COVID-19 tied to increased risk of major adverse cardiac event for up to 3 years

 I had COVID one time for sure and likely two other times. All three were mild cases. Probably because I've had most of the vaccinations. And I'm O negative.

COVID-19 tied to increased risk of major adverse cardiac event for up to 3 years

An increased risk of incident major adverse cardiac event (MACE), including myocardial infarction (MI), stroke, and all-cause mortality, was observed among patients with COVID-19 for up to 3 years, particularly among those requiring hospitalisation, according to a study published in Arteriosclerosis, Thrombosis, and Vascular Biology.

In addition,James R. Hilser, University of Southern California, Los Angeles, California, and colleagues observed that hospitalisation for COVID-19 represented a coronary artery disease risk equivalent, with the risks of post-acute MI and stroke particularly heightened in individuals with non-O blood types. 

Using data from the UK Biobank, the researchers identified 10,005 patients with COVID-19 who had a positive PCR test for severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection (n = 8,062) or had received hospital-based International Classification of Diseases version-10 codes for COVID-19 (n = 1,943) between February 1, 2020, and December 31, 2020. Population controls (n = 217,730) and propensity score-matched controls (n = 38,860) identified from the UK Biobank during the same period were also included in the analysis. 

Overall, the risk of MACE was elevated in patients with COVID-19 at all levels of severity (hazard ratio [HR] = 2.09; 95% confidence interval [CI], 1.94-2.25; P < .0005) over 1,003 days of follow-up, with the risk being more pronounced among patients requiring hospitalisation (HR = 3.85; 95% CI, 3.51-4.24; P < .0005).

More specifically, the risk of MACE was increased among patients hospitalised with COVID-19 who did not have a history of cardiovascular disease (CVD) (HR = 1.21; 95% CI, 1.08-1.37; P < .005) compared with COVID-19-negative controls with CVD, indicating hospitalisation for COVID-19 as a coronary artery disease risk equivalent.

Furthermore, a significant genetic interaction was observed between the ABO blood groups and hospitalisation for COVID-19 (P_interaction = .01), whereby hospitalisation for COVID-19 increased the risk of MI and stroke to a greater extent among individuals with non-O blood types (HR = 1.65; 95% CI, 1.29-2.09; P = 4.8x10^-5) than those with blood type O (HR = 0.96; 95% CI, 0.66-1.39; P = .82).

“Taken together, our data indicate that the elevated risk of MACE in patients with COVID-19 shows no apparent signs of attenuation up to nearly 3 years after SARS-CoV-2 infection and suggest that COVID-19 continues to pose a significant public health burden with lingering adverse cardiovascular risk,” the authors remarked. “These observations suggest that more aggressive cardiovascular risk reduction efforts may be warranted as part of primary prevention in patients hospitalised for COVID-19 and provide new avenues for understanding the biological mechanisms underlying CVD-related adverse outcomes of severe SARS-CoV-2 infection.”

Source: Arteriosclerosis, Thrombosis, and Vascular Biology

Brain changes and associated cognitive deficits evident in patients with neurological long COVID

 Luckily my bout with COVID was short, probably because I was well vaccinated. I didn't want any more brain damage than I already have.

Brain changes and associated cognitive deficits evident in patients with neurological long COVID

Brain changes associated with cognitive deficits were observed in individuals with neurological long COVID, according to a study published in the journal Brain.

“Our data indicate a specific profile of cognitive dysfunction in neurological long COVID characterised by impairment in episodic memory, attention, processing speed, and verbal fluency,”

reported Víctor M. Serrano del Pueblo, University of Castilla-La Mancha, Albacete, Spain, and colleagues. “This altered cognitive performance is associated with reduced integrity of specific white matter regions involved in the interconnection of distal regions responsible for these cognitive functions.”

The study included 83 patients with persistent neurological symptoms after COVID-19 and 22 patients with COVID-19 who had recovered without neurological sequelae. The mean age (50.50 vs 50.82 years) and mean duration from acute infection to neuropsychological and MRI assessments (15 vs 16 months) were similar in the 2 groups. The majority (>90%) of participants were vaccinated after their acute COVID-19 infection.

