Geospatial Analysis of COVID-19: A Scoping Review.

The outbreak of SARS-CoV-2 in Wuhan, China in late December 2019 became the harbinger of the COVID-19 pandemic. During the pandemic, geospatial techniques, such as modeling and mapping, have helped in disease pattern detection. Here we provide a synthesis of the techniques and associated findings in relation to COVID-19 and its geographic, environmental, and socio-demographic characteristics, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) methodology for scoping reviews. We searched PubMed for relevant articles and discussed the results separately for three categories: disease mapping, exposure mapping, and spatial epidemiological modeling. The majority of studies were ecological in nature and primarily carried out in China, Brazil, and the USA. The most common spatial methods used were clustering, hotspot analysis, space-time scan statistic, and regression modeling. Researchers used a wide range of spatial and statistical software to apply spatial analysis for the purpose of disease mapping, exposure mapping, and epidemiological modeling. Factors limiting the use of these spatial techniques were the unavailability and bias of COVID-19 data-along with scarcity of fine-scaled demographic, environmental, and socio-economic data-which restrained most of the researchers from exploring causal relationships of potential influencing factors of COVID-19. Our review identified geospatial analysis in COVID-19 research and highlighted current trends and research gaps. Since most of the studies found centered on Asia and the Americas, there is a need for more comparable spatial studies using geographically fine-scaled data in other areas of the world.

Non-B variants of HIV-1 in San Francisco, California.

The HIV-1 epidemic in the US has historically been dominated by subtype B. HIV subtype diversity has not been extensively examined in most US cities to determine whether non-B variants have become established, as has been observed in many other global regions. We describe the diversity of non-B variants and present evidence of local transmission of non-B HIV in San Francisco. Viral sequences collected from patients between 2000 and 2016 were matched to the San Francisco HIV/AIDS case registry. HIV subtype was determined using COMET. Phylogenies were reconstructed using the pol region of subtypes A, C, D, G, CRF01_AE, CRF02_AG, and CRF07_BC, with reference sequences from the LANL HIV database. Associations of non-B subtypes and circulating recombinant forms (CRFs) with patient characteristics were assessed using multivariable logistic regression. Out of 11,381 sequences, 10,669 were from 7235 registry cases, of which 141 (2%) had non-B subtypes and CRFs and 72 (1%) had unique recombinant forms. CRF01_AE (0.8%) and subtype C (0.5%) were the most prevalent non-B forms. The frequency of non-B subtypes and CRFs increased in San Francisco during years 2000-2016. Out of 146 transmission events involving non-B study sequences, 18% indicated local transmission within the study population and 74% appeared to be inward migration of the virus. Compared to 7016 cases with only subtype B, 141 cases with non-B sequences were more likely to be of non-US country of birth (aOR = 11.02; p < 0.001), of Asian/Pacific-Islander race/ethnicity (aOR = 3.17; p < 0.001), and diagnosed after 2009 (aOR = 4.81; p < 0.001). Results suggest that most non-B infections were likely acquired outside the US and that local transmission of non-B forms has occurred but so far has not produced extensive transmission networks. Thus, non-B variants were not widely established in San Francisco, an observation that differs from cities worldwide with more diverse epidemics.

Integrating Phylogenetic Biomarker Data and Qualitative Approaches: An example of HIV Transmission Clusters as a Sampling Frame for Semistructured Interviews and Implications for the COVID-19 Era.

Mixed methods studies of human disease that combine surveillance, biomarker, and qualitative data can help elucidate what drives epidemiological trends. Viral genetic data are rarely coupled with other types of data due to legal and ethical concerns about patient privacy. We developed a novel approach to integrate phylogenetic and qualitative methods in order to better target HIV prevention efforts. The overall aim of our mixed methods study was to characterize HIV transmission clusters. We combined surveillance data with HIV genomic data to identify cases whose viruses share enough similarities to suggest a recent common source of infection or participation in linked transmission chains. Cases were recruited through a multi-phase process to obtain consent for recruitment to semi-structured interviews. Through linkage of viral genetic sequences with epidemiological data, we identified individuals in large transmission clusters, which then served as a sampling frame for the interviews. In this article, we describe the multi-phase process and the limitations and challenges encountered. Our approach contributes to the mixed methods research field by demonstrating that phylogenetic analysis and surveillance data can be harnessed to generate a sampling frame for subsequent qualitative data collection, using an explanatory sequential design. The process we developed also respected protections of patient confidentiality. The novel method we devised may offer an opportunity to implement a sampling frame that allows for the recruitment and interview of individuals in high-transmission clusters to better understand what contributes to spread of other infectious diseases, including COVID-19.

