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Asymptomatic COVID-19 rate could be ‘much higher’ than previously thought


Evelyn Lewin


2/06/2020 1:13:20 PM

But experts differ on whether that should affect current testing in Australia.

Crowd of people with some wearing face masks.
At least one epidemiologist believes coronavirus infections may be five times higher than currently reported.

‘It’s another piece of the puzzle.’
 
That is University of Queensland virologist Associate Professor Ian Mackay.
 
He is talking to newsGP about the findings of two new papers on the prevalence of asymptomatic COVID-19.
 
One paper, published in JAMA Network Open on 27 May, was a case series with data from 78 patients with COVID-19 in Wuhan, China. These patients were all screened because they were close contacts of confirmed cases of COVID-19, or because they were exposed to the Hunan seafood market.
 
All patients were confirmed to have SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) from nasopharyngeal swabs.
 
Of the 78 confirmed patients, 33 (42.3%) were asymptomatic.
 
Compared to symptomatic patients, the study reported asymptomatic patients were more likely to:

  • be younger (median age 37 versus 56 for symptomatic)
  • female
  • have a lower proportion of liver injuries
  • have less consumption of CD4+T lymphocyte
  • experience faster lung recovery in CT scans
  • display shorter duration of viral shedding from nasopharyngeal swabs.
‘Our finding of less consumption of CD4+T lymphocyte in asymptomatic infections suggests that damage to the immune system in asymptomatic infections was milder compared with symptomatic infections,’ the authors wrote.
 
However, Associate Professor Mackay told newsGP this is not always the case.
 
‘People who are asymptomatic can have just as much virus in their system, in their cells, as people who are symptomatic or later become symptomatic,’ he said.
 
The authors also said patients who were asymptomatic experienced ‘less harm’ to themselves, but as they may have been unaware of their infection they were then less likely to isolate, which could contribute to people unknowingly transmitting the virus to others.
 
A further paper, published in BMJ Journals Thorax, looked at disease spread of COVID-19 in a confined location.
 
That paper describes what the authors believe to be the first instance of complete COVID-19 testing of all passengers and crew on an isolated cruise ship during the pandemic.
 
Of the 217 passengers and crew on board the Antarctic cruise ship, 128 tested positive for COVID-19 on RT- PCR (59%), 104 of whom were asymptomatic (81%).
 
The authors therefore concluded the prevalence of COVID-19 on affected cruise ships is likely to be significantly underestimated.
 
Associate Professor Mackay is surprised by that high percentage rate.
 
‘That makes me think about testing – whether there could be some false positives going on there – [or] some cross-contamination because of the boat situation,’ he said.
 
‘It may have [also] been that some of those cases were pre-symptomatic and then became symptomatic, which might affect that percentage.’
 
Regardless, he said these studies both showed a ‘much higher’ asymptomatic percentage than other studies had found.
 
‘I think this is not the definitive answer,’ he said.
 
‘Neither of these studies provide all the information we need.’
 
Associate Professor Mackay said there are other factors that may change the asymptomatic rate, including variation in PCR tests.
 
‘There is not just “a” PCR test, there are range of them and they vary,’ he said.

Ian-Mackay-Article-1.jpgUniversity of Queensland virologist Associate Professor Ian Mackay believes variation in PCR testing may have affected the asymptomatic rate.
 
Variables include the primers used, test sensitivity and how well they work at different stages of illness, and the ability of the test to detect weak positives.
 
‘There’s a lot of variability and I wouldn’t want to be a GP at the moment, having to know how to interpret some of these results,’ he said.
 
‘It is tricky.’
 
He also said the first study did not specify how long patients were followed-up for, meaning individuals identified as asymptomatic may have been pre-symptomatic instead.
 
Professor Ivo Mueller, an epidemiologist at the Walter and Eliza Hall Institute of Medical Research, believes it is important to know the true asymptomatic rate of COVID-19 in order to understand the ‘burden of infection’ impacting countries.
 
He said that, on the cruise ship described in the Thorax study, there were four asymptomatic carriers for every sick passenger.
 
‘If the same pattern is repeated elsewhere, this means that in countries that only test symptomatic cases, the true burden of infections may be five times higher than currently reported,’ he said.
 
‘Determining the true infectiousness of asymptomatic carriers of all ages must now be an urgent priority.
 
‘This will require detailed contact tracing studies using both molecular and serological diagnostic [testing], including both clinical cases and asymptomatic carriers.’
 
Meanwhile, infectious diseases expert Professor Raina MacIntyre, head of the Biosecurity Program at the Kirby Institute at the University of NSW, said it is less important to focus on the asymptomatic rate, and more vital to test all high-risk contacts, regardless of the presence or absence of symptoms.
 
She said there is already a substantial body of evidence that shows it is ‘common’ to have asymptomatic infection with COVID-19.
 
‘Studies of the Diamond Princess found about two-thirds of passengers were infected, with a high proportion asymptomatic,’ she said.
 
‘Studies in aged care and other outbreaks have also found 50% or more of all positive cases are asymptomatic.
 
‘We should not be debating this any longer.
 
‘High-risk contacts in outbreak situations, whether family contacts or in a closed setting outbreak, should be tested regardless of symptoms or cases will be missed.’
 
However, Associate Professor Mackay believes it is important to understand the asymptomatic rate of COVID-19.
 
‘What we’re trying to gauge is how much transmission goes on that we completely miss,’ he said.
 
‘[That] is a question which research should be looking at.’
 
While that is being investigated, he does not believe there is a need to change testing procedures to include asymptomatic individuals at this stage.
 
‘I don’t think there’s necessarily a great benefit in just screening asymptomatic people,’ he said.
 
‘Especially not in Australia where we have so few cases right now.’
 
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Dr Ian Mark Light   3/06/2020 8:13:29 AM

It will be important then to develop accurate IGG and IgM antibody testing as Convalescent Serum may have a great role in reducing illness severity .
There was a paper in the Proceedings of the National Academy of Sciences of the USA that infusion of serum with Covid 19 antibodies was associated with clearing of the virus in the blood and dramatic clinical improvement
The study was by a team first three authors
Kai Duan Bende Liu Cesheng Li published in the PNAS April 28 2020 on 10 patients .
In the USA now convalescent serum is being used anecdotal reports are very encouraging .
Reference : Podcast Primary Care Rap 6 May 2020 Morrison M and Esmay JB
Australia with CSL surely has the capacity for this convalescent serum development .


Dr Horst Paul Herb   3/06/2020 1:02:31 PM

Why is this in the news section? The same conclusion was already drawn (and more conclusively) 2 months ago from the iceland data, and shortly after from the German and Swedish data - even if we ignore, as always, the data from Korea, Japan, and Taiwan.


Dr Ian Mark Light   3/06/2020 3:20:33 PM

The spread is said to be less in the outside air so gatherings outside with physical distancing ought be far safer than in poorly ventilated rooms .
Another hope is treatment with convalescent serum that is being trialed in the USA .
Anecdotal reports are good validation awaits .