SMART Binary: New Sample Size Planning Resources for SMART Studies with Binary Outcome Measurements.

Sequential Multiple-Assignment Randomized Trials (SMARTs) play an increasingly important role in psychological and behavioral health research. This experimental approach enables researchers to answer scientific questions about how to sequence and match interventions to the unique, changing needs of individuals. A variety of sample size planning resources for SMART studies have been developed, enabling researchers to plan SMARTs for addressing different types of scientific questions. However, relatively limited attention has been given to planning SMARTs with binary (dichotomous) outcomes, which often require higher sample sizes relative to continuous outcomes. Existing resources for estimating sample size requirements for SMARTs with binary outcomes do not consider the potential to improve power by including a baseline measurement and/or multiple repeated outcome measurements. The current paper addresses this issue by providing sample size planning simulation procedures and approximate formulas for two-wave repeated measures binary outcomes (i.e., two measurement times for the outcome variable, before and after intervention delivery). The simulation results agree well with the formulas. We also discuss how to use simulations to calculate power for studies with more than two outcome measurement occasions. Results show that having at least one repeated measurement of the outcome can substantially improve power under certain conditions.

Design of experiments with sequential randomizations on multiple timescales: the hybrid experimental design.

Psychological interventions, especially those leveraging mobile and wireless technologies, often include multiple components that are delivered and adapted on multiple timescales (e.g., coaching sessions adapted monthly based on clinical progress, combined with motivational messages from a mobile device adapted daily based on the person's daily emotional state). The hybrid experimental design (HED) is a new experimental approach that enables researchers to answer scientific questions about the construction of psychological interventions in which components are delivered and adapted on different timescales. These designs involve sequential randomizations of study participants to intervention components, each at an appropriate timescale (e.g., monthly randomization to different intensities of coaching sessions and daily randomization to different forms of motivational messages). The goal of the current manuscript is twofold. The first is to highlight the flexibility of the HED by conceptualizing this experimental approach as a special form of a factorial design in which different factors are introduced at multiple timescales. We also discuss how the structure of the HED can vary depending on the scientific question(s) motivating the study. The second goal is to explain how data from various types of HEDs can be analyzed to answer a variety of scientific questions about the development of multicomponent psychological interventions. For illustration, we use a completed HED to inform the development of a technology-based weight loss intervention that integrates components that are delivered and adapted on multiple timescales.

A Causal Approach to Functional Mediation Analysis with Application to a Smoking Cessation Intervention.

The increase in the use of mobile and wearable devices now allows dense assessment of mediating processes over time. For example, a pharmacological intervention may have an effect on smoking cessation via reductions in momentary withdrawal symptoms. We define and identify the causal direct and indirect effects in terms of potential outcomes on the mean difference and odds ratio scales, and present a method for estimating and testing the indirect effect of a randomized treatment on a distal binary variable as mediated by the nonparametric trajectory of an intensively measured longitudinal variable (e.g., from ecological momentary assessment). Coverage of a bootstrap test for the indirect effect is demonstrated via simulation. An empirical example is presented based on estimating later smoking abstinence from patterns of craving during smoking cessation treatment. We provide an R package, funmediation, available on CRAN at https://cran.r-project.org/web/packages/funmediation/index.html, to conveniently apply this technique. We conclude by discussing possible extensions to multiple mediators and directions for future research.

Sensitivity and specificity of information criteria.

Information criteria (ICs) based on penalized likelihood, such as Akaike's information criterion (AIC), the Bayesian information criterion (BIC) and sample-size-adjusted versions of them, are widely used for model selection in health and biological research. However, different criteria sometimes support different models, leading to discussions about which is the most trustworthy. Some researchers and fields of study habitually use one or the other, often without a clearly stated justification. They may not realize that the criteria may disagree. Others try to compare models using multiple criteria but encounter ambiguity when different criteria lead to substantively different answers, leading to questions about which criterion is best. In this paper we present an alternative perspective on these criteria that can help in interpreting their practical implications. Specifically, in some cases the comparison of two models using ICs can be viewed as equivalent to a likelihood ratio test, with the different criteria representing different alpha levels and BIC being a more conservative test than AIC. This perspective may lead to insights about how to interpret the ICs in more complex situations. For example, AIC or BIC could be preferable, depending on the relative importance one assigns to sensitivity versus specificity. Understanding the differences and similarities among the ICs can make it easier to compare their results and to use them to make informed decisions.

The Interpretation of Statistical Power after the Data have been Gathered.

