Coronavirus Updates October 2023

[missy]

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Convalescent Plasma Improves Survival in COVID Patients With ARDS, New Trial Shows​

— Might be one treatment option for the sickest of patients​

by Tara Haelle October 25, 2023

Convalescent plasma reduced mortality in COVID-19 patients with acute respiratory distress syndrome (ARDS) when provided within 5 days of invasive mechanical ventilation, the randomized open-label CONFIDENT trialopens in a new tab or window showed.
Mortality at 28 days was 35.4% among patients who received donated convalescent plasma with at least 1:160 neutralizing antibody titer, compared with 45% in patients who received standard care (P=0.03), reported Benoît Misset, MD, of University Hospital of Liège at the Domaine Universitaire du Sart Tilman in Belgium, and colleagues in the New England Journal of Medicineopens in a new tab or window. The effect primarily occurred in patients who were randomized within 48 hours after initiation of invasive mechanical ventilation.

"The survival curves in both the overall population and the patients who underwent randomization 48 hours or less after ventilation initiation separated near day 17," the authors reported. "Among the secondary outcomes, the results for inflammation, vasopressor support, and the number of adverse events tended to be better in the convalescent-plasma group."
Todd Rice, MD, MSc, of Vanderbilt University School of Medicine, who was not involved in the study, was surprised by the findings, noting that numerous previous studies of convalescent plasma, including his own, did not show much benefit in patients hospitalized with COVID-19.
"The study suggests that convalescent plasma might be one treatment option in the sickest patients with COVID, especially in ones who there is concern that they have not mounted an adequate immune response and do not already have their own antibodies against COVID," Rice told MedPage Today. "Mortality is a really hard outcome to improve, especially in patients who are already sick enough to need a ventilator. These findings will make us reconsider convalescent plasma in our patients."

He added, however, that the study occurred in patients during earlier phases of COVID with "variants that act a bit differently than the variants that we are seeing today," and that most participants were not vaccinated against COVID. "So it is not clear if this therapy will work for vaccinated patients – who may have already produced their own antibodies to the vaccine – or in patients who have antibodies from prior infections," he said.
An estimated 20-25% of patients hospitalized with COVID-19 had been admitted to ICU during the early part of the pandemic, and 70% of them received invasive mechanical ventilation, according to a 2021 study, the authors noted. Mortality for COVID-19 patients receiving invasive mechanical ventilation in the ICU hovered around 45% in a separate 2021 meta-analysis.

To assess the effect of convalescent plasma in patients like these, researchers enrolled 475 patients from 17 sites in Belgium from September 2020 to March 2022. The patients had an average age of 64, and two-thirds were male. Vaccination rates were 11.4% in the plasma group and 8% in the control group. Rates of hypertension, congestive heart failure, diabetes, COPD, asthma, chronic renal failure and cancer did not statistically differ between groups.

All the patients had been admitted to an ICU with COVID-19-induced ARDS and had received invasive mechanical ventilation for no more than 5 days. Only patients with a Clinical Frailty Score less than 6 (range 1-9) were included, and COVID-19-induced ARDS was defined as "extended interstitial pneumonia on a computed tomographic scan or a chest radiograph within 10 days before inclusion and a positive result of a clinical SARS-CoV-2 nasopharyngeal polymerase-chain-reaction (PCR) test within 15 days before inclusion."
The convalescent plasma donors had a previous SARS-CoV-2 infection and had fully recovered between 28 days to 10 months earlier. Although the researchers sought to use plasma with a 1:320 antibody titer ratio, they accepted a 1:160 ratio during shortages for 17.7% of the plasma group.
Most patients (57.5%) had moderate ARDS, with 9.9% classified with mild ARDS and 32.4% with severe ARDS. Around 6% in both groups received remdesivir (Veklury), and nearly all the patients (around 98%) received glucocorticoids. Enrollment included 41.4% of patients when the ancestral virus was circulating, 34.3% during the Alpha wave, 20.8% during Delta, and 3.4% during Omicron.