How are transgender women acquiring HIV? Insights from phylogenetic transmission clusters in San Francisco.

OBJECTIVE: We explored potential HIV transmission typologies that involve transgender women to obtain insights on sexual and needle-sharing networks as sources of HIV infection. DESIGN: San Francisco residents diagnosed with HIV in care at public facilities who had available viral pol sequences from June 2001 to January 2016 were included in the analysis. METHODS: Viral sequence data were matched to the San Francisco HIV/AIDS Case Registry to obtain demographic and risk classification information. Transmission clusters with at least two cases were identified by bootstrap values at least 90% and mean pairwise genetic distances 0.025 or less substitutions per site. RESULTS: Transgender women represented 275 of 5200 patients; 86 were present in 70 clusters. Four typologies were hypothesized: first, transgender women in clusters with MSM; second, transgender women who inject drugs in clusters with cisgender women and men who inject drugs; third, multiple transgender women in clusters with one man; and fourth, multiple transgender women who do not inject drugs in clusters with men and cisgender women who inject drugs. CONCLUSION: Transmission patterns of transgender women may stand apart from MSM epidemics. Transgender women clustered with people who inject drugs, and with men who have sex with transgender women and cisgender women. Aggregation of transgender women into the category of MSM may obscure understanding of how they acquire HIV and to whom they may transmit infection. Phylogenetic insights strengthen the case that HIV prevention programs for MSM may not be applicable to transgender women or their partners.

Increased uptake of early initiation of antiretroviral therapy and baseline drug resistance testing in San Francisco between 2001 and 2015.

BACKGROUND: Early initiation of antiretroviral therapy (eiART) can improve clinical outcomes for persons with HIV and reduce onward transmission risk. Baseline drug resistance testing (bDRT) can inform regimen selection upon subsequent treatment initiation. We examined the uptake of eiART and bDRT within 3 months and 30 days of HIV diagnosis. METHODS: We analyzed a population-based sample from the San Francisco Department of Public Health HIV/AIDS Case Registry of newly-diagnosed HIV/non-AIDS individuals between 2001 and 2015 who received care at publicly-funded facilities (N = 3,124). RESULTS: Uptake of eiART within 3 months of diagnosis increased significantly from 2001 to 2015 (p<0.001), peaking at 74% in 2015. bDRT uptake also increased significantly (p<0.001), peaking at 55% in 2012. eiART uptake was observed to be significantly associated with gender, age, race/ethnicity and transmission risk. There were no significant differences observed in demographic and risk characteristics of persons receiving bDRT in the more recent years. Of 990 persons diagnosed between 2010 and 2015, eiART uptake within 30 days of diagnosis increased from 13% to 38% (p<0.001); bDRT uptake increased from 35% to 39% but the change was not significant (p = 0.141). CONCLUSIONS: Observed increases in eiART and bDRT uptake from 2010 to 2015 may reflect the adoption of treatment as prevention and a local public health policy statement in 2010 recommending treatment initiation at time of diagnosis irrespective of CD4 count. Concerns about stigma may underlie disparities in eiART, however such concerns would not bear as directly on a provider-initiated laboratory test like bDRT.

Frequent coinfection reduces RNA virus population genetic diversity.

The masking of deleterious mutations by complementation and the reassortment of virus segments (virus sex) are expected to increase population genetic diversity among coinfecting viruses. Conversely, clonally reproducing or noncoinfecting virus populations may experience clonal interference where viral clones compete with one another, preventing selective sweeps. This dynamic reduces the efficiency of selection and increases the genetic diversity. To determine the relative influences of these forces on population genetic diversity, we evolved 6 populations of bacteriophage φ6 under conditions promoting or preventing coinfection. Following 300 generations, we isolated and partially sequenced 10 clones from each population. We found greater diversity among asexual populations than sexual populations. Moreover, sexual populations did not show greater relative fitnesses than asexual populations, implying that reduced genetic variation did not result from purifying selection. However, sexual populations were less genetically robust than asexual populations and likely more prone to the deleterious epistatic effects of mutations. As such, a neutral mutation on the asexually evolved (robust) background could be profoundly deleterious on the sexually evolved (brittle) background. This could facilitate sexual populations undergoing greater purifying selection to remove deleterious mutations, but this selection is not reflected by increases in average population fitness. Our results bolster a growing literature suggesting that RNA virus segmentation is probably not a mechanism that evolved because it provides a generalized benefit of sex.