Post-hoc power estimates (power calculated for hypothesis tests after performing them) are sometimes requested by reviewers in an attempt to promote more rigorous designs. However, they should never be requested or reported because they have been shown to be logically invalid and practically misleading. We review the problems associated with post-hoc power, particularly the fact that the resulting calculated power is a monotone function of the p-value and therefore contains no additional helpful information. We then discuss some situations that seem at first to call for post-hoc power analysis, such as attempts to decide on the practical implications of a null finding, or attempts to determine whether the sample size of a secondary data analysis is adequate for a proposed analysis, and consider possible approaches to achieving these goals. We make recommendations for practice in situations in which clear recommendations can be made, and point out other situations where further methodological research and discussion are required.

Dynamic Features of Problematic Drinking: Alcohol Use Disorder Latent Classes Across Ages 18-64.

AIMS: Alcohol use disorders (AUDs) are linked with numerous severe detrimental outcomes. Evidence suggests that there is a typology of individuals with an AUD based on the symptoms they report. Scant research has identified how these groups may vary in prevalence by age, which could highlight aspects of problematic drinking behavior that are particularly salient at different ages. Our study aimed to (a) identify latent classes of drinkers with AUD that differ based on symptoms of AUD and (b) examine prevalences of latent classes by age. SHORT SUMMARY: Our findings advocate for personalized treatment approaches for AUD and highlight the need for carefully considering the role of age in prevention and intervention efforts. METHODS: We used data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III). Current drinkers aged 18-64 who met criteria for a past-year AUD were included (n = 5402). RESULTS: Latent class analysis (LCA) based on 11 AUD criteria revealed 5 classes: 'Alcohol-Induced Injury' (25%), 'Highly Problematic, Low Perceived Life Interference' (21%), 'Adverse Effects Only' (34%), 'Difficulty Cutting Back' (13%) and 'Highly Problematic' (7%). Using time-varying effect modeling (TVEM), each class was found to vary in prevalence across age. The Adverse Effects Only and Highly Problematic, Low Perceived Life Interference classes were particularly prevalent among younger adults, and the Difficulty Cutting Back and Alcohol-Induced Injury classes were more prevalent as age increased. CONCLUSIONS: Findings suggest that experience of AUD is not only heterogeneous in nature but also that the prevalence of these subgroups vary across age.

Inverse Propensity Score Weighting with a Latent Class Exposure: Estimating the Causal Effect of Reported Reasons for Alcohol Use on Problem Alcohol Use 16 Years Later.

Latent class analysis (LCA) has proven to be a useful tool for identifying qualitatively different population subgroups who may be at varying levels of risk for negative outcomes. Recent methodological work has improved techniques for linking latent class membership to distal outcomes; however, these techniques do not adjust for potential confounding variables that may provide alternative explanations for observed relations. Inverse propensity score weighting provides a way to account for many confounders simultaneously, thereby strengthening causal inference of the effects of predictors on outcomes. Although propensity score weighting has been adapted to LCA with covariates, there has been limited work adapting it to LCA with distal outcomes. The current study proposes a step-by-step approach for using inverse propensity score weighting together with the "Bolck, Croon, and Hagenaars" approach to LCA with distal outcomes (i.e., the BCH approach), in order to estimate the causal effects of reasons for alcohol use latent class membership during the year after high school (at age 19) on later problem alcohol use (at age 35) with data from the longitudinal sample in the Monitoring the Future study. A supplementary appendix provides evidence for the accuracy of the proposed approach via a small-scale simulation study, as well as sample programming code to conduct the step-by-step approach.

A Data Analysis Method for Using Longitudinal Binary Outcome Data from a SMART to Compare Adaptive Interventions.

Sequential multiple assignment randomized trials (SMARTs) are a useful and increasingly popular approach for gathering information to inform the construction of adaptive interventions to treat psychological and behavioral health conditions. Until recently, analysis methods for data from SMART designs considered only a single measurement of the outcome of interest when comparing the efficacy of adaptive interventions. Lu et al. proposed a method for considering repeated outcome measurements to incorporate information about the longitudinal trajectory of change. While their proposed method can be applied to many kinds of outcome variables, they focused mainly on linear models for normally distributed outcomes. Practical guidelines and extensions are required to implement this methodology with other types of repeated outcome measures common in behavioral research. In this article, we discuss implementation of this method with repeated binary outcomes. We explain how to compare adaptive interventions in terms of various summaries of repeated binary outcome measures, including average outcome (area under the curve) and delayed effects. The method is illustrated using an empirical example from a SMART study to develop an adaptive intervention for engaging alcohol- and cocaine-dependent patients in treatment. Monte Carlo simulations are provided to demonstrate the good performance of the proposed technique.

