Coronavirus updates November 2023

[missy]

"

Long COVID Lasts At Least 18 Months for Most People: Study​

Lisa O'Mary
November 03, 2023

A new study out of Denmark showed that more than half of people with severe cases of long COVID failed to improve after a year and a half.
The study also showed that severe symptoms lasted for at least 18 months regardless of which variant of SARS-CoV-2 — the virus that causes COVID — infected the person. The authors called that finding "surprising," noting that other studies have suggested that long COVID became less common as the pandemic progressed.
The findings were published this week in the International Journal of Infectious Diseases. Researchers analyzed data from 806 people in Denmark who were referred to the country's specialized long COVID clinics because of severe symptoms. (Long COVID is a wide-ranging condition in which any mix of more than a dozen COVID-19 symptoms — such as fatigue and brain fog — persist for months, sometimes with disabling effects.)

The commonalities among people in the study who developed long COVID suggest that the condition's cause is the same regardless of which variant led to the initial infection, the authors wrote. When patients did rehab, they showed some improvement, but their symptoms overall remained severe.


Some differences were observed based on the variant that caused the initial infection among people in the study. Those infected during the Omicron era had symptoms that resulted in a lower quality of life, the authors noted. Omicron infections were significantly less likely to lead to long COVID with "disturbed sense of smell," which was somewhat expected because fewer people infected with Omicron overall lost their sense of smell. The study also showed that people infected during the Delta and Omicron waves tended to be more physically exhausted.
More than half of the Danish population was infected with Omicron, and the authors said the prevalence of people in their study infected with Omicron indicated that a "substantial" number of people infected with Omicron may develop long COVID.
CDC survey data from September shows that 15% of U.S. adults have had long COVID, and about 5% say they currently have the condition. Earlier this year, the U.S. government announced a $1.15 billion plan to better understand, treat, and prevent long COVID.

In their conclusion, the Danish researchers suggested that the development of long COVID treatments focus on aiding people with the most severe cases of the condition.
"We suggest the search for long COVID treatment options focus on these severely affected patients to develop future new treatments, which we believe will be effective across all SARS-CoV-2 variants," they wrote.
Sources:
International Journal of Infectious Diseases: "Long-term Prognosis at 1.5 years after Infection with Wild-type strain of SARS-CoV-2 and Alpha, Delta, as well as Omicron Variants."

"

 

[diamondringlover]

my son's long covid got a little better after about a year, he still have some issues with it but he is much, much better, he got covid in January 2022, my neighbor on the other hand got covid in 2020 and now is on permanent oxygen and is on social security disability because of covid, she currently 44

 

[missy]

my son's long covid got a little better after about a year, he still have some issues with it but he is much, much better, he got covid in January 2022, my neighbor on the other hand got covid in 2020 and now is on permanent oxygen and is on social security disability because of covid, she currently 44

I am relieved your son is doing better and hope he fully recovers from this. It is a very scary disease no doubt. I know people who are still getting very very ill and let us not forget people are still dying from Covid. Stay safe everyone and be smart and take precautions. Masks do protect and add another level of safety

 

[diamondringlover]

I am relieved your son is doing better and hope he fully recovers from this. It is a very scary disease no doubt. I know people who are still getting very very ill and let us not forget people are still dying from Covid. Stay safe everyone and be smart and take precautions. Masks do protect and add another level of safety

thank you and I know people are still dying my best friends 88 year old mom got covid and is currently in the hospital dying from it....she has had it for a month and been in the hospital for 2 weeks...I went back to wearing a mask last week and still managed to catch quite a nasty cold.....so I got to wonder sometimes.....

 

[Daisys and Diamonds]

Covid-19 commentator Siouxsie Wiles received 'tsunami of abuse', court hears

Covid expert Dr Siouxsie Wiles has taken her employer, the University of Auckland to court.

www.stuff.co.nz

i rather like this lady and im very mad that her employer, Auckland university did nothing to protect her safety
its totally vile the abuse she had endured from a certain sector of the public over her covid info durring the pandemic

 

[missy]

The Future of COVID-19 and Approaches to Living With a New Endemic​

Matteo Bassetti, MD, PhD; Cristina Mussini, MD




Matteo Bassetti, MD, PhD: Hello. I am Dr Matteo Bassetti. Welcome to Medscape's InDiscussion series on COVID-19. Today we will discuss the future of COVID and sustainable approaches to living with something that we can't eradicate.
We know that COVID now is probably different from the COVID-19 that we faced in 2020 and 2021. But we are close to autumn and winter, and it's important to know what we have to expect from the future of COVID.
First, let me introduce my guest, Dr Cristina Mussini, who is a professor of infectious diseases at the University of Modena and Reggio Emilia, a very well-known expert in Italy and Europe, and is also a good friend. Welcome, Cristina, to InDiscussion.

Cristina Mussini, MD: Hello, Matteo. Thank you for the invitation.