Most participants (72%) were randomized within 48 hours of invasive mechanical ventilation, and they were evenly distributed in the intervention and control groups. All of the 237 patients randomized to receive two units of convalescent plasma received it except one who died before infusion began. None of the 238 patients in the standard care group received plasma.
Mortality rates of 35.4% in the plasma group and 45% in the standard care group were significantly different both before and after accounting for the better outcomes in those who were randomized within 48 hours of ventilation. For only those randomized within 48 hours of ventilation, mortality was 32.7% in the plasma group and 46.8% in the standard care group. However, mortality was 42% in the plasma group and 40% in the standard care group among those randomized more than 48 hours after ventilation. Titer levels of the plasma were not associated with mortality.
No adverse effects were attributed to the plasma, and secondary bacteremia, pneumonia, organ support duration, and length of hospital stay did not differ between the groups. A greater effect occurred among patients with a higher Sequential Organ Failure Assessment (SOFA) score.

Aside from uncertainty about the findings' generalizability to vaccinated and previously infected patients, Rice noted that convalescent plasma is difficult to obtain given the timing needs in donors.
"Patients who donate have to be recovered from their infection with COVID, but not so long after that their antibody levels have decreased, so we have to find patients between 1 and 6 months after they recover from their COVID," Rice said. "Then we have to make sure that they have a high enough level of the antibodies to be able to pass along immunity."
Most U.S. blood banks have stopped offering convalescent plasma because of the difficulty of finding donors and past studies' disappointing results, Rice said, but "this trial will likely result in some blood banks starting to offer convalescent plasma again."

Disclosures
The research was funded by the Belgian Health Care Knowledge Center.
Study authors reported relationships with Boehringer Ingelheim, Merck, Roche, ViiV Healthcare Company, Grand Medical Pty Ltd, Transgene SA, and AM Pharma.
Rice had no disclosures.
Primary Source
New England Journal of Medicine
Source Reference: opens in a new tab or windowMisset B, et al "Convalescent plasma for Covid-19-induced ARDS in mechanically ventilated patients " N Engl J Med 2023; DOI: 10.1056/NEJMoa2209502

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[Karl_K]

Hi Karl! That actually could be a good sign because it means your body is building up a defense against the virus should you get infected. So take heart. And I hope you are feeling much better today!

Thank you.
I am feeling better today.

 

[missy]

Glad you are feeling better @Karl_K !

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The Role of Public Health, Vaccines, and Home Care in COVID-19 Prevention​

Matteo Bassetti, MD, PhD; Giuseppe Remuzzi, MD

Matteo Bassetti, MD, PhD Hello. I am Matteo Bassetti. I am professor of infectious diseases at the University of Genoa and also chief of the infectious disease clinic in San Martino University Hospital in Genoa, Italy. Welcome to Medscape's InDiscussion series on COVID-19. Today we will discuss COVID prevention. I believe that this is particularly important because in autumn we'll start a new campaign regarding the vaccination and because we have a lot of novel treatments for COVID-19, both in the hospital and in the community. First, let me introduce my guest, Professor Giuseppe Remuzzi, who is director of the Mario Negri Institute for Pharmacological Research and Chiara Fama Professor of Nephrology at the University of Milano in Italy. Welcome, Giuseppe, to the Medscape InDiscussion podcast.

Giuseppe Remuzzi, MD: Thank you, Matteo. Thank you for inviting me. I am very pleased to take part in this venture with you.

Bassetti: Before we begin our discussion, I'd like to ask you, what was it that sparked your interest in COVID-19 and what keeps you engaged today?


Remuzzi: Paradoxically, the reason for my interest can be summarized in a beautiful article in The New York Times that appeared in November 2020; the title is exactly the reason why I have been involved: "The Lost Days That Made Bergamo a Coronavirus Tragedy."


Bergamo became one of the deadliest killing fields for the virus in the Western world. As I have a major responsibility as a director of probably one of the largest institutes of pharmacology in Europe, I felt obliged to involve myself and my group in these terrible circumstances that affected villages in Bergamo, and Bergamo itself, from the early beginning [of the pandemic].