People fifty years or older now account for the majority of AIDS cases in San Francisco, California, 2010.

People aged 50 and older are an increasing proportion of the population of persons living with AIDS (PLWA) in the USA. We used San Francisco's population-based HIV/AIDS surveillance registry to examine trends in the age distribution of people diagnosed and living with AIDS in San Francisco, California. AIDS case reporting is highly complete. Death ascertainment is complete through 2009 and 95% complete for 2010. At the end of 2010, 9796 persons were living with AIDS in San Francisco. Of these, more than half (5112 or 52%) were 50-years old or older. This proportion has steadily increased since 1990 in San Francisco. Our data also indicate that age at AIDS diagnosis has increased in San Francisco during the years 1990-2010. The proportion of PLWA who are aged 50 years or older is now a majority among PLWA in San Francisco. We believe that San Francisco is the first local jurisdiction in the USA to reach this milestone. The growing population of older persons with AIDS presents new challenges for research, medical care and support services.

Geographic differences in sexual reassortment in RNA phage.

The genetic structure of natural bacteriophage populations is poorly understood. Recent metagenomic studies suggest that phage biogeography is characterized by frequent migration. Using virus samples mostly isolated in Southern California, we recently showed that very little population structure exists in segmented RNA phage of the Cystoviridae family due to frequent segment reassortment (sexual genetic mixis) between unrelated virus individuals. Here we use a larger genetic dataset to examine the structure of Cystoviridae phage isolated from three geographic locations in Southern New England. We document extensive natural variation in the physical sizes of RNA genome segments for these viruses. In addition, consistent with earlier findings, our phylogenetic analyses and calculations of linkage disequilibrium (LD) show no evidence of within-segment recombination in wild populations. However, in contrast to the prior study, our analysis finds that reassortment of segments between individual phage plays a lesser role among cystoviruses sampled in New England, suggesting that the evolutionary importance of genetic mixis in Cystoviridae phage may vary according to geography. We discuss possible explanations for these conflicting results across the studies, such as differing local ecology and its impact on phage growth, and geographic differences in selection against hybrid phage genotypes.

Widespread genetic exchange among terrestrial bacteriophages.

Bacteriophages are the most numerous entities in the biosphere. Despite this numerical dominance, the genetic structure of bacteriophage populations is poorly understood. Here, we present a biogeography study involving 25 previously undescribed bacteriophages from the Cystoviridae clade, a group characterized by a dsRNA genome divided into three segments. Previous laboratory manipulation has shown that, when multiple Cystoviruses infect a single host cell, they undergo (i) rare intrasegment recombination events and (ii) frequent genetic reassortment between segments. Analyzing linkage disequilibrium (LD) within segments, we find no significant evidence of intrasegment recombination in wild populations, consistent with (i). An extensive analysis of LD between segments supports frequent reassortment, on a time scale similar to the genomic mutation rate. The absence of LD within this group of phages is consistent with expectations for a completely sexual population, despite the fact that some segments have >50% nucleotide divergence at 4-fold degenerate sites. This extraordinary rate of genetic exchange between highly unrelated individuals is unprecedented in any taxa. We discuss our results in light of the biological species concept applied to viruses.

The evolution of virulence in pathogens with frequency-dependent transmission.

Frequency-dependent transmission is an important feature of diseases that are sexually transmitted or transmitted by a vector that actively searches for hosts. Here I describe the evolution of virulence in pathogens that have frequency-dependent transmission. I consider two components of virulence--an increase in host mortality due to infection, as is classically described, and a decrease in host fecundity due to infection, because frequency dependence is common among diseases that fully or partially sterilize their hosts. Theoretical predictions pertaining to host-pathogen numerical dynamics can be quite different between pathogens with frequency-dependent transmission and those with density-dependent transmission. In contrast, this study suggests that the principles governing the evolution of virulence that have been established in the context of density-dependent pathogens may also apply (qualitatively) to frequency-dependent pathogens. I examine the evolutionary trajectories of the mortality and sterility components of virulence as well as the role of spatial population structure in the evolution of the sterility component of virulence.

Playing by different rules: the evolution of virulence in sterilizing pathogens.

We investigate the evolution of virulence of pathogens that reduce their hosts' fitness primarily by affecting host fecundity. We show that, under many conditions, such sterilizing pathogens evolve high rather than intermediate levels of virulence, and this pushes the pathogen population and sometimes the host population toward extinction. We also show that spatial population structure can reverse this evolutionary result and allow the persistence of intermediate-virulence pathogens. Thus, spatial population structure may be vital to the persistence of sterilizing pathogens in nature.