Bassetti: Before beginning our discussion today, I'd like to ask you, what was it that sparked your interest in COVID-19, and what keeps you engaged today regarding this very interesting topic?
Mussini: We are both infectious disease specialists, so a pandemic is something that is related to our specialty. In our lifespan, and also the professional lifespan, we already faced one pandemic that is still here, which is HIV. Obviously, it was not a respiratory infection, so the way of transmission was completely different, and it was less of a threat for the general population. But I think that we were also preparing to have Ebola in our clinic, if you remember, so when COVID arrived, we were, I would say, the natural doctors who could take care of these patients. Not only because of our clinic's structural characteristics that allow the admittance of a patient with a respiratory contagious disease but also because of our expertise.
Bassetti: Before looking at the future, it is important, in my opinion, to look at what is happening now.

Do you think there is any difference in the presentation and the severity of COVID-19 today in comparison with the disease that we faced 2 or 3 years ago?
Mussini: Yes, I mean, it's not a mystery. It's been a long time that we have been admitting in our clinic only patients who have a positive nasal swab but no involvement of the low respiratory tract, aside from a few individuals that we will talk about later. Fortunately, the advent of vaccines and the advent of some treatment strategies that could be either in the viral phase or during the inflammatory phase have changed, dramatically, the natural course, the natural history of the infection of COVID-19. What's happening now is that the virus is still circulating. We are continuing to admit people with a positive swab because we are looking for it. We perform another swab in the emergency room, not only for those who are symptomatic from a respiratory point of view — which is something that for me would be important and relevant for the future, like we do with the flu, for example — but also for those admitted for other reasons.
For example, in my clinic, I have a person who fell in her house. Another one had heart decompensation. It's completely different because for a long period, it's been the new variants that are really more contagious, but they stay in the upper respiratory tract. I don't know what's happening with this in Genoa.
Bassetti: We are following different rules because the Liguria region was the first, in April, to release a recommendation about not using swabs in asymptomatic patients. Actually, I don't have any patients who are asymptomatic with COVID. We have only patients who are symptomatic.

This is a kind of behavior that unfortunately continues to affect the patients in Italy. I don't really know why we are swabbing so much, because I believe this is a classical respiratory tract infectious disease. And we have to only swab the patients who present symptoms of respiratory tract infections and not swab people without symptoms.

On this point, the Minister of Health, a few weeks ago, was very clear, and I hope that hospitals, emergency rooms, and doctors will follow the strict recommendation of our Minister of Health. But let me ask you in general: If you had to describe the typical symptoms that affect not a fragile or not a very old patient with COVID-19 today, what are the classic symptoms? What is the duration of the symptoms? And what are the medications that you believe are important to suggest to be used?

Mussini: We are in Italy, and so the holiday season just stopped. The problem is that many people, even if they had symptoms related to COVID, did not undergo a swab. So now we are seeing the numbers rising because people are starting to use the swabs again because the symptoms are really similar to that of a common flu or common cold. Many times, you don't even have a fever; you just have a runny nose. You could sometimes have a sore throat, but you are not even coughing or something, because it hasn't involved the lungs. So, that's why the symptoms are so non-severe — I would say, so light — that you could think that it's a common cold. And this is important. But on the other hand, we have no idea, for now, of how much the virus is circulating because nobody underwent the nasal swab because everybody wanted to go on vacation, and if they have just a cold or runny nose, they said, "Okay, it's a cold" and they didn't do the swab.

Bassetti: Yes, this is exactly what happened during July and the end of June in the United States, with a very important circulation of SARS-CoV-2. And the phenomenon is going down rapidly without any type of intervention and without any consequences on hospital admissions and severe forms (of disease). But this is one side of the coin. Looking at the other side of the coin at the fragile and the elderly patients, are you still seeing severe disease, and what do you think will be the future? Next autumn or next winter, fragile, elderly, and very elderly patients will be affected by more severe forms (of disease). What do you suggest for them?

Mussini: This is something that we actually do not know because fragile patients, especially hematology patients or terminally ill patients, are people who are affected by many other causes of lung involvement in many cases. So it's complicated to understand if it's really a COVID pneumonia because the clinical picture really differs from the one that we were used to seeing during the early phase of the pandemic. What I can say is that our future will depend on the variants. It seems that now we have Eris and Pirola. In Italy, we don't have Pirola now; we have Eris and Eris has, in the animal model, affinity to the lung. And it seems like Pirola, which is more prevalent in the United States for now, could affect the lungs more. So this could make a difference, but still the only weapon that we have for these fragile people is to recommend vaccination, especially the most recently developed vaccines. This would be very important because we are running after the virus, but we are never there because the virus changes, and the vaccine takes some time to develop. And so, when the vaccines arrive, they are always for the old variant, not for the present variants. It's the same for monoclonal antibodies. So it's important to maintain the efficacy of antivirals, like nirmatrelvir/ritonavir or remdesivir, because these are the real weapons that we have for patients. In many cases, these people already had an infection and were not well when they were admitted to the hospital, but they could not mount an immunologic response.

