Severe fatigue common in COVID-19, independent of disease severity


Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often complain of fatigue, but now a new study shows that it also causes severe and frequent fatigue in those who recover after mild illness too. The study, published on the preprint server medRxiv* in July 2020, reports a startling prevalence of fatigue in people who recovered from acute COVID-19 illness, even when they had only a mild illness.

Colorized scanning electron micrograph of a cell (blue) heavily infected with SARS-CoV-2 virus particles (red), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Fatigue is the presenting symptom in many patients with COVID-19, ranging from 44% to 70% of cases. The extent and duration of this symptom remain an unknown area, mainly whether it represents a post-viral fatigue syndrome triggered by the virus.

A prior report dealing with the long-term sequelae of the earlier severe acute respiratory syndrome (SARS) outbreak reports that patients had long-term fatigue, muscle aches, weakness, and depression even at one year from acute infection, severe enough to hinder their return to work. Another study reported fatigue in patients assessed at 40 months from infection in over 40%. Similar findings were reported after the Middle East Respiratory Syndrome (MERS) at six months or more.

The same results are seen with other viral infections too, including Epstein-Barr Virus (EBV), Q-Fever, and Ross River Virus (RRV) infections. Many earlier studies have described these post-viral fatigue syndromes, especially regarding the immune changes.

Immunological Changes in COVID-19

The immunological changes seen in COVID-19 are well recognized, including lymphopenia, leukocytosis, and a higher proportion of neutrophils to lymphocytes. Severe COVID-19 is marked by higher levels of C-reactive protein, ferritin, and D-dimers (markers of tissue damage and coagulation dysregulation), and IL-6, among other inflammatory cytokines. Intermediate monocytes, a class of monocytes that is found in infection and inflammation, are also increased.

The Study: COVID-19 Patients and Fatigue

The current study by a team of Irish researchers was aimed at a prospective evaluation of patients who had COVID-19 and then recovered, to detect chronic fatigue symptoms after recovery. The researchers wanted to avoid multiple etiologies for the fatigue by using a single infection as the population characteristics, to allow greater accuracy of the syndrome description. The link, if any, between the fatigue and any particular characteristic of the infection, was sought, as also the uncovering of any persistent disease markers after the resolution of infection.

The study included 128 patients with a mean age of 50 years, of whom about 56% were hospitalized with COVID-19, and the rest were outpatients. Over half were healthcare workers, as is characteristic of Irish COVID-19 outbreaks. The median duration from discharge from hospital or diagnosis of outpatients to testing during the study was 72 days, at which point only 2 of 5 patients said they felt fully recovered. Of the 82% who were employed before the illness, about a third were still not back at work at the time of the study.

The researchers used the Chalder Fatigue Scale (CFQ-11), along with clinical characteristics and blood tests, to arrive at their conclusions. The mean fatigue score was ~16, with the score for physical fatigue and psychological fatigue being 11 and ~5, respectively. Over half the patients were diagnosed with fatigue based on this score, and in this group, the mean score was 20.

High Prevalence of Post-COVID Fatigue

Thus, the current study shows that at ten weeks from infection (median 72 days), over half of the patients who had COVID-19 continue to experience severe fatigue. In other words, these patients who have been medically certified as fully recovered fail to experience good health.

Secondly, as a result of such fatigue, daily functioning is impaired, and over a third do not return to work even by 10 weeks. This goes against the recommendation that following a viral infection, the patient should return to work four weeks later to prevent loss of conditioning. Again, given the high percentage of healthcare workers affected, this kind of employee attrition will significantly hit healthcare systems.

A third observation is that post-COVID-19 fatigue is much more frequent than that reported after the infections mentioned above but at a level comparable to that of post-SARS fatigue. However, the levels of fatigue in this cohort, though more significant than the fatigue levels in the general population, and meeting the CFQ-11 criteria for fatigue, were lower than required for a diagnosis of chronic fatigue syndrome. The CFQ-11 scores were comparable to those found in patients diagnosed with CFS.

Such levels are more typical of those seen in chronic disease states, and this is a concerning observation since most of these patients were not, in fact, actively infected at the time of testing, nor did they have severe disease. This is a surprising finding, and the researchers comment, “Our findings would suggest that all patients diagnosed with SARS-CoV-2 will require screening for fatigue.”

Also, females seem to be at higher risk for the development of fatigue following COVID-19, as is the case with previous CFS studies. Patients with pre-existing depression and on anti-depressants are also at higher risk of severe fatigue. However, further research is needed to find out if depression develops after fatigue sets in post-COVID and to trace the course of fatigue over time.

Inflammation Not Related to Fatigue

There was no relationship between the values recorded in six inflammatory/cell death parameters and the occurrence of fatigue or the total CFQ-11 score. In the same way, IL-6 levels were independent of fatigue diagnosis or the total score. On the other hand, over 85% of the study subjects had normal CRP and IL-6 levels. Another inflammatory cytokine, soluble CD25, was normal in 94% of cases.

Thus, the development of fatigue is not apparently the result of any specifically inflammatory pattern, as none was found in the test results. In previous studies, CFS has been linked to a lot of different alterations in inflammatory markers and the populations of various immune cell types. Still, none have been found to remain constant across many studies.

