Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data (preprint)

The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England; extrapolation to other transmission contexts therefore requires caution.

Estimating the potential impact of COVID-19-related disruptions on HIV incidence and mortality among men who have sex with men in the United States: a modelling study (preprint)

BackgroundDuring the COVID-19 pandemic, gay and other men who have sex with men (MSM) in the United States (US) report similar or fewer sexual partners and reduced HIV testing and care access. Pre-exposure prophylaxis (PrEP) use has declined. We estimated the potential impact of COVID-19 on HIV incidence and mortality among US MSM. MethodsWe used a calibrated HIV transmission model for MSM in Baltimore, Maryland, and available data on COVID-19-related disruptions to predict impacts of data-driven reductions in sexual partners(0%,25%,50%), condom use(5%), HIV testing(20%), viral suppression(10%), PrEP initiations(72%), PrEP use(9%) and ART initiations(50%), exploring different disruption durations and magnitudes. We estimated the median (95% credible interval) change in cumulative new HIV infections and deaths among MSM over one and five years, compared with a scenario without COVID-19-related disruptions. FindingsA six-month 25% reduction in sexual partners among Baltimore MSM, without HIV service changes, could reduce new HIV infections by 12{middle dot}2%(11{middle dot}7,12{middle dot}8%) and 3{middle dot}0%(2{middle dot}6,3{middle dot}4%) over one and five years, respectively. In the absence of changes in sexual behaviour, the six-month data-driven disruptions to condom use, testing, viral suppression, PrEP initiations, PrEP use and ART initiations combined were predicted to increase new HIV infections by 10{middle dot}5%(5{middle dot}8,16{middle dot}5%) over one year, and by 3{middle dot}5%(2{middle dot}1,5{middle dot}4%) over five years. A 25% reduction in partnerships offsets the negative impact of these combined service disruptions on new HIV infections (overall reduction 3{middle dot}9%(-1{middle dot}0,7{middle dot}4%), 0{middle dot}0%(-1{middle dot}4,0{middle dot}9%) over one, five years, respectively), but not on HIV deaths (corresponding increases 11{middle dot}0%(6{middle dot}2,17{middle dot}7%), 2{middle dot}6%(1{middle dot}5,4{middle dot}3%)). The predicted impacts of reductions in partnerships or viral suppression doubled if they lasted 12 months or if disruptions were twice as large. InterpretationMaintaining access to ART and adherence support is of the utmost importance to minimise excess HIV-related mortality due to COVID-19 restrictions in the US, even if accompanied by reductions in sexual partnerships. FundingNIH Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe COVID-19 pandemic and responses to it have disrupted HIV prevention and treatment services and led to changes in sexual risk behaviour in the United States, but the overall potential impact on HIV transmission and HIV-related mortality is not known. We searched PubMed for articles documenting COVID-related disruptions to HIV prevention and treatment and changes in sexual risk behaviour in the United States, published between 1st January and 7th October 2020, with no language restrictions, using the terms COVID* AND (HIV OR AIDS) AND ("United States" OR US). We identified three cross-sectional surveys assessing changes in sexual risk behaviour among men who have sex with men (MSM) in the United States, one finding a reduction, one a slight increase, and one no change in partner numbers during COVID-19 restrictions. Two of these studies also found reductions in reported HIV testing, HIV care and/or access to pre-exposure prophylaxis (PrEP) among MSM due to COVID-19. A separate study from a San Francisco clinic found declines in viral suppression among its clients during lockdown. We searched PubMed for articles estimating the impact of COVID-related disruptions on HIV transmission and mortality published between 1st January 2020 and 12th October 2020, with no language restrictions, using the following terms: COVID* AND model* AND (HIV OR AIDS). We identified two published studies which had used mathematical modelling to estimate the impact of hypothetical COVID-19-related disruptions to HIV programmes on HIV-related deaths and/or new HIV infections in Africa, another published study using modelling to estimate the impact of COVID-19-related disruptions and linked HIV and SARS-CoV-2 testing on new HIV infections in six cities in the United States, and a pre-print reporting modelling of the impact of COVID-19-related disruptions on HIV incidence among men who have sex with men in Atlanta, United States. None of these studies were informed by data on the size of these disruptions. The two African studies and the Atlanta study assessed the impact of disruptions to different healthcare disruptions separately, and all found that the greatest negative impacts on new HIV infections and/or deaths would arise from interruptions to antiretroviral therapy. They all found smaller effects on HIV-related mortality and/or incidence from other healthcare disruptions, including HIV testing, PrEP use and condom supplies. The United States study assessing the impact of linked HIV and SARS-CoV-2 testing estimated that this could substantially reduce HIV incidence. Added value of this studyWe used mathematical modelling to derive estimates of the potential impact of the COVID-19 pandemic and associated restrictions on HIV incidence and mortality among MSM in the United States, directly informed by data from the United States on disruptions to HIV testing, antiretroviral therapy and pre-exposure prophylaxis services and reported changes in sexual risk behaviour during the COVID-19 pandemic. We also assessed the impact of an HIV testing campaign during COVID-19 lockdown. Implications of all the available evidenceIn the United States, maintaining access to antiretroviral therapy and adherence support for both existing and new users will be crucial to minimize excess HIV-related deaths arising from the COVID-19 pandemic among men who have sex with men. While reductions in sexual risk behaviour may offset increases in new HIV infections arising from disruptions to HIV prevention and treatment services, this will not offset the additional HIV-related deaths which are also predicted to occur. There are mixed findings on the impact of an HIV testing campaign among US MSM during COVID-19 lockdown. Together, these studies highlight the importance of maintaining effective HIV treatment provision during the COVID-19 pandemic.

