The SARS-CoV-2 pandemic: remaining uncertainties in our understanding of the epidemiology and transmission dynamics of the virus, and challenges to be overcome

Great progress has been made over the past 18 months in scientific understanding of the biology, epidemiology and pathogenesis of SARS-CoV-2. Extraordinary advances have been made in vaccine development and the execution of clinical trials of possible therapies. However, uncertainties remain, and this review assesses these in the context of virus transmission, epidemiology, control by social distancing measures and mass vaccination and the effect on all of these on emerging variants. We briefly review the current state of the global pandemic, focussing on what is, and what is not, well understood about the parameters that control viral transmission and make up the constituent parts of the basic reproductive number R0. Major areas of uncertainty include factors predisposing to asymptomatic infection, the population fraction that is asymptomatic, the infectiousness of asymptomatic compared to symptomatic individuals, the contribution of viral transmission of such individuals and what variables influence this. The duration of immunity post infection and post vaccination is also currently unknown, as is the phenotypic consequences of continual viral evolution and the emergence of many viral variants not just in one location, but globally, given the high connectivity between populations in the modern world. The pattern of spread of new variants is also examined. We review what can be learnt from contact tracing, household studies and whole-genome sequencing, regarding where people acquire infection, and how households are seeded with infection since they constitute a major location for viral transmission. We conclude by discussing the challenges to attaining herd immunity, given the uncertainty in the duration of vaccine-mediated immunity, the threat of continued evolution of the virus as demonstrated by the emergence and rapid spread of the Delta variant, and the logistics of vaccine manufacturing and delivery to achieve universal coverage worldwide. Significantly more support from higher income countries (HIC) is required in low- and middle-income countries over the coming year to ensure the creation of community-wide protection by mass vaccination is a global target, not one just for HIC. Unvaccinated populations create opportunities for viral evolution since the net rate of evolution is directly proportional to the number of cases occurring per unit of time. The unit for assessing success in achieving herd immunity is not any individual country, but the world

Fig 4 -

The difference between coverage and compliance figures reported by 21 studies as either proportions (A), raw data (B) or other parameters (C). Datapoints are coloured by the study type, either cross-sectional (13 studies, 69 datapoints) or longitudinal (8 studies, 104 datapoints). An average trendline of the reported data is shown in solid grey. The shaded line represents the conditional mean function using a linear model calculated by geom_smooth within the ggplot2 R package [21]. A guideline through intercept = 0 is shown to highlight the discrepancy between the two parameters.</p

A selection of the extracted columns for the 12 studies satisfying the criteria for individual-level data–both annually surveyed by CDD or self-reported by participants (grey shading), and self-reported during a cross-sectional analysis.

Available stratifications of compliance data are shown from the possible categories of age, gender, or location. The species targeted for control by MDA, and the drug offered for which compliance to is measured, is also given. The country, and the type and number of participants is also provided. The terminology used to describe compliance is shown, along with the ‘true’ definition according to this review given the numerator and denominator recorded (where given). Where there are incomplete numerator or denominators provided, compliance can only be assumed given the large heterogeneity of calculations used for the parameter. Abbreviations: ALB–Albendazole, IVM–Ivermectin, LF–lymphatic filariasis, OV–onchocerciasis, SAC–school-aged children, SCH–schistosomiasis, STH–soil-transmitted helminths.</p

Workflow of screening and inclusion of studies as defined by the PRISMA guidelines.

Workflow of screening and inclusion of studies as defined by the PRISMA guidelines.</p

Summary overview of the 89 studies included in the analysis split by the epidemiological classification of cross-sectional or longitudinal data.

The full data extraction of the 165 studies is provided in S2 Data. Frequency and percentage of studies falling into each category is shown as “n (%)”. Note for ‘Sample Population’, each stratification totals the number of studies, whilst the remaining rows of the table represents a single stratum. Abbreviations: LF–lymphatic filariasis, N–number of studies, OV–onchocerciasis, preSAC–preschool-aged children, SAC–school-aged children, SCH–schistosomiasis, STH–soil-transmitted helminths.</p

Decision tree of MDA treatment behaviour, showing the three behavioural decision points of MDA delivery and their definitions, according to these previously defined parameters by Shuford et al. (2016) [8].

Decision tree of MDA treatment behaviour, showing the three behavioural decision points of MDA delivery and their definitions, according to these previously defined parameters by Shuford et al. (2016) [8].</p

Choropleth map of studies published globally from 2016 to 2022 (Papers).

Countries where no papers were published are shown in grey. Four studies are represented as 11 datapoints where studies reported data for more than one country, totalling 96 datapoints from 89 studies. (LF, OV, STH, SCH, Trachoma) Maps showing total population of each country requiring treatment for each of the five (PC)-NTDs. Note: STH map shows total preSAC and SAC population only requiring treatment. All maps have been focused to latitude less than 50 degrees. Data taken from WHO global observatory PCT databank [28]. Abbreviations: LF–lymphatic filariasis, OV–Onchocerciasis, SCH–schistosomiasis, STH–soil-transmitted helminths. Map data acquired from the open source tidyverse package using the map_data() function [29].</p

The search strategy employed to generate the review.

The search strategy employed to generate the review.</p

PRISMA guidelines for full text of review and abstract.

PRISMA guidelines for full text of review and abstract.</p

Data type and definition used to classify 57 compliance papers included in the analysis.

Longitudinal compliance data was reported by both longitudinal studies (cohort, randomised controlled trials) and cross-sectional studies. Abbreviations: CDD–community drug distributor, DOT–directly observed treatment.</p