How COVID-19 causes neurological damage

Authors: Date:nnNovember 14, 2022 University of Basel

Summary:It’s not uncommon for people to lose their sense of taste and smell due to a COVID-19 infection. In others, the disease has had an even stronger impact on the nervous system, with effects ranging from lasting concentration problems to strokes. Now, researchers have reported new insights into the development of ‘neuro-COVID’.

It’s not uncommon for people to lose their sense of taste and smell due to a Covid-19 infection. In others, the disease has had an even stronger impact on the nervous system, with effects ranging from lasting concentration problems to strokes. Now, researchers led by Professor Gregor Hutter from the Department of Biomedicine at the University of Basel and University Hospital of Basel have reported new insights into the development of “neuro-Covid” in the journal Nature Communications.

Specifically, the team investigated how different severities of neuro-COVID can be detected and predicted by analyzing the cerebrospinal fluid and blood plasma of affected individuals. Their findings also offer some indications of how to prevent neurological damage due to Covid-19.

The study included 40 Covid-19 patients with differing degrees of neurological symptoms. In order to identify typical changes associated with neuro-Covid, the team of researchers compared these individuals’ cerebrospinal fluid and blood plasma with samples from a control group. They also measured the brain structures of test subjects and surveyed participants 13 months after their illness in order to identify any lasting symptoms.

Holes in the blood-brain barrier

Particularly in the group with the most serious neurological symptoms, the researchers identified a link with an excessive immune response. On the one hand, affected individuals showed indications of impairment of the blood-brain barrier, which the study’s authors speculate was probably triggered by a “cytokine storm” — a massive release of pro-inflammatory factors in response to the virus.

On the other hand, the researchers also found antibodies that targeted parts of the body’s own cells — in other words, signs of an autoimmune reaction — as a result of the excessive immune response. “We suspect that these antibodies cross the porous blood-brain barrier into the brain, where they cause damage,” explains Hutter. They also identified excessive activation of the immune cells specifically responsible for the brain — the microglia.

Blood test as a long-term objective

In a further step, Hutter and his team investigated whether the severity of neurological symptoms is also perceptible in brain structures. Indeed, they found that people with serious neuro-Covid symptoms had a lower brain volume than healthy participants at specific locations in the brain and particularly at the olfactory cortex — that is, the area of the brain responsible for smell.

“We were able to link the signature of certain molecules in the blood and cerebrospinal fluid to an overwhelming immune response in the brain and reduced brain volume in certain areas, as well as neurological symptoms,” says Hutter, adding that it is now important to examine these biomarkers in a greater number of participants. The aim would be to develop a blood test that can already predict serious cases, including neuro-Covid and long Covid, at the start of an infection.

Targets for preventing consequential damage

These same biomarkers point to potential targets for drugs aimed at preventing consequential damage due to a Covid-19 infection. One of the biomarkers identified in blood, the factor MCP-3, plays a key role in the excessive immune response, and Hutter believes there is the potential to inhibit this factor medicinally.

“In our study, we show how coronavirus can affect the brain,” he says. “The virus triggers such a strong inflammatory response in the body that it spills over to the central nervous system. This can disrupt the cellular integrity of the brain.” Accordingly, Hutter says that the primary objective must be to identify and halt the excessive immune response at an early stage.

Journal Reference:

  1. Manina M. Etter, Tomás A. Martins, Laila Kulsvehagen, Elisabeth Pössnecker, Wandrille Duchemin, Sabrina Hogan, Gretel Sanabria-Diaz, Jannis Müller, Alessio Chiappini, Jonathan Rychen, Noëmi Eberhard, Raphael Guzman, Luigi Mariani, Lester Melie-Garcia, Emanuela Keller, Ilijas Jelcic, Hans Pargger, Martin Siegemund, Jens Kuhle, Johanna Oechtering, Caroline Eich, Alexandar Tzankov, Matthias S. Matter, Sarp Uzun, Özgür Yaldizli, Johanna M. Lieb, Marios-Nikos Psychogios, Karoline Leuzinger, Hans H. Hirsch, Cristina Granziera, Anne-Katrin Pröbstel, Gregor Hutter. Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional studyNature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-34068-0

What Is COVID Tongue, and What Does It Mean?

Authors: Medically reviewed by Elizabeth Thottacherry, MD — By S. Behring — Updated on January 20, 2022 HealthLine

In March 2020, the World Health Organization (WHO) declared a pandemic in response to the spread of the COVID-19 infection.

Since then, more than 50 million casesTrusted Source occurred in the United States alone. Medical professionals gathered data to determine the symptoms of COVID-19. The early symptoms observed included fatigue, shortness of breath, and fever.

But as COVID-19 cases continue, new symptoms are documented, including a rare symptom known as COVID tongue. People with COVID tongue have swollen tongues that might develop bumps, ulcers, and white patches. Read on to learn more about this unusual COVID-19 symptom.

What is COVID tongue?

Along with the more well-known symptoms of COVID-19, some people experience bumps, ulcers, swelling, and inflammation of the tongue. This is known as “COVID tongue.”

People with COVID tongue might notice that the top of their tongue looks white and patchy, or that their tongue looks red and feels swollen. They sometimes find bumps or open areas called ulcers on their tongue. Additionally, many people with COVID tongue report experiencing a loss of taste and a burning sensation in their mouth.

2021 study documented COVID tongue as a possible COVID-19 symptom. But just like many things about COVID-19, there’s a lot we don’t know right now about COVID tongue.

What’s happening inside your body to cause COVID tongue?

Another reason there are many questions about COVID tongue is that there are several possible causes. It’s common for illnesses and infections to cause changes to your tongue.

What looks like COVID tongue could easily be a symptom of a different viral or bacterial infection. Even when the bumps and swelling are clearly connected to COVID, there are many possible reasons. COVID tongue might be caused by:

  • A high number of ACE receptors in your tongue. ACE receptors are proteins found on cells in your body. When the virus that causes COVID-19, SARS-CoV-2, attaches to ACE receptors, it can get into your cells. You have many ACE receptors in your tongue, which could lead to swellingTrusted Source when you have a COVID-19 infection.
  • Your immune system fighting COVID-19. When your immune system is fighting a bacterial or viral infection, it can cause swelling throughout your body. This could include the tongue swelling associated with COVID tongue.
  • COVID-causing oral thrush. Oral thrush is a fungus in your mouth that can be caused by a number of infections. This might include COVID-19. Plus, oral thrush is a side effect of some medications used to treat COVID-19.
  • Changes to the surface of your tongue. Infections sometimes lead to changes on the surface of your tongue, such as mouth ulcers and other symptoms. It’s possible COVID-19 can lead to this sort of change as well.
  • Dry mouth. COVID-19 can affect your salivary glands and cause them to secrete less saliva. This could lead to dry mouth. Research shows that dry mouth can lead to multiple other oral health concerns.
  • COVID-activating oral herpes. The inflammation caused by COVID-19 can activate other viruses in your body. This might include the herpes simplex virus, which lays dormant in your body even when you don’t have symptoms. COVID-19 could causeTrusted Source the herpes virus to activate and cause mouth ulcers.

COVID tongue could be caused by any one of these factors or by a combination of them. There’s also a chance that COVID tongue is sometimes caused by breathing tubes and other COVID treatments that could irritate your mouth and lead to a swollen tongue.

Until we know more about COVID-19, we won’t know the exact cause of COVID tongue.

How many people get COVID tongue?

Currently, scientists don’t know how rare COVID tongue is. In one small study, up to 11 percent of people hospitalized with COVID-19 had COVID tongue, but such studies are too small to make a conclusion.

As more data from hospitals around the world come in, we might get a better idea of how common COVID tongue is.

Many people with COVID-19 have mild or moderate symptoms and can recover at home. But right now, even less is known about how many people in this group develop COVID tongue. Often they recover without contacting a doctor at all, so their symptoms are never recorded.