Overall, the mean global cognitive function of patients with neurological long COVID, assessed by the Addenbrooke’s Cognitive Examination 20 (ACE III) screening test, was significantly lower compared with those who had recovered (overall cognitive level [OCL_z] = -0.39 vs 0.32; P < .01). Of the patients with long COVID, 27% had an impaired overall cognitive function (OCL_z ≤ -0.7), with cognitive severity spanning from severe impairment (12%) to relatively mild deficit (15%).

Furthermore, 48% of patients scored below the 24th percentile in the Rivermead Behavioural Memory Test (RBMT) for episodic memory assessment (global index), with 50% of them exhibiting a severe deficit. Of the 14 RBMT subtests, 8 were significantly below normal, including delayed object recognition, delayed face recognition, delayed spatial route recall, and delayed story recall. 

In addition, specific cognitive functions and executive domains were significantly below the population norms and controls for attention (ACE III_z < 0; P < .001), verbal fluency (ACE III_z < 0; P < .006), processing speed (trail making test-A_z< 0; P = .005), and verbal working memory (Wechsler Adult Intelligence Scale IV Digit span_z< 0; P < .017), with 24% to 34% of patients having some degree of deficit and up to 20% showing severe impairment.

MRI examination, including grey matter morphometry and whole brain structural connectivity, showed that patients with long COVID had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus compared with patients who had recovered.

In addition, lower fractional anisotropy and higher radial diffusivity were observed in widespread areas of the patients’ cerebral white matter relative to controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency.

“To the best of our knowledge, this is the first study involving cognitive testing and neuroimaging from both patients with neurological long COVID and previously SARS-CoV-2-infected subjects who no longer present persistent neurological symptoms (our control group),” the authors noted. “It allows us, therefore, to argue that the neuropsychological and brain alterations found in our long COVID patients are specific to this syndrome, and responsible for chronic cognitive dysfunction.”

“Our study supports the now-increasing evidence for there being a diverse manifestation of neurological symptoms associated with cognitive alterations and brain changes,” the authors concluded.

Source: Brain

Early Stroke Scare With Bivalent COVID Vaccines Unsupported by Large Study

 I am vastly more concerned about stroke post COVID-19 than anything to do with the vaccinations.

Early Stroke Scare With Bivalent COVID Vaccines Unsupported by Large Study

Low absolute risk emerged for flu vaccines, however

by Nicole Lou, Senior Staff Writer, MedPage Today March 19, 2024

Investigation of an early signal for stroke associated with COVID-19 bivalent vaccines turned into suspicion of high-dose or adjuvanted flu shots instead, based on a large U.S. population-based study.

When researchers inspected a large Medicare database, they found no evidence of a significantly elevated risk for stroke at 1-21 days or 22-42 days after vaccination with either of the mRNA COVID vaccines distributed for the 2022-2023 respiratory season when compared with the 43-90 day control window, reported researchers led by Yun Lu, PhD, a statistician of the FDA in Silver Spring, Maryland.

There was a significant excess of nonhemorrhagic stroke for people with concomitant administration of Pfizer-BioNTech's bivalent vaccine plus a high-dose or adjuvanted influenza vaccine during the 22-42 days risk window (risk difference of 3.13 out of 100,000 doses); and a significant excess of transient ischemic attack for people with concomitant administration of Moderna's bivalent COVID vaccine plus a high-dose or adjuvanted influenza vaccine during the 1-21 days risk window (risk difference of 3.33 out of 100,000 doses).

But the researchers found that people with administration of a high-dose or adjuvanted influenza vaccine alone (without concomitant COVID vaccination) had an elevated risk for the combined outcome of nonhemorrhagic stroke or transient ischemic attack in both the 1-21 days risk window (risk difference of 1.65 per 100,000 doses) and 22-42 days risk window (risk difference of 1.60 per 100,000 doses).

"This finding suggests that the observed association between vaccination and stroke in the concomitant subgroup was likely driven by a high-dose or adjuvanted influenza vaccination," the investigators reported in JAMAopens in a new tab or window.