COVID-19 epidemic severity is associated with timing of non-pharmaceutical interventions (preprint)

Background: Unprecedented public health interventions including travel restrictions and national lockdowns have been implemented to stem the COVID-19 epidemic, but the effectiveness of non-pharmaceutical interventions is still debated. International comparisons are hampered by highly variable conditions under which epidemics spread and differences in the timing and scale of interventions. Cumulative COVID-19 morbidity and mortality are functions of both the rate of epidemic growth and the duration of uninhibited growth before interventions were implemented. Incomplete and sporadic testing during the early COVID-19 epidemic makes it difficult to identify how long SARS-CoV-2 was circulating in different places. SARS-CoV-2 genetic sequences can be analyzed to provide an estimate of both the time of epidemic origin and the rate of early epidemic growth in different settings. Methods: We carried out a phylogenetic analysis of more than 29,000 publicly available whole genome SARS-CoV-2 sequences from 57 locations to estimate the time that the epidemic originated in different places. These estimates were cross-referenced with dates of the most stringent interventions in each location as well as the number of cumulative COVID-19 deaths following maximum intervention. Phylodynamic methods were used to estimate the rate of early epidemic growth and proxy estimates of epidemic size. Findings: The time elapsed between epidemic origin and maximum intervention is strongly associated with different measures of epidemic severity and explains 46% of variance in numbers infected at time of maximum intervention. The reproduction number is independently associated with epidemic severity. In multivariable regression models, epidemic severity was not associated with census population size. The time elapsed between detection of initial COVID-19 cases to interventions was not associated with epidemic severity, indicating that many locations experienced long periods of cryptic transmission. Interpretation: Locations where strong non-pharmaceutical interventions were implemented earlier experienced much less severe COVID-19 morbidity and mortality during the period of study.

Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity (preprint)

Global dispersal and increasing frequency of the SARS-CoV-2 Spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of Spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large data set, well represented by both Spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the Spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.

Sequencing analysis of the spread of SARS-CoV2 in the Greater New York City region (preprint)

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 864 SARS-CoV-2 sequences from cases in the New York City metropolitan area during the COVID-19 outbreak in Spring 2020. The majority of cases had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that early transmission was most linked to cases from Europe. Our data are consistent with numerous seeds from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of genomic surveillance in addition to traditional epidemiological indicators.

Genomic epidemiology of a densely sampled COVID19 outbreak in China (preprint)

Analysis of genetic sequence data from the pandemic SARS Coronavirus 2 can provide insights into epidemic origins, worldwide dispersal, and epidemiological history. With few exceptions, genomic epidemiological analysis has focused on geographically distributed data sets with few isolates in any given location. Here we report an analysis of 20 whole SARS-CoV 2 genomes from a single relatively small and geographically constrained outbreak in Weifang, People's Republic of China. Using Bayesian model-based phylodynamic methods, we estimate the reproduction number for the outbreak to be 1.99(95% CI:1.48-3.14). We further estimate the number of infections through time and compare these estimates to confirmed diagnoses by the Weifang Centers for Disease Control. We find that these estimates are consistent with reported cases and there is unlikely to be a large undiagnosed burden of infection over the period we studied.