Thursday, February 27, 2020

Osaka Japan: `Recovered' Patient Tests Positive For COVID-19










#14,965


Although COVID-19 is known for its `flu-like' characteristics, it isn't influenza, and our understanding of it - and how it affects humans hosts - is still in its infancy. What we do know is based on a fairly short (8 week) history of dealing with this virus, and not surprisingly, we already know it can produce a wide range of illness among patients.
Each of us has a unique immune system, and how it reacts to exposure to this previously unknown virus can vary widely.  
Some people remain asymptomatic, while others may develop symptoms (on average) 2 to 4 days after exposure. We've seen some reports of `outliers' - people who appear to incubate the virus for  longer than 14 days - but based on what we know now, that appears to be rare.

Some patients are lucky enough to have mild or even asymptomatic infections, and recover quickly. Others may require prolonged hospital care, and some percentage go on to die.
Again, the variable appears to have more to do with the host, than with the virus. 
Overnight we've seen media reports of one of Japan's earliest cases (F, 40s) who worked as a tour bus guide in Osaka -  who was hospitalized with COVID-19  in late January and released from the hospital on Feb. 6th after testing negative - who has tested positive again 3 weeks later.
It isn't entirely clear whether this is a relapse, or if the patient may have been re-exposed to and reinfected by the virus, or if the tests used to clear her for discharge simply weren't sensitive enough to pick up a lingering, low grade, infection. 
We've seen a few anecdotal reports out of China suggesting this can happen, and those (at least in Hubei Province) who are discharged from the hospital have been instructed to self-isolate for an additional 14 days and monitor themselves for symptoms.
Once again, this appears to be an outlier, and is probably rare  
But we have seen similar reports with other viral infections (see UK Ebola Survivor Cafferkey Back In Isolation After Relapse), including with another novel coronavirus; MERS-CoV. 

Two quick examples:
Middle East respiratory syndrome coronavirus (MERS-CoV) – Jordan
Disease outbreak news
1 September 2015
A 60-year-old male living in Jeddah city, Saudi Arabia travelled to Amman city, Jordan on 28 July. He developed symptoms on 31 July and, on 10 August, was admitted to hospital. The patient, who had comorbidities, was treated symptomatically and discharged on 18 August. As symptoms relapsed, on 20 August, the patient was admitted to another hospital in Amman on 23 August. He tested positive for MERS-CoV on 25 August and passed away on 27 August. Investigation of history of exposure to known risk factors in the 14 days prior to the onset of symptoms is ongoing.
And barely a month later, we saw it happen again at the end of South Korea's 2015 MERS epidemic (see Korean Govt. Statement On MERS Patient `Relapse’ and Isolation). This patient had significant comorbidities, which may have led to a longer-than-normal carriage of the virus.

It is also possible the tests used to `clear' MERS-CoV, and COVID-19 cases just aren't sensitive enough to reliably detect low levels of the virus (see AJIC:Intermittent Positive Testing For MERS-CoV).
We've seen anecdotal reports out of China that suggest this could be a factor (see Problematic Lab Testing For The Novel Coronavirus). 
And lastly, there are reports (still unconfirmed) that COVID-19 infection may not produce a particularly robust, or long-lasting immunity. That it may be possible to be re-infected with this  virus, even shortly after recovery from an earlier infection.
Once again, we've seen some serological evidence that human coronavirus (hCov) and MERS-CoV infection may not produce long-term immunity. 
From 2016's EID Journal: Antibody Response & Disease Severity In HCW MERS Survivors, we looked at a study that tested 9 Health care workers who were infected during the 2014 Jeddah outbreak (2 severe pneumonia, 3 milder pneumonia, 1 URTI, and 3 asymptomatic), that found only those with severe pneumonia still carried detectable levels of antibodies 18 months later.
Those who experienced a milder pneumonia had shorter lived antibody responses (1 out to 10 months, 2 out to 3 months), while the URTI and asymptomatic cases tested negative at 3 months post infection.
It isn't at all clear whether this applies to COVID-19 since we don't have serological test results yet. Nor do we know the impact this might have on re-infection risks, the feasibility of using convalescent plasma therapy, or even the creation of a vaccine.
But it does remind us we aren't dealing with influenza.
The good news is, most of these outliers appear to be rare - and as such - probably won't have a huge impact on the treatment and release of patients.

While we'd like it very much if we could count on COVID-19 to `follow the rules', whenever we see a novel virus emerge, we have to be ready for some surprises.