Even when people with mild or moderate COVID-19 do seek treatment, they often wear masks or use telehealth for a video appointment. That makes it difficult for medical professionals to see their tongues and document any abnormalities.

What is the treatment for COVID tongue?

There is currently no single set treatment for COVID tongue. You might not need treatment targeted to COVID tongue. In some cases, the treatments you already receive for COVID will be enough to resolve COVID tongue.

When COVID tongue is more severe and doesn’t respond to overall treatment, you might receive specialized treatment. This could include:

  • corticosteroids or other anti-inflammatory medications to bring down tongue swelling
  • antibacterial, antiviral, or antifungal mouth rinses to treat bumps, patches, and ulcers
  • artificial saliva mouth rinses to help combat dry mouth and promote overall tongue healing
  • low level laser therapy to treat ulcers

Treatment for swollen tongue

COVID-19 may cause the tongue to swell. Tongue swelling can quickly become a medical emergency if your airway becomes blocked. If you think your tongue is swelling, seek medical attention immediately.

The treatment for a swollen tongue is designed to reduce the swelling and relieve pain and discomfort.

Treatment options for swollen tongue include:

  • over-the-counter medications such as ibuprofen (Advil)
  • prescription anti-inflammatory medications
  • medications to treat the underlying condition causing your tongue to swell

What to do if your tongue swells

Call 911 if your tongue swells and you feel like it’s harder to breathe. Do not drive yourself to the ER because your condition could worsen on the way. For many people, calling 911 means help will reach you faster than going to an ER.

  • Have someone stay with you until help arrives.
  • Contact your healthcare professional immediately if you notice that your tongue swells.
  • If you have mild tongue swelling that gets worse, contact your doctor or healthcare professional immediately for an examination.

What’s the outlook for people with COVID tongue?

It’s currently unclear whether COVID tongue is an early symptom of COVID-19, or a symptom that develops as the condition progresses.

No matter when it develops, you might also have other, more-common COVID-19 symptoms:

  • fever
  • cough
  • shortness of breath
  • fatigue
  • nausea
  • pain

Studies are being done to see if COVID tongue is an early or warning symptom.

Mild to moderate COVID-19

People with mild and moderate cases of COVID-19 usually recover at home without medical intervention. Rates of recovery are also improving for people hospitalized with COVID-19 as doctors learn how to best treat the infection.

But since COVID-19 is still a relatively new illness, we don’t know for sure right now what the long-term effects for people will be. Some symptoms of COVID-19 might linger for weeks or even months.

Geographic tongue

While research on COVID tongue is limited now, we do know that viral infections can sometimes lead to a condition called geographic tongue.

This condition causes smooth red patches with white borders to appear on your tongue and can last for months — or even years. Geographic tongue doesn’t generally cause pain or other health concerns, but flare-ups can make it difficult to eat spicy foods.

It’s currently unclear whether COVID tongue is related to geographic tongue, or whether COVID-19 can lead to geographic tongue. As more people recover from COVID-19 and more data become available, doctors will have a better understanding of COVID tongue and any possible long-term effects.

If you have COVID-19 and are experiencing any mouth or tongue health concerns, talk with your doctor.

The bottom line

Some people with COVID-19 develop bumps, white patches, and swelling on their tongues. This is known as COVID tongue and it’s still being studied.

Right now, there are a lot of unanswered questions about COVID tongue. We currently don’t know how many people get COVID tongue or what causes it. More information about COVID tongue will be available as doctors learn more about COVID tongue and more research occurs.

Psoriasis Flares in Patients With COVID-19 Infection or Vaccination: A Case Series

Authors: Hemali ShahAna C. Busquets

Published: June 16, 2022 (see history) DOI: 10.7759/cureus.25987 Cite this article as: Shah H, Busquets A C (June 16, 2022) Psoriasis Flares in Patients With COVID-19 Infection or Vaccination: A Case Series. Cureus 14(6): e25987. doi:10.7759/cureus.25987

Abstract

Much of the literature involving COVID-19 and chronic inflammatory dermatological conditions have focused on the safety of immunomodulatory therapy in the setting of this highly infectious virus. While general mortality associated with the infection and vaccine has been studied in depth, the effects of the virus and vaccine on inflammatory skin disease states have not been. It is well known that psoriasis can be triggered by stress, infection, certain medications, and, although not as common, vaccinations. Further, existing literature has briefly commented on psoriasis flares after COVID vaccination, but these have not touched on flares among their patients’ current therapy, nor flares after COVID infection. In this case report, we report five cases observed at our institution over the last year of either new-onset psoriasis or flares of previously well-controlled psoriasis shortly after infection with COVID-19 or COVID-19 vaccination, with no other identifiable triggers. These cases can serve to raise awareness of issues related to managing stubborn psoriatic flares and bring to the forefront conversations that are likely to arise with our patients regarding the risks and benefits of COVID vaccination and boosters. While the definitive etiology of the association between COVID and psoriasis remains unclear, it is important that the dermatologic community be aware when evaluating patients with new-onset or worsening psoriasis as we move forward in times of this COVID-19 era.

Introduction

Much of the literature involving COVID-19 and chronic inflammatory dermatological conditions have focused on the safety of immunomodulatory therapy in the setting of this highly infectious virus. While general mortality associated with the infection and vaccine has been studied in depth, the effects of the virus and vaccine on inflammatory skin disease states have not been. Certainly, there are possible adverse effects of COVID vaccination with no long-term sequelae that are accepted as risks when compared to the severity of infection, but these have not been widely addressed in the literature [1,2].

It is well known that psoriasis can be triggered by stress, infection, certain medications, and, although not as common, vaccinations [1]. In this series, we report five cases observed at our institution over the last year of either new-onset psoriasis or flares of previously well-controlled psoriasis shortly after infection with COVID-19 or COVID-19 vaccination, with no other identifiable triggers. With this series, we hope to add to the limited existing literature by revealing that flares of psoriasis can occur in both untreated and chronically managed patients and as the result of both infection and vaccination.

Case Presentation

The first of our patients is a 22-year-old male who was well controlled on ustekinumab for four years. He was unvaccinated when he contracted a COVID-19 infection in December 2020. He developed a severe flare two weeks later that was not responsive to ustekinumab, risankizumab, or secukinumab, which is his current therapy. Further, he had an influenza infection in February 2021, which significantly worsened his flare. To date, his rash remains uncontrolled with plans to change therapy underway.

Next is a 70-year-old COVID-vaccinated male well controlled on apremilast for one year. He contracted a COVID-19 infection in August 2021 and flared one week later on his hands, left greater than right, which was similar to his initial presentation. His flare lasted four weeks and subsided without any additional therapeutic intervention. He had previously been vaccinated against COVID months earlier with no issues and received his booster shot one week prior to this office visit with no further flares.

The third patient is a 40-year-old COVID-vaccinated female with psoriasis refractory to secukinumab. She was then treated with adalimumab with improvement, but her course was then complicated by frequent urinary tract infections and worsening inverse psoriasis at the onset of the COVID pandemic. These isolated issues were managed and resolved with oral antibiotics and topical therapy. Because she was stable, she discontinued her immunobiological therapy due to personal concerns about tumor necrosis factor (TNF)-inhibitor therapy during the pandemic. She remained clear for seven months. Within two weeks of receiving her COVID booster vaccination, her psoriasis and psoriatic arthritis began to flare, with plaques re-appearing on her thighs and forearms, as well as below her breasts, leading to a body surface area (BSA) involvement similar to her refractory period presentations while on secukinumab. Plans to restart a TNF inhibitor are underway.

The fourth patient is a 51-year-old COVID-vaccinated female with longstanding, uncontrolled psoriasis for 20 years. She had been completely clear and stable on risankizumab for 2.5 years. She was infected with COVID despite being vaccinated months prior with no issues and noted her psoriasis began to flare several weeks after becoming infected. Her BSA involvement was limited enough to manage with mid- and high-potency topical corticosteroids.