Two-Part Predictors in Regression Models.

Researchers often build regression models to relate a response to a set of predictor variables. In some cases, there are predictors that apply to some participants, or to some measurement occasions, but not others. For example, a romantic partner's substance use may be a key predictor of one's own substance use. However, not all participants have a partner, and in a longitudinal study, participants may have a partner during only some occasions. This could be viewed as missing data, but of a very distinctive type: the values are not just unknown but also undefined. In this paper, we present a simple method to accommodate this situation, along with a motivating example, the algebraic justification, a simulation study, and examples on how to carry out the technique.

Time-varying effect models for ordinal responses with applications in substance abuse research.

Ordinal responses are very common in longitudinal data collected from substance abuse research or other behavioral research. This study develops a new statistical model with free SAS macros that can be applied to characterize time-varying effects on ordinal responses. Our simulation study shows that the ordinal-scale time-varying effects model has very low estimation bias and sometimes offers considerably better performance when fitting data with ordinal responses than a model that treats the response as continuous. Contrary to a common assumption that an ordinal scale with several levels can be treated as continuous, our results indicate that it is not so much the number of levels on the ordinal scale but rather the skewness of the distribution that makes a difference on relative performance of linear versus ordinal models. We use longitudinal data from a well-known study on youth at high risk for substance abuse as a motivating example to demonstrate that the proposed model can characterize the time-varying effect of negative peer influences on alcohol use in a way that is more consistent with the developmental theory and existing literature, in comparison with the linear time-varying effect model.

Self-relevant appeals to engage in self-monitoring of alcohol use: A microrandomized trial.

OBJECTIVE: While self-monitoring can help mitigate alcohol misuse in young adults, engagement with digital self-monitoring is suboptimal. The present study investigates the utility of two types of digital prompts (reminders) to encourage young adults to self-monitor their alcohol use. These prompts leverage information that is self-relevant (i.e., represents and is valuable) to the person. METHOD: Five hundred ninety-one college students (Mage = 18; 61% = female, 76% = White) were enrolled in an 8-week intervention study involving biweekly digital self-monitoring of their alcohol use. At baseline, participants selected an item they would like to purchase for themselves and their preferred charitable organization. Then, biweekly, participants were microrandomized to a prompt highlighting the opportunity to either (a) win their preferred item (self-interest prompt); or (b) donate to their preferred charity (prosocial prompt). Following self-monitoring completion, participants allocated reward points toward lottery drawings for their preferred item or charity. RESULTS: The self-interest (vs. prosocial) prompt was significantly more effective in promoting proximal self-monitoring at the beginning of the study, Est = exp(.14) = 1.15; 95% confidence interval (CI) [1.01, 1.29], whereas the prosocial (vs. self-interest) prompt was significantly more effective at the end, Est = exp(-.17) = 0.84; 95% CI [0.70, 0.98]. Further, the prosocial (vs. self-interest) prompt was significantly more effective among participants who previously allocated all their reward points to drawings for their preferred item, Est = exp(-.15) = 0.86; 95% CI [.75, .97]. CONCLUSIONS: These results suggest that the advantage of prompts that appeal to a person's self-interest (vs. prosocial) motives varies over time and based on what reward options participants prioritized in previous decisions. Theoretical and practical implications for intervention design are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Association between neighborhood disadvantage and children's oral health outcomes in urban families in the Chicago area.

Purpose: The prevalence of childhood caries in urban Chicago, compared with national and state data, indicates that neighborhood context influences oral health. Our objective was to delineate the influence of a child's neighborhood on oral health outcomes that are predictive of caries (toothbrushing frequency and plaque levels). Methods: Our study population represents urban, Medicaid-enrolled families in the metropolitan Chicago area. Data were obtained from a cohort of participants (child-parent dyads) who participated in the Coordinated Oral Health Promotion (CO-OP) trial at 12 months of study participation (N = 362). Oral health outcomes included toothbrushing frequency and plaque levels. Participants' neighborhood resource levels were measured by the Area Deprivation Index (ADI). Linear and logistic regression models were used to measure the influence of ADI on plaque scores and toothbrushing frequency, respectively. Results: Data from 362 child-parent dyads were analyzed. The mean child age was 33.6 months (SD 6.8). The majority of children were reported to brush at least twice daily (n = 228, 63%), but the mean plaque score was 1.9 (SD 0.7), classified as "poor." In covariate-adjusted analyses, ADI was not associated with brushing frequency (0.94, 95% CI 0.84-1.06). ADI was associated with plaque scores (0.05, 95% CI 0.01-0.09, p value = 0.007). Conclusions: Findings support the hypothesis that neighborhood-level factors influence children's plaque levels. Because excessive plaque places a child at high risk for cavities, we recommend the inclusion of neighborhood context in interventions and policies to reduce children's oral health disparities. Existing programs and clinics that serve disadvantaged communities are well-positioned to support caregivers of young children in maintaining recommended oral health behaviors.

