Skip to main content

Our take —

This study used daily case rates and genomic sequences sampled throughout South Africa from May to December 2020 to describe how the SARS-CoV-2 501Y.V2 variant arose in South Africa during the second wave of the nation’s epidemic. The 501Y.V2 variant contains new mutations that appear to lead to increased transmissibility of the virus and may allow for immune escape, although recent data released by Johnson & Johnson indicate that their COVID-19 vaccine still provides protection against 501Y.V2. Continuing to track viral genetic changes will allow public health entities to effectively respond to variants that increase transmission or immune escape. This work clearly illustrates how variants can emerge in areas with ongoing community transmission, reinforcing the importance of public health measures aimed at minimizing the spread of SARS-CoV-2.

Study design

Other

Study population and setting

This study described the emergence and spread of the SARS-CoV-2 501Y.V2 variant during the second wave of the South African epidemic. Daily COVID-19 case rates were obtained from publicly available databases maintained by the National Department of Health and the National Institute for Communicable Diseases. Phylogenetic analysis included SARS-CoV-2 genomic sequences (n=2,759) randomly sampled across South Africa between March and December 2020, and a global background sequence data set (n=2,753). 501Y.V2 variant sequences (n=341) collected between October and December 2020 were used to establish a mutation profile for the variant and to create a structural model of the variant spike protein.

Summary of Main Findings

The second wave of the South African COVID-19 epidemic started in October 2020, beginning with a resurgence of cases in the Nelson Mandela Bay region of the Eastern Cape (EC) and rapidly expanding to include both the Western Cape (WC) and KwaZulu-Natal (KZN). In response, genomic surveillance efforts were intensified in these provinces, leading to the identification of a new variant of concern (501Y.V2). By mid-November, 501Y.V2 became the predominant lineage in EC, WC, and KZN, and preliminary models indicate that its rate of transmission may be increased by as much as 50%. The 501Y.V2 variant contains eight lineage-defining non-synonymous mutations in the spike protein, three of which (K417N, E484K, and N501Y) correspond to the receptor binding domain and have previously been associated with either increased transmissibility or immune escape. Structural modeling demonstrated that two of these mutations (K417N, E484K) are found in key locations targeted by host neutralizing antibodies.

Study Strengths

This study included a large dataset of randomly sampled SARS-CoV-2 whole genome sequences from South Africa, including 341 501Y.V2 sequences. Mutations specific to the 501Y.V2 variant were assessed using structural modeling, estimates of selection pressure, and prior studies.

Limitations

Sequence metadata did not include location information, so health facility location was used to approximate the geographic origin for each sample. Additionally, functional relevance of lineage-defining mutations was assumed based on prior work describing the impact of individual mutations on variants from other areas. Although authors indicate that they have preliminary data supporting the 501Y.V2 variant’s ability to escape neutralization, these data were not presented here.

Value added

This work describes how high levels of SARS-CoV-2 transmission in South Africa led to the emergence and spread of a new variant of concern (501Y.52). This study also describes variant-defining mutations and explores their potential functional relevance in terms of both transmissibility and the ability of 501Y.V2 to evade host immune responses.

Our take —

Several variants with mutations in the S protein, the target of most vaccines including Pfizer/BioNTech, have been identified, and concerns have been raised about the efficacy of the vaccines against these variants. While the data from this study were derived from in-vitro experiments, these findings suggest that antibodies induced by the Pfizer/BioNTech vaccine robustly neutralize the three new variants from the UK, South Africa and Brazil. However, further clinical data will be needed to fully estimate the level of protection that the vaccine provides against these variants.

Study design

Other

Study population and setting

This study analyzed the ability of sera from 15 individuals who received two doses of the Pfizer/BioNTech mRNA vaccine to neutralize several of the newly identified SARS-CoV-2 variants. The authors generated mutated S-proteins from one early viral isolate to contain all the mutations in the variants of interest that were identified in the UK, South Africa and Brazil. To determine the S protein region that is more significant in lowering immune response against viral variants, 2 other viruses were made that have all the deletions seen in the South African plus two other sets of mutations in receptor binding region.