And this is one reason. I'd like to tell you the second reason, which is quite bizarre. One day, one of our colleagues — and probably one of your colleagues, probably an infectious disease person — said on [a television show on which I was a panelist], "I am curious as to why nephrologists should be dealing with coronavirus." I should have been offended because I was the only nephrologist present [on the panel] on the television program. But I took this critique seriously. And why? The spike protein, as everyone knows, binds to a receptor — actually, to multiple receptors; a new one was just discovered — but the main one that the spike protein uses in order to enter the cells is angiotensin converting enzyme (ACE) type 2. This is part of the larger family of the renin-angiotensin axis, and nephrologists have been dealing with the renin-angiotensin axis for many years. My group in particular was involved in the past 30 years with the renin-angiotensin axis. So there is a good reason for nephrologists to be involved. We were probably the first to describe the electron microscopy finding of the SARS-CoV-2 virus in kidney proximal tubular cells and also in podocytes of the glomerulus. There is a sentence that I like very much. It was published in Science by Dr Wadman: "If these folks are not dying of lung failure, they will die of renal failure." So our friend should know that there are several reasons for nephrologists to be involved with coronavirus. Besides the fact that, as opposed to obesity, hypertension, diabetes, and all the comorbidities that we know as being associated with severe COVID, the most important of all of them is having chronic kidney failure. This means having four times more probability of dying as compared to all other comorbidities.

Bassetti: I knew very well that you were one of the most important international experts in the field of COVID-19. I didn't have any doubt that you are one of the most balanced, high-level scientists in this field, and I really believe that we need nephrologists to take care of the patients.


I believe that what we learned from coronavirus is that it is important to have a multidisciplinary approach. It was not a disease of one expert, but it was, and is still, a disease of many experts working together.

What was the lesson that we learned from COVID and how can we prepare for the future?

Remuzzi: Before that, Matteo, may I spend 10 seconds to tell you how important what you said was? And I will go a little bit farther. COVID-19 taught us that there is no infectious disease, pneumology, digestive disease, heart, and kidney [disease]. There is a patient who has several problems, all of them linked. And this is very important for the future and for other diseases.

But let's come back to the first lesson. To me, the first lesson we learned is about public health. We have to create an appropriate balance between protecting the health of all those who live in a given country — this is public health — while minimizing the disruption to the normal, functioning society. And the goal is to offer science-driven recommendations that balance protection and practicality in the context of one individual risk. The second lesson, and this is a very personal view, is that we learned that things are extremely complicated and decisions are not easy to make.


Let's offer an example. If a new, potentially lethal respiratory virus is circulating, we have to decide whether to close school. School closures have two theoretical benefits. Certainly it reduces illness in children and adults present in school, and it reduces community spread. But this is associated with harm as well: impaired education, social and emotional development, and physical and mental health; and loss of economical activity for parents.


So, we have to be capable of balancing in different circumstances, in different contexts, in different territories, in different countries, these advantages vs the harm. And this is not easy. What do we do? It's a question of balance. Science-driven recommendations are extremely important, and practicality is also associated with that in public health. So then politicians should decide. They don't have to say, "I am following the science." They have to decide after scientists have told them what they know.


Bassetti: This is an important point because in the past 4 years, we have seen many situations — not only in Italy — where politicians did our job, and sometimes they didn't listen to what the science was suggesting. This is a problem of the past; I really believe that it is not going to be a problem for the future. And I believe that we have to be prepared for a new pandemic because we know that there are a lot of viruses circulating. The avian flu is going to be a problem. And I agree with you that we have to build a public health system that helps everybody better than we did, at least at the beginning of the pandemic in 2020.


We are talking again about the new rise of COVID, and every day, even in the newspaper and on TV shows, they talk about the new variants. What are your thoughts regarding the new rise in variants? Is it going to be a topic for scientists or is it going to be a topic for mass media and not specific journals?


