#15,815
While there are multiple COVID variants of concern on the horizon, the two that appear to pose the most immediate threat are the B.1.1.7 variant from the UK, and the B.1.351 variant first detected in South Africa.
- B.1.1.7 appears to be roughly 70% more transmissible than the old `wild type' COVID, and has been tentatively linked to a 40%-70% increased fatality rate (see UK: Updated NERVTAG Report On Increased Severity With COVID Variant B.1.1.7). Based on (admittedly limited) genomic surveillance, it is the variant of concern that has made the greatest inroads into the United States.
- Less is known about the B.1.351 variant, although it is believed to be highly transmissible as well, and it has shown signs of reduced antibody recognition, which may impact the effectiveness of some vaccines and monoclonal antibody treatments, and cause a higher rate of reinfection.
Yesterday the CDC's MMWR published two early releases on these rising threats. While there are no bombshells in either of these reports, they do illustrate how insidiously these variants are spreading around the world.
First stop, a look at the detection - and epidemiological investigation into the first 8 cases - of the B.1.1.7 variant in Minnesota, which was announced in January, 2021. As of their last CDC update, Minnesota has reported an additional 10 cases.
First Identified Cases of SARS-CoV-2 Variant B.1.1.7 in Minnesota — December 2020–January 2021
Early Release / February 17, 2021 / 70
Melanie J. Firestone, PhD1,2; Alexandra J. Lorentz, PhD1; Xiong Wang, PhD, DVM1; Kathryn Como-Sabetti, MPH1; Sara Vetter, PhD1; Kirk Smith, PhD, DVM1; Stacy Holzbauer, DVM1,3; Stephanie Meyer, MPH1; Kristin Ehresmann, MPH1; Richard Danila, PhD1; Ruth Lynfield, MD1
On January 9, 2021, the Minnesota Department of Health (MDH) announced the identification of the SARS-CoV-2 variant of concern (VOC) B.1.1.7, also referred to as 20I/501Y.V1 and VOC 202012/01, in specimens from five persons; on January 25, MDH announced the identification of this variant in specimens from three additional persons. The B.1.1.7 variant, which is reported to be more transmissible than certain other SARS-CoV-2 lineages*,† (1), was first reported in the United Kingdom in December 2020 (1). As of February 14, 2021, a total of 1,173 COVID-19 cases of the B.1.1.7 variant had been identified in 39 U.S. states and the District of Columbia (2). Modeling data suggest that B.1.1.7 could become the predominant variant in the United States in March 2021 (3).
The B.1.1.7 variant has a mutation in the spike protein that causes S-gene target failure (SGTF) in the Thermo Fisher Scientific TaqPath COVID-19 reverse transcription–polymerase chain reaction (RT-PCR) assay. The overall RT-PCR result is positive but is negative for the S-gene target and positive for the other two assay targets; SGTF has served as a proxy for identifying the B.1.1.7 variant (1). The MDH Public Health Laboratory (MDH-PHL) requested SARS-CoV-2 RT-PCR–positive specimens with SGTFs collected during November 1, 2020–January 12, 2021, from clinical laboratories that used the TaqPath assay, and 30 specimens were received. An additional specimen that had been collected from a household contact of a person with an SGTF specimen was requested and obtained from a clinical laboratory using another COVID-19 assay that does not detect SGTFs. MDH-PHL conducted whole genome sequencing to analyze the 31 specimens.§
The SARS-CoV-2 variant B.1.1.7 was identified in eight specimens from Minnesota residents, including six (19%) of the 31 specimens sequenced by MDH-PHL and two specimens sequenced through CDC’s national SARS-CoV-2 surveillance system.¶ The eight specimens were collected during December 18, 2020–January 11, 2021, from eight Minnesota residents in five counties in the Minneapolis–St. Paul metropolitan area. Seven persons were interviewed after receiving positive SARS-CoV-2 test results; after those with the B.1.1.7 variant were identified, MDH case investigators recontacted the patients to obtain additional information on exposures and close contacts. Six of the eight patients were successfully contacted, including one who had not been interviewed previously. This activity was reviewed by CDC and was conducted consistent with applicable federal law and policy.**
The eight persons from whom the specimens were collected ranged in age from 15 to 41 years. Three persons had a history of international travel during the 14 days before illness onset, including two who traveled to West Africa (MN-MDH-2252 and MN-MDH-2254) (Figure) and one who traveled to the Dominican Republic (MN-CDC-STM-0000013).
