Credit CDC Selected Characteristics of SARS-CoV-2 Variants of Interest
#15,920
While thousands of COVID variants have been detected around the world, only a handful have been identified as having traits that make them potentially more dangerous than `Classic COVID', which has been circulating for more than a year.
While the nomenclature, and number of variants, varies by nation - here in the United States - the CDC has identified 4 Variants of Interest (VOIs) and 5 Variants of Concern (VOCs). From the SARS-CoV-2 Variant Classifications and Definitions webpage (updated 4/21), we get the following synopsis.
Key Points:
- 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.
- A US government interagency group developed a Variant Classification scheme that defines three classes of SARS-CoV-2 variants:
- The B.1.526, B.1.526.1, B.1.525, and P.2 variants circulating in the United States are classified as variants of interest.
- The B.1.1.7, B.1.351, P.1, B.1.427, and B.1.429 variants circulating in the United States are classified as variants of concern.
- To date, no variants of high consequence have been identified in the United States.
- In laboratory studies, specific monoclonal antibody treatments may be less effective for treating cases of COVID-19 caused by variants with the L452R or E484K substitution in the spike protein.
- L452R is present in B.1.526.1, B.1.427, and B.1.429.
- E484K is present in B.1.525, P.2, P.1, and B.1.351, but only some strains of B.1.526 and B.1.1.7.
Viruses constantly change through mutation. A variant has one or more mutations that differentiate it from other variants in circulation. As expected, multiple variants of SARS-CoV-2 have been documented in the United States and globally throughout this pandemic. To inform local outbreak investigations and understand national trends, scientists compare genetic differences between viruses to identify variants and how they are related to each other.
As new variants emerge, demonstrate an enhanced threat, and begin to spread geographically they may be added to theses lists. Some variants, currently on the watchlist, may be dropped. Others may be elevated from VOI to VOC status, or demoted. This is a constantly evolving situation.
For many of these emerging variants, we have relatively little concrete data. While the P.1 Brazilian variant is on the VOC list, less is known about the P.2 variant (also from Brazil), and so it remains on the VOI list.
Every week, however, more and more information emerges on these lesser known variants, primarily from reports published in scientific journals, like the CDC's EID Journal. Adding to that knowledge, yesterday the following research article was published on a reinfection case in Brazil involving the P.2 lineage.
I've only reproduced the link, Abstract, and discussion. Follow the link to read the report in its entirety. I'll have a brief postscript when you return.
Volume 27, Number 7—July 2021
Research
Severe Acute Respiratory Syndrome Coronavirus 2 P.2 Lineage Associated with Reinfection Case, Brazil, June–October 2020
Figure 1 Figure 2 Table Appendix RIS [TXT - 2 KB]Paola Cristina Resende, João Felipe Bezerra, Romero Henrique Teixeira Vasconcelos, Ighor Arantes, Luciana Appolinario, Ana Carolina Mendonça, Anna Carolina Paixao, Ana Carolina Duarte, Thauane Silva, Alice Sampaio Rocha, Ana Beatriz Machado Lima, Alex Pauvolid-Corrêa, Fernando Couto Motta, Dalane Loudal Florentino Teixeira, Thiago Franco de Oliveira Carneiro, Francisco Paulo Freire Neto, Isabel Diniz Herbster, Anderson Brandao Leite, Irina Nastassja Riediger, Maria do Carmo Debur, Felipe Gomes Naveca, Walquiria Almeida, Mirian Livorati, Gonzalo Bello1, and Marilda M. Siqueira1
Abstract
A 37-year-old healthcare worker from the northeastern region of Brazil experienced 2 clinical episodes of coronavirus disease. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by reverse transcription PCR in samples collected 116 days apart. Whole-genome sequencing revealed that the 2 infections were caused by the most prevalent lineage in Brazil, B.1.1.33, and the emerging lineage P.2.The first infection occurred in June 2020; Bayesian analysis suggests reinfection at some point during September 14–October 11, 2020, a few days before the second episode of coronavirus disease.Of note, P.2 corresponds to an emergent viral lineage in Brazil that contains the mutation E484K in the spike protein. The P.2 lineage was initially detected in the state of Rio de Janeiro, and since then it has been found throughout the country. Our findings suggest not only a reinfection case but also geographic dissemination of the emerging Brazil clade P.2.
The efficiency and persistence of natural protective immunity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination are currently unknown. Reinfection cases have been reported in different countries (1), but the differentiation between cases of reinfection and viral persistence remains a challenge. The detection of 2 coronavirus disease (COVID-19) episodes >90 days apart and caused by 2 different lineages of SARS-CoV-2 remains the most reliable evidence of reinfection (2).