Bassetti: Talking about the new variants, particularly the Eris variant, I read the article about the possibility of higher pathogenicity for the lung. However, honestly, we have to remember that the research was based just on 10 hamsters and is not already published; it is just in the preprint.

I would be a bit cautious about saying that Eris is more virulent for the lungs than the other variants because we are talking about a subvariant of Omicron. We will see what happens in the future, but this is my question for you: After November 2021, when the Omicron variant began its course from South Africa, we have not seen any increase in virulence, more contagious disease, but probably less virulence. Do you agree with that?

Mussini: Absolutely, yes. And also about Eris. Already in Italy, 40% of the swabs that we have, have this variant, and actually, we didn't see any increase in lung disease. The only caution is that I know that the number of swabs is so low that it could happen that we could see some lung disease (in the future), but we have also seen that Omicron really does not affect the lung. And even in patients who are admitted for pneumonia, in the vast majority of the cases, they have a bacterial pneumonia and a positive nasal swab. I don't know your experience, but what we have seen even in hematology patients is that with Omicron, we don't see severe lung involvement by SARS-CoV-2.

Bassetti: Honestly, with Eris and in general, during the summer, we have seen cases with a shorter duration in terms of positive swabs compared with the past. In the past, the average duration was between 7 and 10 days, sometimes even more than 2 weeks. Now we have infections that have a duration of no more than 4 or 5 days, and sometimes 7 days — except for the fragile patients who are hematology patients and the immunocompromised.

So my question now is about strategies. First of all, if you had to decide who is the target population to be vaccinated with the monovalent vaccine, which was approved by the European Medicines Agency a few days ago and will be approved soon for Pfizer and for Moderna, who would be the target population for vaccination, age, and underlying conditions?

Mussini: I think that the age should probably be older than 75 or 80. I would not say for those who are 65 years old. I will go older. I think 80 years old and fragile patients, especially hematology patients, much more than oncology patients, but also oncology patients with severe diabetes or severe cardiovascular comorbidities. We should also not forget that we have a population that not only received at least three vaccine doses but also experienced a lot of positivity for SARS-CoV-2 because they had several infections. I think that I had two — Delta and Omicron, for example — on top of the vaccination. In the general population, in people who can mount a normal immune response, the antigen has been seen many times; it's easy to recall it. So that's why the duration of symptoms that you were mentioning before is due to the fact that our immune system — the memory — says to just jump in because we have seen this virus many times. This probably is the best defense that we have.

Bassetti: People cannot see us because they are just listening to us, but when you said that you suggest the vaccination in patients over 75 years old, I applauded you because obviously 60 years old is a very young population. And I prefer to have one 80-year-old patient vaccinated than 100 people who are 60 years old vaccinated.

In the end, for the health system, for our public health system, it is much better to have all or more than 75% of the 80-year-old patients vaccinated than having 25% of all the people over 60 years old vaccinated. It is much more important.

The other question I have is regarding the fragile and the elderly patients. Do you believe that there is any type of new strategy, particularly for patients who [have hematologic conditions] or are immunosuppressed, who present with a long course of positive swab testing? Do you know if there are any particular strategies for this type of patient?

Mussini: We have all been artists in this setting. So what we do is we use everything that we have: all the antivirals — if we have monoclonal antibodies also, we know that a few of them can retain some activity. But just think of a cake: I think that each of these strategies could represent slices that all together make a cake. We don't have one single strategy that could help us in this. We are re-treating patients, for example, with a longer period of remdesivir; we are re-treating patients with Paxlovid; we are using, for example, sotrovimab; we are trying to combine different strategies, but nothing is really written in guidelines. When I say that we are artists, it's because of this. But what is your experience now?

Bassetti: We are using the combination of at least double antivirals. Unfortunately, we cannot use the third antiviral anymore because molnupiravir has been stopped in Italy by the Italian Medicines Agency. And we usually and routinely treat hematology patients with remdesivir plus Paxlovid in combination.

I hope that in the future we will have new monoclonal antibodies that maybe should help us in the cocktail. But before closing this episode, I'd like to ask you what advice you would share with clinicians treating COVID, and what is your advice for the future with COVID? Do we have to live with COVID, or do we have to live terrified by COVID?

Mussini: I always think of the data that we have. I don't like when people try to predict the future. What we know for now is that the virus is less virulent, and it's more contagious, but it's part of our differential diagnosis. An important mutation in COVID that makes it as pathogenic as before has the same chance as having a flu pandemic. For now — maybe I will be a terrible predictor; we will see — there are no data, no reason to think that it will change soon.

