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ACEP COVID-19 Field Guide

Table of Contents

Characteristics of COVID-19 Variants and Mutants

Characteristics of COVID-19 Variants and Mutants

Genetic variants of SARS-CoV-2 have been emerging and circulating around the world throughout the COVID-19 pandemic. Viral mutations and variants in the United States are routinely monitored through sequence-based surveillance, laboratory studies, and epidemiological investigations. In collaboration with the SARS-CoV-2 Interagency Group (SIG), CDC established a classification scheme for variants of SARS-CoV-2:

  • Variants Being Monitored
    • Variants for which there are data indicating a potential or clear impact on approved or authorized medical countermeasures or that has been associated with more severe disease or increased transmission but are no longer detected or are circulating at very low levels in the United States, and as such, do not pose a significant and imminent risk to public health in the United States.
  • Variants of Interest
    • A variant with specific genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity. 
    • Possible attributes of a variant of interest:
      • Specific genetic markers that are predicted to affect transmission, diagnostics, therapeutics, or immune escape
      • Evidence that demonstrates it is the cause of an increased proportion of cases or unique outbreak clusters
      • Limited prevalence or expansion in the US or in other countries
  • Variants of Concern
    • A variant for which there is evidence of an increase in transmissibility, more severe disease (increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures. 
    • Possible attributes of a variant of concern (in addition to the possible attributes of a variant of interest): 
      • Evidence of impact on diagnostics, treatments, and vaccines
      • Widespread interference with diagnostic test targets
      • Evidence of substantially increased resistance to one or more class of therapies
      • Evidence of significant decreased neutralization by antibodies generated during previous infection or vaccination
      • Evidence of reduced vaccine-induced protection from severe disease
      • Evidence of increased transmissibility
      • Evidence of increased disease severity
  • Variants of High Consequence
    • A variant of high consequence has clear evidence that prevention measures or medical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants.
    • Possible attributes of a variant of high consequence (In addition to the possible attributes of a variant of concern):
      • Impact on Medical Countermeasures (MCM)
      • Demonstrated failure of diagnostics
      • Evidence to suggest a significant reduction in vaccine effectiveness, a disproportionately high number of vaccine breakthrough cases, or very low vaccine-induced protection against severe disease
      • Significantly reduced susceptibility to multiple EUA or approved therapeutics
      • More severe clinical disease and increased hospitalizations

Current CDC Classifications for COVID-19 Variants:

  • Variant Being Monitored (VBM)
    • Alpha (B.1.1.7 and Q lineages)
    • Beta (B.1.351 and descendent lineages)
    • Gamma (P.1 and descendent lineages)
    • Epsilon (B.1.427 and B.1.429)
    • Eta (B.1.525)
    • Iota (B.1.526)
    • Kappa (B.1.617.1)
    • 1.617.3
    • Mu (B.1.621, B.1.621.1)
    • Zeta (P.2)
  • Variant of Interest (VOI)
    • Currently, there are no SARS-CoV-2 Variants of Interest.
  • Variant of Concern (VOC)
    • Delta (B.1.617.2 and AY lineages)
  • Variant of High Consequence (VOHC)
    • Currently, there are no SARS-CoV-2 variants that rise to the level of high consequence.

Omicron Variant

  • The Omicron (B.1.1.529) variant of concern (VOC) has become the dominant variant in many parts of the United States. The Omicron variant, which includes numerous mutations in the spike protein, is predicted to have markedly reduced susceptibility to several anti-SARS-CoV-2 monoclonal antibodies (mAbs), especially bamlanivimab plus etesevimab and casirivimab plus imdevimab. Sotrovimab appears to retain activity against the Omicron variant.
  • With the rapid rise in the prevalence of the Omicron VOC, it is anticipated there will be a limited supply of therapeutic agents that are active against the variant (e.g., the anti-SARS-CoV-2 mAb sotrovimab and small molecule antiviral agents, once they become available) for patients who are at high risk of progression to severe COVID-19 and who might benefit from these therapies.
  • Some SARS-CoV-2 variants, including the Omicron variant, have Δ69-70 deletion in the spike (S) gene. 
    • TaqPath™ tests for three proteins of SARS-CoV-2 so will still detect the virus but will fail to detect the S gene protein specifically. 
    • This particular mutation leads to failure of one of the polymerase chain reaction (PCR) targets (sometimes called S-gene target failure (SGTF)) when the virus is tested with assays that include an S gene target, including the Thermo Fisher Scientific TaqPath™ COVID-19 Combo Kit diagnostic assay
    • Such assays can be used as a screen to presumptively identify SARS-CoV-2 variants that have the Δ69-70 deletion, including the Omicron variant.
    • Delta does not have this Δ69-70 deletion; therefore, infections due to Delta variant would not produce a SGTF profile.

This NIH COVID Guidelines statement provides guidance on the use of anti-SARS-CoV-2 mAbs or remdesivir when the Omicron VOC is the predominant circulating variant. Ritonavir-boosted nirmatrelvir and molnupiravir, 2 new oral antiviral therapies, have just received EUAs for use in nonhospitalized patients at high risk of progression to severe COVID-19 (see the FDA EUAs for recommendations). 

Recommendations

When the Omicron variant represents the majority (e.g., >80%) of infections in a region, it is expected that bamlanivimab plus etesevimab and casirivimab plus imdevimab will not be active for treatment or post-exposure prophylaxis (PEP) of COVID-19. In this setting, the NIH COVID Guidelines recommend using 1 of the following options to treat nonhospitalized patients with mild to moderate COVID-19 who are at high risk of clinical progression:

  • Sotrovimab 500 mg IV as a single infusion (AIIa) administered as soon as possible and within 10 days of symptom onset; or
  • Remdesivir 200 mg IV on Day 1, then 100 mg once daily on Days 2 and 3 (BIIa) initiated as soon as possible and within 7 days of symptom onset.
    • Because remdesivir requires IV infusion for 3 consecutive days, logistical constraints may make it difficult to administer the drug in some settings.
    • Remdesivir should be administered in a setting where management of severe hypersensitivity reactions, such as anaphylaxis, is possible. Patients should be monitored during the infusion and observed for at least 1 hour after the infusion.
    • Remdesivir is currently FDA-approved for hospitalized individuals; however, use of the drug for outpatient treatment would be an off-label indication.

If neither sotrovimab nor remdesivir are feasible to use, and the Delta VOC still represents a significant, but not dominant proportion (e.g., ≥20%) of infections in the region:

  • Patients could be offered bamlanivimab plus etesevimab or casirivimab plus imdevimab with the understanding that treatment would be ineffective if they are infected with the Omicron variant.
  • Consider the use of bamlanivimab plus etesevimab or casirivimab plus imdevimab for PEP on a case-by-case basis with the understanding that the drugs may be ineffective if the person has been exposed to the Omicron variant.

Assessment

Laboratory Abnormalities

The clinical presentation and progression of patients suspected of having COVID-19 can range from mi...

Assessment

Chest X-Ray and CT

The CDC does not currently recommend chest CT or chest x-ray (CXR) as a diagnostic method for COVID-...

Assessment

Ultrasound

Author: Nova Panebianco, MD, MPH, EM Ultrasound Division Director, Ultrasound Fellowship Director, A...

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