The last patient is a 34-year-old COVID-vaccinated male who presented with new-onset psoriasis involving his scalp, ankles, knees, hips, and nails within one month of COVID infection. He had previously been vaccinated against COVID months prior to infection with no issues. His case is being successfully managed with topical clobetasol foam and calcipotriene cream. 

Discussion

The hallmark of psoriasis is sustained inflammation led by a T-cell-driven autoimmune response with elevated levels of interleukin (IL)-23, IL-17, and TNF-a [1,3]. Known psoriasis triggers, such as infections, can indirectly affect the interplay of these mediators. Psoriasis has also been associated with higher levels of angiotensin-converting enzyme type 2 (ACE2) than the general population. COVID-19 spike protein has been noted to have a high affinity for ACE2 receptors. This could be a possible causal mechanism of reactivity in the association between psoriasis and COVID-19 infection and vaccination [4].

Vaccination is an uncommon trigger for psoriasis flares. However, there have been reports of psoriasis flares after vaccination for influenza, pneumococcal pneumonia, and yellow fever [1]. With the recent increase in mRNA vaccinations, McMahon et al. studied (N=414) cutaneous reactions after COVID-19 vaccination and found only two cases of psoriasis flares [5]. Wei and colleagues reported seven cases at their institution as well as investigated 79 cases reported in the Vaccine Adverse Events Reporting System. This report, however, did not specify whether patients were controlled on therapy prior to flare. Other studies have also shown that while patients have flared with vaccination, there have not been documented flares among patients on biologic therapy. Rather, this has been assessed and deemed to not be a correlation [6]. The patients observed at our institution, however, flared with infection or vaccination while on current biologic therapy in three out of five cases.

Psoriasis is also known to be triggered by infections. For example, the streptococcal infection has been associated with new-onset or flares of guttate psoriasis, which has been well reported in the literature [7]. A review article by Aram et al. found that flares of psoriasis were common after COVID infection, but these were largely attributed to the use of anti-malarial drugs or discontinuation of immunomodulatory therapy secondary to infection [8]. Our patients, in contrast, flared without the use of these medications or concurrent discontinuation of long-term therapy.

The pandemic has been a cause for irregular dermatological consultations and difficulty obtaining medications, and it has led to significant stress in the lives of many individuals, from social isolation to concerns about employment to the inability to seek medical care in a timely manner [9]. Psoriasis is often triggered by stress, including psychosocial stressors as well as physical stress on the body, which is important to note when addressing flares during the pandemic. However, all of our patients with these flares denied significant life or psychosocial stressors around the time preceding the onset of their psoriasis.

These cases are interesting for several reasons. First, the psoriasis flares noted occurred secondary to both COVID infection and vaccination. This suggests that one’s immune response to the virus is being replicated during vaccination; thus, these psoriatic manifestations are more certainly a result of the immune response rather than a direct viral assault. We, therefore, can likely continue to expect similar skin reactions whether a patient gets infected with COVID or receives the vaccination. Second, reactions happened in both stable, treated patients, as well as undiagnosed patients. It is possible that the hyper-inflammatory state induced by COVID-19 causes an upregulation of previously controlled cytokines, unmasking a genetic predisposition for psoriasis and that treatment with targeted anti-psoriatic systemic medication does not necessarily mitigate this risk.

Conclusions

These cases can serve to raise awareness of issues related to managing stubborn psoriatic flares and bring to the forefront conversations that are likely to arise with our patients regarding the risks and benefits of COVID vaccination and boosters. Further, our cases show that these flares can occur in previously stable patients treated with immunobiologic therapies. While the definitive etiology of the association between COVID and psoriasis remains unclear, it is important that the dermatologic community be aware when evaluating patients with new-onset or worsening psoriasis as we move forward in times of this COVID-19 era, and we urge our colleagues to contribute to the literature surrounding this topic.


References

  1. Munguía-Calzada P, Drake-Monfort M, Armesto S, Reguero-Del Cura L, López-Sundh AE, González-López MA: Psoriasis flare after influenza vaccination in Covid-19 era: a report of four cases from a single center. Dermatol Ther. 2021, 34:e14684. 10.1111/dth.14684
  2. Wei N, Kresch M, Elbogen E, Lebwohl M: New onset and exacerbation of psoriasis after COVID-19 vaccination. JAAD Case Rep. 2022, 19:74-7. 10.1016/j.jdcr.2021.11.016
  3. Rendon A, Schäkel K: Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019, 20:1475. 10.3390/ijms20061475
  4. Shahidi-Dadras M, Tabary M, Robati RM, Araghi F, Dadkhahfar S: Psoriasis and risk of the COVID-19: is there a role for angiotensin converting enzyme (ACE)?. J Dermatolog Treat. 2022, 33:1175-6. 10.1080/09546634.2020.1782819
  5. McMahon DE, Amerson E, Rosenbach M, et al.: Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases. J Am Acad Dermatol. 2021, 85:46-55. 10.1016/j.jaad.2021.03.092
  6. Skroza N, Bernardini N, Tolino E, et al.: Safety and impact of anti-COVID-19 vaccines in psoriatic patients treated with biologics: a real life experience. J Clin Med. 2021, 10:3355. 10.3390/jcm10153355
  7. Griffiths CE, Barker JN: Pathogenesis and clinical features of psoriasis. Lancet. 2007, 370:263-71. 10.1016/S0140-6736(07)61128-3
  8. Aram K, Patil A, Goldust M, Rajabi F: COVID-19 and exacerbation of dermatological diseases: a review of the available literature. Dermatol Ther. 2021, 34:e15113. 10.1111/dth.15113
  9. Rob F, Hugo J, Tivadar S, et al.: Compliance, safety concerns and anxiety in patients treated with biologics for psoriasis during the COVID-19 pandemic national lockdown: a multicenter study in the Czech Republic. J Eur Acad Dermatol Venereol. 2020, 34:e682-4. 10.1111/jdv.16771

COVID Variant That Beats Our Immunity Is Finally Here

Authors: David Axe Updated Oct. 16, 2022

A new subvariant of the novel-coronavirus called XBB dramatically announced itself earlier this week, in Singapore. New COVID-19 cases more than doubled in a day, from 4,700 on Monday to 11,700 on Tuesday—and XBB is almost certainly why. The same subvariant just appeared in Hong Kong, too.

A highly mutated descendant of the Omicron variant of the SARS-CoV-2 virus that drove a record wave of infections starting around a year ago, XBB is in many ways the worst form of the virus so far. It’s more contagious than any previous variant or subvariant. It also evades the antibodies from monoclonal therapies, potentially rendering a whole category of drugs ineffective as COVID treatments.

“It is likely the most immune-evasive and poses problems for current monoclonal antibody-based treatments and prevention strategy,” Amesh Adalja, a public-health expert at the Johns Hopkins Center for Health Security, told The Daily Beast.

That’s the bad news. The good news is that the new “bivalent” vaccine boosters from Pfizer and Moderna seem to work just fine against XBB, even though the original vaccines are less effective against XBB. They won’t prevent all infections and reinfections, but they should significantly reduce the chance of severe infection potentially leading to hospitalization or death. “Even with immune-evasive variants, vaccine protection against what matters most—severe disease—remains intact,” Adalja said.

As the novel-coronavirus evolves to become more contagious and more resistant to certain types of drugs, keeping current on your boosters is “the most impactful thing you can do in preparation for what might come,” Peter Hotez, an expert in vaccine development at Baylor College, told The Daily Beast.

Scientists first identified XBB in August. It’s one of several major subvariants that have evolved from the basic Omicron variant, piling on more and more mutations on key parts of the virus—especially the spike protein, the part of the virus that helps it grab onto and infect our cells.

XBB has at least seven new mutations along the spike. Mutations that, taken together, make the subvariant harder for our immune systems to recognize—and thus more likely to evade our antibodies and enter our cells to cause infection.