Time-varying model of engagement with digital self reporting: Evidence from smoking cessation longitudinal studies.

Objective: Insufficient engagement is a critical barrier impacting the utility of digital interventions and mobile health assessments. As a result, engagement itself is increasingly becoming a target of studies and interventions. The purpose of this study is to investigate the dynamics of engagement in mobile health data collection by exploring whether, how, and why response to digital self-report prompts change over time in smoking cessation studies. Method: Data from two ecological momentary assessment (EMA) studies of smoking cessation among diverse smokers attempting to quit (N = 573) with a total of 65,974 digital self-report prompts. We operationalize engagement with self-reporting in term of prompts delivered and prompt response to capture both broad and more granular engagement in self-reporting, respectively. The data were analyzed to describe trends in prompt delivered and prompt response over time. Time-varying effect modeling (TVEM) was employed to investigate the time-varying effects of response to previous prompt and the average response rate on the likelihood of current prompt response. Results: Although prompt response rates were relatively stable over days in both studies, the proportion of participants with prompts delivered declined steadily over time in one of the studies, indicating that over time, fewer participants charged the device and kept it turned on (necessary to receive at least one prompt per day). Among those who did receive prompts, response rates were relatively stable. In both studies, there is a significant, positive and stable relationship between response to previous prompt and the likelihood of response to current prompt throughout all days of the study. The relationship between the average response rate prior to current prompt and the likelihood of responding to the current prompt was also positive, and increasing with time. Conclusion: Our study highlights the importance of integrating various indicators to measure engagement in digital self-reporting. Both average response rate and response to previous prompt were highly predictive of response to the next prompt across days in the study. Dynamic patterns of engagement in digital self-reporting can inform the design of new strategies to promote and optimize engagement in digital interventions and mobile health studies.

Using the multiphase optimization strategy to adapt cognitive processing therapy (CPT MOST): study protocol for a randomized controlled factorial experiment.

BACKGROUND: Approximately ten percent of US military veterans suffer from posttraumatic stress disorder (PTSD). Cognitive processing therapy (CPT) is a highly effective, evidence-based, first-line treatment for PTSD that has been widely adopted by the Department of Veterans Affairs (VA). CPT consists of discrete therapeutic components delivered across 12 sessions, but most veterans (up to 70%) never reach completion, and those who discontinue therapy receive only four sessions on average. Unfortunately, veterans who drop out prematurely may never receive the most effective components of CPT. Thus, there is an urgent need to use empirical approaches to identify the most effective components of CPT so CPT can be adapted into a briefer format. METHODS: The multiphase optimization strategy (MOST) is an innovative, engineering-inspired framework that uses an optimization trial to assess the performance of individual intervention components within a multicomponent intervention such as CPT. Here we use a fractional factorial optimization trial to identify and retain the most effective intervention components to form a refined, abbreviated CPT intervention package. Specifically, we used a 16-condition fractional factorial experiment with 270 veterans (N = 270) at three VA Medical Centers to test the effectiveness of each of the five CPT components and each two-way interaction between components. This factorial design will identify which CPT components contribute meaningfully to a reduction in PTSD symptoms, as measured by PTSD symptom reduction on the Clinician-Administered PTSD Scale for DSM-5, across 6 months of follow-up. It will also identify mediators and moderators of component effectiveness. DISCUSSION: There is an urgent need to adapt CPT into a briefer format using empirical approaches to identify its most effective components. A brief format of CPT may reduce attrition and improve efficiency, enabling providers to treat more patients with PTSD. The refined intervention package will be evaluated in a future large-scale, fully-powered effectiveness trial. Pending demonstration of effectiveness, the refined intervention can be disseminated through the VA CPT training program. TRIAL REGISTRATION: ClinicalTrials.gov NCT05220137. Registration date: January 21, 2022.

MCMTC: A Pragmatic Framework for Selecting an Experimental Design to Inform the Development of Digital Interventions.