Summary of Main Findings

The study found that the sera from the fully vaccinated participants efficiently neutralized the early US isolate of the virus, as well as all tested variants. Neutralization of the South African variant was lower than other variants, but still robust relative to the US isolate and other variants, with neutralization dilution more than 1:40. Neutralization of viruses with the South African variant deletion, but with different receptor binding region mutations were higher than that of the viruses with all mutations seen in the South African variant, suggesting mutations in the receptor binding region are more significant in antibody neutralization than the deletion.

Study Strengths

The study included analysis of the mutations found in all three of the current variants of interest.

Limitations

This is an in-vitro study that focuses only on the ability of the sera from vaccinated individuals to neutralize the variants of interest. In addition to antibodies, The Pfize/BioNTech vaccine was shown to induce a cell mediated immune response as well. Given that the actual correlate of protection is unknown, further clinical studies are needed to fully determine the actual efficacy of Pfize/BioNTech vaccine against the new variants.

Value added

This study showed that Pfizer/BioNTech (BNT162b2) vaccine-induced neutralizing antibodies are effective against the three main SARS-CoV-2 variants of interests.

Our take —

In this preprint that has not yet been peer-reviewed, the authors report new evidence of alphacoronaviruses and betacoronaviruses in bats sampled in Yunnan, China, in 2019 and 2020. The results contribute to evidence that Rhinolophus species bats are a rich source of viruses related to SARS-CoV and SARS-CoV-2. However, a virus with sufficient similarity to SARS-CoV-2 to represent a direct ancestor in bats was not found in the study.

Study design

Other

Study population and setting

To examine the diversity of coronaviruses circulating in bats in southern China, authors collected samples from 23 bat species in the Xishuangbanna Tropical Botanical Garden and nearby areas in Mengla County, Yunnan province, China between May 2019 and November 2020. In total, 411 samples from 342 bats were collected, including 283 fecal samples, 109 oral swabs, and 19 urine samples. Samples were merged into 100 pooled libraries based on sample type, species, and collection date; 18 pools were discussed in a previous study (https://doi.org/10.1016/j.cub.2020.05.023). Metatranscriptomic sequencing was performed on pools to detect viral RNA and pools that were positive for coronaviruses related to SARS-CoV-2 were further tested using PCR and sequencing to identify individual samples that were positive prior to pooling. In addition to viral detection, the authors used occurrence data and numerous environmental variables to predict the geographic distributions of 49 Rhinolophus bat species in Southeast Asia and China.

Summary of Main Findings

Coronavirus sequences were detected in 40/100 libraries, producing 26 long sequences from 20 libraries. Of the 26 sequences, 9 were identified as the genus Betacoronavirus and 17 were genus Alphacoronavirus. All 9 betacoronaviruses were related to SARS-CoV or SARS-CoV-2. PCR tests confirmed that 9 individual samples from Rhinolophus malayanus, R. pusillus, and R. stheno sampled between May and July 2020 were positive for betacoronaviruses. Two viruses (RmYN01 and RmYN02) closely related to SARS-CoV-2 from one pool of fecal samples from R. malayanus were described previously (https://doi.org/10.1016/j.cub.2020.05.023). Three viruses shared between 91.6 and 93.3% sequence identity across the genome with SARS-CoV and other related viruses from bats sampled previously in Yunnan. Four viruses (RpYN06, RsYN04, RmYN05, and RmYN08) were more similar to SARS-CoV-2. RpYN06 from R. pusillus shared 94.5% sequence identity with SARS-CoV-2 across the genome while the latter three were more distantly related to SARS-CoV-2 and were more similar to pangolin coronaviruses. Models using environmental variables showed high accuracy in their prediction of Rhinolophus bat species distributions, showing that up to 23 Rhinolophus species can coexist in Southeast Asia, particularly in Thailand, Laos, Vietnam, and southern China.

Study Strengths

This is the first study reporting results of new sampling and detection of coronaviruses in bats in China after the beginning of the COVID-19 pandemic. Specific methodological strengths include correcting for the possibility of false positives due to sequencing errors (e.g., index hopping) by removing short sequences with high similarity to others within the same chip and same lane in the sequencer. They also confirmed via RT-PCR which bat samples were positive within the pools with amplified coronavirus sequences. Finally, the identities of bat species that were positive for coronaviruses were confirmed by sequencing mitochondrial DNA.