Multidisciplinary Interventions

The researchers rule out obvious associations of specific disease conditions with either CFS or post-COVID fatigue, instead saying, “CFS may be the endpoint of a variety of distinct pathways, or maybe the consequence of pathological changes that are no longer systemically detectable.” This is an important suggestion since it means that immunomodulation is not a valid strategy in treating these conditions.

Instead, non-pharmacological interventions are favored to counter the multiple factors, including depression, that are involved in its etiology. Such interventions include graduated physical exercise and cognitive behavioral therapy, as well as implementing suggestions from occupational health experts.

The short period between the diagnosis/discharge and the study is a significant limitation since other studies on fatigue take place six months or more after the viral illness, which is supposed to have precipitated it. The researchers recommend that follow-up studies be done to examine the health of patients over time, in larger groups, and using multidisciplinary modes of treatment to identify the most effective therapies.  

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.





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Government could have avoided severity of COVID-19


The warning signs of the pandemic were there but our Government acted too late, despite faring better than many other countries.

The following article contains language that may offend some readers.

GIVE ME a fucking break.

Social media is kind of like a democracy. There is a massive over-subscription of loud mouth know-it-alls (guilty as charged, by the way). That’s the yin part; the yang is that if you watch it closely enough you can get a strong feel for how the sentiments of the population drift over time.

Recently, I have noticed a shift in the public perception of the way the Government has been handling the COVID-19 thing.

Prime Minister Scott Morrison has become a true leader, they say. That is a pretty big leap from the dithering idiot who snuck out for a Hawaiian holiday while the nation burned.

I can kind of understand it. Australia has certainly performed well in flattening the curve. People are feeling safer, more comfortable and more optimistic. All of which has happened on Scott Morrison’s watch.

We seem to have averted the tragedy besetting Europe, Asia and the Americas, but I think we should be less emotive and a bit more analytical when we apportion credit for the outcome.

Italy

Here’s a theory: The single biggest factor that saved Australia from succumbing to COVID-19 in the way Italy did, wait for it… wait… it was fucking Italy.

We saw the horror on our TVs and digital news services. We watched Italians die, then the South Koreans and Iranians. And it scared us shitless.

The Chinese, the Italians, the Iranians, the French, the Spanish. The citizens of those countries were completely blindsided. They did not know the potential of this disease and, as a result, the population were not overly concerned. They thought it was a storm in a teacup.

Social distancing

Try implementing social distancing to contain something as simple as the common cold. Or even the flu.

Social distancing is a fundamental change in the way we interact in society. It goes against the fabric of our being. We are social animals. There are actual hormones (oxytocin) that are released in our bodies when embrace that make us feel good. And I am not talking about a sexual embrace.

There is no chance you could successfully implement such a drastic change to the way we live if there were no dire consequences to maintaining the status quo.

We knew the consequences of not acting, so we acted.

When the PM stood before us and steadfastly refused to shut down schools, a significant number of us kept our kids home in spite of his advice.

I think those people deserve credit over the PM. Strike one.

Hong Kong

In early January, we had some friends over from Hong Kong and they explained to us what was happening there. Companies were splitting their workforce into shifts, where team A would use one elevator to enter the building and team B would use another. When the team A shift was over, they left by the same elevator, a cleaning crew went through and disinfected the office space before team B would enter through their lift.

This was the first thing my practice adopted when the pandemic hit Australia. The PM played no part in that.

The most chilling thing they told us was that during the recent uprising it became illegal to wear a face mask in public because it concealed your identity. Within a month of the pandemic hitting Asia, it became illegal not to.

The Chinese Government had become more concerned about the virus than they were about the uprising. That should be enough to send chills down anyone’s spine.

And still, it was left to the states to close schools. Strike two.

All at sea

The Ruby Princess. Strike three, four, five and six.

Fucking useless and fucking disgraceful.

The Chinese

If you look up the definition of “scapegoat” on Wikipedia, you’ll see a picture of the Chinese flag. In fact, you probably won’t as I just made that up, but it should be.

I was watching Q+A a few months back and they showed the Chinese police forcibly removing people from their homes as they had contracted COVID-19, but refused to leave their home. The panel was brutal in their assessment of this footage. They portrayed these actions as the diabolical actions of an authoritarian regime. They rounded on the Chinese bloke on the panel.

At the time, I was disgusted and deeply concerned by the actions of the Chinese regime.

I wonder how they would react to that footage now? I know my opinion has changed.

The point I’d like to make here is that the signs were there. We had footage of an authoritarian regime taking decisive action against a viral threat, but rather than assess it, we dismissed it as the oppressive actions of an authoritarian regime.

Ground zero: Wuhan, China

How do you think a disease outbreak occurs?

We know that the majority of COVID-19 cases are asymptomatic or mildly symptomatic at worst. Let’s have a glance at the numbers.

Let’s use 10%. If 10% of the infected require respirators, that would mean that ten people need to be infected before one person hits an emergency room. Would a single person presenting at a hospital in respiratory distress raise any concern? I don’t think so.