Bassetti: Thank you very much. Today we have talked with Dr Cristina Mussini about the future of COVID and about sustainable approaches to living with something that we know we can't eradicate. Thank you for tuning in. Be sure to download the Medscape app and share, save, and subscribe if you enjoyed this episode. This is Matteo Bassetti for InDiscussion.

Resources​

Barriers to and Strategies to Address COVID-19 Testing Hesitancy: A Rapid Scoping Review

Factors Associated With Mortality Among Elderly People in the COVID-19 Pandemic (SARS-CoV-2): A Systematic Review and Meta-Analysis

COVID-19 and Lung Pathologies

Editorial: A Rapid Global Increase in COVID-19 Is Due to the Emergence of the EG.5 (Eris) Subvariant of Omicron SARS-CoV-2

Covid-19: Scientists Sound Alarm Over New BA.2.86 "Pirola" Variant

Recommendations for the Management of Drug-Drug Interactions Between the COVID-19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications

Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients

Characterization of an EG.5.1 Clinical Isolate in Vitro and in Vivo

Omicron: The Pandemic Propagator and Lockdown Instigator - What Can Be Learnt From South Africa and Such Discoveries in Future

Systematic Lung Ultrasound in Omicron-Type vs. Wild-Type COVID-19

Sospensione di Utilizzo del Medicinale Lagevrio® (Molnupiravir)

 

[SparkleMax]

Maybe I'm just a filthy hippy but I get on board with what this bloke has to say.

He's an intensive care doctor who also sells education content to other doctors. I get the sense that he does what he does because he's genuinely terrified of another outbreak that would result in him having to decide who lives and who dies.

Summery - The warm feeling you get from the sun might be really really good for you.

So edgy - It may be the case that most of the benefit associated with Vitamin D could be attributed to the other human-sunlight interactions.

 

[missy]

"

The US beefs up pandemic infrastructure​

“We were born out of mistakes of the past,” Nikki Romanik, the deputy director and chief of staff of the White House’s newly minted Office of Pandemic Preparedness and Response Policy, told me over coffee in California on Tuesday. We’d just finished a panel discussion about US government priorities for defending against future pandemic threats. Romanik, a Centers for Disease Control and Prevention official-turned-key leader of the US mpox response, said to the audience that the nation has a tough road ahead. Without the billions of dollars unleashed during the Covid-19 emergency, pandemic readiness will be difficult to sustain. Budgets will be cut. People laid off. Programs abandoned, she stated candidly. Creating a permanent office dedicated to pandemics is a start, she said. “We need longevity for this kind of office,” she said. “Having a structure and the building blocks in place is important so that we’re not rotating in and out with every outbreak.” The new Office of Pandemic Preparedness and Response Policy, which was mandated by Congress, officially opened in August — three months after the US public health emergency came to a close. Though it still doesn’t have its own budget, Romanik and others have been wrangling staffers. There are nine now, including its inaugural director: Major General Paul Friedrichs, a retired Defense Department official who served as medical adviser to the chairman of the Joint Chiefs of Staff, among his other positions. Friedrichs reports into President Joe Biden’s Chief of Staff, Jeff Zients, who, before taking on the West Wing role, was the administration’s Covid-19 response coordinator. That’s helped “elevate interest” in the new office’s work, Romanik said. Its responsibilities include coordinating how the federal government navigates natural, accidental and deliberate health threats that could cause significant disruption. It’s also tasked with working with the Department of Health and Human Services to develop and procure new drugs and vaccines, and must repeatedly report to Congress on the state of US preparedness. Its scope goes beyond the obvious pandemic threats. OPPR, as the office is called, will play a role in assessing dangerous pathogens created or augmented by artificial intelligence. And it’ll support a new White House effort to strengthen the pharmaceutical supply chain. Among Romanik’s own priorities is improving US testing infrastructure. “During the pandemic, diagnostics were clearly the elephant in the room of what went wrong,” she said. “There was such a significant delay in early warning and detection that we will never actually know how much it delayed us, or how much mortality it caused.” The US can’t ready its defenses without the private sector, Romanik said. During “peace times,” the government must work to forge those partnerships — even if resources are limited. “This is a promise to the American people that we will actually get this right,” she said. — Riley Griffin

"

 

[missy]

"

COVID Tied to Changes in Brain Microstructure​

— Alterations seen in both long COVID patients and those who recovered from infection​

by Ed Susman, Contributing Writer, MedPage Today November 28, 2023


CHICAGO -- People who had SARS-CoV-2 infection showed brain changes on diffusion microstructure imaging (DMI), cross-sectional data suggested.
Widespread microstructural alterations were seen in people with long COVID neurologic symptoms and in people who had COVID but recovered, reported Alexander Rau, MD, of the University Hospital Freiburg in Germany, at the annual meeting of the Radiological Society of North Americaopens in a new tab or window.
"We did see a signature in the brain microstructure that is associated with COVID-19 infection, but the pattern is different among those people with long COVID-19 and those who do not have long COVID-19," Rau said.