This accumulation of mutations isn’t surprising. Changes along the spike protein have characterized most of the major new variants and subvariants of SARS-CoV-2 as the pandemic grinds toward its fourth year.

What is surprising is how much competition XBB has as it fights to become the next dominant form of the novel-coronavirus. Several other Omicron subvariants are also in circulation. All of them are highly evolved. Many of them actually share a subset of key mutations, especially on the spike.

So while XBB appears to be gaining traction in Asia, a close cousin of XBB called BQ.1.1 is spreading fast in Europe and some U.S. states. There are others in contention, too, including BA.2.75.2. Hotez calls these viral cousins the “Scrabble” subvariants, a nod to the classic word game and the jumble of scientific designations of closely related viruses.

The Scrabble variants are indicative of what scientists call “convergent evolution.” That is, separate viral sublineages that are picking up more and more of the same mutations. It’s as though Omicron’s children are all separately learning how to be a better virus than their parent, and becoming more like each other in the process.

Immune-escape is the common quality. At least two of the Scrabble subvariants—XBB and BQ.1.1—are pretty much unrecognizable to existing antibody therapies and somewhat less recognizable to the antibodies produced by the prime doses of the leading messenger-RNA vaccines.

In evading some of our therapies and, to a lesser extent, our original vaccines, XBB and its cousins are showing us where the novel-coronavirus is heading, genetically speaking. The current surge in infections in places like Singapore is a preview of a potential global surge, this coming winter or spring, as XBB or one of its relatives becomes dominant everywhere.

It’s possible to mitigate the worst outcomes. Natural antibodies from past infection are still the best and most durable antibodies. They don’t last forever. But while they do last—a few months or potentially a whole year—the chance of catching a bad case of COVID is pretty low.

So if you had an earlier form of Omicron—say, during the wave of infections that started last Thanksgiving and peaked around February—you might still have good antibodies for a few months. More than enough time to reinforce those fading natural antibodies with a dose of the latest mRNA boosters.

Pfizer and Moderna formulated these new boosters to include some genetic instructions specifically for attacking the BA.5 subvariant of Omicron, which is still the dominant form of SARS-CoV-2 but is disappearing fast as XBB and the other Scrabble subvariants outcompete it.

The bivalent boosters should work pretty well against forms of the virus that are closely related to BA.5, including the Scrabbles. “That is because one of the two components [in the boosters] induces an immune response to BA.5, and most of the new Scrabble variants look more BA.5 like than [the] original China lineage,” Hotez told The Daily Beast.

The implication, of course, is that we’re eventually going to need another new booster in order to keep pace with the fast-evolving virus. Sure, the bivalent boosters work against BA.5 and BA.5’s immediate descendants. But what about the next generation of Omicron subvariants, the one after XBB and its cousins?

More and more health officials are coming around to the idea of an annual COVID booster. U.S. president Joe Biden even endorsed the idea in a statement last month. “As the virus continues to change, we will now be able to update our vaccines annually to target the dominant variant,” Biden said. “Just like your annual flu shot, you should get it sometime between Labor Day and Halloween.”

But one booster a year might not be enough if, as some epidemiologists fear, natural antibodies fade faster and the novel-coronavirus mutates at an accelerating rate. One concern, if it turns out we need twice-a-year new boosters, is whether industry can develop fresh jabs fast enough and health agencies can swiftly approve them.

There’s an even bigger question, however. “The more important factor is just having folks get a more recent booster,” James Lawler, an infectious disease expert at the University of Nebraska Medical Center, told The Daily Beast.

Even if a new booster is available every six months or so, will enough people get it to make a difference in the overall rates of severe illness and death? Booster uptake is declining globally, but especially in the United States, where just 10 percent of people have gotten the bivalent booster since federal regulators approved them in August.

XBB is a nasty little subvariant. But it’s not the final word on COVID. The novel-coronavirus will keep mutating, and finding new ways to evade our antibodies, whether or not many people are paying attention.

The virus isn’t done with us. Which means we can’t be done with it. Get boosted. And be prepared to get boosted again in 2023.

Adverse effects of COVID-19 vaccines and measures to prevent them

Authors: Kenji Yamamoto  Virology Journal volume 19, Article number: 100 (2022) 

Abstract

Recently, The Lancet published a study on the effectiveness of COVID-19 vaccines and the waning of immunity with time. The study showed that immune function among vaccinated individuals 8 months after the administration of two doses of COVID-19 vaccine was lower than that among the unvaccinated individuals. According to European Medicines Agency recommendations, frequent COVID-19 booster shots could adversely affect the immune response and may not be feasible. The decrease in immunity can be caused by several factors such as N1-methylpseudouridine, the spike protein, lipid nanoparticles, antibody-dependent enhancement, and the original antigenic stimulus. These clinical alterations may explain the association reported between COVID-19 vaccination and shingles. As a safety measure, further booster vaccinations should be discontinued. In addition, the date of vaccination should be recorded in the medical record of patients. Several practical measures to prevent a decrease in immunity have been reported. These include limiting the use of non-steroidal anti-inflammatory drugs, including acetaminophen to maintain deep body temperature, appropriate use of antibiotics, smoking cessation, stress control, and limiting the use of lipid emulsions, including propofol, which may cause perioperative immunosuppression. In conclusion, COVID-19 vaccination is a major risk factor for infections in critically ill patients.

Dear Editor,

The coronavirus disease (COVID-19) pandemic has led to the widespread use of genetic vaccines, including mRNA and viral vector vaccines. In addition, booster vaccines have been used, but their effectiveness against the highly mutated spike protein of Omicron strains is limited. Recently, The Lancet published a study on the effectiveness of COVID-19 vaccines and the waning of immunity with time [1]. The study showed that immune function among vaccinated individuals 8 months after the administration of two doses of COVID-19 vaccine was lower than that among unvaccinated individuals. These findings were more pronounced in older adults and individuals with pre-existing conditions. According to the European Medicines Agency’s recommendations, frequent COVID-19 booster shots could adversely affect the immune response and may not be feasible [2]. Several countries, including Israel, Chile, and Sweden, are offering the fourth dose to only older adults and other groups rather than to all individuals [3].

The decrease in immunity is caused by several factors. First, N1-methylpseudouridine is used as a substitute for uracil in the genetic code. The modified protein may induce the activation of regulatory T cells, resulting in decreased cellular immunity [4]. Thereby, the spike proteins do not immediately decay following the administration of mRNA vaccines. The spike proteins present on exosomes circulate throughout the body for more than 4 months [5]. In addition, in vivo studies have shown that lipid nanoparticles (LNPs) accumulate in the liver, spleen, adrenal glands, and ovaries [6], and that LNP-encapsulated mRNA is highly inflammatory [7]. Newly generated antibodies of the spike protein damage the cells and tissues that are primed to produce spike proteins [8], and vascular endothelial cells are damaged by spike proteins in the bloodstream [9]; this may damage the immune system organs such as the adrenal gland. Additionally, antibody-dependent enhancement may occur, wherein infection-enhancing antibodies attenuate the effect of neutralizing antibodies in preventing infection [10]. The original antigenic sin [11], that is, the residual immune memory of the Wuhan-type vaccine may prevent the vaccine from being sufficiently effective against variant strains. These mechanisms may also be involved in the exacerbation of COVID-19.