Advances in digital technologies have created unprecedented opportunities to deliver effective and scalable behavior change interventions. Many digital interventions include multiple components, namely several aspects of the intervention that can be differentiated for systematic investigation. Various types of experimental approaches have been developed in recent years to enable researchers to obtain the empirical evidence necessary for the development of effective multiple-component interventions. These include factorial designs, Sequential Multiple Assignment Randomized Trials (SMARTs), and Micro-Randomized Trials (MRTs). An important challenge facing researchers concerns selecting the right type of design to match their scientific questions. Here, we propose MCMTC - a pragmatic framework that can be used to guide investigators interested in developing digital interventions in deciding which experimental approach to select. This framework includes five questions that investigators are encouraged to answer in the process of selecting the most suitable design: (1) Multiple-component intervention: Is the goal to develop an intervention that includes multiple components; (2) Component selection: Are there open scientific questions about the selection of specific components for inclusion in the intervention; (3) More than a single component: Are there open scientific questions about the inclusion of more than a single component in the intervention; (4) Timing: Are there open scientific questions about the timing of component delivery, that is when to deliver specific components; and (5) Change: Are the components in question designed to address conditions that change relatively slowly (e.g., over months or weeks) or rapidly (e.g., every day, hours, minutes). Throughout we use examples of tobacco cessation digital interventions to illustrate the process of selecting a design by answering these questions. For simplicity we focus exclusively on four experimental approaches-standard two- or multi-arm randomized trials, classic factorial designs, SMARTs, and MRTs-acknowledging that the array of possible experimental approaches for developing digital interventions is not limited to these designs.

Hybrid Experimental Designs for Intervention Development: What, Why, and How.

Advances in mobile and wireless technologies offer tremendous opportunities for extending the reach and impact of psychological interventions and for adapting interventions to the unique and changing needs of individuals. However, insufficient engagement remains a critical barrier to the effectiveness of digital interventions. Human delivery of interventions (e.g., by clinical staff) can be more engaging but potentially more expensive and burdensome. Hence, the integration of digital and human-delivered components is critical to building effective and scalable psychological interventions. Existing experimental designs can be used to answer questions either about human-delivered components that are typically sequenced and adapted at relatively slow timescales (e.g., monthly) or about digital components that are typically sequenced and adapted at much faster timescales (e.g., daily). However, these methodologies do not accommodate sequencing and adaptation of components at multiple timescales and hence cannot be used to empirically inform the joint sequencing and adaptation of human-delivered and digital components. Here, we introduce the hybrid experimental design (HED)-a new experimental approach that can be used to answer scientific questions about building psychological interventions in which human-delivered and digital components are integrated and adapted at multiple timescales. We describe the key characteristics of HEDs (i.e., what they are), explain their scientific rationale (i.e., why they are needed), and provide guidelines for their design and corresponding data analysis (i.e., how can data arising from HEDs be used to inform effective and scalable psychological interventions).

College students' COVID-19 vaccine beliefs and intentions: Implications for interventions.

On college campuses, effective management of vaccine-preventable transmissible pathogens requires understanding student vaccination intentions. This is necessary for developing and tailoring health messaging to maximize uptake of health information and vaccines. The current study explored students' beliefs and attitudes about vaccines in general, and the new COVID-19 vaccines specifically. This study provides insights into effective health messaging needed to rapidly increase COVID-19 vaccination on college campuses-information that will continue to be informative in future academic years across a broad scope of pathogens. Data were collected from 696 undergraduate students ages 18-29 years old enrolled in a large public university in the Northeast during fall 2020. Data were collected via an online survey. Overall, we found COVID-19 vaccine hesitancy in college students correlated strongly with some concerns about vaccines in general as well as with concerns specific to COVID-19 vaccines. Taken together, these results provide further insight for message development and delivery and can inform more effective interventions to advance critical public health outcomes on college campuses beyond the current pandemic.

Two-Part Models for Father-Child Relationship Variables: Presence in the Child's Life and Quality of the Relationship Conditional on Some Presence.

Parent-child relationship variables are often measured using a two-part approach. For example, when assessing the warmth of the father-child relationship, a child is first asked if they have contact with their father; if so, the level of warmth they feel toward him is ascertained. In this setting, data on the warmth measure is missing for children without contact with their father, and such missing data can pose a significant methodological and substantive challenge when the variable is used as an outcome or antecedent variable in a model. In both cases, it is advantageous to use an analytic method that simultaneously models whether the child has contact with the father, and if they do, the degree to which the father-child relationship is characterized by warmth. This is particularly relevant when the two-part variable is measured over time, as contact status may change. We offer a pragmatic tutorial for using two-part variables in regression models, including a brief overview of growth modeling, an explanation of the techniques to handle two-part variables as predictors and outcomes in the context of growth modeling, examples with real data, and syntax in both R and Mplus for fitting all discussed models.

Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure.

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).

Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure.

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease.