Bad vibrations: Quantum tunnelling in the context of SARS-CoV-2 infection (preprint)

The SARS-CoV-2 pandemic has added new urgency to the study of viral mechanisms of infection. But while vaccines offer a measure of protection against this specific outbreak, a new era of pandemics has been predicted. In addition to this, COVID-19 has drawn attention to post-viral syndromes and the healthcare burden they entail. It seems integral that knowledge of viral mechanisms is increased through as wide a research field as possible. To this end we propose that quantum biology might offer essential new insights into the problem, especially with regards to the important first step of virus-host invasion. Research in quantum biology often centres around energy or charge transfer. While this is predominantly in the context of photosynthesis there has also been some suggestion that cellular receptors such as olfactory or neural receptors might employ vibration assisted electron tunnelling to augment the lock-and-key mechanism. Quantum tunnelling has also been observed in enzyme function. Enzymes are implicated in the invasion of host cells by the SARS-CoV-2 virus. Receptors such as olfactory receptors also appear to be disrupted by COVID-19. Building on these observations we investigate the evidence that quantum tunnelling might be important in the context of infection with SARS-CoV-2. We illustrate this with a simple model relating the vibronic mode of, for example, a viral spike protein to the likelihood of charge transfer in an idealised receptor. Our results show a distinct parameter regime in which the vibronic mode of the spike protein enhances electron transfer. With this in mind, novel therapeutics to prevent SARS-CoV-2 transmission could potentially be identified by their vibrational spectra.

Implementation of an efficient SARS-CoV-2 specimen pooling strategy for high throughput diagnostic testing (preprint)

The rapid identification and isolation of infected individuals remains a key strategy for controlling the spread of SARS-CoV-2. Frequent testing of populations to detect infection early in asymptomatic or presymptomatic individuals can be a powerful tool for intercepting transmission, especially when the viral prevalence is low. However, RT-PCR testing – the gold standard of SARS-CoV-2 diagnosis – is expensive, making regular testing of every individual unfeasible. Sample pooling is one approach to lowering costs. By combining samples and testing them in groups the number of tests required is reduced, substantially lowering costs. Here we report on the implementation of pooling strategies using 3-d and 4-d hypercubes to test a professional sports team in South Africa. We have shown that infected samples can be reliably detected in groups of 27 and 81, with minimal loss of assay sensitivity for samples with individual Ct values up to 32. We report on automation of sample pooling, using a liquid-handling robot and an automated web interface to identify positive samples. We conclude that hypercube pooling allows for the reliable RT-PCR detection of SARS-CoV-2 infection, at significantly lower cost than lateral flow antigen (LFA) tests.

Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa (preprint)

Continued uncontrolled transmission of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in many parts of the world is creating the conditions for significant virus evolution. Here, we describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y) that may have functional significance. This lineage emerged in South Africa after the first epidemic wave in a severely affected metropolitan area, Nelson Mandela Bay, located on the coast of the Eastern Cape Province. This lineage spread rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces. Whilst the full significance of the mutations is yet to be determined, the genomic data, showing the rapid displacement of other lineages, suggest that this lineage may be associated with increased transmissibility.

Early transmission of SARS-CoV-2 in South Africa: An epidemiological and phylogenetic report (preprint)

Background: The emergence of a novel coronavirus, SARS-CoV-2, in December 2019, progressed to become a world pandemic in a few months and reached South Africa at the beginning of March. To investigate introduction and understand the early transmission dynamics of the virus, we formed the South African Network for Genomics Surveillance of COVID (SANGS_COVID), a network of ten government and university laboratories. Here, we present the first results of this effort, which is a molecular epidemiological study of the first twenty-one SARS-CoV-2 whole genomes sampled in the first port of entry, KwaZulu-Natal (KZN), during the first month of the epidemic. By combining this with calculations of the effective reproduction number (R), we aim to shed light on the patterns of infections that define the epidemic in South Africa. Methods: R was calculated using positive cases and deaths from reports provided by the four major provinces. Molecular epidemiology investigation involved sequencing viral genomes from patients in KZN using ARCTIC protocols and assembling whole genomes using meticulous alignment methods. Phylogenetic analysis was performed using maximum likelihood (ML) and Bayesian trees, lineage classification and molecular clock calculations. Findings: The epidemic in South Africa has been very heterogeneous. Two of the largest provinces, Gauteng, home of the two large metropolis Johannesburg and Pretoria, and KwaZulu-Natal, home of the third largest city in the country Durban, had a slow growth rate on the number of detected cases. Whereas, Western Cape, home of Cape Town, and the Eastern Cape provinces the epidemic is spreading fast. Our estimates of transmission potential for South Africa suggest a decreasing transmission potential towards R=1 since the first cases and deaths have been reported. However, between 06 May and 18 May 2020, we estimate that R was on average 1.39 (1.04 - 2.15, 95% CI). We also demonstrate that early transmission in KZN, and most probably in all main regions of SA, was associated with multiple international introductions and dominated by lineages B1 and B. The study also provides evidence for locally acquired infections in a hospital in Durban within the first month of the epidemic, which inflated early mortality in KZN. Interpretation: This first report of SANGS_COVID consortium focuses on understanding the epidemic heterogeneity and introduction of SARS-CoV-2 strains in the first month of the epidemic in South Africa. The early introduction of SARS-CoV-2 in KZN included caused a localized outbreak in a hospital, provides potential explanations for the initially high death rates in the province. The current high rate of transmission of COVID-19 in the Western Cape and Eastern Cape highlights the crucial need to strength local genomic surveillance in South Africa.