Conventional MRI showed no brain volume loss in these patients. "While comparing their structural or conventional brain scans, we did not find any lesion or alteration that could explain the severe symptoms in patients with post-COVID syndrome," Rau pointed out.
How SARS-CoV-2 may affect the brain is largely unknown. In 2022, a longitudinal study of U.K. Biobank participantsopens in a new tab or window showed that mild SARS-CoV-2 infection was associated with brain volume loss and structural changes on MRI. More recently, researchers in Swedenopens in a new tab or window reported that diffusion MRI showed damaged white matter in people previously hospitalized for COVID with persistent post-COVID symptoms.
Rau and colleagues assessed 89 people with neurologic long COVID symptoms (mean age 49 years, 57% female), 46 people who recovered from COVID (mean 42 years, 66% female), and 38 people who never had SARS-CoV-2 infection (mean 42 years, 50% female). To look for possible alterations, the researchers used DMI, a technique that allows the brain's microstructure to be approximated using a diffusion weighted imaging sequence. Participants were scanned in 2020.

Long COVID was defined by World Health Organization criteriaopens in a new tab or window as new or continued symptoms 3 months after initial SARS-CoV-2 infection, with these symptoms lasting at least 2 months.
Participants with long COVID were recruited from the hospital's post-COVID clinic. Cognitive performance was measured with the Montreal Cognitive Assessment (MoCAopens in a new tab or window). Olfactory disturbance was tested with Sniffin' Sticksopens in a new tab or window, and fatigue level was assessed with the Würzburger Fatigue Inventory for Multiple Sclerosis (WEIMuSopens in a new tab or window).
The researchers found distinct brain networks that correlated with long COVID symptoms, after adjusting for age and sex. Altered brain microstructure in the mesiotemporal cortex was associated with cognitive dysfunction. Patients who had problems with their sense of smell had microstructural changes in the olfactory cortex, while those with fatigue had altered microstructure in the brain stem, including the ascending arousal network.
"We can see there is an altered microstructure that is associated with COVID-19 infection, and when we take our findings along with data from other sources, we see that this is compatible with accelerated aging, rather than with neurodegeneration," Rau said. "However, this is most speculative. To make this conclusive, we need a lot more research."

Confounding factors may have influenced the outcomes in this cross-sectional study, observed neuroradiologist Max Wintermark, MD, of the University of Texas MD Anderson Cancer Center in Houston, who wasn't involved with the research.
"The study is limited in generalization by the lack of a longitudinal perspective," Wintermark told MedPage Today. "We would really want to know if the longitudinal imaging changes parallel evolution of symptoms over time."
Rau said the next step is to perform longitudinal scans to see whether alterations persist and uncover prognostic factors that may identify who will recover from long COVID.
"We also need to corroborate the information from the scans with other bio data, such as obtained from blood draws, to gain a more profound insight in being able to predict which patients will have a post COVID-19 condition," he added.

• 
  
  Ed Susman is a freelance medical writer based in Fort Pierce, Florida, USA.
• "

 

[missy]

"

New Tests May Finally Diagnose Long COVID​

Sara Novak
November 29, 2023




One of the biggest challenges facing clinicians who treat long COVID is a lack of consensus when it comes to recognizing and diagnosing the condition. But a new study suggests testing for certain biomarkers may identify long COVID with accuracy approaching 80%.
Effective diagnostic testing would be a game-changer in the long COVID fight, for it’s not just the fatigue, brain fog, heart palpitations, and other persistent symptoms that affect patients. Two out of three people with long COVID also suffer mental health challenges like depression and anxiety. Some patients say their symptoms are not taken seriously by their doctors. And as many as 12% of long COVID patients are unemployed because of the severity of their illness and their employers may be skeptical of their condition.
Quick, accurate diagnosis would eliminate all that. Now a new preprint study suggests that the elevation of certain immune system proteins are a commonality in long COVID patients and identifying them may be an accurate way to diagnose the condition.
Researchers at Cardiff University School of Medicine in Cardiff, Wales, United Kingdom, tracked 166 patients, 79 of whom had been diagnosed with long COVID and 87 who had not. All participants had recovered from a severe bout of acute COVID-19.

In an analysis of the blood plasma of the study participants, researchers found elevated levels of certain components. Four proteins in particular — Ba, iC3b, C5a, and TCC — predicted the presence of long COVID with 78.5% accuracy.




"I was gobsmacked by the results. We’re seeing a massive dysregulation in those four biomarkers," says study author Wioleta Zelek, PhD, a research fellow at Cardiff University. "It’s a combination that we showed was predictive of long COVID."
The study revealed that long COVID was associated with inflammation of the immune system causing these complement proteins to remain dysregulated. Proteins like C3, C4, and C5 are important parts of the immune system because they recruit phagocytes, cells that attack and engulf bacteria and viruses at the site of infection to destroy pathogens like SARS-coV-2.
In the case of long COVID, these proteins remain chronically elevated. While the symptoms of long COVID have seemed largely unrelated to one another, researchers point to elevated inflammation as a connecting factor that causes various systems in the body to go haywire.