Some studies suggest a link between COVID-19 vaccines and reactivation of the virus that causes shingles [1213]. This condition is sometimes referred to as vaccine-acquired immunodeficiency syndrome [14]. Since December 2021, besides COVID-19, Department of Cardiovascular Surgery, Okamura Memorial Hospital, Shizuoka, Japan (hereinafter referred to as “the institute”) has encountered cases of infections that are difficult to control. For example, there were several cases of suspected infections due to inflammation after open-heart surgery, which could not be controlled even after several weeks of use of multiple antibiotics. The patients showed signs of being immunocompromised, and there were a few deaths. The risk of infection may increase. Various medical algorithms for evaluating postoperative prognosis may have to be revised in the future. The media have so far concealed the adverse events of vaccine administration, such as vaccine-induced immune thrombotic thrombocytopenia (VITT), owing to biased propaganda. The institute encounters many cases in which this cause is recognized. These situations have occurred in waves; however, they are yet to be resolved despite the measures implemented to routinely screen patients admitted for surgery for heparin-induced thrombocytopenia (HIT) antibodies. Four HIT antibody-positive cases have been confirmed at the institute since the start of vaccination; this frequency of HIT antibody-positive cases has rarely been observed before. Fatal cases due to VITT following the administration of COVID-19 vaccines have also been reported [15].

As a safety measure, further booster vaccinations should be discontinued. In addition, the date of vaccination and the time since the last vaccination should be recorded in the medical record of patients. Owing to the lack of awareness of this disease group among physicians and general public in Japan, a history of COVID-19 vaccination is often not documented, as it is in the case of influenza vaccination. The time elapsed since the last COVID-19 vaccination may need to be considered when invasive procedures are required. Several practical measures that can be implemented to prevent a decrease in immunity have been reported [16]. These include limiting the use of non-steroidal anti-inflammatory drugs, including acetaminophen, to maintain deep body temperature, appropriate use of antibiotics, smoking cessation, stress control, and limiting the use of lipid emulsions, including propofol, which may cause perioperative immunosuppression [17].

To date, when comparing the advantages and disadvantages of mRNA vaccines, vaccination has been commonly recommended. As the COVID-19 pandemic becomes better controlled, vaccine sequelae are likely to become more apparent. It has been hypothesized that there will be an increase in cardiovascular diseases, especially acute coronary syndromes, caused by the spike proteins in genetic vaccines [1819]. Besides the risk of infections owing to lowered immune functions, there is a possible risk of unknown organ damage caused by the vaccine that has remained hidden without apparent clinical presentations, mainly in the circulatory system. Therefore, careful risk assessments prior to surgery and invasive medical procedures are essential. Randomized controlled trials are further needed to confirm these clinical observations.

In conclusion, COVID-19 vaccination is a major risk factor for infections in critically ill patients.

References

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Impacts of COVID on the immune system

Authors: Lara Herrero, The Conversation Medical Xpress September 19, 2022

So you’ve had COVID and have now recovered. You don’t have ongoing symptoms and luckily, you don’t seem to have developed long COVID.

But what impacts has COVID had on your overall immune system?

It’s early days yet. But growing evidence suggests there are changes to your immune system that may put you at risk of other infectious diseases.

Here’s what we know so far.

A round of viral infections

Over this past winter, many of us have had what seemed like a continual round of viral illness. This may have included COVID, influenza or infection with respiratory syncytial virus. We may have recovered from one infection, only to get another.

Then there is the re-emergence of infectious diseases globally such as monkeypox or polio.

Could these all be connected? Does COVID somehow weaken the immune system to make us more prone to other infectious diseases?

There are many reasons for infectious diseases to emerge in new locations, after many decades, or in new populations. So we cannot jump to the conclusion COVID infections have given rise to these and other viral infections.

But evidence is building of the negative impact of COVID on a healthy individual’s immune system, several weeks after symptoms have subsided.

What happens when you catch a virus?

There are three possible outcomes after a viral infection:

  1. your immune system clears the infection and you recover (for instance, with rhinovirus which causes the common cold)
  2. your immune system fights the virus into “latency” and you recover with a virus dormant in our bodies (for instance, varicella zoster virus, which causes chickenpox)
  3. your immune system fights, and despite best efforts the virus remains “chronic,” replicating at very low levels (this can occur for hepatitis C virus).

Ideally we all want option 1, to clear the virus. In fact, most of us clear SARS-CoV-2, the virus that causes COVID. That’s through a complex process, using many different parts of our immune system.

But international evidence suggests changes to our immune cells after SARS-CoV-2 infection may have other impacts. It may affect our ability to fight other viruses, as well as other pathogens, such as bacteria or fungi.

How much do we know?

An Australian study has found SARS-CoV-2 alters the balance of immune cells up to 24 weeks after clearing the infection.

There were changes to the relative numbers and types of immune cells between people who had recovered from COVID compared with healthy people who had not been infected.

This included changes to cells of the innate immune system (which provides a non-specific immune response) and the adaptive immune system (a specific immune response, targeting a recognised foreign invader).

Another study focused specifically on dendritic cells—the immune cells that are often considered the body’s “first line of defence.”

Researchers found fewer of these cells circulating after people recovered from COVID. The ones that remained were less able to activate white blood cells known as T-cells, a critical step in activating anti-viral immunity.

Other studies have found different impacts on T-cells, and other types of white blood cells known as B-cells (cells involved in producing antibodies).

After SARS-CoV-2 infection, one study found evidence many of these cells had been activated and “exhausted.” This suggests the cells are dysfunctional, and might not be able to adequately fight a subsequent infection. In other words, sustained activation of these immune cells after a SARS-CoV-2 infection may have an impact on other inflammatory diseases.

One study found people who had recovered from COVID have changes in different types of B-cells. This included changes in the cells’ metabolism, which may impact how these cells function. Given B-cells are critical for producing antibodies, we’re not quite sure of the precise implications.

Could this influence how our bodies produce antibodies against SARS-CoV-2 should we encounter it again? Or could this impact our ability to produce antibodies against pathogens more broadly—against other viruses, bacteria or fungi? The study did not say.

What impact will these changes have?

One of the main concerns is whether such changes may impact how the immune system responds to other infections, or whether these changes might worsen or cause other chronic conditions.

So more work needs to be done to understand the long-term impact of SARS-CoV-2 infection on a person’s immune system.

For instance, we still don’t know how long these changes to the immune system last, and if the immune system recovers. We also don’t know if SARS-CoV-2 triggers other chronic illnesses, such as chronic fatigue syndrome (myalgic encephalomyelitis). Research into this is ongoing.

What we do know is that having a healthy immune system and being vaccinated (when a vaccine has been developed) is critically important to have the best chance of fighting any infection.

COVID-19 pandemic: Viral infections and Vitamin D

Authors: Nurshad Ali*Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, Bangladesh Optom Open Access 2022, Vol 7(3): 3DOI: 10.4172/2476-213X.1000152

Introduction

Vitamin D is a steroid hormone, produced endogenously with the effect of ultraviolet radiation on the skin or available from exogenous food sources or dietary supplements. Vitamin D insufficiency is a public health problem affecting over a billion people across all life stages worldwide. In the past decade, several studies demonstrated a potential link between vitamin D deficiency and various diseases, including systemic infection. Vitamin D insufficiency affects the immune functions as vitamin D exerts an immunomodulation role, increasing innate immunity by secretion of antiviral peptides, which improves mucosal defenses [1]. In clinical studies, low levels of serum vitamin D were associated with acute respiratory tract infections including epidemic influenza.

The outbreak and fast spreading of SARS-CoV-2 are a global health threat with an unstable outcome worldwide. A recent data reported the antiviral effects of vitamin D, which can hinder viral replication directly, and also be effective in an anti-inflammatory and immunomodulatory way. It seems that SARS-CoV-2 primarily uses the immune evasion process during infection, which is followed by hyper reaction and cytokine storm in some patients, as a known pathogenic process of acute respiratory disease syndrome (ARDS) development [2]. SARS-CoV-2 uses angiotensin-converting enzyme 2 as the host receptor to enter into alveolar and intestinal epithelial cells. Subsequent dysregulation of the renin–angiotensin system may lead to excess cytokine production resulting in prospective fatal ARDS.