Limitations

The supplementary material is not currently available with the preprint, so it is unclear how many pools or individual samples from each bat species were positive for coronaviruses. Additionally, the authors only validated the presence of coronaviruses in individual bat samples with PCR for pools positive for betacoronaviruses. Thus, it is not clear which individual bat samples were positive for the alphacoronaviruses described.

Value added

The paper provides valuable new information on the circulation of coronaviruses in bat species in Yunnan sampled in 2019 and throughout 2020. The results indicate multiple betacoronaviruses related to SARS-CoV and SARS-CoV-2 can be found in Rhinolophus species bats in this region. Paired with the ecological modeling of Rhinolophus species ranges, this manuscript contributed to existing evidence that Yunnan and other parts of Southeast Asia are regions with high diversity of Rhinolophus species and are likely important hotspots for betacoronavirus diversity. Nevertheless, the viruses amplified do not provide evidence that bats harbor the direct ancestor of SARS-CoV-2. Even though the described RpYN06 virus was 94.5% similar to SARS-CoV-2 across the whole genome, this virus is still too genetically divergent to be the progenitor of SARS-CoV-2.

Our take —

This study, available as a preprint and thus not yet peer-reviewed, documented the emergence of the P.1 variant of concern in Manaus, Brazil and the wave of COVID-19 infections associated with its spread. The authors demonstrate that this variant is likely more transmissible than other lineages circulating locally, and presented several hypotheses for why this variant may be more transmissible. The paper demonstrated that genomic surveillance is crucial to the detection of new SARS-CoV-2 variants of concern. Further studies will be needed to understand the cause of this increased transmissibility, which may be useful in curtailing the variant’s spread.

Study design

Other

Study population and setting

This study analyzed SARS-CoV-2 genomes from 184 samples from patients seeking COVID-19 testing in Manaus, Brazil, with the goal of understanding the second wave of disease in the region. The 184 genomes were derived from 436 PCR-confirmed or suspected SARS-CoV-2 samples collected between November 1, 2020 and January 9, 2021, and these sequences were analyzed alongside publicly available genomes from Brazil. The authors also used a larger sample of 942 samples from Brazil for which quantitative RT-PCR data were available (cycle threshold [Ct] values) to explore potential viral load differences between sequences belonging to the P.1 lineage identified in Manaus and other virus lineages. Finally, the authors used mobility data (airline data from Brazil’s Civil Aviation Agency and cell phone data from In Loco) to explore movement of the P.1 lineage, and epidemiological data such as death records (from a hospitalization database) to model the transmission dynamics of P.1 and non-P.1 virus.

Summary of Main Findings

The authors found that the second wave of COVID-19 in Manaus, Brazil was associated with the emergence and spread of a new SARS-CoV-2 lineage of concern: P.1. This lineage contains 17 amino acid changes compared to the Wuhan-Hu-1 reference genome, including 10 mutations in the spike protein, and is a descendent of lineage B.1.1.128, which was detected in Brazil in March 2020. The data presented in this study suggest the P.1 lineage emerged approximately one month prior to the resurgence of COVID-19 in Manaus, which supports the hypothesis that the second wave of disease was associated with the new variant. They also found evidence that this variant likely emerged in Manaus, and that the variant spread from Amazonas (the state in which Manaus is located) into Brazil’s southeastern states, a finding supported by both genomic and air travel data. Mathematical modeling showed that virus belonging to the P.1 lineage is likely 1.4–2.2 times more transmissible than local non-P1 lineages, though these results are not generalizable to other settings (since the authors were only able to compare to the other lineages circulating locally). To explain variations in transmissibility, the authors investigated viral Ct values over time, and found that increased transmissibility of P.1 virus could be due to higher viral loads or longer infection, though this finding was inconclusive. The authors also hypothesized that mutations in the receptor binding domain that are present in the P.1 lineage (as well as the B.1.351 lineage of concern) could improve host cell entry, but they are not able to confirm this hypothesis.

Study Strengths

The authors performed robust phylogenetic analyses of SARS-CoV-2 genomes from Brazil, which allowed them to estimate the date and location of emergence of theP.1 variant. The availability of epidemiological and mobility data allowed them to corroborate their findings, lending additional certainty to their conclusions.