Three additional persons traveled to California (MN-MDH-2415, MN-MDH-2416, and MN-CDC-STM-153) in the 14 days before illness onset or specimen collection, including one who received a positive test result while in California and isolated there before returning to Minnesota. Five persons reported COVID-19–like symptoms and had illness onset dates during December 16, 2020–January 10, 2021; three were asymptomatic. Two sequences (MN-MDH-2253 and MN-MDH-2255) were identical, and the MN-MDH-2252 sequence differed by one single nucleotide variant (SNV). The three sequences for cases from California clustered together within one to three SNVs and are genetically distinct from the other sequences. Two specimens from international travelers, MN-MDH-2254 and MN-CDC-STM-0000013, did not have sequences similar to those identified in Minnesota.
Persons identified with the variant B.1.1.7 in Minnesota had exposure histories related to travel (six), the household (one), and others in the community (one). None had a history of travel to the United Kingdom, although three persons traveled internationally and three persons traveled domestically in the 14 days before illness onset or specimen collection, including one who received a positive test result before returning to Minnesota.
Identification of this variant in Minnesota, a variant that epidemiologic and genomic evidence suggests has increased transmissibility, highlights the importance of mitigation measures such as mask use, physical distancing, avoiding crowds and poorly ventilated indoor spaces, isolation of persons with diagnosed COVID-19, quarantine of close contacts of persons with COVID-19,†† and adherence to CDC travel guidance§§ to slow transmission. As SARS-CoV-2 continues to evolve, timely genomic surveillance and disease mitigation strategies will be critical for monitoring variant emergence and protecting public health.
In December of 2020 the number of COVID Cases in Zambia increased 16-fold at the same time that the B.1.351 variant was detected in 96% of sequenced samples.
Detection of B.1.351 SARS-CoV-2 Variant Strain — Zambia, December 2020
Early Release / February 17, 2021 / 70
Mulenga Mwenda1*; Ngonda Saasa, PhD2*; Nyambe Sinyange, MD3; George Busby, PhD4; Peter J. Chipimo, MD, PhD3; Jason Hendry, PhD4; Otridah Kapona, MSc3; Samuel Yingst, DVM, PhD5; Jonas Z. Hines, MD5; Peter Minchella, PhD5; Edgar Simulundu, PhD2; Katendi Changula2; King Shimumbo Nalubamba, PhD2; Hirofumi Sawa, PhD6; Masahiro Kajihara, PhD, DVM6; Junya Yamagishi, PhD6; Muzala Kapin’a, MD3; Nathan Kapata, MD, PhD3; Sombo Fwoloshi, MD7; Paul Zulu, MD3; Lloyd B. Mulenga, MD, PhD7; Simon Agolory, MD4; Victor Mukonka, MD, PhD3; Daniel J. Bridges, PhD1
The first laboratory-confirmed cases of coronavirus disease 2019 (COVID-19), the illness caused by SARS-CoV-2, in Zambia were detected in March 2020 (1). Beginning in July, the number of confirmed cases began to increase rapidly, first peaking during July–August, and then declining in September and October (Figure).
After 3 months of relatively low case counts, COVID-19 cases began rapidly rising throughout the country in mid-December. On December 18, 2020, South Africa published the genome of a SARS-CoV-2 variant strain with several mutations that affect the spike protein (2). The variant included a mutation (N501Y) associated with increased transmissibility.†,§ SARS-CoV-2 lineages with this mutation have rapidly expanded geographically.¶,** The variant strain (PANGO [Phylogenetic Assignment of Named Global Outbreak] lineage B.1.351††) was first detected in the Eastern Cape Province of South Africa from specimens collected in early August, spread within South Africa, and appears to have displaced the majority of other SARS-CoV-2 lineages circulating in that country (2).