Considering the differences in the severity and fatality of COVID-19 in the globe, it is important to understand the reasons behind it. Improvement of immunity through better nutrition might be a considerable factor. The nutrient such as vitamin D shows significant roles in immune function. However, little is known about the role of vitamin D in preventing COVID-19 infection and fatality. This study evaluated the correlation of vitamin D concentrations with COVID-19 cases and deaths per one million of the population in 20 European countries using data from the COVID-19 pandemic data portal for 20 May 2020 (most countries after peak). This review also discussed the possible preventing role of vitamin D in acute respiratory tract infections [3]. Furthermore, the available studies that determined the role of vitamin D in COVID-19 severity and mortality have been discussed. PubMed, Google Scholar, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and medRXiv were searched for relevant literature about the role of vitamin D in COVID-19 infections, severity, and mortality.

Vitamin D and mechanisms to decrease viral infections

Some recent reviews demonstrated some pathways by which vitamin D decreases the risk of microbial infections. Vitamin D follows different mechanisms in reducing the risk of viral infection and mortality. To reduce the risk of common cold, vitamin D uses three pathways: physical barrier, cellular natural immunity, and adaptive immunity [4]. A recent review also supported the possible role of vitamin D in decreasing the risk of COVID-19 infections and mortality. These comprise maintaining of cell junctions, and gap junctions, increasing cellular immunity by decreasing the cytokine storm with influence on interferon γ and tumor necrosis factor α and regulating adaptive immunity through inhibiting T helper cell type 1 responses and stimulating of T cells induction. Vitamin D supplementation was also found to enhance CD4+ T cell count in HIV infection.

One of the major manifestations of severe SARS-CoV-2 infection is lymphopenia. In both the mouse models and in human cell lines, vitamin D exerted activity in lung tissue and played protective effects on experimental interstitial pneumonitis . Several in vitro studies demonstrated that vitamin D plays a significant role in local “respiratory homeostasis” either by stimulating the exhibition of antimicrobial peptides or by directly interfering with the replication of respiratory viruses. Vitamin D insufficiency can, therefore, be involved in ARDS and heart failure and these are the manifestations of severely ill COVID-19 subjects [5]. Therefore, vitamin D deficiency promotes the renin-angiotensin system (RAS), which may lead to chronic cardiovascular disease (CVD) and reduced lung function. Although, many studies supported the immunomodulatory characteristics of vitamin D and its significant role in the maintenance of immune homeostasis; well-designed randomized controlled trials are required to elucidate the plausible role of vitamin D in protective immune responses against respiratory microbes and in preventing various types of acute respiratory tract infections.

The relevance of vitamin D to COVID-19

Yet, it is important to fully elucidate the virulence mechanisms of COVID-19, several cellular mechanisms including Papainlike protease (PLpro)-mediated replication, dipeptidyl peptidase-4 receptor (DPP-4/CD26) binding, disruption of M-protein mediated type-1 IFN induction and MDA5 and RIG-I host-recognition evasion have been recognized in the closely-related COVID-MERS virus. Of the above processal, human DPP-4/CD26 has been exhibited to connect with the S1 domain of the COVID-19 spike glycoprotein, suggesting that it could also be a salient virulence factor in Covid-19 infection. The expression of the DPP-4/CD26 receptor is reduced significantly in vivo upon the correctness of vitamin D insufficiency [6]. There is also an indication that maintaining of vitamin D may reduce some of the unfavorable downstream immunological sequelae thought to extract poorer clinical outcome in Covid-19 infection, such as interleukin 6 elevation, delayed interferon-gamma response, and, a negative prognostic marker in subjects with acutely-ill pneumonia, including those having Covid-19.

Epidemiological and clinical observations regarding COVID-19

Some clinical and epidemiological studies support to outline the hypothesis regarding COVID-19 and its relationship with vitamin D status. Recent studies indicated that COVID-19 is associated with the increased generation of pro-inflammatory cytokines, C-reactive protein (CRP), ARDS, pneumonia, and heart failure. In China, chronic fatality rates were 6-10% for people with chronic respiratory tract disease, cardiovascular disease, hypertension, and diabetes [7]. In other studies, serum concentrations of 25(OH) D were inversely associated with pro-inflammatory cytokines, IL-6, increased CRP, and increased risk of pneumonia, ARDS, diabetes and heart failure. In randomized control trials, vitamin D supplementation has been shown to reduce the risk of respiratory diseases. A placebo-controlled trial with 5660 subjects showed that vitamin D supplementation significantly reduces the risk of respiratory tract infections. A review included five clinical studies reported that respiratory tract infections were significantly lower in the vitamin D supplementation group than the control group [8]. Another study included 25 randomized controlled trials, with 10,933 participants in total from 14 different countries indicated the beneficial effects of vitamin D supplementation in reducing the risk of at least one acute respiratory tract infection.

References

  1. M.F.Holick (2017)The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocrine Metab Disord18:153-165.
  2. W.Dankers,E.M.Colin,J.P.van Hamburg,E.Lubberts (2017) Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential. Front Immunol7:697-702.
  3. M.Infante,C.Ricordi,J.Sanchez,M.J.Clare Salzler,N.Padilla et al. (2019) Influence of vitamin d on islet autoimmunity and beta-cell function in type 1 diabetes. Nutrients11:2185-2190.
  4. R.Bouillon,C.Marcocci,G.Carmeliet,D.Bikle,J.H.White et al(2019) Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocrine Rev40:1109-1151.
  5. C.L.Greiller,A.R.Martineau (2015) Modulation of the immune response to respiratory viruses by vitamin D. Nutrients7: 4240-4270.
  6. A.F.Gombart,N.Borregaard,H.P.Koeffler (2005) Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3 Nutrients 19:1067-1077.
  7. T.Wang,B.Dabbas,D.Laperriere,A.J.Bitton,H.Soualhine et al.(2010)Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin β2 innate immune pathway defective in Crohn disease. J Biol Chem 285: 2227-2231.
  8. J.J.Cannell,R.Vieth,J.C.Umhau,M.F.Holick,W.B.Grant et al(2006) Epidemic influenza and vitamin D. Epidemiol Infect134:1129-1140.

More people are catching coronavirus a second time, heightening long COVID risk, experts say

Authors: Rong-Gong Lin II, Luke Money Mon, August 1, 2022  LA Times

Emerging evidence suggests that catching the coronavirus a second time can heighten long-term health risks, a worrisome development as the circulation of increasingly contagious Omicron subvariants leads to greater numbers of Californians being reinfected.

Earlier in the pandemic, it was assumed that getting infected afforded some degree of lasting protection, for perhaps a few months.

As the coronavirus mutates, though, that’s no longer a given. And each individual infection carries the risk not only for acute illness but the potential to develop long COVID.

“The additive risk is really not trivial, not insignificant. It’s really substantial,” said Dr. Ziyad Al-Aly, clinical epidemiologist at Washington University in St. Louis and chief of research and development at the Veterans Affairs Saint Louis Healthcare System.

According to a preprint study examining U.S. veterans, of which Al-Aly was the lead author, getting infected twice or more “contributes to additional risks of all-cause mortality, hospitalization and adverse health outcomes” in various organ systems, and can additionally worsen risk for diabetes, fatigue and mental health disorders.

“Reinfection absolutely adds risk,” Al-Aly said. The study suggested that, compared with those infected only once, individuals who caught the coronavirus a second time were at 2½ times greater risk of developing heart or lung disease and blood clotting issues. Subsequent infections also were associated with a higher risk of potentially serious health problems, as well as death from COVID-19.

It’s possible that a repeat coronavirus infection will leave someone just fine, which is what happens to most people, Al-Aly said. “But you might be one of the unlucky ones and … get some really serious health problem with an infection.”

Los Angeles County Public Health Director Barbara Ferrer recently cited Al-Aly’s pre-print study as rationale for wearing masks in indoor public settings to avoid reinfection.