Limitations

As the authors point out, their observation of increased transmission potential of the P.1 lineage is specific to the local context – without using a more global dataset, they are not able to make more general conclusions about the transmissibility of the variant. Similarly, not enough data were presented on Ct values (e.g., minimal details on where these samples were from, no lineage information available for the majority of samples, no data presented on what day of infection each sample was tested) to understand if viral loads were truly higher in virus belonging to the P.1 lineage.

Value added

This study documents the emergence of the P.1 variant of concern and describes a large outbreak associated with this new variant. It highlights the importance of tracking these variants and the need for further studies to characterize transmissibility of the variant compared to other circulating lineages, both in Brazil and worldwide.

Our take —

This study aimed to estimate the origin and spread of SARS-CoV-2 in Europe prior to spring 2020 border closures by using a phylodynamic model with geographic structure to SARS-CoV-2 genomes from Hubei, China, and France, Germany, Italy, and 16 other European countries. The results suggest that the event was likely seeded by an earlier transmission event in either Hubei, China, or Germany. These findings suggest that SARS-CoV-2 was introduced from Hubei into France, Germany, Italy, and other European countries approximately two to four times each before March 8, 2020, and that there were approximately 18 estimated introductions from Italy to other European countries from these samples. Prior to the first border closures in Europe, the authors estimated that the rate of occurrence of new cases from within-country transmission was within the bounds of the estimated rate of new cases from migration. These results suggest that community transmission was sustained in Europe prior to border closures and therefore outbreaks would have continued to emerge without re-introduction events from other countries. These types of analyses suggest migration patterns may be a key driver, but bias in sampling limited the study’s ability to trace the exact movement of such a fast spreading virus.

Study design

Other

Study population and setting

The goal of this study was to estimate the origin and spread of SARS-CoV-2 in Europe prior to spring 2020 border closures. This study applied a phylodynamic model with geographic structure to SARS-CoV-2 genomes from Hubei, China, and France, Germany, Italy, and a composite of 16 European countries. All genomic sequences were obtained from GISAID, a global science initiative providing open-access to genomic data. A random selection of 10 sequences from Hubei collected on or before January 23, 2020 were selected to represent the virus origin. Additionally, all available sequences from France, Germany, and Italy collected on or before March 8, 2020 were considered to understand emergence in Europe; and sequences from 16 other European countries collected pre-March 8 were down-sampled to scale with COVID deaths and outbreak size in each country. The study estimated the rate of new cases arising from migration compared with the rate of new cases arising from within region transmission within the European regions. The authors combined case count data and estimates for migration and transmission rates to provide a timeline of early SARS-CoV-2 introduction and spread before border closures were implemented in Europe.

Summary of Main Findings

Findings from this study suggest that the predominant lineage (A2a viruses) spreading in Europe prior to border closures had a most recent common ancestor in Italy between mid-January and early February 2020. The results suggest that this was likely seeded by an earlier transmission event in either Hubei, China, or Germany. These findings suggest that SARS-CoV-2 was introduced from Hubei into France, Germany, Italy, and other European countries approximately two to four times each before March 8, 2020, and that there were approximately 18 estimated introductions from Italy to other European countries from these samples. Prior to the first border closures in Europe, the authors estimated that the rate of occurrence of new cases from within-country transmission was within the bounds of the estimated rate of new cases from migration. Shortly after the first evidence of sustained within-region transmission in Italy, outbreaks in the rest of Europe emerged.

Study Strengths

This study linked a model of viral evolution to describe the mutational process of SAR-CoV-2 to an epidemiological model describing the transmission process, and was able to construct a timeline of early transmission events prior to border closures in Europe.

Limitations

There are several limitations of this study, which the authors acknowledge and attempted to mitigate. Data from early cases identified represented those that were identified by ministries of health, and therefore were not a random sample. However, the model assumed uniform and random sampling of the total infected population in each region and therefore may be subject to bias. The analysis did not consider introduction of cases from any non-European regions other than Hubei; therefore, authors would not have been able to capture transmission from Hubei to Europe through an intermediate country of region. Under-sampling and biased sampling limit the inferences about migrations, and therefore migrations estimated in this analysis give a sense of general dynamics and the number of total migrations rather than provide precise estimates.

Value added

This study provides evidence suggesting the presence of sustained community transmission within European countries prior to border closures. These results suggest that border closure policies alone would not have prevented continued outbreaks within European countries.