So to raise any concerns, you’d need a cluster. Let’s, for argument sake, say a cluster is five people. Five people showing up in respiratory distress would represent 50 people infected in the population. At that point, you might then think that there is something going on.

But no one is dead yet. You have an outbreak, but for all you know at this stage, it could be next year’s cold.

A fatality rate of 0.2%. That means that there needs to be 500 infections to have a single death.

Now 500 people are infected, 50 of them in hospital, and one of them is dead. You have an outbreak of a serious nature.

Five hundred people in the population carrying a deadly virus, but you don’t know what it is or how it’s transmitted and you don’t have a test for it.

I could continue this line of argument, but I’d rather just make this point.

The Chinese were fighting enormous odds to prevent this thing from spreading.

When it hit Australia, we knew the enemy. We had testing available from day one. We knew how it could be transmitted. We had modelling available from other countries. We are girt by sea.

We’ve done well to contain the threat, but we can probably ease up a bit on the Chinese. Their task was orders of magnitude more difficult than our own.

I have no love for the Chinese regime, but I know scapegoating when I see it.

Feeble men with feeble minds

And that brings us to the good old U-S of A.

The COVID-19 pandemic is merely a trigger. The calamity that will ensue can be traced back to 8 November 2016.

I have a great deal of sympathy for those who voted against Trump in 2016. I’m less sympathetic to those who voted for him and now regret it.

I pity those who still support him. Feeble minds.

Back to the point

Is Scott Morrison really the messiah or just a very lucky dithering idiot?

You tell me.

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China hid coronavirus’ severity to hoard supplies: US Homeland Security report


WASHINGTON: US officials believe China covered up the extent of the coronavirus outbreak — and how contagious the disease is — to stock up on medical supplies needed to respond to it, intelligence documents show.
Chinese leaders “intentionally concealed the severity” of the pandemic from the world in early January, according to a four-page Department of Homeland Security intelligence report dated May 1 and obtained by The Associated Press. The revelation comes as the Trump administration has intensified its criticism of China, with Secretary of State Mike Pompeo saying Sunday that that country was responsible for the spread of disease and must be held accountable.
Lockdown 3.0: Latest updates
The sharper rhetoric coincides with administration critics saying the government’s response to the virus was slow and inadequate. President Donald Trump‘s political opponents have accused him of lashing out at China, a geopolitical foe but critical US trade partner, in an attempt to deflect criticism at home.
Not classified but marked “for official use only,” the DHS analysis states that, while downplaying the severity of the coronavirus, China increased imports and decreased exports of medical supplies. It attempted to cover up doing so by “denying there were export restrictions and obfuscating and delaying provision of its trade data,” the analysis states.
More on Covid-19

The report also says China held off informing the World Health Organization that the coronavirus “was a contagion” for much of January so it could order medical supplies from abroad — and that its imports of face masks and surgical gowns and gloves increased sharply.
Those conclusions are based on the 95% probability that China’s changes in imports and export behavior were not within normal range, according to the report.
In a tweet on Sunday, the president appeared to blame US intelligence officials for not making clearer sooner just how dangerous a potential coronavirus outbreak could be. Trump has been defensive over whether he failed to act after receiving early warnings from intelligence officials and others about the coronavirus and its potential impact.
“Intelligence has just reported to me that I was correct, and that they did NOT bring up the CoronaVirus subject matter until late into January, just prior to my banning China from the US,” Trump wrote without citing specifics. “Also, they only spoke of the Virus in a very non-threatening, or matter of fact, manner.”
Trump had previously speculated that China may have unleashed the coronavirus due to some kind of horrible “mistake.” His intelligence agencies say they are still examining a notion put forward by the president and aides that the pandemic may have resulted from an accident at a Chinese lab.
Speaking Sunday on ABC’s “This Week,” Pompeo said he had no reason to believe that the virus was deliberately spread. But he added, “Remember, China has a history of infecting the world, and they have a history of running substandard laboratories.”
“These are not the first times that we’ve had a world exposed to viruses as a result of failures in a Chinese lab,” Pompeo said. “And so, while the intelligence community continues to do its work, they should continue to do that, and verify so that we are certain, I can tell you that there is a significant amount of evidence that this came from that laboratory in Wuhan.”
The secretary of state appeared to be referring to previous outbreaks of respiratory viruses, like SARS, which started in China. His remark may be seen as offensive in China. Still, Pompeo repeated the same assertion hours later, via a tweet Sunday afternoon.
Speaking Sunday on Fox News Channel’s “Sunday Morning Futures,” Sen. Ted Cruz, R-Texas, echoed that sentiment, saying he believes China “is the most significant geopolitical threat to the United States for the next century.”
“The communist government in China bears enormous responsibility, enormous direct culpability for this pandemic. We know they covered it up,” Cruz said. “Had they behaved responsibly and sent in health professionals and quarantined those infected, there’s a real possibility this could have been a regional outbreak, and not a global pandemic. And the hundreds of thousands of deaths worldwide are in a very real sense the direct responsibility of the communist Chinese government’s lies.”



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