"Anything that could help to better diagnose patients with long COVID is research we’re greatly appreciative of within the clinical community," said Nisha Viswanathan, MD, director of the University of California Los Angeles Long COVID program at UCLA Health in Los Angeles.
Testing for biomarkers highlighted in the study, as well as others like serotonin and cortisol, may help doctors separate patients who have long COVID from patients who have similar symptoms caused by other conditions, said Viswanathan. For example, a recent study published in the journal Cell found lower serotonin levels in long COVID patients compared with patients who were diagnosed with acute COVID-19 but recovered from the condition.



Viswanathan cautions that the biomarker test does not answer all the questions about diagnosing long COVID. For example, Viswanathan said scientists don’t know whether complement dysregulation is caused by long COVID and not another underlying medical issue that patients had prior to infection, because "we don’t know where patients’ levels were prior to developing long COVID." For example, those with autoimmune issues are more likely to develop long COVID, which means their levels could have been elevated prior to a COVID infection.
It is increasingly likely, said Viswanathan, that long COVID is an umbrella term for a host of conditions that could be caused by different impacts of the virus. Other research has pointed to the different phenotypes of long COVID. For example, some are focused on cardiopulmonary issues and others on fatigue and gastrointestinal problems.

"It looks like these different phenotypes have a different mechanism for disease," she said. This means that it’s less likely to be a one-size-fits-all condition and the next step in the research should be identifying which biomarker is aligned with which phenotype of the disease.

Better diagnostics will open the door to better treatments, Zelek said. The more doctors understand about the mechanism causing immune dysregulation in long COVID patients, the more they can treat it with existing medications. Zelek’s lab has been studying certain medications like pegcetacoplan (C3 blocker), danicopan (anti-factor D), and iptacopan (anti-factor B) that can be used to break the body’s cycle of inflammation and reduce symptoms experienced in those with long COVID.

These drugs are approved by the US Food and Drug Administration for the treatment of a rare blood disease called paroxysmal nocturnal hemoglobinuria. The C5 inhibitor zilucoplan has also been used in patients hospitalized with COVID-19 and researchers have found that the drug lowered serum C5 and interleukin-8 concentration in the blood, seeming to reduce certain aspects of the immune system’s inflammatory response to the virus.




The Cardiff University research is one of the most detailed studies to highlight long COVID biomarkers to date, said infectious disease specialist Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. The research needs to be duplicated in a larger study population that might include the other biomarkers like serotonin and cortisol to see if they’re related, she said.

Researchers are learning more everyday about the various biomarkers that may be linked to long COVID, she added. This Cardiff study showed that a huge percentage of those patients had elevated levels of certain complements. The next step, said McComsey, "is to put all these puzzle pieces together" so that clinicians have a common diagnostic tool or tools that provide patients with some peace of mind in starting their road to recovery.

"

 

[missy]

"

Has Covid messed with our immune systems?​

China, immune debt, and the latest immunology data story​

KATELYN JETELINA AND EDWARD NIRENBERG NOV 30

​

Last week, a scare around an undiagnosed cluster of pediatric pneumonia in China rippled through social media. This was coupled with reports of overwhelmed pediatric hospitals in certain regions. The WHO confirmed this isn’t likely due to some novel pathogen but rather a resurgence of our “regular” viruses, like flu.

​

(Source: Chinese Centers for Disease Control)
As you may remember, the U.S. experienced a similar resurgence of flu and RSV last year (and still somewhat this year).
This has, nonetheless, reignited a discussion around “immunity debt” and whether Covid-19 infections make us immunocompromised.

“Immunity debt”​

In the first 2-3 years of the pandemic, RSV and flu, for example, were incredibly suppressed due to pandemic control measures. This led to a new phrase: “immunity debt” or “immunity gap.”
It’s centered around an increasing “susceptibility” pool, or how many people are vulnerable to infection. During the emergency, more and more people became susceptible due to a lack of infection (or maternal antibodies), susceptible people were born, and recovered people died. Then, when restrictions were lifted and the “normal” viruses returned, there was a HUGE susceptibility pool leading to many infections. This resulted in more infections than in the pre-pandemic seasons, which caused crowded hospitals in China, for example.
The U.S.—which is one year ahead of China in lifting restrictions—still has higher than “normal” RSV infections. It will likely take a few years to re-synchronize viral dynamics, but the dramatic effect is less apparent every subsequent year. Below is my best attempt at visualizing this phenomenon.

​

Susceptibility cycle, drawn by yours truly
While the term might be new to the public, this phenomenon has been seen before. For example, when sanitation improved, polio initially got much worse.