Our take —

In this study, the authors found evidence of incidental SARS-CoV-2 infection in escaped American mink captured on farms in Utah, USA, with reported outbreaks of SARS-CoV-2 in the farmed mink population. While the sample size was limited, the results indicate that SARS-CoV-2 infection had not yet established in wildlife populations in Utah, the potential for escaped infected mink to interact with susceptible species, such as wild mink or deer mice, is a potential risk that should be actively managed through surveillance of animals around farms and better management practices to prevent mink escape.

Study design

Other

Study population and setting

Following an outbreak of SARS-CoV-2 on a mink farm in Utah, USA that was confirmed on August 17, 2020, researchers sampled wild mammals around the farm premises and on public lands within a 3.5 km radius. Between August 22 and 30, 2020, 102 animals were captured, including 45 deer mice (Peromyscus maniculatus), 5 Peromyscus spp. mice, 25 house mice (Mus musculus), 3 rock squirrels (Otospermophilus variegatus), 11 presumed escaped American mink (Neovison vison) and 2 presumed wild American mink, 5 raccoons (Procyon lotor), and 6 striped skunks (Mephitis mephitis). Escaped mink were distinguished from wild mink based on their close association with barns and differences in coat color and size. Samples from each animal included oral, nasal, and rectal swabs or washes; tissue specimens; and blood specimens. Samples were tested for the presence of SARS-CoV-2 RNA with two real-time reverse transcription PCR (rRT-PCR) assays targeting the N1 and N2 genes; samples were considered positive only if both N1 and N2 were detected. The presence of SARS-CoV-2 antibodies in sera was tested using a virus neutralization assay in Vero E6 cell culture.

Summary of Main Findings

Of the 11 escaped mink captured on the farm premises, 3 had detectable SARS-CoV-2 in nasal swabs or lung tissue specimens; all animals had detectable neutralizing antibodies against SARS-CoV-2. None of the other captured animals had detectable antibodies, including the wild mink. One rectal swab specimen from a house mouse capture on the farm premises was PCR-positive, but with a high Ct value indicating a low quantity of viral RNA likely resulting from excretion following ingestion of contaminated material rather than from infection. Two deer mice individuals collected from farm premises were positive for SARS-CoV-2 RNA in oral or rectal swabs, although only the N1 gene was detected.

Study Strengths

The detection of both SARS-CoV-2 RNA and neutralizing antibodies helps to distinguish between animals with current infection and past exposure to SARS-CoV-2.

Limitations

Due to the very small sample size and limited geographical scope, it is not possible to know how frequently mink infected with SARS-CoV-2 escape from farms, and how frequently they interact with other wildlife species on or off farm premises. More data is necessary to assess the risk of SARS-CoV-2 establishing ongoing transmission in susceptible wildlife species. Additionally, no sequence data was produced, which would have been useful for comparing with sequences from infected mink inside the farms, although such information is not yet available.

Value added

SARS-CoV-2 outbreaks have been reported on mink farms in multiple European countries and several US states, including Utah, Michigan, Wisconsin, and Oregon. There is concern that infected farms may spread the virus to other farms through movement of animals, people, or materials, including via incidental infection of domestic or wild animals on farm premises. This paper demonstrates that escaped mink had evidence of current or past SARS-CoV-2 infection. While some deer mice captured on farms may have been infected, thereby confirming experimental evidence showing this species is susceptible to infection, SARS-CoV-2 detection was only successful for one target gene and thus may not represent a true infection.

Our take —

In the first month of vaccination against SARS-CoV-2 in the US, over 13 million doses of the Pfizer-BioNTech and Moderna vaccines were administered, and about 7,000 (0.05%) adverse events were reported to a nationwide surveillance network. Over 90% of these were non-serious reactions, of which headache, fatigue, and dizziness were the most common. There were 62 anaphylactic reactions, the proportion of which (0.0004%) is similar to that found with other commonly administered vaccines. Although 113 deaths were reported to the surveillance system, there were no indications that any of these were related to vaccination itself.

