March 11, 2021
COVID-19 Variants: Vaccines, Diagnostics, and Therapeutics
Introduction
countermeasures, including with respect to emerging
As SARS-CoV-2, the virus that causes COVID-19, has
variants.
spread widely over time, a number of new variants have
been identified globally. According to the Centers for
Identifying and Tracking Variants
Disease Control and Prevention (CDC), “a new virus
Identifying and tracking virus variants primarily relies on
variant has one or more mutations that differentiate it from
genomic surveillance. Genomic surveillance—ongoing and
the wild-type or predominant virus variants already
systematic genomic sequencing of virus samples collected
circulating among the general population.” Genetic
from patients—is relatively new to the public health field,
variation in circulating viruses is expected, especially with
though some countries (e.g., the UK) have more robust
RNA viruses (e.g., influenza virus), which have high rates
systems than others. Genomic surveillance capabilities are
of mutation generally. When a virus infects its host, it uses
uneven across U.S. public health agencies, and the United
the host cell machinery to replicate itself. This replication
States currently sequences less than 1% of its COVID-19
process is error prone and offers chances to introduce
samples. Even with new investment, it is uncertain if
changes to the virus’s genetic code. Many of these changes
genomic surveillance can be scaled before variants spread
are inconsequential, but a few improve the fitness of the
widely. Genomic surveillance is complex, involving not
virus, providing a selective advantage and establishing new
only sequencing viral genomes, but also developing
strains of the virus, which would be expected to increase in
capabilities to process and analyze large volumes of data.
prevalence over time. Although they may occur in any part
Such efforts involve specialized equipment, software,
of the viral genome, changes in the genetic code for the
personnel, bioinformatics expertise, and systems to share,
virus part (known as the “spike protein”) that locks onto the
harmonize, and analyze data. Genome sequences collected
host cell, have been noted in the SARS-CoV-2 variants of
through surveillance and other sequencing efforts are
concern. These changes appear to strengthen viral
shared to public repositories, such as GenBank or GISAID
attachment to the host cell, which can result in more
(global initiative on sharing avian influenza data), by public
efficient viral transmission (increased infectiousness). This
health, academic, or other research institutions. These
type of change does not have to correlate with a change in
efforts support better understanding of global patterns of
the clinical severity of infection (virulence), although it
transmission, identify outbreaks potentially driven by new
may.
variants, and guide mitigation measures, among other
things.
To date, several COVID-19 variants of concern have been
identified globally, including B.1.1.7 (identified by the
CDC leads national variant tracking through various efforts.
United Kingdom, UK); B.1.351 (emerged in South Africa);
First, CDC conducts national SARS-CoV-2 strain
and P.1 (emerged in Brazil). Each of these variants have
surveillance, which combines genomic surveillance with
been found in the United States as of January 2021. Recent
characterization of biological features of the strains (e.g.,
evidence indicates that additional variants have emerged
virulence or transmissibility). CDC ramped up collection of
and are circulating in parts of the United States as well. The
specimens from state and jurisdictional health departments
variants pose potential challenges to the effectiveness of
through its National SARS-CoV-2 Strain Surveillance
existing countermeasures—vaccines, diagnostics, and
(NS3) starting in November 2020. CDC also supports
therapeutics—and the development of new ones. Efforts
genomic surveillance capacity at s tate and other public
have increased nationally to track the emergence and spread
health agencies through its Advanced Molecular Detection
of new variants, primarily through increasing genomic and
(AMD) program. Guidance for recent Epidemiology and
other surveillance.
Laboratory Capacity grant awards to jurisdictions made
with funding from the Consolidated Appropriations Act,
Given these concerns, Congress, in the American Rescue
2021 (P.L. 116-260) provides that recipients are to increase
Plan Act of 2021 (H.R. 1319), appropriated $1.75 billion to
both samples sent to CDC and genomic surveillance
CDC specifically for SARS-CoV-2 genomic sequencing
capabilities within the jurisdiction using AMD. In addition,
and surveillance; other funding in the bill, such as for data
CDC partners with academic, commercial, and public
modernization and forecasting, may also aid with variant
health laboratories to collect genomic sequence data. In
tracking, as well as with coordination of such efforts at the
mid-February 2021, the CDC Director announced further
federal level. CDC has also used appropriations from
investment of $200 million for genomic surveillance, with
several prior coronavirus supplemental appropriations acts
the goal of increasing sequencing to 25,000 samples per
to expand such efforts. H.R. 1319 further provided funding
week. CDC had already increased weekly specimens
to the Food and Drug Administration (FDA) to support,
processed from 750 in January 2021 to 7,000 in February
among other things, the continued evaluation of COVID-19
2021. Both CDC and some commentators note that even
this level of sequencing may not be adequate to track
https://crsreports.congress.gov