Immunocompromised after Covid-19 infections? ​

There has been discussion around whether anything else could be causing this rise in pediatric infections, like: Could there be more viral infections because Covid-19 is doing something weird with our immune systems?
This does happen with other viruses. HIV and measles are notorious for it, for example.
However, the case for Covid-19 is weak thus far:

1. T cells. Early in the pandemic, scientists found that the T cells expressed many markers that implied exhaustion (or low T-cell count). After more inquiry, it was clear the actual behavior of the T cells was still very much functional. Another concern was a drop in the blood’s T cell levels. But low counts can be attributed to T cells doing their job: leaving the blood and going to the tissues to fight off infections. This can happen after any infection, even with the common cold.
2. B cells. One paper argues that Covid-19 infections might harm B cell responses (i.e., our antibody factories). This hasn’t been reproduced. Also, the high antibody levels we see after vaccination and infections show our antibody factories are still working.
3. Epidemiological RSV data. One study has shown that children are at increased risk for RSV infections after a positive Covid-19 test. While this concerns us parents, there were many limitations. For example, the Covid-19 negative patients were not tested for SARS-CoV-2 antibodies. If severe RSV and Covid-19 share risk factors in young kids, this could lead to artifactual findings exaggerating the risk.

We certainly need more studies. But there are specific situations that are genuinely concerning regarding immunocompromise after Covid-19 infections:

1. Severe Covid-19 disease can cause you to develop antibodies against certain messengers (called cytokines like interferon), which can block critical messages from being sent, drastically reducing your ability to respond to infections. This is seen after critical pneumonia, too. The good news is that, now, these severe cases of disease are more rare, and in most people, this issue fades over time.
2. Some niche immune cells seem to change a lot after Covid-19 infection, but they are relatively minor populations, and the consequences to our overall health from these changes aren’t entirely clear. (Also, these data are all pre-vaccine.)

Neither of these states is common enough in young children to explain current epidemiological trends.
This is not to say that Covid-19 is something that we can just ignore—it comes with plenty of risks unrelated to what it may or may not do to the immune system (such as blood clots), and many still suffer from long Covid-19 for reasons we don’t fully understand.

Bottom line ​

We will continue to see “immunity debt” play out on a population level. Keep up to date on vaccines and take reasonable precautions against respiratory viruses. This will help keep both healthcare systems and ourselves as healthy as possible.
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[SparkleMax]

showed that mild SARS-CoV-2 infection was associated with brain volume loss and structural changes on MRI.

Terrifying..

 

[missy]

COVID hospitalizations increased for the third week in a row, surpassing 19,000 admissions in the most recent week reported. (U.S. News & World Report)

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New COVID-19 Hospitalizations Increase for 3rd Week in a Row​

CDC Director Mandy Cohen this week told Congress that ‘not enough’ Americans have gotten the updated coronavirus vaccine.
By Cecelia Smith-Schoenwalder
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Dec. 1, 2023, at 4:47 p.m.

COVID Hospitalizations on the Rise

A pharmacist prepares to give a Moderna COVID-19 vaccine on Sept. 20, 2023, in Cypress, TX.

(MELISSA PHILLIP/HOUSTON CHRONICLE VIA GETTY IMAGES)​

New coronavirus hospitalizations have increased for the third week in a row.
More than 19,400 new COVID-19 hospital admissions were reported last week, according to datahttps://covid.cdc.gov/covid-data-tracker/#trends_weeklyhospitaladmissions_select_00from the Centers for Disease Control and Prevention. While the numbers are a fraction of the massive surges the U.S. previously saw during the pandemic, it still means that the country is entering winter with elevated coronavirus levels.

After a period of limited change, COVID-19 activity is increasing again especially in the Midwest and Mid-Atlantic regions,” the CDC said in a published Friday.
Federal health officials are likely watching the increase given that they a “moderate” winter wave of coronavirus and this could be the start of it. Holiday gatherings and travel are also typically followed by an increase in coronavirus cases and hospitalizations.
COVID-19 vaccination rates, meanwhile, have been for many.
CDC Director Mandy Cohen told Congress this week that about 16% of Americans have gotten the updated COVID-19 vaccine.
“That’s not enough,” Cohen said.

National vaccination coverage for COVID-19, influenza and RSV vaccines increased less than 1 percentage point for children and adults last week, according to the CDC.
The CDC on Friday also said it is monitoring increases in respiratory illnesses reported among children – a similar problem to what has recently been observed in China.
“These reported increases do not appear to be due to a new virus or other pathogen but to several viral or bacterial causes that we expect to see during the respiratory illness season,” the CDC said.

