SARS-CoV-2 containment and elimination strategy will require long-term population-wide prevention measures

By Dr. Tomislav Meštrović, MD, Ph.D.Sep 7 2020

By introducing a model that reveals long SARS-CoV-2 transmission chains and inadequate passive surveillance systems, a new medRxiv* preprint paper shows that bringing the infection completely under control will have to rely on presumptive, stringent, longer and more burdensome population-wide prevention measures already employed against community transmission.

As the world continues to cope with the disruptive global pandemic of the coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is pivotal to understand why the causative agent of the original SARS outbreak (i.e., SARS-CoV-1) followed a dramatically different epidemic trajectory.

Despite the highly similar rapid spread of both pathogens and non-specific symptoms, SARS presented with a significantly higher fatality rate; nonetheless, the epidemic curve of SARS-CoV-1 was swiftly quashed, with only 774 deaths before the primary outbreak ended in July 2003.

The declining probabilities over time, expressed in terms of full viral generation durations (g), each lasting approximately two weeks but overlapping so approximately one week apart for both SARS-CoV-1 and SARS-CoV-2,² for transmission chains seeded by single individual primary cases remain unconfirmed by routine passive surveillance of self-reporting symptomatic cases (P_uc,g), assuming a range of values for the effective reproductive number in the absence of any contact tracing and isolation intervention (R_e). The horizontal dashed lines in both panels represents a probability of 50%, from which median chain length can be interpolated onto the horizontal axis.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

So, on the one hand, we have the original SARS outbreak decisively eradicated, while the COVID-19 pandemic has spiraled wildly out of control. Even more worryingly, why has COVID-19 proven so arduous to eliminate locally, even for countries that managed to shrunk their national outbreaks to only a handful of residual cases?

While pre-symptomatic disease transmission is thought to be a key feature of SARS-CoV-2 epidemiology, primarily by facilitating spread into new contexts, this alone does not automatically preclude effective contact tracing and isolation. Instead, it rather exacerbates the need to do so expeditiously and with greater retrospective reach.

In a new preprint paper, Dr. Gerry F. Killeen from the School of Biological, Earth & Environmental Sciences and Environmental Research Institute of the University College Cork (Ireland) presented a simple deterministic model to outline how SARS-CoV-2 infections result in long transmission chains of several weeks without being detected via conventional, self-reporting, passive surveillance efforts.

A schematic illustration of how (A) SARS-CoV-1 transmission chains may be consistently contained through effective contact tracing and isolation because the vast majority of infections result in clinical symptoms overt enough to motivate self-reporting to health facilities or testing centres, whereas (B) for SARS-CoV-2 only a small minority of infections cause sufficiently overt symptoms to motivate self-reporting, so transmission chains often extend too long before being detected for retrospective contact tracing and isolation to completely contain them.

Modeling the transmission chains

In this model, new infections are assumed to belong in one of three symptomological category outcomes, each associated with a well-defined probability of self-reporting to clinical facilities or disease-specific testing centers.

These categories are the proportion of infected individuals with severe symptoms at some stage of the infections (all reporting for testing), the proportion of infected individuals with mild symptoms during the disease course (sometimes reporting for testing), and the proportion of infected individuals without any obvious symptom (do not self-report for testing).

Moreover, the baseline reproductive number used in this paper specifies an intervention scenario without tracing and contact isolation for confirmed cases identified via routine, symptom-based passive surveillance at testing centers and health facilities.

Implications of the phenomenon

In any case, long and thin transmission chains of SARS-CoV-2 that hinder passive surveillance have several implications according to this model. First and foremost, such surveillance is less sensitive as an indicator of infection-free status at the low reproductive number needed to achieve elimination endpoints, which means follow up periods should be prolonged.

Likewise, reproductive numbers should be kept at the lowest level possible to ensure that lifting the restrictions will not result in a rebound. Still, we have to have in mind that more extended transmission chains at lower reproductive numbers are frequently overly long to trace retrospectively, which makes them underrepresented in surveillance data.

"This analysis also underlines the importance of understanding the big differences that local effective reproductive numbers may have upon the traceability of SARS-CoV-2 infections, and the implications of those detection biases for interpretation of surveillance data", further state study authors in this medRxiv paper.

In instances when surveillance systems are weak or younger age groups without overt symptoms dominate transmission, containment effectiveness of isolation and contact tracing may be more severely restricted – even at the higher reproduction numbers that are linked to larger outbreaks.

Population-wide efforts with 'special ingredients'

"If indeed contact tracing and isolation is far less effective against slow, steady, undetected community transmission of SARS-CoV-2, it follows that containment and elimination efforts will have to rely predominantly upon the more burdensome and presumptive population-wide prevention measures that have proven so effective thus far", conclude study authors.

In a nutshell, in comparison to measures implemented for SARS-CoV-1, COVID-19 suppression efforts will have to be sustained at a very stringent level and for protracted time periods after the last detected case of community transmission.

Finally, taking into account the lack of current alternatives, the most important ingredients that will be needed for many countries to progress towards elimination of SARS-CoV-2 transmission are political will, ambition, persistence, patience, and ample public support.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources