Coronastream: countermeasures, secondary infections and aerosol transmission
Posted on August 5, 2020 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.
If a week is a long time in a pandemic, a month seems like an age. To mix the liquid metaphors; the tide of events has swept a lot of water under the bridge. In this corner of the world, resurgent infection in Australia's southeast has shattered any sense of complacency and forced the reintroduction of community restrictions. In this second time around, people are not as enthusiastic about trading off their personal liberty for biosecurity. SARS-CoV-2 is on the march again, as can be seen from the national case figures.
On the other side of the country, high-level border restrictions are widely seen as a contributor to the State's 100-day run of no community transmission. Even so, there is public dismay at a national, government-supported challenge to restrictions on travel between states; which has now been hurriedly withdrawn. You would have thought that protection of the health and welfare of the population was at the heart of government responsibility. In a past post, this blog touched on our field trials of a mobile coronavirus lab. That capability is now on permanent standby should the legal challenge to border controls succeed.
Congruence: clinico-pathological features
Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis
Ever since the start of the pandemic, experienced infectious diseases specialists have expressed their concern about bacterial co-infections, since these are well-recognised in epidemic influenza. As the pandemic evolved, it became clear that the all-consuming focus on diagnosing COVID-19 by any means came at the expense of a careful, systematic microbiology workup for all patients with signs and symptoms of respiratory infection. In this paper, Langford and colleagues provide a valuable reality check and usefully distinguish between co-infection at the time of diagnosis and secondary bacterial infection. The surprisingly low initial co-infection rate (3.5%) is not high enough to justify the very high rate of antibiotic use (71.3%). However, the much higher rate (15.5%) of secondary infections should alert us to the risk of selecting intrinsically resistant bacteria in already vulnerable patients and promoting the emergence of acquired antimicrobial resistance.
There has been much discussion about the cause of resurgent infection in countries that appeared to have got the initial COVID-19 pandemic wave under control. The role of airborne transmission has come under particularly close scrutiny as developed countries experience second and even third tides of pandemic transmission. In a Lancet Respiratory Medicine article, Kevin Fennelly advocates for a new paradigm for respiratory transmission and explores its implications for disease control. He points out that there is a noteworthy lack of evidence that transmission is restricted to coarse respiratory droplets with relatively short trajectories. Now that the World Health Organisation has recognised the possibility that some SARS-CoV-2 transmission may occur in the smaller respirable particles produced during coughing, sneezing, singing and even talking, the data presented in this review is a valuable recalibration of the issue. Fennelly finishes on the specifics of COVID-19 and brings us back to the fraught issue of face coverings. This is a very practical paper and raises an important caveat about mask/respirator fit testing in published studies. You have to wonder how much mask-use training has been provided in places where face covering is a newly discovered habit.
Cumulative dissonance: pathogenesis and pathophysiology
Mechanistic insights of host cell fusion of SARS-CoV-1 and SARS-CoV-2 from atomic resolution structure and membrane dynamics
The interaction between SARS coronaviruses and human respiratory epithelial cells is mediated by the protein at the tips of the points in the virus' crown that give the virus group its name. The spike protein is a key mediator of a series of events that cascade into cellular invasion. The trigger for cellular invasion is the locking of the spike protein onto the angiotensin-converting enzyme (ACE2) receptor site. In this paper, Chakraborty and Bhattacharjya explain the cellular processes that enable SARS-CoV-1 and -2 to penetrate the cell membrane without spilling its contents. The figures neatly illustrate complex molecular processes and show how these viruses can penetrate intact cells so that they can hijack their intracellular machinery for viral replication. This is a cellular counterpart of the initial stealth with delayed damaging processes that occur at organ, systems, patient and community level.
Curtailment: therapeutic and preventive countermeasures
While the world holds its breath and waits for a COVID-19 vaccine, a flurry of activity is under way to identify effective treatment for SARS-CoV-2 infection. There was a big fanfare when the first tangible evidence of efficacy came out of the RECOVERY trial. The group have now published their preliminary findings which show a reduction in 28-day mortality from 41.4% to 29.3% in the group treated with a daily 6 mg dose of dexamethasone. The apparent benefit was restricted to patients receiving respiratory support, either mechanical ventilation or supplemental oxygen. Though this seems like a modest advance, it is the first encouraging news for treatment of established infection and will be accessible to low- and middle-income countries.