Life-threatening inflammation is turning COVID-19 into a chronic disease

Authors: Chris Melore MAY 13, 2022 Study Finds

Long COVID continues to be a lingering problem for more and more coronavirus patients in the months following their infection. Now, a new study contends that the life-threatening inflammation many patients experience — causing long-term damage to their health — is turning COVID-19 into a chronic condition.

“When someone has a cold or even pneumonia, we usually think of the illness being over once the patient recovers. This is different from a chronic disease, like congestive heart failure or diabetes, which continue to affect patients after an acute episode. We may similarly need to start thinking of COVID-19 as having ongoing effects in many parts of the body after patients have recovered from the initial episode,” says first author Professor Arch G. Mainous III, vice chair for research in the Department of Community Health and Family Medicine at the University of Florida Gainesville, in a media release.

“Once we recognize the importance of ‘long COVID’ after seeming ‘recovery’, we need to focus on treatments to prevent later problems, such as strokes, brain dysfunction, and especially premature death.”

COVID inflammation increases risk of death one year later

The study finds COVID patients experiencing severe inflammation while in the hospital saw their risk of death skyrocket by 61 percent over the next year post-recovery.

Inflammation raising the risk of death after an illness is a seemingly confusing concept. Typically, inflammation is a natural part of the body’s immune response and healing process. However, some illnesses including COVID-19 cause this infection-fighting response to overshoot. Previous studies call this the “cytokine storm,” an event where the immune system starts attacking healthy tissue.

“COVID-19 is known to create inflammation, particularly during the first, acute episode. Our study is the first to examine the relationship between inflammation during hospitalization for COVID-19 and mortality after the patient has ‘recovered’,” Prof. Mainous says.

“Here we show that the stronger the inflammation during the initial hospitalization, the greater the probability that the patient will die within 12 months after seemingly ‘recovering’ from COVID-19.”

There is a way to stop harmful inflammation

The study examined the health records of 1,207 adults hospitalized for COVID-19 in the University of Florida health system between 2020 and 2021. Researchers followed them for at least one year after discharge — keeping track of their C-reactive protein (CRP) levels. This protein is secreted by the liver and is a common measure of systemic inflammation.

Results show patients with a more severe case of the virus and those needing oxygen or ventilation had higher CRP levels during their hospitalization. The patients with the highest CRP concentrations had a 61-percent increased risk of death over the next year after their release from the hospital.

However, the team did find that prescribing anti-inflammatory steroids after hospitalization lowered the risk of death by 51 percent. Study authors say their findings show that the current recommendations for care after a coronavirus infection need to change. Researchers recommend more widespread use of orally taken steroids following a severe case of COVID.

Growing Number Of COVID-19 Deaths Among Vaccinated People: Federal Data

Authors: Katabella Roberts via The Epoch Times MY 13, 2022

An increasing number of COVID-19 deaths are occurring among individuals in the United States who have been vaccinated, according to federal data.

In August of 2021, roughly 18.9 percent of COVID-19 deaths happened among individuals who were vaccinated, an ABC News analysis of the data shows. Six months later in February 2022, that figure had risen to over 40 percent as the highly-transmissible Omicron variant made its way across the globe.

Similarly, in September 2021, just 1.1 percent of COVID-19 deaths occurred among Americans who had been fully vaccinated and boosted once. Five months later in February, that percentage had jumped to about 25 percent, according to ABC News.

A separate analysis of federal data by CNN shows that in the second half of September 2021—when the Delta variant was at its peak—less than a quarter of all COVID-19 deaths were among individuals who were vaccinated with at least two doses of the Moderna or Pfizer/BioNTech mRNA vaccines or a single dose of the Johnson & Johnson vaccine. However, just months later in January and February as Omicron surged, that figure had jumped to 40 percent.

Some experts believe the increase in deaths among fully vaccinated people or “breakthrough infections” in those who have received all their shots is not overly concerning, saying it is because while more and more people become fully vaccinated, new variants emerge and vaccine protection begins to wane as fewer people continue to get booster shots.

These data should not be interpreted as vaccines not working. In fact, these real-world analyses continue to reaffirm the incredible protection these vaccines afford especially when up to date with boosters,” said John Brownstein, an epidemiologist at Boston Children’s Hospital and an ABC News contributor.