COVID-19 bivalent vaccines were made to blend protection against the ancestral COVID strain and the Omicron BA.4/5 subvariants. They were not as widely adopted as the original vaccines but still remained on the market until they were replaced in September 2023 with monovalent vaccines targeting the XBB.1.5 Omicron subvariantopens in a new tab or window alone for the 2023-2024 respiratory virus season.

Lu and colleagues conducted their study as a follow-up to the CDC and FDA's January 2023opens in a new tab or window warning of an early signal of nonhemorrhagic stroke in older adults who had received Pfizer-BioNTech's bivalent COVID-19 vaccine. That preliminary notice had been based on reports to the Vaccine Safety Datalink during the immediate period after vaccination, though later analyses also suggested a connection with concomitant flu vaccination.

Regarding these now-retired bivalent COVID vaccines, the present data are "reassuring" and consistent with reports from Franceopens in a new tab or window and Israelopens in a new tab or window, according to vaccine researchers Kathryn Edwards, MD, and Marie Griffin, MD, MPH, both of Vanderbilt University in Nashville, Tennessee.

Edwards and Griffin emphasized the small magnitude of the stroke risk associated with high-dose influenza vaccination identified by Lu's team.

"From a population health perspective, a risk of serious outcomes of 1 per 100,000 vaccinated individuals would be more than balanced by the benefits of most recommended vaccines. For example, influenza virus results in thousands of potentially preventable illnesses, medical care visits, hospitalizations, and deaths among persons aged 65 years or older in the U.S. annually and missed days from school and work in younger persons," they commented in an accompanying editorialopens in a new tab or window.

The duo nevertheless cautioned that the risk-benefit calculus of these vaccines may not be so favorable for some relatively healthy older adults who are at an extremely low risk of serious influenza complications.

"It is encouraging that the current U.S. vaccine safety system can identify small vaccine risks on the order of 1 per 100,000. Importantly, public health professionals should be prepared to effectively communicate the level of certainty about potential risks," Edwards and Griffin urged. "The study by Lu et al illustrates the value of a timely, well-designed analysis and has provided reassurance about the COVID-19 boosters. Ongoing monitoring of influenza vaccines marketed for older adults will provide additional data on stroke risk."

For their study, the authors relied on a large representative database that identified over 5.3 million Medicare beneficiaries (median age 74 years, 56% women) who got either mRNA bivalent COVID vaccine starting from Aug. 31, 2022, the emergency use authorization dateopens in a new tab or window for these products, to Feb. 4, 2023. Excluded were people with a recent prior stroke, residents of long-term care facilities, and those in hospice care.

There were ultimately 11,001 individuals recorded as having a stroke after getting a COVID-19 bivalent vaccine. Approximately 10-15% of this case population had a COVID-19 diagnosis claim in the months prior to stroke, and 34-45% had had a concomitant high-dose or adjuvanted influenza vaccination.

"Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination," Lu's group wrote. "More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke."

The study authors also acknowledged that they likely did not capture all cases of SARS-CoV-2 infection among participants due to non-reported at-home tests.

• 

  Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The study was funded by the FDA and CMS via a contract with Acumen.

Lu had no relevant disclosures.

Edwards reported receiving grant funding from the NIH and the CDC; being a consultant to Bionet, Dynavax, GSK, and IBM; and being a member of data safety and monitoring committees for Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, Merck, Roche, Novavax, and CEPI. Griffin disclosed being a member of the CDC's Advisory Committee on Immunization Practices RSV Vaccines Adult Work Group.

Primary Source

JAMA

Source Reference: opens in a new tab or windowLu Y, et al "Stroke risk after COVID-19 bivalent vaccination among US older adults" JAMA 2024; DOI: 10.1001/jama.2024.1059.

Secondary Source

JAMA

Source Reference: opens in a new tab or windowEdward KM, Griffin MR "Postmarketing vaccine safety assessments: important work in progress" JAMA 2024; DOI: 10.1001/jama.2023.26630.

How SARS-CoV-2 contributes to heart attacks and strokes

So make sure you're vaccinated.