In this article, we describe a reinfection case and highlight details about the genomic features of the 2 COVID-19 episodes. In addition, we demonstrate that the virus in the second episode was related to the emerging variant of interest (VOI) designated as lineage P.2, which is currently circulating throughout Brazil.
(SNIP)
Discussion
We demonstrate that this reinfection case in Brazil corresponds to a primary infection with the lineage B.1.1.33 and a reinfection with the VOI P.2, which harbors the mutation S-E484K. The age of the common ancestor of the P.2 virus of the reinfection case and a nonrelated virus sampled in the state of Amazonas provide a maximum limit for the reinfection episode during September 14–October 11. The estimated period excludes the possibility of long-term persistence of the P.2 virus since primary infection (before June 23, 2020).
Of note, the reinfection case reported here coincides with a recently reported case in the state of Bahia that also described a primary infection with the B.1.1.33 variant and reinfection with the P.2 viral variants (14). These studies also confirm that the P.2 initially described in the state of Rio de Janeiro (13) is more widely distributed across different states in Brazil. Our analysis supports that the P.2 lineage probably emerged in Rio de Janeiro around late August, but defining the precise location and time of emergence of this novel lineage will require a denser sampling from different states in Brazil from the second half of 2020.
The mutation E484K is located in the receptor-binding domain and has also been recently described in multiple SARS-CoV-2 VOI and variants of concern rapidly spreading in the Americas, Europe, and Africa (15). The rapid dissemination of these variants, combined with the ability of viruses harboring the mutation E484K to potentially escape from neutralizing antibodies mounted for older lineages (13,16), should raise concern about the potential effect on infectivity, pathogenicity, and reinfection.
We also speculate that the reinfection case described resulted from a weak and transient protective immunity that occurred after primary infection. Consistent with this notion, despite the positive result for IgG by CMIA in the serum sample collected 2 months after the second SARS-CoV-2 infection, PRNT90 titers for all 4 lineages of SARS-CoV-2 tested, including P.2, were below the detectable level. The prevalence of neutralizing antibodies also varies among patients and low levels or absence of neutralizing antibody has been reported in mildly affected COVID-19 convalescent patients (17). In a study conducted with SARS-CoV-2–infected healthcare workers, neutralizing activity rapidly declined and might even be lost beginning 2 months after disease onset (18).
Whether reinfected persons might contribute substantially to the onwards transmission of SARS-CoV-2 in the population is currently unclear. The negative results from viral isolation after 2 sequential passages of nasopharyngeal swab specimens suggests absence (or low levels) of infectious virus in the second episode of COVID-19. Viral isolation prevalence among COVID-19 patient samples varies and is usually lower in mild infections with high Ct values (17).
Our results demonstrate that previous exposure to SARS-CoV-2 might not guarantee immunity, and that sequential infections might not mount detectable neutralizing antibodies in all cases. These findings reinforce the need to maintain nonpharmacologic protective measures not only by persons who test negative but also for those who have already tested positive for SARS-CoV-2. Characterization of the immune response in persons who become reinfected with SARS-CoV-2 will be crucial to learn more about the role of viral and host factors on this rare phenotype.
Dr. Paola Cristina Resende is a public health researcher at the Fundação Oswaldo Cruz (FIOCRUZ), Brazil, and a member of the Fiocruz COVID-19 Genomic Surveillance Network. Her primary research interests are genetic epidemiology and molecular evolution of viruses.
Earlier this week, in EID Journal: Reinfection & Viral Shedding Of HCW's With Non-VOC COVID - Brazil, 2020, we looked at 4 Brazilian HCWs who were reinfected with more mundane COVID variants, which suggests it doesn't necessarily require the presence of one of the more exotic mutations (e.g. E484K, L452R, etc.) to erode `herd immunity'.
For now, it isn't clear on how common reinfections are, or are likely to become.
Two weeks ago, in order to better gauge the threat, we looked at the ECDC's attempt to standardize case definitions and reporting (see ECDC Technical Rpt: Reinfection with SARS-CoV-2 (Surveillance Case Definition).
Whether driven by new variants, or facilitated by weak or short-duration post-infection immunity, the ability of SARS-CoV-2 to reinfect hosts - or breakthrough vaccination protection (see CDC: COVID-19 Breakthrough Case Investigations and Reporting) - remains largely unquantified.