Study design

Other

Study population and setting

This was a descriptive analysis of safety data for the Pfizer-BioNTech and Moderna SARS-CoV-2 vaccines during the first month of vaccination in the United States, from December 14, 2020 to January 13, 2021. Data were reported to the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system with follow-up for serious adverse events, and to v-safe, an active safety monitoring system into which patients self-enroll. Serious adverse events reported to VAERS were followed up to obtain medical records, additional health care information, and death certificates and autopsy reports in the case of death. V-safe enrollees are sent links to online surveys via text message, and provide information related to local and systemic vaccine reactions, as well as whether they missed work, could not perform normal activities, or sought medical care (those who seek medical care are contacted by v-safe). Participants are asked about their pregnancy status and pregnancies are followed up through a registry.

Summary of Main Findings

During the first month of vaccination, 13,794,904 vaccine doses were administered. The median age of recipients was 42 years, and 61% were women. During this period, VAERS received 6,994 (0.05%) reports of adverse events. Of these, 6,354 (91%) were classified as non-serious, and 640 (9%) were classified as serious, including 113 deaths (78 of which were among residents of long-term care facilities). For 38 deaths, half of which occurred among residents in long-term care facilities, record review was ongoing at time of publication; for all other deaths, underlying conditions were listed as the primary cause, and there were no causal links seen between vaccination and mortality. There were 62 confirmed cases of anaphylaxis. Headache (22% of those with any adverse event), fatigue (17%), and dizziness (17%) were the most commonly reported symptoms. V-safe respondents who reported adverse events most commonly reported pain at the injection site, fatigue, headache, myalgia, and chills; reactions were most commonly reported the day after vaccination. Reported reactions occurred at similar frequencies with the Pfizer-BioNTech and Moderna vaccines. 10,825 respondents (0.68%) reported being pregnant at the time of vaccination.

Study Strengths

VAERS is a pre-existing national surveillance network with follow-up for serious adverse events. Supplementing results with those from v-safe reinforced findings regarding the most commonly reported events.

Limitations

Because VAERS is a passive surveillance network, underreporting of events is possible due to lack of compliance with reporting requirements. Alternatively, it is possible that the attention and sensitivity surrounding COVID-19 vaccine rollout lowered the threshold for reportable events below that established for other vaccines such as that for seasonal influenza. V-safe relies on self-enrollment and is thus subject to selection effects that limit generalizability of results in unpredictable ways. The total number of vaccines administered was not reported for important strata in VAERS results (e.g., Moderna vs. Pfizer-BioNTech, dose 1 vs. dose 2), limiting comparisons of the incidence of adverse events. Investigations of 38/113 deaths were incomplete at time of publication.

Value added

This is the first comprehensive report of adverse events associated with SARS-CoV-2 vaccination in the United States outside of clinical trials.

Our take —

Results from two nationally representative online panel surveys (September to October 2020 and December 2020) revealed that COVID-19 vaccination intentions increased significantly among adults in the United States (39.4% to 49.1%), and vaccine hesitancy declined nearly across all age groups and socio-demographic strata. Vaccine hesitancy, however, remained high among Black, uninsured, and low-income individuals, respectively, as well as essential workers and adults with underlying medical conditions.

Study design

Other

Study population and setting

From September 3 to October 1, 2020 (baseline) and December 1 to 3, 2020 (endline), adults aged 18 years and older in the United States were recruited to complete an online survey assessing COVID-19 vaccination intentions, measured using a 4-point scale (absolutely certain, very likely, somewhat likely, not likely). Vaccination intentions, including reasons for vaccine hesitancy (among those who self-reported being “not likely” to receive COVID-19 vaccine), were compared over time and across socio-demographic strata.

Summary of Main Findings

From baseline (N = 3,541) to endline (N = 2,003), vaccination intention increased significantly (39.4% to 49.1%), while vaccine hesitancy declined (38.1% vs. 32.1%). Reasons for vaccine hesitancy included concerns over vaccine side effects and safety (29.8%), mistrust in the government (12.5%), and concern about the pace at which COVID-19 vaccines were developed (10.4%). While vaccine hesitancy declined across socio-demographic strata over time, by endline, participants who were Black (46.5%), lacked health insurance (44.5%), lived in nonmetropolitan areas (39.6%), had low (<$35,000) annual household incomes (38.3%), and had secondary or less education (39.1%) reported significantly higher rates of COVID-19 vaccine hesitancy. Among priority groups for U.S. vaccine rollout, vaccine hesitancy declined over time but remained moderate among adults ages 65 and older (18.7%), essential workers (35.4%), and adults with underlying medical conditions (38.3%) by endline.