Despite an increasing number of deaths among the vaccinated, the Centers for Disease Control and Prevention (CDC) states that vaccines are safe and effective. Data from the government agency says that overall, the risk of death from COVID-19 is roughly five times higher in unvaccinated individuals than in those who have had at least their initial dose of a vaccine.

However, in some cases, serious adverse events such as thrombosis with thrombocytopenia syndrome (blood clots), myocarditis (inflammation of the heart muscle), and pericarditis (inflammation of the outer lining of the heart) have been documented.

As of May 4, around 257.9 million people in the United States, or 77.7 percent of the total population in the nation have received at least one dose of vaccine, while roughly 219.9 million people, or 66.2 percent of the total U.S. population, have been fully vaccinated.

Around 100.9 million of those who are fully vaccinated have received a booster shot, while 49.4 percent of those eligible for booster shots have not yet had one.

As the Omicron variant swept through the nation, an increasing number of vulnerable, older populations were being hospitalized, and 73 percent of deaths have been among those 65 and older, despite the fact that 90 percent of seniors have had all of their vaccine shots.

However, a large percentage—a third of them—have not yet had their booster jab.

“This trend in increased risk among the elderly further supports the need for community-wide immunization,” Brownstein said. “Older populations, especially those with underlying conditions, continue to be at great risk of severe complications, especially as immunity wanes. The best way to protect them is to make sure everyone around them is fully immunized.”

The data comes a month after pharmaceutical and biotechnology company Moderna said that preliminary results from its study on a COVID-19 vaccine intended to protect against variants showed that it outperformed the company’s currently authorized booster shot, mRNA-1273.

Moderna said on April 19 that its mRNA-1273.211 shot, its first bivalent booster vaccine candidate, showed “superiority” against the Beta, Delta, and Omicron variants of the virus one month after being administered, compared to the booster shot of its original vaccine currently in use.

Deaths from COVID begin to rise again

Authors: Tina Reed Kavya Beheraj May 12, 2022 Axios

Deaths from COVID-19 are on the rise again after several weeks of upward ticking case rates sparked by Omicron variants.

Driving the news: The U.S. averaged roughly 365 daily deaths, up 7% from about 342 two weeks ago. That’s still a fraction of where things stood several months ago when the daily average was in the thousands.

Yes, but: The increase in deaths comes after several weeks of declines. While increasingly transmissible Omicron variants have generally not appeared to cause more serious illness, some people are still dying.

  • Waning immunity and low booster uptake has also meant a growing share of the deaths are among the vaccinated, officials warn.

By the numbers: There were roughly 77,000 new daily cases over the last week, up 44% from about 53,000 two weeks ago.

  • Reported cases rates remained highest in the Northeast, with Rhode Island marking 67.3 new cases per 100,000 people, up from 38.4 per 100,000 two weeks ago.
  • Rhode Island, Massachusetts, Vermont and Maine were the four states with 50 or more new cases per 100,000 people over the last two weeks.
  • On the flip side, 15 states reported having 10 or fewer new cases per 100,00o people over the same time, including Alabama, Arizona, Arkansas, Georgia, Idaho, Louisiana Mississippi, Montana, Nebraska, Oklahoma, Pennsylvania, Texas, South Carolina, South Dakota and Wyoming.
  • Five states reported declines in COVID case rates, including Montana, which reported 5.2 new cases per 100,000 people, down from 5.5 per 100,000 two weeks ago. Alaska, Colorado, Pennsylvania and Washington also reported dips. D.C. also reported a drop, however, the CDC said Wednesday the District had a two-week lapse in reporting, Axios’ Chelsea Cirruzzo reports.

Reality check: As we’ve warned before, the data on new cases are getting less reliable as the public testing infrastructure continues to wind down and home test results are less likely to be reported to officials.

  • But it still offers a window into the broad trends of COVID spread in the states.

The bottom line: As variants spread, warm weather returns and more people let their guard down, cases are on the rise. While numbers appear far better than what they once were, officials warn the virus isn’t done with us yet.

