Coronastream: of streaks and leaks

Posted on May 19, 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.

The tragedy unfolding in front of our eyes in India demonstrates the enduring capacity of SARS-CoV-2 to shock us. You don't need family, friends or colleagues on the subcontinent to get caught up in the growing clamour of questions about why this is happening. Talk of so-called 'double mutant' variants of the virus, recriminations about patchy health infrastructure, intervention hesitancy and super-spreader events, and badly concealed fears of spread to neighbouring countries suggest we don't really know how to respond to a public health emergency on this scale over such a long period. 
The ripples have been felt on the far shores of the Indian Ocean, where positive SARS-CoV-2 arrivals have increased in quarantine centres. The Australian government has been roundly criticised for responding to the perceived biosecurity threat by suspending repatriation flights and threatening returning Australians who travel home by an indirect route with legal action. After a public outcry, they backed down and reinstated direct repatriation flights. Closer to home, Western Australia's streak of more than one year without community transmission came to an abrupt end with a leak from one of the quarantine hotels via a hotel security guard. A flurry of public health interventions and investigations followed, including a snap lockdown, a surge in RT-PCR testing and mandatory mask wearing. After a short period of relaxed controls, we had another small community cluster and went back to heightened restrictions.  
In the midst of this, the Australian mass vaccination programme hit a speedbump due to concerns over rare adverse effects. After a pause and reset, vaccinations have recommenced with the over 50s receiving the AstraZeneca vaccine and the under 50s getting the Pfizer/BioNTech vaccine. Vaccination uptake took a dive last month, but in Western Australia picked up after the first snap lockdown. There is growing concern about the risk of transmission in quarantine hotels, whose ventilation was never designed for biocontainment. 

Congruence: ChAdOx1 nCov-19 vaccination rare adverse events 

Analysis of thrombotic adverse reactions of COVID-19 AstraZeneca Vaccine reported to EudraVigilance database 

In this retrospective study of thrombotic adverse reactions associated with the Oxford-AstraZeneca vaccine (ChAdOx1 nCov-19) from 17th February to 12th March 2021; 28 of 54,571 adverse reaction reports concerned thrombotic adverse reactions. This descriptive study used reports submitted to the EudraVigilance database. There were three deaths related to pulmonary embolism and one related to thrombosis. As 17 million people had had the AstraZeneca vaccine, these are extremely rare events, leading the European Medical Agency's Pharmacovigilance Risk Assessment Committee to conclude on 18th March that the vaccine was safe, effective and its benefits outweighed the risks. Further work is clearly needed on causality. 

A Flow cytometric assay to detect platelet activating antibodies in VITT after ChAdOx1 nCov-19 vaccination 

This group describe a flow cytometer assay method to identify antibodies associated with vaccine-induced immune thrombotic thrombocytopenia (VITT) after ChAdOx1 nCov-19 vaccination.  

Consistency: falling in-hospital mortality in the USA 

Trends in patient characteristics and COVID-19 in-hospital mortality in the United States during the COVID-19 pandemic 

The high hospital mortality rates from COVID-19 in American hospitals appear to be decreasing in parts of the USA. In this retrospective cohort study of over 20,000 adult patients with COVID-19, logistic regression was used to assess the risk of death, while adjusting for age, gender and other patient variables. The adjusted odds ratios were lower in May and June, July and August and September to November compared to March and April. The authors conclude that the initially high rate of in-hospital COVID-19 mortality fell by over a third by June 2020. While this reduction may look modest, improved patient outcomes at a population level are an encouraging sign that, if sustained, points to a better future for a country that has been ravaged by the pandemic. It will be most interesting to see the impact of vaccine rollout in follow-up studies. 

Cumulative dissonance: mechanisms of post-vaccine thrombotic thrombocytopoenia 

Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination 

Concerns that the ChAdOx1 nCov-19 vaccine (AstraZeneca) might cause rare adverse effects including clotting disorders has led to temporary suspensions and revised vaccination plans, resulting in a loss of confidence in the vaccination programme.  This report on clinical and laboratory characteristics of a series of patients in Europe who developed thrombosis or thrombocytopenia after vaccination with ChAdOx1 nCov-19 throws some light on the pathogenesis of these adverse effects. The study used a platelet factor 4-heparin antibody ELISA and a modified platelet activation test to detect platelet-activating antibodies. Eleven patients were studied, of whom six died. Nine had cerebral venous thrombosis, three splanchnic vein thrombosis, three pulmonary embolism and four other thromboses. All 28 patients who had a positive screening assay for antibodies against PF4-heparin tested positive on the platelet-activation assay. Platelet activation was inhibited by high levels of heparin and Fc receptor-blocking monoclonal antibody. The authors conclude that vaccination with ChAdOx1 nCov-19 may rarely result in immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4. 

Curtailment: aerosol interruption 

Investigation of potential aerosol transmission and infectivity of SARS-CoV-2 through central ventilation systems 

Concerns about airborne transmission of SARS-CoV-2 in droplets or small-particle aerosols has raised questions about the spread of the virus in buildings such as quarantine hotels. There have been few studies on aerosol spread of the virus in air conditioning systems. This study looks at concentration and infection probability following interior and exterior source exposure in a multi-room building supplied by a central air handling system. The contribution of filtration, air changes, and outdoor air fraction were studied, leading the authors to observe that a mixture of recirculated indoor and outdoor air, filtration lowers the concentration and probability of infection in connected rooms. However, increasing air changes removes virus from the source room faster but may increase exposure in connected rooms. The take-home message seems to be that lowering air change rates in rooms and increasing uncontaminated outdoor air are both beneficial.  

Copper-coated polypropylene filter face mask with SARS-CoV-2 antiviral ability 

This blog has featured studies on mask-wearing as a personal protective measure previously. This paper takes a look at the effect of depositing a 20 nm copper film on spun polypropylene mask material to provide additional protection. Sodium Chloride and paraffin oil particles were filtered with an efficiency of 95 and 92%, respectively. SARS-CoV-2 virus inactivation was assessed by exposing the virus to the copper-coated filters then adding Vero cells, to demonstrate that Vero cells added after mask contact did not express RdRp or envelope genes. SARS-CoV-2 nucleocapsid immunofluorescence was used to show that virus quantity had been reduced by over 75%. The early observation that copper surfaces appeared inhibitory to SARS-CoV-2 led to some excitement about copper coatings for multi-user surfaces, but this more recent study by materials scientists raises the interesting possibility of exploiting copper in personal protective equipment and collective air handling systems.  

Coronavirus (Covid-19) vaccinations  
How do we actually investigate rare COVID-19 vaccine side effects?