Study Strengths

The study measured changes in COVID-19 vaccination intentions over time using nationally representative online panel surveys, which allowed investigators to examine longitudinal trends in COVID-19 vaccine acceptance/hesitancy, as well as reasons for vaccine hesitancy.

Limitations

Response options for questions measuring vaccination intentions were collapsed in the analysis, which introduces potential for misclassifying participants’ vaccine intentions and makes estimates incomparable to results from other studies using more nuanced measures of vaccine acceptance/hesitancy. Because data are derived from two separate panel surveys, observations were not available from the same participants over time; as such, longitudinal estimates are calculated at an ecological scale and may not reflect true changes in individuals’ vaccine intentions over time. Additionally, only univariate associations between vaccine hesitancy and socio-demographic factors were reported in the study; these associations may have been confounded by other unmeasured factors, including behavioral determinants (i.e., perceived susceptibility to COVID-19, norms around vaccination). Lastly, adults who were eligible to participate in the online surveys may be substantially different from those who were excluded, which limits the inferences that can be made about the target population for these surveys (i.e., the US general population).

Value added

This is among the first studies to report changes in COVID-19 vaccination intentions among adults in the United States.

Our take —

Qualitative interviews with contact tracers, contact tracing managers, and close contacts being monitored for COVID-19 revealed that limited personal protective equipment, delayed payments to staff, poor coordination between contact tracing and laboratory activities in a centralized system, and patient-level factors (i.e., limited resources for self-quarantine, anticipated stigma) posed early implementation challenges in Ghana’s SARS-CoV-2 contact tracing program. Findings from this study are likely not transferable to other contexts, particularly as the COVID-19 burden has increased in Ghana since April 2020.

Study design

Other

Study population and setting

Between April 6 and 26th, 2020, 27 in-depth interviews were conducted with SARS-CoV-2 contact tracers, contact tracing supervisors, and close contacts under investigation for COVID-19 in the Greater Accra Region of Ghana. Interview transcripts were analyzed thematically to explore experiences implementing and participating in a national contact tracing program implemented in Ghana following its first confirmed case of SARS-CoV-2 on March 12, 2020.

Summary of Main Findings

Contact tracers including qualified health professionals (i.e., epidemiologists, district health officers), were rapidly trained in COVID-19 contact tracing, and deployed in pairs into communities when conducting contact tracing. Primary motivations for complying with quarantine recommendations reported by identified contacts and contact tracers included lockdowns, preventing onward SARS-CoV-2 transmission, and perceived stigma towards those infected with SARS-CoV-2. Quarantine compliance, however, was challenged by limited household resources (i.e. income, food/water) to support self-quarantine, internalized disease stigma by being visited daily by contact tracers, and delays in receiving SARS-CoV-2 test results, which demotivated testing among close contacts and resulted in close contacts questioning the legitimacy of delayed test results. Barriers to effective implementation of contact tracing included limited provision of personal protective equipment (PPE) for contact tracers, delayed salary payments to staff, and suboptimal coordination between contact tracing activities and laboratory testing.

Study Strengths

Investigators interviewed managers and field staff, as well as close contacts being monitored for COVID-19, to more explore different dimensions of and parallel experiences with Ghana’s national contact tracing program for SARS-CoV-2.

Limitations

Results principally focused on describing contact tracing procedures and summarizing experiences implementing contact tracing, rather than outlining solutions adopted to respond to emerging contact tracing challenges and comparing perspectives across participants. Because all interviews were conducted in early April 2020 (during the early stage of Ghana’s COVID-19 epidemic), insights gleaned from interviews may not reflect the experiences implementing contact tracing at later stages in the epidemic, when COVID-19 case burdens were higher. Interviews were also all conducted in a single metropolitan area in Ghana, and results may not be transferable to other regions in Ghana. Fewer than seven interviews were conducted with close contacts being monitored for COVID-19 and contact tracing supervisors, respectively, raising concerns about sufficient thematic saturation within these participant subgroups. Lastly, investigators did not include any index COVID-19 cases in their sampling plan, which could have supplemented perspectives from the participant subgroups actually included in the study.

Value added

This is among the first studies to qualitatively examine early experiences implementing contact tracing for SARS-CoV-2 in sub-Saharan Africa.