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[missy]

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Prone Positioning Falls Flat for Weaning COVID Patients Off ECMO​

— Similar ECMO duration, mortality compared with supine position in randomized trial​

by Elizabeth Short, Staff Writer, MedPage Today December 1, 2023

Early application of prone positioning did not help patients with severe acute respiratory distress syndrome (ARDS) -- mostly from COVID -- get off venovenous extracorporeal membrane oxygenation (VV-ECMO) any faster compared to supine positioning, a randomized trial found.
Among ARDS patients receiving ECMO, an identical 44% of patients were successfully weaned off ECMO after 60 days whether they were placed in sessions of prone positioning or simply kept supine (P=0.64), reported Matthieu Schmidt, MD, of the Hôpital de la Pitié-Salpêtrière in Paris, and colleagues.

Within 90 days, there was no significant difference seen in ECMO duration between prone and supine groups (28 vs 32 days, P=0.13). Also no different were 90-day mortality rates between positions (51% vs 48%, P=0.62), according to the French PRONECMO study published in JAMAopens in a new tab or window.
"Despite promising findings in observational studies, prone positioning of patients undergoing ECMO failed to reduce ECMO duration or mortality in this randomized trial," Schmidt and coauthors concluded.
Prone positioning has been shown to reduce mortality in ARDSopens in a new tab or window, and promotes "better overall ventilation/perfusion matching through a more homogeneous distribution of gas-tissue ratios along the dependent-nondependent axis in addition to decreased levels of lung stress and strain," the investigators explained in their introduction.
But whether the benefit extended to ARDS patients on VV-ECMO was unclear. One recent meta-analysis of 13 observational studiesopens in a new tab or window had found prone positioning during ECMO for ARDS -- COVID-19 or not -- to be associated with a significant improvement in ventilator-free days and intensive care unit (ICU) survival, Schmidt's group noted.

Prone positioning is strongly recommended in current clinical practice guidelines, noted Ricardo Teijeiro-Paradis, MD, and Niall Ferguson, MD, MSc, both of the University of Toronto, in an accompanying editorialopens in a new tab or window.
"Based on these results, routine prone positioning during VV-ECMO does not facilitate earlier liberation from ECMO or improve outcomes. This suggests that on average, prone positioning does not facilitate further lung protection than that already provided with an ultraprotective ventilation strategy facilitated by VV-ECMO," Teijeiro-Paradis and Ferguson wrote.
"Results of the PRONECMO trial may lead us to turn our backs on routine prone-position ventilation during VV-ECMO and face forward toward novel group-specific interventions targeting lung and diaphragm-protective ventilation, early awakening, and patient mobility," the duo commented.
Study authors and editorialists posed several factors that may explain PRONECMO's neutral results for prone positioning.
"First, the majority of enrolled patients were placed in prone position before ECMO, compared with widely variable proportions of patients in previous cohorts. Second, the majority of patients had COVID-19-related ARDS, perhaps with a greater severity of pulmonary injury," Schmidt and colleagues wrote.

They added that a person's response to prone positioning may depend on his or her specific etiology or severity of respiratory illness. "The COVID-19 variant may also contribute to prone positioning response, as less favorable pandemic outcomes were observed in late 2020, and the Delta variant was predominant in France during part of the trial. This contrasts with early reports of prone positioning benefit in COVID-19 patients receiving ECMO during predominance of the wild-type SARS-CoV-2 strain," they wrote.
Additionally, Teijeiro-Paradis and Ferguson suggested that sedation may have played a role in prone positioning's lack of benefit in the trial.
"Not infrequently, our patients develop complete lung collapse/consolidation with resulting tidal volumes far below anatomical dead space," the pair wrote. "Such derecruitment is exacerbated by the lack of respiratory effort due to deep sedation and paralysis often needed to maintain adequate ECMO flow and safe inspiratory pressures. A similar phenomenon may explain the progressive decrease in respiratory system compliance observed in both groups in the PRONECMO study."

The randomized trial was conducted at 14 ICUs in France with clinicians having the experience and capability to perform prone positioning during ECMO. Study participants were patients undergoing ECMO for severe ARDS. From March to December 2021, adult patients were enrolled if they were undergoing invasive mechanical ventilation and were supported by VV-ECMO for less than 48 hours.
The study cohort included 170 patients (median age 51, 35% women). Approximately 93% of the cohort presented with COVID-19-related ARDS, the remainder having bacterial pneumonia or another etiology.
Those assigned to prone positioning underwent at least four prone position sessions of 16 hours during the first 4 days (unless a patient met predefined criteria for early stopping of the prone intervention), whereas the supine ECMO group was not allowed to be put in prone before day 60.
All individuals in the prone group were placed in this position immediately after randomization. Overall, 80% received at least four prone sessions, with discontinuation most commonly due to respiratory system compliance and improvements in oxygenation.
Among the study's limitations were its small sample size and unblinded trial methods. A caveat to the study's generalizability was the observation that approximately 40% of study participants had been enrolled from a single very experienced center, Schmidt and colleagues cautioned.

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