“They also saw that those with repeat infections had a higher risk of gastrointestinal, kidney, mental health, musculoskeletal and neurologic disorders, as well as diabetes,” Ferrer said of the study. “Moreover, the risk of developing a long-term health problem increased further with each reinfection. The risk of having long-term health conditions was three times higher for those infected compared to those who were uninfected.”

Older viruses, such as those that cause measles and chickenpox, are quite stable — meaning that the vaccinations are highly effective and surviving either illness typically confers lifelong immunity.

Not so with the coronavirus, which has mutated wildly since the pandemic began. Someone who got infected with the variant that dominated California in late 2020, for instance, was vulnerable to catching the Delta variant the following summer. And those who survived Delta faced the risk of catching the later Omicron variant.

But the reinfection landscape has been upended even further as California has been walloped with a family of increasingly transmissible Omicron subvariants. The most recent of those, BA.5, has shown particular proficiency for reinfection — with the ability to target even those who survived an earlier Omicron case mere weeks before.

“This concept of building immunity, it really only works if you’re encountering the same beast again and again and again,” Al-Aly said. But in the world of COVID-19, BA.5 is actually a “very different beast” than earlier variants.

It’s possible that the acute phase of a second bout of COVID-19 could be milder than the first. But a subsequent attack can still leave more extensive cumulative damage to the body than if there had been only one infection.

Think of coronavirus infections like earthquake sequences: It’s possible an aftershock could be less severe than the first temblor but cumulatively could add more damage. And just because your home is still standing after one quake doesn’t mean you shouldn’t explore ways to make it seismically safer.

“Part of the reason why things, for many people, feel like they’re not so bad right now is because we are being very aggressive in countering the virus with vaccines, with treatments,” Dr. Ashish Jha, the White House COVID-19 response coordinator, said during a healthcare summit hosted by the Hill. “If we took our foot off the pedal, we’re going to see this virus come back in a way that’s much more dangerous. So we’ve got to stay on that front footing and continue fighting this thing.”

As it relates specifically to long COVID — a condition in which symptoms can persist months or even years after an initial infection — getting vaccinated and boosted likely reduces risk, but studies differ as to the degree of protection.

“I think having some preexisting immunity — whether it’s natural or from a vaccine — appears to reduce your risk of long COVID, but it’s still there. It’s not zero,” said Dr. Steven Deeks, a professor of medicine at UC San Francisco and principal investigator of the Long-term Impact of Infection With Novel Coronavirus, or LIINC, study.

Another report, observing triple-vaccinated Italian healthcare workers who weren’t hospitalized for COVID-19, found that two or three doses of vaccine were associated with a lower prevalence of long COVID.

A separate report suggested that even adults who had received a booster dose still have to consider the risk of long COVID. A British report said that, during the initial Omicron wave, about 1 in every 25 triple-vaccinated adults self-reported having long COVID three to four months after their first infection.

Still, some clinicians say that long COVID sufferers tend to be either unvaccinated or missing their boosters.

“The number of patients I’m seeing who were vaccinated and boosted who are coming in with long COVID is very low,” said Dr. Nisha Viswanathan, director of the UCLA Health Long COVID Program.

Long COVID also doesn’t prevent you from becoming infected with the coronavirus again. Viswanathan said she’s had patients who have seen their long COVID symptoms improve, then get sickened with another bout of COVID-19, and then see long COVID signs return.

The best way to prevent long COVID is to not get COVID-19. Many officials and experts cite non-pharmaceutical interventions such as masking as key tools, since vaccinations reduce, but do not entirely eliminate, the risk.

Masking is not a terrible thing to ask of people, especially in probably the places that are the most crowded, and the places that maybe are the highest risk of transmission,” Viswanathan said. Taking activities outside is also safer than being unmasked indoors.

Some of Viswanathan’s patients have downplayed the risk of COVID-19, commenting how it’s become a mild illness, and adding they don’t see the point of taking precautions. But, she said, better knowledge about long COVID and its disabling effects would help people understand the importance of masking and getting vaccinated and boosted.

A UCLA study published in the Journal of General Internal Medicine, of which Viswanathan was a co-author, found that of 1,038 patients with symptomatic COVID-19 between April 2020 and February 2021, nearly 30% developed long COVID. The most common symptoms were fatigue and shortness of breath among hospitalized patients.

While many are weary of COVID-19 preventive measures after nearly two and a half years, they remain important, said Dr. Anne Foster, vice president and chief clinical strategy officer for the University of California Health system.

The burden of long COVID following this wave is unknown. The official case tallies are likely vast undercounts, given that so many at-home tests are being used, and that could suggest that the burden of long COVID in subsequent months will be hard to predict, Foster said.

“I know everyone has moved on and people are going back to the way things were, and I sort of get it,” Deeks said. “But people do need to be aware that there is this additional risk that’s not going away and they might adjust their lives accordingly.

“But everyone’s going to figure this out on their own.”

Adverse effects of COVID-19 vaccines and measures to prevent them

Authors: Kenji Yamamoto Virol J. 2022; 19: 100. Published online 2022 Jun 5. doi: 10.1186/s12985-022-01831-0 PMCID: PMC9167431PMID: 35659687

Abstract

Recently, The Lancet published a study on the effectiveness of COVID-19 vaccines and the waning of immunity with time. The study showed that immune function among vaccinated individuals 8 months after the administration of two doses of COVID-19 vaccine was lower than that among the unvaccinated individuals. According to European Medicines Agency recommendations, frequent COVID-19 booster shots could adversely affect the immune response and may not be feasible. The decrease in immunity can be caused by several factors such as N1-methylpseudouridine, the spike protein, lipid nanoparticles, antibody-dependent enhancement, and the original antigenic stimulus. These clinical alterations may explain the association reported between COVID-19 vaccination and shingles. As a safety measure, further booster vaccinations should be discontinued. In addition, the date of vaccination should be recorded in the medical record of patients. Several practical measures to prevent a decrease in immunity have been reported. These include limiting the use of non-steroidal anti-inflammatory drugs, including acetaminophen to maintain deep body temperature, appropriate use of antibiotics, smoking cessation, stress control, and limiting the use of lipid emulsions, including propofol, which may cause perioperative immunosuppression. In conclusion, COVID-19 vaccination is a major risk factor for infections in critically ill patients.

COVID Vaccines Increase Adverse Events and Weaken The Immune System

The coronavirus disease (COVID-19) pandemic has led to the widespread use of genetic vaccines, including mRNA and viral vector vaccines. In addition, booster vaccines have been used, but their effectiveness against the highly mutated spike protein of Omicron strains is limited. Recently, The Lancet published a study on the effectiveness of COVID-19 vaccines and the waning of immunity with time [1]. The study showed that immune function among vaccinated individuals 8 months after the administration of two doses of COVID-19 vaccine was lower than that among unvaccinated individuals. These findings were more pronounced in older adults and individuals with pre-existing conditions. According to the European Medicines Agency’s recommendations, frequent COVID-19 booster shots could adversely affect the immune response and may not be feasible [2]. Several countries, including Israel, Chile, and Sweden, are offering the fourth dose to only older adults and other groups rather than to all individuals [3].

The decrease in immunity is caused by several factors. First, N1-methylpseudouridine is used as a substitute for uracil in the genetic code. The modified protein may induce the activation of regulatory T cells, resulting in decreased cellular immunity [4]. Thereby, the spike proteins do not immediately decay following the administration of mRNA vaccines. The spike proteins present on exosomes circulate throughout the body for more than 4 months [5]. In addition, in vivo studies have shown that lipid nanoparticles (LNPs) accumulate in the liver, spleen, adrenal glands, and ovaries [6], and that LNP-encapsulated mRNA is highly inflammatory [7]. Newly generated antibodies of the spike protein damage the cells and tissues that are primed to produce spike proteins [8], and vascular endothelial cells are damaged by spike proteins in the bloodstream [9]; this may damage the immune system organs such as the adrenal gland. Additionally, antibody-dependent enhancement may occur, wherein infection-enhancing antibodies attenuate the effect of neutralizing antibodies in preventing infection [10]. The original antigenic sin [11], that is, the residual immune memory of the Wuhan-type vaccine may prevent the vaccine from being sufficiently effective against variant strains. These mechanisms may also be involved in the exacerbation of COVID-19.