Analysis of Federal Data Shows Increase in Covid-19 Deaths Occurred Among the Vaccinated – Experts Warn More Breakthrough Deaths to be Expected with More Americans Reaching Fully Vaxx Status

Authors:  Jim Hoft Published May 11, 2022  ABC News

Analysis of federal data conducted by ABC News showed that more Covid-19 deaths occurred among the vaccinated, and more breakthrough deaths are expected with more Americans reaching full vaccination status, experts warned.

According to the new analysis, about 18.9% of COVID-19 deaths recorded were among the vaccinated in August 2021. After six months, in February 2022, the number of deaths increased to more than 40%.

Comparatively, in September 2021, just 1.1% of COVID-19 deaths occurred among Americans who had been fully vaccinated and boosted with their first dose. By February 2022, that percentage had increased to about 25%.

Experts said the increase in breakthrough deaths is expected with more Americans reaching full vaccination status.

“These data should not be interpreted as vaccines not working. In fact, these real-world analyses continue to reaffirm the incredible protection these vaccines afford especially when up to date with boosters,” said Dr. John Brownstein, an epidemiologist at Boston Children’s Hospital and an ABC News contributor.

In addition, many vulnerable Americans are more than one year out from their primary vaccinations and have yet to receive booster doses.

To date, more than 220 million Americans have been fully vaccinated, 100 million of whom have received their first COVID-19 booster. However, about 91.5 million eligible Americans — about half of those currently eligible — have yet to receive their first booster shot.

The increase in breakthrough deaths comes as a growing proportion of older Americans enter the hospital for COVID-19 related care.

Last summer, after more vulnerable, older populations had been vaccinated, the share of Americans ages 65 years and older in the hospital had dipped to a pandemic low — with younger populations representing the largest age groups of people in need of care. However, throughout the omicron surge, the average age of those in the hospital with COVID-19 has steadily gotten older again.

More than 90% of seniors have been fully vaccinated, but a third of them have yet to receive their first booster shot. Even with overall high vaccination rates in older populations, in recent months, during the omicron surge, 73% of deaths have been among those 65 and older.

Not only that the Covid-19 mRNA vaccine effectiveness wanes after four months, but it also posed a life-threatening risk to people who received it.

The Gateway Pundit previously reported that a new German study with around 40,000 participants concluded that severe complications after receiving the COVID vaccine is 40 times higher than previously recorded.

Germany’s MDR.de reported:

The study “Safety Profile of Covid-19 Vaccines” (“ImpfSurv” for short), which focuses on the effects and side effects of the various vaccines, has been running for a year. Around 40,000 vaccinated people are interviewed at regular intervals throughout Germany. Participation in the study is voluntary and independent of how the vaccines work in the subjects.

One result: eight out of 1,000 vaccinated people struggle with serious side effects. “The number is not surprising,” explains Prof. Dr. Harald Matthes, head of the study: “It corresponds to what is known from other countries such as Sweden, Israel or Canada. Incidentally, even the manufacturers of the vaccines had already determined similar values ​​in their studies.” With conventional vaccines, such as against polio or measles, the number of serious side effects is significantly lower.

Growing share of Covid-19 deaths are among vaccinated people, but booster shots substantially lower the risk

Authors: Deidre McPhillips, CNN Updated 7:58 AM ET, Wed May 11, 2022 CNN Health

Since Covid-19 vaccines became widely available, there has been a wide gap in deaths between the vaccinated and unvaccinated. But recent Covid deaths are much more evenly split as highly transmissible variants take hold, vaccine protection wanes and booster uptake stagnates. Breakthrough infections have become more common in recent months, putting vulnerable populations at increased risk of severe disease or death as more and more transmissible variants continue to spread. This seems to be especially true for seniors in the United States, who were among the first to get their initial vaccine series. In the second half of September — the height of the Delta wave — less than a quarter of all Covid-19 deaths were among vaccinated people, federal data shows. But in January and February, amid the Omicron surge, more than 40% of Covid-19 deaths were among vaccinated people.

Covid-19 vaccines have saved millions of lives in the United States since the first shot was administered in December 2020, and the unvaccinated are still far more likely to be hospitalized or die than people who are vaccinated with at least two doses of the Moderna or Pfizer/BioNTech mRNA vaccines or a single dose of the Johnson & Johnson vaccine.