Our take —

Sampling of Rhinolophus acuminatus bats in Thailand has detected a new virus related to SARS-CoV-2. While this virus is not the direct genetic ancestor of SARS-CoV-2, these findings expand the possible range of bat hosts of SARS-CoV-2-related viruses, and provides further support for the role of bats as important reservoirs of these viruses. The study also found that Malayan pangolins confiscated in Thailand in 2020 had evidence of exposure to SARS-CoV-2-related viruses, confirming similar reports in China, but without sequences from these animals it is unclear what virus had infected these animals.

Study design

Other

Study population and setting

To investigate the evolutionary origins of SARS-CoV-2 in animals, researchers sampled 100 Rhinolophus acuminatus bats from a roost in an irrigation pipe in Chachoengsao, Thailand, in June 2020. Coronavirus RNA was detected in rectal swabs using PCR targeting the RNA-dependent RNA polymerase gene (RdRp). Samples with high viral RNA levels were chosen for next-generation sequencing to assemble a complete virus genome. Phylogenetic analysis was performed on the RdRp gene, the whole genome, the full-length spike protein, and the spike receptor-binding domain (RBD). The ability of the RBD to bind to the human angiotensin-converting enzyme 2 (ACE2) and enter human cells was evaluated with a binding assay and via infection of cell cultures with vesicular stomatitis virus (VSV) pseudoviruses expressing coronavirus spike protein. In addition to bats, the researchers sampled ten Malayan pangolins (Manis javanica) confiscated at three checkpoint stations central and southern Thailand between February and July 2020; an additional seven Malayan pangolin samples from imported animals confiscated in Guangdong, China, in May 2003 were also included. Serum samples from R. acuminatus and M. javanica were tested for the presence of neutralizing antibodies against SARS-CoV-2 or related viruses.

Summary of Main Findings

Thirteen of the 100 rectal swabs from R. acuminatus were positive for coronavirus RNA, all with an identical RdRp sequence that had 95.86% sequence identity to SARS-CoV-2. Next generation sequencing of five samples with high viral RNA produced nearly identical genomes, the highest quality of which was named RacCS203. The novel coronavirus RacCS203 fits within the phylogenetic group of betacoronaviruses closely related to SARS-CoV-2 found in Rhinolophus bats and trafficked Malayan pangolins. The closest relative of RacCS203 is the RmYN02 virus isolated from R. malayanus in Yunnan province, China, sharing 93.7% sequence identity across the whole genome. Phylogenetic analysis of the RBD indicated that RacCS203 did not cluster closely to SARS-CoV-2 or other related viruses capable of binding human ACE2, which was confirmed through cell experiments, demonstrating that VSV pseudovirus expressing RacCS203 spike was unable to infect cells expressing human ACE2. Serological analysis showed that 4/98 serum samples from R. acuminatus and 1/10 pangolins from Thailand had neutralizing antibodies against SARS-CoV-2 (all four bats had PCR-positive rectal swabs); 1/7 pangolins sampled in China in 2003 had antibodies against SARS-CoV.

Study Strengths

This is this first study to report detection of SARS-CoV-2-related viruses in bats and pangolins sampled in 2020 during the COVID-19 pandemic. The study not only produced a full genome of the novel virus, but also assessed the potential for the virus to enter human cells.

Limitations

Due to the very limited sample size from bats and pangolins, the prevalence and geographic distribution of SARS-CoV-2-related viruses in these animals in Thailand is unclear. While the researchers performed some analysis of the cross-reactivity of SARS-CoV-2 antibodies to other related viruses, it is not clear from this work whether the neutralizing antibodies detected in Thai bats and pangolins were against SARS-CoV-2, RacCS203, or another related but undetected coronavirus. Finally, none of the pangolins were positive for viral RNA, so it is unknown which virus or viruses these animals may have been exposed to and whether this differed from the infections in bats.

Value added

This study expands the observed geographic distribution of SARS-CoV-2 related viruses in bats, which now covers Thailand, Cambodia, southern China, and Japan. In addition, the RacCS203 virus had similar amino acid insertions to RmYN02 in the furin cleavage site of the spike protein. While these insertions had been thought to be unique to SARS-CoV-2, the RacCS203 genome independently confirms similar insertions in a bat virus, providing further evidence that this unique feature in SARS-CoV-2 likely derives from variation in viruses circulating naturally in animal reservoirs.