How SARS-CoV-2 contributes to heart attacks and strokes

At a Glance

• SARS-CoV-2 infected coronary arteries and increased inflammation in atherosclerotic plaques.
• The findings suggest how COVID-19 could increase the risk of heart attack and stroke.

Foam cells, which accumulate within arteries to form plaques in atherosclerosis, proved particularly susceptible to infection with SARS-CoV-2. Kateryna Kon / Shutterstock

COVID-19 is known to increase the risk of heart attack and stroke. The intense inflammation that occurs throughout the body in severe cases likely contributes to this increased risk. But it’s not clear whether SARS-CoV-2, the virus that causes COVID-19, also affects blood vessels directly.  

To find out, an NIH-funded research team, led by Dr. Chiara Giannarelli at New York University School of Medicine, analyzed coronary artery tissue samples from eight people who died of COVID-19 between May 2020 and May 2021. Results appeared in Nature Cardiovascular Research on September 28, 2023.

The team found SARS-CoV-2 viral RNA in coronary artery tissue from all patients. They found more viral RNA in the arterial walls than in the surrounding fat tissue. Many of the infected cells were macrophages, a type of white blood cell that ingests pathogens. Samples with more macrophages had more viral RNA.

Macrophages also help remove cholesterol from blood vessels. When macrophages become laden with cholesterol, they are known as foam cells. Accumulation of foam cells within arteries forms plaques that are a hallmark of atherosclerosis. The team confirmed that SARS-CoV-2 could infect human macrophages and foam cells in a petri dish. The foam cells were much more susceptible to infection than the macrophages. This could explain why people with atherosclerosis are more vulnerable to COVID-19.

In both cell types, infection depended on a protein on the surface of the cells called neuropilin. Turning off the gene for neuropilin in these cells reduced infection. So did blocking the virus from binding to neuropilin.

Infection triggered several inflammatory pathways in macrophages and foam cells. The cells also released molecules that are known to contribute to heart attacks and strokes. In arterial plaques that had been surgically removed from patients, the researchers saw an inflammatory response to SARS-CoV-2 infection like that seen in the cultured cells.  

The findings suggest that SARS-CoV-2 may increase the risk of heart attacks and stroke by infecting artery wall tissue, including associated macrophages. This provokes inflammation in atherosclerotic plaques, which could lead to heart attack or stroke.

“These results shed light onto a possible connection between preexisting heart issues and Long COVID symptoms,” Giannarelli says. “It appears that the immune cells most involved in atherosclerosis may serve as a reservoir for the virus, giving it the opportunity to persist in the body over time.”

“Since the early days of the pandemic, we have known that people who had COVID-19 have an increased risk for cardiovascular disease or stroke up to one year after infection,” says Dr. Michelle Olive of NIH’s National Heart, Lung, and Blood Institute. “We believe we have uncovered one of the reasons why.”

The authors plan to further investigate the potential link between infection of the arteries and Long COVID. They also aim to see if their results also hold true for newer SARS-CoV-2 variants.

—by Brian Doctrow, Ph.D.

Getting COVID and Flu Shots Together May Slightly Increase Risk of Stroke in Older Adults

 Well, I got them both at the same time since I needed to for a trip to Spain, but then I'm only 67.  And I figure the danger from getting COVID is vastly greater than this risk.

Getting COVID and Flu Shots Together May Slightly Increase Risk of Stroke in Older Adults

• New research from the Food and Drug Administration (FDA) found that getting the COVID-19 vaccine and high-dose flu shot together may increase the risk of stroke in people 85 and older.1
• The potential risk is small, so more research is needed for clinical certainty.
• Experts still recommend getting both vaccines, despite the new study’s results.

Getting a high-dose flu shot and COVID-19 vaccine at the same time may slightly raise the risk of stroke for people 85 years and older, according to a new study from the Food and Drug Administration (FDA).1

It’s worth noting that the study has not yet been published in a peer-reviewed journal, and experts agree the results should not dissuade people who are eligible for both vaccines from getting them.

“These results in no manner change our very strong recommendation to get vaccinated,” Thomas Russo, MD, an infectious diseases expert at the University of Buffalo Jacobs School of Medicine and Biomedical Sciences, told Health.

