There has been ‘a lot of denial’ about the role of asymptomatic and pre-symptomatic disease in the spread of COVID-19, argues one leading infectious diseases expert, as new evidence emerges about the significant transmission by people not showing any symptoms, the role of face masks and how quickly hospitals can become hotbeds for COVID-19 contamination.

Speaking at a webinar on COVID-19 sponsored by Janssen-Cilag Professor Raina MacIntyre, Head of Biosecurity at the Kirby Institute in Sydney, said there was now a large body of evidence on pre-symptomatic and asymptomatic transmission of COVID-19.

“The first evidence came from the Japanese evacuees from Wuhan where they tested everybody they evacuated and found that more than half of the positive cases were asymptomatic,” Professor MacIntyre said.

And on the infamous Diamond Princess cruise ship which docked in Sydney, health officials tested all passengers and found that about one third tested positive for the virus, half of whom were asymptomatic.

“The pillars of epidemic control are detecting every case and isolating them. Testing, testing and more testing including asymptomatic people, which we don’t do – we still restrict our testing criteria to people with symptoms – every high-risk person and their contacts should be tested regardless of symptoms,” she stressed.

The advice comes as a slew of new research reveals just how persistent the virus is.

Studies from China have shown asymptomatic transmission,^1,2 with doctors finding pneumonia in patients without symptoms and sometimes without a positive throat swab.

Meanwhile, a recently published study³ revealed that maximal viral load occured on the day of onset, and by inference on the days before, with other studies showing that the last two days before symptom onset and day of onset were the most infectious^4.

Several studies now also show that children can be asymptomatic, with one report in The Lancet⁵  detailing the case of a 10 year old boy who was asymptomatic but had the ground-glass appearance on CT, noted Professor MacIntyre.

“I think what this tells us is that children have much higher respiratory reserves than adults. We know that adults will start to feel short of breath when the oxygen saturation drops a little bit but children can actually go to quite low oxygen saturation levels without being short of breath,” she suggested.

Widespread contamination in hospitals

Concern around containing hospital outbreaks is also growing said Professor MacIntyre with recent reports⁶  highlighting the experience of one COVID-19 ward in a hospital in Wuhan that found a high level of coronavirus contamination on swabs taken from the ICU floor and the general wards used to treat patients with severe symptoms of COVID-19.

“They found the virus everywhere – the ICU was highly contaminated but the general ward next door was also contaminated, the floor samples, the computer mouse, the trashcan, the handrails and doorknobs even the cuffs and gloves of medical staff were contaminated,” she said.

Air samples also returned positive for COVID-19 in the ICU as well as in the general ward. A study⁷ from the University of Nebraska has also detailed widespread contamination of surfaces, positive air samples and air vent samples.

“It’s fairly clear that it’s in the air; and that somebody working in that environment would be exposed to high levels of aerosolised virus,” Professor MacIntyre added.

The case for masks

As concern grows about dwindling supplies of personal protective equipment (PPE) across the globe Professor MacIntyre argued that the most important advice for healthcare workers during the COVID-19 pandemic was not to work without adequate PPE.

She said a new study⁹ had shown that without a mask, ‘enormous’ amounts of virus-containing droplets were expelled from the upper respiratory tract just by speaking and through normal breathing.

Furthermore, randomised controlled trials^10,11 had shown that the N95 respiratory mask provided protection around 8-12 times greater than medical masks but they had to be worn continuously when hospital staff were on the ward and not just when there was a perceived risk.

“That’s because there is already likely a high level of contamination within hospitals – you’re getting exposed to it [COVID-19] not just when you’re doing aerosol generating procedures,” Professor MacIntyre said.

Generally, the degree of protection increased from cloth masks, to medical masks, and finally to respirators¹¹. There was evidence surgical face masks could reduce respiratory virus shedding in respiratory droplets and aerosols of symptomatic people with coronavirus, influenza virus or rhinovirus infection¹², she added.