Remuzzi: It has to be a topic for everyone, provided that what people announce or what they say or do is, in fact, informed by knowledge. I think that people who write in the press — besides scientific papers — those who conduct television shows, or people who are involved in politics, should base their decisions on solid knowledge rather than on an impression or on something that they found on social media. For instance, another lesson that we learned from the pandemic is that it's not enough to support public health when there is an emergency. Our government did that and probably did that reasonably well, but the influx of resources during a crisis cannot be followed by underfunding after we treat — exactly as it happened in our country — because that is the way to put future lives at risk. Long-standing, sustainable investments are needed for public health to be something that people really take care of, and this has to be continued over time.


Bassetti: Yes, I agree. I think it's quite strange that the new variants get their name from social media and not from scientists. When you talk about "Pirola" or "Kraken" or other terrible names of variants taken from mythology, it's quite strange, because usually in science, we name the variants with an acronym or with numbers. But now we have names that are quite strange.


Do you think any of the new variants would be problematic for vaccines, antivirals, monoclonal antibodies and, in general, any type of treatment that we are using for COVID-19?


Remuzzi: Well, concern is rising about COVID-19 variants EG.5 — as you said, social media has named it Eris — and BA.2.86. Actually, in August, EG.5 became the dominant variant, according to the World Health Organization, which classified it as a variant of interest, meaning that it has genetic changes that give it an advantage and it's prevalent. We also have BA.2.86, nicknamed Pirola; it is much less widespread, making up only a thin fraction of cases. So, you may ask me, how worried should people be about these variants? BA.2.86 is descendant from the Omicron variant, and scientists indeed are particularly concerned about this variant because it carries more than 30 mutations on spike protein.


However, according to some scientists, this mutation represents an evolutionary jump, similar in size to the changes that we had seen in the first Omicron variant compared with the original coronavirus strain. BA.2.86, in terms of an updated vaccine, will not be very different against it. So the research indicates that it is probably less infectious than other variants as per the studies in the lab, but we know that studies in cells do not always translate into something that has a clinical significance. Scientists today tend to say that treatments such as the antiviral Paxlovid should still be effective, even with such a highly mutated virus. The reason is that they target a different part of the virus and not the spike.


EG.5 is descendant from XBB.1.9.2, an Omicron offspring, with the same spike protein as XBB.1.5. It is the variant that is targeted by the forthcoming vaccines. But unlike those variants, EG.5 has a spike protein mutation which, in laboratory experiments, allows it to evade most of XBB.1.5 neutralizing antibodies. So the issue of neutralizing antibodies is currently under attention and careful investigation.


Bassetti: Absolutely. Now we are moving to the last part of our discussion, and the next question is about the vaccines. What do you think is going to be the future for vaccines and their update for the autumn and winter? Who is going to be a candidate for receiving the new vaccine?


Remuzzi: As per the European Medicines Agency, EMA, they have given the green light to Pfizer for a new vaccine, upgraded to Omicron XBB.1.5, one of the most popular [variants] in recent months. This will probably be given in the autumn and winter together with influenza vaccines. They are probably effective, as far as we know, against the new variants. This is something that will also be issued by the US Food and Drug Administration. There are encouraging preliminary trial data from Moderna regarding the effectiveness of this monovalent vaccine against the new variants of concern, including EG.5. I think that the way of preparation for the vaccines now is such that there will also be a possibility to follow the evolution of a new variant.


I think we can be reasonably optimistic. Certainly, people who are older than 60 years, fragile, those who are on dialysis or transplanted, and those who are on immunosuppressive therapy, should be encouraged to take another shot. But I wouldn't say the fifth, the fourth, or the third shot; I think we will encourage people to have probably one shot every year.


Bassetti: I fully agree with your point that the number of vaccinations was not communicated correctly, and that was probably one of the reasons why not enough people received a vaccination during 2022 and part of 2023.


Will home be the new frontier or will the hospital again be the setting for taking care of COVID?


Remuzzi: I like something very much that I heard from a doctor from Israel speaking in South Africa. They said, "Home will be the new frontier, used for the never-ending capacity of home beds. This is the future." I like "never-ending capacity" very much because if you are very careful at home — consider that approximately 80% of patients, even if unvaccinated, have a mild disease that does not require medical intervention or hospitalization. And the proportion is higher in those who are vaccinated. If we are careful in taking care of our patients at home, we or a general practitioner really can create a condition by which hospitals will not be saturated, and emergency care can be done with a proper amount of time to do things in the best possible way.