But evidence continues to build around the critical importance of booster shots.

Why Covid-19 vaccine boosters may be more important than ever Of those vaccinated people who died from a breakthrough case of Covid-19 in January and February, less than a third had gotten a booster shot, according to a CNN analysis of data from the US Centers for Disease Control and Prevention. The remaining two-thirds had only received their primary series. Overall, the risk of dying from Covid-19 is still about five times higher for unvaccinated people than it is for those vaccinated with at least their primary series, CDC data shows.

But there’s a significant disparity by level of vaccination, too: When adjusted for age, people vaccinated with only their initial series faced about three times greater risk of dying than those who also have their booster shot.The CDC encourages people to be “up-to-date” on Covid-19 vaccinations — which includes getting boosters at the appropriate time — but still defines a person to be “fully vaccinated” if they’ve received at least their initial vaccination series.But this week, a senior Biden administration official was more direct: All adults need a third shot.Vaccination is the best way for individuals to protect themselves against Covid-19, and protection is most effective with at least three shots, the official said.Others have emphasized the importance of boosters to save lives, too.”Almost no one in this country should be dying from Covid” with up-to-date vaccinations and appropriate antiviral treatments, Dr. Robert Califf, commissioner of the US Food and Drug Administration, said Saturday on CNN Newsroom.”What we really should be worried about is getting the boosters that we need to stay up to date so with the new variants that we have, we don’t have unnecessary deaths and hospitalizations.”

Boosters benefit high-risk seniors most

In the first year of the pandemic, before vaccines were available, the vast majority of Covid-19 deaths — more than 80% — were among seniors age 65 and older.

In 2021, especially during the Delta surge, the average age of people dying of Covid-19 shifted younger. Less than 60% of those who died in September were 65 or older, according to provisional data from the CDC.

Covid-19’s full death toll is nearly three times higher than reported, WHO data suggests But 2022 has looked a lot more like 2020 and the first winter surge; so far this year, about three-quarters of all Covid-19 deaths have been among seniors. Studies have suggested that Covid-19 vaccine effectiveness wanes over time. Data from the CDC published in January found that getting boosted was 90% effective at preventing hospitalizations during a period when Omicron was the dominant variant. In comparison, getting two shots was 57% effective when it had been at least six months past the second shot.The vast majority of seniors completed their initial series more than a year ago now. And while booster uptake among seniors is better than other age groups, less than two-thirds of seniors have gotten a booster shot.The CDC now recommends a second booster shot for this age group, too, and uptake is even lower.CNN’s analysis of CDC data from recent months suggests that disparities in risk among vaccinated people who are boosted compared with those who only have their initial series are most prominent among this vulnerable age group.

Covid-19 deaths are preventable

Daily Covid-19 deaths in the US have fallen to a fraction of what they were in January and February amid the Omicron surge, but hundreds are still dying each day.Cases are rising in nearly all states right now, and the White House has warned that another wave in the coming fall and winter could cause 100 million new cases — both raising the potential for more severe disease and tragic loss. But experts say we have the tools to ensure infections don’t turn tragic.

Getting more Americans boosted against Covid-19 could make a big difference as the country heads into the fall and winter, Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said Monday.”It’s really important that we try to get the half — or a little bit more than a half — of Americans who have only received two doses to get that third dose,” he said. “That may make a difference moving forward here, and it may particularly make a difference now that we’re coming into yet another wave of Covid-19.”

Trends and associated factors for Covid-19 hospitalisation and fatality risk in 2.3 million adults in England

Authors: T. BeaneyA. L. NevesA. AlboksmatyH. AshrafianK. FlottA. FowlerJ. R. Benger

P. AylinS. ElkinA. Darzi & J. Clarke  Nature Communications volume 13, Article number: 2356 (2022) 

Abstract

The Covid-19 mortality rate varies between countries and over time but the extent to which this is explained by the underlying risk in those infected is unclear. Using data on all adults in England with a positive Covid-19 test between 1st October 2020 and 30th April 2021 linked to clinical records, we examined trends and risk factors for hospital admission and mortality. Of 2,311,282 people included in the study, 164,046 (7.1%) were admitted and 53,156 (2.3%) died within 28 days of a positive Covid-19 test. We found significant variation in the case hospitalisation and mortality risk over time, which remained after accounting for the underlying risk of those infected. Older age groups, males, those resident in areas of greater socioeconomic deprivation, and those with obesity had higher odds of admission and death. People with severe mental illness and learning disability had the highest odds of admission and death. Our findings highlight both the role of external factors in Covid-19 admission and mortality risk and the need for more proactive care in the most vulnerable groups.

Introduction

The Covid-19 case fatality ratio (CFR) varies widely between countries1 and definitions of mortality differ across the world, making comparisons challenging2. In England, the most widely reported measure is mortality within 28 days of a positive test3. Up to 21 September 2021, 539,921 hospital admissions and 118,846 deaths have occurred in England, out of a total of 6,398,633 cases, giving a crude case hospitalisation ratio (CHR) of 8.4% and a CFR of 1.9%4. Previous epidemiological studies have shown variation in the CFR over time1,5, but without individual level data, it is unclear the extent to which this variation is accounted for by differences in the risk of those infected.

Many risk factors for death from Covid-19 have been characterised, such as increased age, male gender, and obesity6. Several long-term conditions are strongly linked to a higher mortality risk; in England, this led to the early adoption of a ‘clinically extremely vulnerable’ (CEV) status for those deemed to be at highest risk, subsequently advised to isolate to reduce transmission7. Previous studies have focussed on the first wave of the pandemic in the first half of 2020, which may not be representative of subsequent pandemic waves, particularly given advances in the management of Covid-19 patients and the emergence of new variants8. Furthermore, to our knowledge, no study to date has used data with national coverage, including all laboratory-confirmed Covid-19 test results linked to electronic health record (EHR) data.

The main aim of this paper is to describe the changing trends in the Covid-19 case hospitalisation risk (CHR) and case fatality risk (CFR) in England, during the ‘second wave’ of the pandemic (i.e., from 1st October 2020 to 30th April 2021). The secondary aims are to identify patient characteristics associated with hospitalisation and mortality risk; and to evaluate whether residual unexplained variation in the CHR and CFR remains after accounting for differences in the underlying risk factors of those infected.

Results

From 1st October 2020 to 30th April 2021, data were available for 2,433,768 individuals with a positive Covid-19 test result in England. Data for 34,317 (1.4%) participants with a positive test result could not be linked to either primary or secondary care records and were excluded. Care home residents accounted for 3.7% of the total (n = 88,169) and were excluded from further analyses, resulting in a total population of 2,311,282.

Characteristics of the study population are provided in Table 1. The mean (SD) age of participants was 44.3 (17.1) years, with 43.6% under 40 years. The majority were female (54.3%) and of White ethnicity (72.8%). There were relatively higher proportions from more deprived deciles of IMD, with 56.7% in the bottom five deciles. Similar proportions of subjects with a healthy weight (28.4%), overweight (28.1%) or obese (26.1%) were observed, and only 3.4% were underweight. 16.3% were current smokers and 8.3% were designated as CEV. Chronic respiratory disease (21.2%), hypertension (15.0%) and diabetes (8.6%) were the three most prevalent chronic conditions in the population.Table 1 Characteristics of the study population with hospital admissions and deaths within 28 days (N = 2,311,282).Full size table

Case hospitalisation and fatality risk over time

Of the study population, 164,046 people were admitted to hospital at least once within 28 days of a positive test, giving a crude CHR of 7.1% over the seven-month period. 53,156 deaths occurred within 28 days of a positive test, giving a crude CFR of 2.3%. Of these, 49,172 (92.5%) had Covid-19 as a cause of death on the death certificate. There were significant differences over time in both the CHR and CFR (Supplementary Fig. 1). The age distribution of people with a positive test varied over time, with the highest proportions of all infection in people aged 60 years and above infected in November 2020 and January 2021 (Supplementary Table 1). Within all age groups, a similar pattern of change in the CHR and CFR over time was seen, with risk peaking in December 2020–February 2021 (Supplementary Tables 2 and 3, respectively, and Supplementary Fig. 2).