Bed numbers influence case fatality rates

Professor MacIntyre noted that the proportion of critical or severe COVID-19 patients with cancer was 54%, a figure that was significantly higher than the general population at 20%.¹³

Overall, the reported case fatality rate varied considerably from about 1% to 15% in China once patients were hospitalised and from 2% to 15% for patients in the ICU.^14,15

This compared to around 2-5% during the 1918 pandemic, 0.3-0.6% during the 1957 pandemic and .01% throughout the 2009 influenza pandemic with seasonal influenza coming in at even less than that around 0.0001%, she told participants.¹⁶

“So the people who are telling you COVID-19 is just like seasonal flu can’t explain why in the US the army is building tent hospitals to cope with the extra capacity and why in Spain they’ve had to use ice rinks as morgues…we never see that in seasonal flu.”

She remarked that a country’s case fatality rate generally came down to its capacity to ventilate patients.

“When you run out of ICU beds, when you run out of ventilators the case fatality goes up, otherwise it can be an ascertainment issue in terms of how cases and deaths are counted but, in general, I think that explains the very high case fatality rate in Europe.”

This is backed up by Germany’s comparatively low case fatality rate of about 1 percent.¹⁶

“Germany has almost three times as many ICU beds per head of population compared to Italy, which is similar position to Australia – about nine beds per hundred thousand people. That’s now been expanded quite substantially in the last month or so by about 150% so hopefully we’ll be in a good position,” Professor MacIntyre added.

If you would like to view a recording of the event when it is available online, please notify Janssen here.

References

1. Chan et al. The Lancet DOI: (10.1016/S0140-6736(20)30154-9)
2. Bai, Y. Y., Lingsheng;Wei, Tao; Tian, Fei; Jin, Dong-Yan; Chen,Lijuan; Wang, Meiyun (2020). “Presumed Asymptomatic Carrier Transmission of COVID-19.” JAMA Published online February 21, 2020. doi:10.1001/jama.2020.2565
3. He, X., Lau, E.H.Y., Wu, P. et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med (2020). https://doi.org/10.1038/s41591-020-0869-5
4. N van Doremalen et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1N Engl J Med 2020;382:1564-1567.
5. Jasper Fuk-Woo Chan,Shuofeng Yuan,Kin-Hang Kok et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet. 2020 Jan https://doi.org/10.1016/S0140-6736(20)30154-9
6. Guo Z-D, Wang Z-Y, Zhang S-F, Li X, Li L, Li C, et al. Aerosol and surface distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards, Wuhan, China, 2020. Emerg Infect Dis. 2020 Jul [date cited]. https://doi.org/10.3201/eid2607.200885
7. Joshua L Santarpia, Danielle N Rivera, Vicki Herrera et al. Transmission Potential of SARS-CoV-2 in Viral Shedding Observed at the University of Nebraska Medical Center. medRxiv 2020.03.23.20039446; doi: https://doi.org/10.1101/2020.03.23.20039446
8. Meselson Matthew. (2020) Droplets and Aerosols in the Transmission of SARS-CoV-2. N Engl J Med DOI: 10.1056/NEJMc2009324.
9. Lee, S.-A., S. A. Grinshpun, and T. Reponen. 2008. Respiratory performance offered by N95 respirators and surgical masks: Human subject evaluation with NaCl aerosol representing bacterial and viral particle size range. Annals of Occupational Hygiene 52(3):177-185.
10. Balazy, A., M. Toivola, A. Adhikari, S. K. Sivasubramani, T. Reponen, and S. A. Grinshpun. 2006. Do N95 respirators provide 95% protection level against airborne viruses, and how adequate are surgical masks? American Journal of Infection Control 34(2):51-57
11. MacIntyre CR, Chughtai AA. Facemasks for the prevention of infection in healthcare and community settings. BMJ (Clinical research ed). 2015;350:h694. http://er.library.unsw.edu.au/er/cgibin/eraccess.cgi?url=http://www.bmj.com/content/350/bmj.h694
12. Leung, N.H.L., Chu, D.K.W., Shiu, E.Y.C. et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat Med (2020). https://doi.org/10.1038/s41591-020-0843-2