Bassetti: We learned why we have talked with Dr Giuseppe Remuzzi: because Dr Remuzzi, a friend and colleague, has underlined clearly why a nephrologist should talk about COVID — not only in the past but I hope also in the future, because we need a multidisciplinary approach to this disease.


We also learned a lot of very interesting points regarding public health for the future, but also regarding what the most interesting variants are, who should be vaccinated in the autumn and winter, and that home probably will be the setting in which doctors will take care of people with COVID-19.


Thank you for tuning in. There's much more ahead in the coming episode. And thank you very much, Giuseppe. I think you did a great job. Be sure to download the Medscape appand share, save, and subscribe if you enjoyed this episode. This is Dr Matteo Bassetti for InDiscussion.

Resources​

Coronavirus Disease 2019 (COVID-19) Treatment & Management


The Lost Days That Made Bergamo a Coronavirus Tragedy


ACE2 Angiotensin Converting Enzyme


Renin Angiotensin System


A Rampage Through the Body


Avian Influenza (Bird Flu)


WHO EG.5 Initial Risk Evaluation, 9 August 2023


Updated Working Definitions and Primary Actions for SARS-CoV-2 Variants


Risk Assessment Summary for SARS-CoV-2 Sublineage BA.2.86

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[missy]

"

mRNA Vaccine Cuts COVID-Related
Guillain-Barré Risk​

Kelli Whitlock Burton
October 26, 2023

TOPLINE:​

The risk for Guillain-Barré syndrome (GBS) is six times higher in people with COVID-19 in the 6 weeks following infection, according to a new study that also showed receipt of the Pfizer-BioNTech mRNA vaccine reduced GSB risk by 59%.

METHODOLOGY:​

• The nested-case control study analyzed data from the largest healthcare provider in Israel for 3.2 million patients aged 16 years and older, with no history of GBS.
• GBS cases (n = 76) were identified based on hospital discharge data from January 2021 to June 2022.
• For every GBS case, investigators chose 10 controls at random, matched for age, gender, and follow up duration (n = 760).
• Investigators examined the association between GBS and SARS-CoV-2 infection, established through documentation of prior positive SARS-CoV-2 test (PCR or antigen), and any COVID-19 vaccine administration.

TAKEAWAY:​

• Among those diagnosed with GBS, 8 were exposed to SARS-CoV-2 infection only, 7 were exposed to COVID-19 vaccination only, and 1 patient was exposed to both SARS-CoV-2 infection and COVID-19 vaccination in the prior 6 weeks, leaving 60 GBS patients without exposure to either infection or vaccination.
• All COVID-19 vaccine doses administered in GBS cases within 6 weeks of the index date, and all but two doses administered in controls in the same timeframe, were Pfizer-BioNTech vaccines.
• Compared to people without GBS, those with the condition were more than six times as likely to have had SARS-CoV-2 infection within 6 weeks of GBS diagnosis (adjusted odds ratio [aOR], 6.30; 95% CI, 2.55 - 15.56).
• People who received the COVID-19 vaccine were 59% less likely to develop GBS than those who did not get the vaccine (aOR, 0.41; 95% CI, 0.17 - 0.96).

IN PRACTICE:​

"While Guillain-Barré is extremely rare, people should be aware that having a COVID infection can increase their risk of developing the disorder, and receiving an mRNA vaccine can decrease their risk," study author Anat Arbel, MD, of Lady Davis Carmel Medical Center and the Technion-Israel Institute of Technology, Haifa, Israel, said in a press release.

SOURCE:​

In addition to Arbel, the other lead author is Haya Bishara, MD, of Lady Davis Carmel Medical Center. The research was published online October 18 in the journal Neurology.

LIMITATIONS:​

There is a possibility of misclassification of SARS-CoV-2 infection, which could lead to an overestimation of the magnitude of association between infection and GBS. The diagnosis of GBS relied solely on ICD-9 coding, which has been shown in prior studies to contain errors.




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