Some studies suggest a link between COVID-19 vaccines and reactivation of the virus that causes shingles [1213]. This condition is sometimes referred to as vaccine-acquired immunodeficiency syndrome [14]. Since December 2021, besides COVID-19, Department of Cardiovascular Surgery, Okamura Memorial Hospital, Shizuoka, Japan (hereinafter referred to as “the institute”) has encountered cases of infections that are difficult to control. For example, there were several cases of suspected infections due to inflammation after open-heart surgery, which could not be controlled even after several weeks of use of multiple antibiotics. The patients showed signs of being immunocompromised, and there were a few deaths. The risk of infection may increase. Various medical algorithms for evaluating postoperative prognosis may have to be revised in the future. The media have so far concealed the adverse events of vaccine administration, such as vaccine-induced immune thrombotic thrombocytopenia (VITT), owing to biased propaganda. The institute encounters many cases in which this cause is recognized. These situations have occurred in waves; however, they are yet to be resolved despite the measures implemented to routinely screen patients admitted for surgery for heparin-induced thrombocytopenia (HIT) antibodies. Four HIT antibody-positive cases have been confirmed at the institute since the start of vaccination; this frequency of HIT antibody-positive cases has rarely been observed before. Fatal cases due to VITT following the administration of COVID-19 vaccines have also been reported [15].

As a safety measure, further booster vaccinations should be discontinued. In addition, the date of vaccination and the time since the last vaccination should be recorded in the medical record of patients. Owing to the lack of awareness of this disease group among physicians and general public in Japan, a history of COVID-19 vaccination is often not documented, as it is in the case of influenza vaccination. The time elapsed since the last COVID-19 vaccination may need to be considered when invasive procedures are required. Several practical measures that can be implemented to prevent a decrease in immunity have been reported [16]. These include limiting the use of non-steroidal anti-inflammatory drugs, including acetaminophen, to maintain deep body temperature, appropriate use of antibiotics, smoking cessation, stress control, and limiting the use of lipid emulsions, including propofol, which may cause perioperative immunosuppression [17].

To date, when comparing the advantages and disadvantages of mRNA vaccines, vaccination has been commonly recommended. As the COVID-19 pandemic becomes better controlled, vaccine sequelae are likely to become more apparent. It has been hypothesized that there will be an increase in cardiovascular diseases, especially acute coronary syndromes, caused by the spike proteins in genetic vaccines [1819]. Besides the risk of infections owing to lowered immune functions, there is a possible risk of unknown organ damage caused by the vaccine that has remained hidden without apparent clinical presentations, mainly in the circulatory system. Therefore, careful risk assessments prior to surgery and invasive medical procedures are essential. Randomized controlled trials are further needed to confirm these clinical observations.

In conclusion, COVID-19 vaccination is a major risk factor for infections in critically ill patients.

References

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Duration of Shedding of Culturable Virus in SARS-CoV-2 Omicron (BA.1) Infection

Authors: Julie Boucau, Ph.D. Caitlin Marino, B.S. Ragon Institute, Cambridge, MA

James Regan, B.S. Brigham and Women’s Hospital, Boston, MA Rockib Uddin, B.S.
Massachusetts General Hospital, Boston, MA Manish C. Choudhary, Ph.D.
James P. Flynn, B.S. Brigham and Women’s Hospital, Boston, MA Geoffrey Chen, B.A.
Ashley M. Stuckwisch, B.S. Josh Mathews, A.B. May Y. Liew, B.A. Arshdeep Singh, B.S.
Taryn Lipiner, M.P.H. Massachusetts General Hospital, Boston, MA Autumn Kittilson, B.S. Meghan Melberg, B.S. Yijia Li, M.D. Brigham and Women’s Hospital, Boston, MARebecca F. Gilbert, B.A. Zahra Reynolds, M.P.H. Surabhi L. Iyer, B.A. Grace C.Chamberlin, B.A. Tammy D. Vyas, B.S. Marcia B. Goldberg, M.D.Jatin M. Vyas, M.D., Ph.D.Massachusetts General Hospital, Boston, MAJonathan Z. Li, M.D.Brigham and Women’s Hospital, Boston, MA Jacob E. Lemieux, M.D., D.Phil. Mark J. Siedner, M.D., M.P.H.Amy K. Barczak, M.D.Massachusetts General Hospital, Boston, MA

July 21, 2022 N Engl J Med 2022; 387:275-277 DOI: 10.1056/NEJMc2202092

The B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a shorter incubation period and a higher transmission rate than previous variants.1,2 Recently, the Centers for Disease Control and Prevention recommended shortening the strict isolation period for infected persons in non–health care settings from 10 days to 5 days after symptom onset or after the initial positive test, followed by 5 days of masking.3 However, the viral decay kinetics of the omicron variant and the duration of shedding of culturable virus have not been well characterized.

We used longitudinal sampling of nasal swabs for determination of viral load, sequencing, and viral culture in outpatients with newly diagnosed coronavirus disease 2019 (Covid-19).4 From July 2021 through January 2022, we enrolled 66 participants, including 32 with samples that were sequenced and identified as the B.1.617.2 (delta) variant and 34 with samples that were sequenced and identified as the omicron subvariant BA.1, inclusive of sublineages. Participants who received Covid-19–specific therapies were excluded; all but 1 participant had symptomatic infection. This study was approved by the institutional review board and the institutional biosafety committee at Mass General Brigham, and informed consent was obtained from all the participants. Figure 1.Viral Decay and Time to Negative Viral Culture.

The characteristics of the participants were similar in the two variant groups except that more participants with omicron infection had received a booster vaccine than had those with delta infection (35% vs. 3%) (Tables S1 and S2 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). In an analysis in which a Cox proportional-hazards model that adjusted for age, sex, and vaccination status was used, the number of days from an initial positive polymerase-chain-reaction (PCR) assay to a negative PCR assay (adjusted hazard ratio, 0.61; 95% confidence interval [CI], 0.33 to 1.15) and the number of days from an initial positive PCR assay to culture conversion (adjusted hazard ratio, 0.77; 95% CI, 0.44 to 1.37) were similar in the two variant groups (Figure 1A through 1C and S1 through S3, and Tables S3 through S5). The median time from the initial positive PCR assay to culture conversion was 4 days (interquartile range, 3 to 5) in the delta group and 5 days (interquartile range, 3 to 9) in the omicron group; the median time from symptom onset or the initial positive PCR assay, whichever was earlier, to culture conversion was 6 days (interquartile range, 4 to 7) and 8 days (interquartile range, 5 to 10), respectively. There were no appreciable between-group differences in the time to PCR conversion or culture conversion according to vaccination status, although the sample size was quite small, which led to imprecision in the estimates (Figure 1D and 1E).

In this longitudinal cohort of participants, most of whom had symptomatic, nonsevere Covid-19 infection, the viral decay kinetics were similar with omicron infection and delta infection. Although vaccination has been shown to reduce the incidence of infection and the severity of disease, we did not find large differences in the median duration of viral shedding among participants who were unvaccinated, those who were vaccinated but not boosted, and those who were vaccinated and boosted.

Our results should be interpreted within the context of a small sample size, which limits precision, and the possibility of residual confounding in comparisons according to variant, vaccination status, and the time period of infection. Although culture positivity has been proposed as a possible proxy for infectiousness,5 additional studies are needed to correlate viral-culture positivity with confirmed transmission in order to inform isolation periods. Our data suggest that some persons who are infected with the omicron and delta SARS-CoV-2 variants shed culturable virus more than 5 days after symptom onset or an initial positive test.