Factors associated with 28-day mortality and hospitalisation risk

Multiple imputation was used to impute missing data for 381,283 people. Multivariable logistic regression models were constructed for each outcome adjusting for all patient level covariates (model 2). Calibration plots indicated adequate calibration (Supplementary Figs. 3 and 4). Results for hospital admissions and mortality are presented in Figs. 1 and 2 (also Supplementary Tables 4 and 5). Males had 41% higher adjusted odds of admission (95% CI: 1.39–1.42) and 62% higher adjusted odds of mortality (95% CI: 1.58–1.65) compared to females. People of all four non-White ethnicities had higher odds of admission, and those of Asian and Black ethnicities also had higher odds of mortality compared to those of White ethnicity. People living in less deprived areas had lower odds of both admission and mortality compared to those in the most deprived areas. Compared to people of a healthy weight, those underweight had 10% higher odds of admission (95% CI: 1.05–1.14) and 99% higher odds of death (95% CI: 1.87–2.11). People who were overweight had a 24% increase in odds of admission (95% CI: 1.22–1.26) but 20% lower odds of death (95% CI: 0.77-0.82); those who were obese had 93% higher odds of admission (1.90–1.97) and 4% increased odds of death (95% CI: 1.01–1.07). Current smokers had lower odds of admission compared to non-smokers but an increase in the odds of death after adjustment.

figure 1
Fig. 1: Adjusted odds ratios for emergency hospital admission within 28 days of positive Covid-19 test.
figure 2
Fig. 2: Adjusted odds ratios for death within 28 days of positive Covid-19 test.

All chronic conditions included were strongly associated with an increase in odds of admission and death, except for dementia, which was associated with 6% lower odds of admission. People identified as CEV had 85% higher odds of being admitted to hospital (95% CI: 1.83–1.88) but 12% lower odds of death (95% CI: 0.86–0.90) after full adjustment. In a sub-analysis adjusting CEV status for age, time (and their interaction), sex, ethnicity, and deprivation only, odds of admission were significantly higher (aOR 2.62, 95% CI: 2.58–2.65) as were odds of death (aOR 1.52, 95% CI: 1.49–1.55).

A sensitivity analysis of the 1,929,999 complete cases showed similar estimates to the fully adjusted model (Supplementary Tables 6 and 7).

CHR and CFR over time

A significant association remained with time for both CHR and CFR models after adjusting for all patient covariates (p < 0.0001 in each model from likelihood ratio tests). The predicted CHR and CFR from the fully adjusted models are plotted for the whole population (Supplementary Fig. 5) and by age category in Fig. 3, showing that a significant time-varying relationship remained after adjustment. The relative change in predicted CHR and CFR from the baseline predicted risk in the first full week of October is shown in Fig. 4 (and Supplementary Figs. 6 and 7). The CFR increased across all age groups, peaking between late December 2020 to early February 2021in different age groups before declining towards April. A smaller relative increase in hospitalisation risk was seen across age groups. In most age groups, CHR peaked in January, except in the 18–39 age group, which continued to increase throughout the study period. After adjustment, the trends in absolute mortality and hospitalisation risk in each age group were similar to those in the unadjusted analyses (Fig. 4 and Supplementary Fig. 2) indicating that the distributions of risk factors of those infected within age groups did not change significantly over time.

figure 3
Fig. 3: 28-day case hospitalisation risk and fatality risk over time in people with Covid-19.
figure 4
Fig. 4: Relative change in 28-day case hospitalisation risk and fatality risk over time in people with Covid-19.

Discussion

In this retrospective cohort study including all adults in England with a positive Covid-19 test result, there was significant variation in the 28-day CHR and CFR by age group and over time, which remained after accounting for individual risk. Demographics and chronic conditions were strongly associated with hospitalisation and death.

Variation in CHR and CFR over time

Across the whole study population, CHR and CFR varied over time from 1st October 2020 to 30th April 2021. This was partially explained by the changing age distributions of those infected, but significant variation remained after adjustment. Within age groups, absolute differences in the CHR and CFR over time were greatest in older age groups, reflecting higher baseline risk, but the relative risk varied significantly across all groups. Historically, there is a strong seasonal component to mortality in England, with figures indicating 16.8% higher mortality in winter months compared to summer months9. An increased incidence of respiratory diseases, including influenza, are one of the main drivers of increased winter mortality, and the 28-day mortality metric used in this study includes deaths from non-Covid-19 causes. However, with influenza rates at lower levels than previous years, it is unlikely the variation in CFR over time can be explained by the incidence of other infectious diseases alone10.

