Coronastream: buckle down for a wild ride
Posted on January 26, 2021 by Dr Tim Inglis
In this special blog series, medical microbiologists led by Dr Tim Inglis summarise some of the research that will be essential to inform COVID-19 countermeasures. Find out more about the project in Dr Inglis' Editorial 'Logic in the time of coronavirus', published in the Journal of Medical Microbiology.
As we enter the second year of this pandemic, the New Year brings new challenges, new variants and new countermeasures. We have to ask how long it takes to learn that stop-start, piecemeal interventions do not constitute a coordinated disease control strategy. As SARS-CoV-2 continues to evolve at a pace that public health struggles to match, you have to wonder whether on—off measures have enabled the virus to adapt its way through each successive evolutionary bottleneck.
The arrival on the scene of a slew of vaccines introduces another level of complexity to an already confusing pandemic landscape. If keeping up with the twists and turns of clinical syndromes, epidemiology, pathophysiology and countermeasures weren’t enough, prepare for a bumpy ride as we pick our way through different flavours of vaccine, at different stages of rollout, with their respective impact on clinical profile, epidemiology and vaccine responsiveness.
In 2021, this monthly blog will continue to reflect on the COVID pandemic. Like SARS-CoV-2, it will evolve from the current authorship arrangements to deliver a greater diversity of insight and opinion.
Congruence: clinico-pathological features
Real Time PCR and Culture-Based Virus Isolation Test in Clinically Recovered Patients: Is the Subject Still Infectious for SARS-CoV2?
Heavy reliance on rt-PCR for detection of SARS-CoV-2 due to its high sensitivity has led to a problem with persistent positive PCR assays during convalescence. This causes practical problems such as known when to release people from hospital or quarantine and providing public health clearance for international air travel.
Manzuelli and colleagues’ study provides useful insight into the difference between a positive PCR assay and viral culture results during recovery from infection. Noting that viral fragment shedding may persist for days or even weeks after recovery, they used viral culture to verify viral clearance. Their subjects ranged from asymptomatic to severe and the specimens were nasopharyngeal swabs. Control swabs were collected on day 14 in asymptomatic subjects and at least three days after clinical remission in symptomatic subjects. The samples from 83/84 patients were viral culture negative and all supernatant PCR results were negative. Ct values were significantly higher in control swabs. While these are preliminary results, they support the clearance of culturable SARS-CoV-2 by the time of the control swab. Follow up epidemiological studies will be necessary to confirm that these in vitro laboratory results translate into an absence of transmission.
In this Country in Focus article, Tony Kirby discusses the emergence of the SARS-CoV-2 new variant in England, its rise to two-thirds of cases by December 2020 and the government response to this surge in COVID cases. He notes the variations in extent and timing public health restrictions across the UK, where different countries have responsibility for their own COVID control plans. In the face of record numbers of cases and deaths, the start of vaccination, and disruption to seasonal hospitality, education and other sectors of the UK economy, the Westminster government has been forced to make sudden changes to their control measures. Even the most seasoned corona watchers are finding this hard to follow.
Cumulative dissonance: pathophysiology
SARS-CoV-2 relies on its viral spike protein (S) to stick to and enter human cells. A protease on these cells cleaves the S glycoprotein into two polypeptides; S1 and S2. Daly and colleagues elegantly demonstrate how S1 and S2 bind to cell surface neuropilin receptors, NRP1 and NRP2. They show that NRP1 depletion reduces virus uptake and that NRP1 binding is mediated by an S1 C terminal motif generated by protease cleavage of S1 and S2. In turn, neuropilins mediate internalisation of these C terminal motifs through endocytosis. Blocking this process reduced SARS-CoV-2 cell entry and infectivity. NRP1 may thus represent a potential therapeutic target for COVID.
Complexity analysis of cold chain transportation in a vaccine supply chain considering activity inspection and time-delay
As COVID vaccines start to enter widespread use, the practical logistics of vaccine delivery become an important constraint on the speed and extent of the rollout. Dai and colleagues investigated some of the complexity surrounding vaccine introduction by modelling the supply chain with a time delay, investigating its impact on vaccine cold chain stability, and the influence of decision adjustment on vaccine supply chain stability. In this study, the vaccine supply chain was adversely affected by decision delay time or adjustment speed of decision. Importantly, they note that “when the vaccine supply chain is in a state of chaos, the effect of external control over the system is superior to that of internal control over the system”. Vaccine cold chain stability will be challenging. We have been warned.
COVID resources of the month
- The conversation, a discussion of the significance of new insights into SARS-CoV-2 cell entry.
- The common feature in the series of New South Wales COVID clusters.
- 2020: the year of living cautiously.