to pick circumstances on this earlier timeframe utilizing a better index of suspicion for reinfection. If proof of reinfection throughout this time window is recognized, it should additional inform future prevention efforts and guideline improvement.

CDC notes that SARS-CoV-2 reinfection is a quickly evolving space of analysis. This preliminary set of proposed standards may not seize all cases of reinfection; we provide these preliminary investigative standards in an effort to higher perceive the potential for reinfection. This preliminary set of proposed standards will probably be refined if new proof suggests different avenues of investigation, with the aim of making a standardized case definition of SARS-CoV-2 reinfection.

  1. Examine circumstances that meet criterion A or B
      1. For individuals with detection of SARS-CoV-2 RNA ≥90 days since first SARS-CoV-2 an infection
        Individuals with detection of SARS-CoV-2 RNA* ≥90 days after the primary detection of SARS-CoV-2 RNA, whether or not or not signs had been current
        AND
        Paired respiratory specimens (one from every an infection episode) can be found
        *If detected by RT-PCR, solely embrace if Ct worth <33 or if Ct worth unavailable
      2. For individuals with COVID-19–like signs and detection of SARS-CoV-2 RNA 45–89 days since first SARS-CoV-2 an infection
        Individuals with detection of SARS-CoV-2 RNA* ≥45 days after the primary detection of SARS-CoV-2 RNA
        AND
        With a symptomatic second episode and no apparent alternate etiology for COVID-19–like signs OR shut contact with an individual recognized to have laboratory-confirmed COVID-19
        AND
        Paired respiratory specimens (one from every an infection episode) can be found*If detected by RT-PCR, solely embrace if Ct worth <33 or if Ct worth unavailable.
        In settings of restricted genomic testing capability, CDC suggests prioritizing investigation of individuals within the ≥90 day time window as a result of the longer time interval between first and second an infection might need larger suspicion for reinfection.
  1. Deciding which laboratory exams to conduct
    Genomic sequencing of paired specimens—that meet the standard standards beneath—is required to research reinfection. Single nucleotide polymorphism evaluation alone could or is probably not enough to tell apart reinfection from long-term shedding, as intra-host variation within the mutation fee of SARS-CoV-2 is poorly understood. Nevertheless, identification of paired specimens from distinct lineages (as outlined in Nextstrain or GISAID) serves as larger high quality proof for SARS-CoV-2 reinfection. The standard standards for testing and ranges of proof are described in additional element beneath. Genomic testing ought to meet all the following high quality standards for investigation of reinfection with SARS-CoV-2:
  • Genome protection >100/per base place is really useful for consensus technology
  • Q rating of consensus >30 with 99% of the genome coated
  • 1000x common genome protection really useful for evaluation of minor variation
  • Removing of amplicon primer contamination from meeting

As well as:

  • Use of high-fidelity sequencing platforms (Q rating per learn >30) most well-liked for consensus technology
  • If low constancy sequencing platforms (Q rating per learn <30) are used, verification of SNPs by way of alternate sequencing methodology is inspired

Proof stage for reinfections utilizing genomic information is as follows:

Finest proof

Differing clades as outlined in Nextstrain and GISAID of SARS-CoV-2 between the primary and second an infection, ideally coupled with different proof of precise an infection (e.g., excessive viral titers in every pattern, constructive for sgmRNA, or tradition)

Reasonable proof

>2 nucleotide variations monthly* in consensus between sequences that meet high quality metrics above, ideally coupled with different proof of precise an infection (e.g., excessive viral titers in every pattern, constructive for sgmRNA, or tradition)

Poor proof however attainable

≤2 nucleotide variations monthly* in consensus between sequences that meet high quality metrics above or >2 nucleotide variations monthly* in consensus between sequences that don’t meet high quality metrics above, ideally coupled with different proof of precise an infection (e.g., excessive viral titers in every pattern, constructive for sgmRNA, or tradition)

* The mutation fee of SARS-CoV-2 is estimated at 2 nucleotide variations monthly; thus if suspected reinfection happens 90 days after preliminary an infection, reasonable proof would require >6 nucleotide variations.

Right now, solely paired specimens are being examined to find out reinfection, as protocols for figuring out reinfection from a single specimen don’t but exist.

Different info can present supporting however not definitive proof for reinfection, reminiscent of tradition or sub-genomic mRNA evaluation (to detect the presence of replication-competent virus) or serology, which might be helpful to doc a serologic response to SARS-CoV-2. Except for laboratory proof, different supporting proof for reinfection might embrace scientific course (COVID-19–like signs) and epidemiologic hyperlinks to a confirmed case.



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