---

COVID-19 Variants: Vaccines, Diagnostics, and Therapeutics
variants nationwide, with many experts recommending
eventual structure of viral proteins that are targeted by the
sequencing at least 5% of test samples.
tests, and serology tests—tests that detect antibodies to the
virus—can be affected if the structure of the viral protein
Variants and Vaccines
that elicits an antibody response to the virus is altered. In
To date, FDA has granted emergency use authorization
both cases, these changes may lead to false negative results.
(EUA) to three COVID-19 vaccines, based on analyses of
data from Phase 3 clinical trials evaluating each vaccine’s
FDA notes that the agency has been “routinely monitoring
safety and effectiveness in tens of thousands of participants.
publicly available databases and has coordinated efforts to
The vaccines available under EUA thus far, as well as many
evaluate the impact of new virus variants on tests that have
of the vaccines that are under investigation in clinical trials,
received … EUA.” FDA uses reports in the peer-reviewed
are designed to elicit a protective immune response to the
literature on variants of clinical significance, as well as
SARS-CoV-2 spike protein. SARS-CoV-2 variants with
identification of mutations appearing with increasing
mutations in the spike protein raise concerns that currently
frequency in public sequence repositories, to identify
authorized vaccines may provide reduced protection against
potential mutations or variants of concern. Test components
these variants. While FDA indicates that currently available
are routinely compared against these mutations to
vaccines remain effective against circulating strains of the
determine the effect, if any, on test performance. FDA
virus, some evidence suggests reduced effectiveness against
released a safety communication in January 2021 based on
certain variants (e.g., the B.1.351 [South African] variant).
this work to alert the diagnostics community about potential
As such, researchers have begun assessing the effectiveness
impacts on specific EUA tests. To date, the agency has
of EUA-authorized vaccines against the SARS-CoV-2
focused its efforts on monitoring the effects of genetic
variants and exploring modifications to the vaccines.
changes on molecular tests, but FDA is currently also
considering approaches to monitoring for possible effects of
Any changes to the currently authorized vaccines, including
changes on antigen and serology tests.
any change in composition, dose, or dosing schedule, would
have to be reviewed and approved by FDA. To assist
Variants and Therapeutics
vaccine developers with generating data to support
Several therapeutics are now available for the treatment of
modifications to authorized vaccines, FDA has updated its
COVID-19, and they differ with respect to their intended
guidance, Emergency Use Authorization for Vaccines to
use (e.g., treatment of mild to moderate or severe disease)
Prevent COVID-19, outlining what data and information are
and mechanism of action (e.g., whether they target the virus
needed to support an EUA amendment. With respect to
itself or the body’s inflammatory response). To date, FDA
clinical data, FDA does not expect vaccine developers to
has approved one drug, the antiviral Veklury (remdesivir),
conduct the same large-scale clinical trials that were
which is intended for treatment of patients hospitalized with
required for EUA issuance. Instead, the effectiveness of a
COVID-19. It works by stopping viral replication, thereby
modified COVID-19 vaccine may be demonstrated by
reducing the time it takes for symptoms to improve. FDA
conducting immunogenicity studies comparing the immune
also has granted EUA to several monoclonal antibody
response induced by the modified vaccine against the
(mAb) products, which are intended for the treatment of
SARS-CoV-2 variant(s) with the immune response induced
mild to moderate COVID-19 in patients who are at high
by the EUA-authorized vaccine against the SARS-CoV-2
risk for progressing to severe disease. mAbs are designed to
virus upon which the vaccine was originally based. The
bind to the spike protein that allows the virus to infect the
guidance provides recommendations for conducting
host cell in order to stop infection.
immunogenicity studies assessing the effectiveness of a
modified COVID-19 vaccine as part of the primary vaccine
The emergence of SARS-CoV-2 variants has raised
series and as a booster dose.
concerns about the effectiveness of existing therapeutics.
FDA has indicated that it is aware that some authorized
Variants and Diagnostics
mAb products are less active against some of the SARS-
The performance of COVID-19 tests, including molecular,
CoV-2 variants that have emerged. As such, FDA has
antigen, and serology tests, may be affected by the
issued a new guidance, Development of Monoclonal
emergence of new variants. FDA has released guidance—
Antibody Products Targeting SARS-CoV-2, Including
Policy for Evaluating Impact of Viral Mutations on
Addressing the Impact of Emerging Variants, During the
COVID-19 Tests—to provide test developers with
COVID-19 Public Health Emergency, which provides
recommendations on evaluating the impact of new viral
recommendations for design of mAb development
genetic mutations on their tests’ designs and performance
programs and considerations for emerging variants. FDA
over time as new variants emerge. Molecular tests, such as
recommends that individual mAb products be developed
polymerase chain reaction (PCR) tests, identify the virus by
with the expectation that they will be combined with other
recognizing specific snippets of the viral genome, and have
antibody products that can bind to different parts of the
generally been developed based on the same reference
viral protein. FDA also updated its guidance, COVID-19:
sequences. If a test’s viral targets are altered in a variant,
Developing Drugs and Biological Products for Treatment
then the diagnostic may not detect them, generating a false
or Prevention, to include recommendations for conducting
negative result. This may be mitigated through the use of
drug resistance analyses (e.g., characterizing a drug’s
multiple targets in a molecular test; most EUA-authorized
antiviral activity against SARS-CoV-2 variants).
PCR tests do have multiple targets, often in different parts
of the viral genome. Separately, antigen test performance
Amanda K. Sarata, Specialist in Health Policy
may be affected if a viral genetic mutation affects the
Agata Bodie, Analyst in Health Policy
https://crsreports.congress.gov

---

COVID-19 Variants: Vaccines, Diagnostics, and Therapeutics

IF11789
Kavya Sekar, Analyst in Health Policy


Disclaimer
This document was prepared by the Congressional Research Service (CRS). CRS serves as nonpartisan shared staff to
congressional committees and Members of Congress. It operates solely at the behest of and under the direction of Congress.
Information in a CRS Report should not be relied upon for purposes other than public understanding of information that has
been provided by CRS to Members of Congress in connection with CRS’s institutional role. CRS Reports, as a work of the
United States Government, are not subject to copyright protection in the United States. Any CRS Report may be
reproduced and distributed in its entirety without permission from CRS. However, as a CRS Report may include
copyrighted images or material from a third party, you may need to obtain the permissio n of the copyright holder if you
wish to copy or otherwise use copyrighted material.

https://crsreports.congress.gov | IF11789 · VERSION 1 · NEW

---