As of January 10, 2021, eight countries had reported cases with the B.1.351 variant. In Zambia, the average number of daily confirmed COVID-19 cases increased 16-fold, from 44 cases during December 1–10 to 700 during January 1–10, after detection of the B.1.351 variant in specimens collected during December 16–23. Zambia is a southern African country that shares substantial commerce and tourism linkages with South Africa, which might have contributed to the transmission of the B.1.351 variant between the two countries.
Since September 2020, University of Zambia and PATH (https://www.path.orgexternal icon) have routinely been conducting genetic epidemiologic studies using whole genome sequencing (WGS) on SARS-CoV-2–positive specimens. A subset of specimens collected during March 18–December 23, 2020, were sequenced, from which 268 high-quality genomes were generated. Specimens were selected for WGS based on availability and real-time reverse transcription–polymerase chain reaction (RT-PCR) diagnostic test cycle threshold (Ct) values of <30; lower Ct values are correlated with larger amounts of virus in the sample. Sequences were linked to case investigation information including patient age, sex, and geographic location from routine public health data maintained by the Zambia National Public Health Institute. For WGS, complementary DNA was prepared using random primers from viral RNA extracted from SARS-CoV-2 real-time RT-PCR–positive specimens. Multiplex PCR was then performed using custom primers (3) to generate overlapping amplicons for nanopore sequencing on a MinION (Oxford Nanopore Technology, United Kingdom).§§ Consensus sequence reads were generated using the standard ARTIC Network bioinformatic pipeline,¶¶ a system for processing samples from viral disease outbreaks to generate real-time, actionable epidemiologic information.
Among the 23 specimens collected during December 16–23, 22 (96%) were the B.1.351 variant. None of the 245 previously sequenced genomes was from this lineage. Among the 22 specimens containing the variant strain, 21 (95%) contained all nine B.1.351 lineage-defining mutations. Thirteen (57%) were from males, and the median patient age was 32 years (interquartile range = 27–45 years). Specimens with the B.1.351 variant were obtained from persons in four districts (Lusaka, 16; Livingstone, four; Chingola, one; and Chibombo, one) across four provinces (Lusaka, Southern, Copperbelt, and Central). Five (23%) specimens were obtained from persons in two different clusters, with no known epidemiologic links among other cases.
Detection of the B.1.351 variant coincided with a rapid rise in confirmed cases in Zambia. This detection establishes an epidemiologic linkage between COVID-19 outbreaks in Zambia and South Africa. Spread of the B.1.351 variant is of public health concern because of the potential for increased transmissibility and, thus, increases in cases, hospitalizations, and deaths.*** The B.1.351 variant might be associated with higher viral loads and contains another spike protein mutation (E484K) that might hinder antibody binding,†††,§§§ which could blunt naturally developed immunity or reduce vaccine efficacy. The predominance of the B.1.351 variant in a small cohort of recent specimens suggests that it might have become the dominant lineage in Zambia, although additional WGS of specimens from other districts is needed to characterize the full extent of its spread. Further, the available genomic data could not identify when and from where the B.1.351 variant was introduced to Zambia. Because the B.1.351 variant has been detected in Zambia, it might be circulating elsewhere in southern Africa, where many countries reported rapid increases in numbers of COVID-19 cases during December 2020–January 2021.¶¶¶ Phylogenetic analysis and additional sequencing are ongoing to better understand the origin, prevalence, and transmission characteristics of this lineage in Zambia. Expanding capacity for genetic epidemiology in Africa will help strengthen surveillance for the B.1.351 variant as well as early detection of emerging variants that might affect the implementation of vaccination programs.
Corresponding author: Daniel Bridges, dbridges@path.org.