Brandon Giglio, MD, the director of vascular neurology at NYU Langone Hospital in Brooklyn, said that the new data hasn't changed his suggestions to patients.

“I would still recommend [both vaccines] to my patients because the benefits of them getting vaccinations most likely outweigh the risks,” Giglio said.

The FDA investigators who worked on the new study were not available for comment, but a spokesperson for the agency reiterated that the vaccines are still considered to be safe and effective in a statement to Health.

The review conducted in the study is simply a piece of ongoing safety surveillance efforts—the benefits still far outweigh the risks.

“The FDA is confident in the safety, effectiveness, and quality of the COVID-19 vaccines that the agency has authorized and approved,” the statement said. “The available data continue to demonstrate that the benefits of these vaccines outweigh the risks.”

Though the data might sound concerning, it’s crucial to contextualize the potential risk outlined in the new report.

“The FDA is being transparent here, which is important,” Russo said. “They’re letting people know the data, but it’s important to realize the uncertainties of this data.”

Here’s what you need to know about the new research, what it means for people 85 and older, and whether or not staggering vaccines may be an effective strategy for minimizing risk of stroke.

Getty Images / fotostorm

What Is the Booster Shot and Why Is It Necessary?

Experts Aren’t Yet Sure the Increased Risk Is Real, Despite the Data

The new study relied on data from Medicare beneficiaries who got a Pfizer or Moderna COVID vaccine, a high-dose flu vaccine, or both together from August 31 to November 6, 2022.1

High-dose flu vaccines, technically known as adjuvanted vaccines, are sometimes given to people 65 or older because their immune systems aren’t as strong as those of younger people.2

The researchers found that there were three extra cases of transient ischemic attack (TIA), sometimes called “mini-stroke,” per every 100,000 immunizations.1

“The differences that we’re seeing were very small and may or may not with future studies prove to be real,” Russo said. “This may be a statistical quirk that doesn’t bear out.”

There was a slightly elevated risk of stroke among people aged 65 to 74 who received the Moderna vaccine. Among people aged 85 and older, the risk increased in those who got the Pfizer vaccine.1

That the data did not show an increased risk for people 75 to 84 is unusual—since risk should increase with age—and is one reason to pause before putting too much emphasis on the new findings, Russo explained.

In addition to a very slight increase of TIA among people who got both the COVID and high-dose flu vaccines, the researchers noted a “slightly elevated” risk of stroke in some people who had only gotten a flu shot.

“This finding suggests that the observed risk of stroke in the concomitant subgroup [i.e., people who got both vaccines] was likely driven by influenza vaccination alone rather than concomitant administration,” the study authors wrote.1

It’s important to note, Russo said, that there is no proof that the vaccinations are responsible for the TIAs.

“This is an observational study; it does not connote cause and effect,” he explained.

Both COVID and the flu increase the risk of stroke, Giglio said; the elevated risk of stroke after COVID, specifically, can remain up to nine months after the infection has ended.

Both viruses can also cause several other life-threatening complications, particularly in older adults.

Flu has been linked to an increased risk of respiratory failure and heart attack in older adults, Giglio said, while COVID is more likely to cause severe disease in everyone 50 and older. This means they’re more likely to require hospitalization, be admitted to the intensive care unit (ICU), rely on a ventilator, or even die from the virus.3

Should You Stagger Your COVID and Flu Vaccines?

Though it’s considered safe to get your COVID and flu vaccines at the same time, you ultimately may be more comfortable staggering them.

Both shots can cause irritating side effects such as redness or swelling at the site of vaccination, muscle aches, and fatigue.4

“I would still recommend to my patients that they should get their [vaccinations], but they could definitely separate them by at least two weeks,” Giglio said.

Doing this may make the side effects slightly more palatable since at least you won’t be experiencing them all at once, Russo said.

However, if you live in a rural area, don’t drive, or are otherwise limited in the number of times per month you can visit a vaccination site, you shouldn’t hesitate to get both vaccines at the same time.

“If this is your only opportunity, go for it,” Russo said.