Strain on the health system may also contribute to the patterns seen, with Covid-19 bed occupancy and critical care occupancy in England peaking in January 2021, associated with a lower proportion of patients seen in Accident & Emergency departments within 4 hours than in November 2020 and February 20214,11. Larger relative increases were seen in the CFR compared to the CHR, which may indicate a health system reaching full capacity and struggling to meet demand. A previous UK study of patients admitted to hospital with Covid-19 found a fall in mortality from March to July 2020, a time over which bed occupancy fell and evidence for new treatments, such as dexamethasone, became available, with similar findings from a US cohort between March and September 202012,13. Changes to care delivery at an organisational level may also have an impact, with triage models for Covid-19 patients on the national 111 urgent care service varying between services and over time14. The Alpha variant became the dominant Covid-19 strain in England in December 2020, and has been associated with a 64% increase in 28-day mortality compared to prior variants, which may explain part of the rise in the CHR and CFR15.

Declines in the CHR and CFR from January 2021 onwards are likely to be explained at least partially by the development of immunity, both through natural infection and by the vaccination programme, which was implemented from 8th December 2020 in England for the highest risk cohorts16. By February 2021, over 80% of over 80s had been vaccinated in most regions of the UK, with similar vaccine coverage in the 70–79 year age group by mid-February and in the 60–69 year age group by mid-March (Supplementary Figs. 810)17. However, our study population includes people with a positive Covid-19 test, who are more likely to be unvaccinated than the general population; population vaccine coverage is, therefore, unlikely to be representative of our study population and estimates could not be incorporated robustly into our modelling. Declines in CFR and CHR are most marked in older age groups, who were the first groups eligible for vaccination. However, declines in mortality are seen across all age groups, including the 18–39 year group, many of whom would not have been eligible for vaccination, suggesting vaccination does not fully account for the declines observed. Availability of new treatments may also explain the falls in mortality, with the RECOVERY trial demonstrating the benefit of tocilizumab published in February 2021, but is unlikely to explain the fall in admissions8,18.

Factors associated with hospitalisation and mortality

The findings of a higher risk of mortality in males, people of Asian and Black ethnic backgrounds, and those living in more deprived areas are consistent with a previous UK cohort and confirmed in our study, including an increased risk of admission6. People who were underweight were more likely to be admitted and had significantly higher risk of death, which might be partly accounted for by unmeasured associated conditions, such as frailty. People who were overweight and obese had higher risk of admission than those of a healthy weight, but mortality risk was lower in those overweight, which may indicate higher perceived risk amongst clinicians and a lower threshold for admission.

People identified as CEV were significantly more likely to be admitted but were found to have significantly lower mortality, after adjusting for other risk factors including co-morbidities. However, in partially adjusted models not including BMI, smoking, or clinical co-morbidities, those identified as CEV had significantly higher odds of death. Taken together, these findings indicate a lower threshold for clinical assessment and/or admission and escalation in CEV patients with a protective effect on mortality. All twelve included clinical co-morbidities were associated with significant increases in the odds of mortality and admission. Severe mental illness and learning disability had the strongest associations with mortality and admission, highlighting a need for more proactive care in these groups and more research into the reasons for mortality differences19. Those with dementia had significantly increased odds of mortality but were less likely to be admitted, suggesting they are more likely to receive care at home, although the cohort did not include those living in care homes and so will not represent the full population of those with dementia.

The emergence of the Delta and Omicron variants have shown the potential of Covid-19 to vary in both transmissibility and pathogenicity over time. In England, December 2021–January 2022 saw the highest case numbers but without the resulting number of hospitalisations and deaths associated with earlier variants and before widespread vaccination4. Despite the emergence of new variants, the findings of our study are relevant in highlighting that the risk of mortality was independent of an extensive panel of clinical and demographic factors in the winter of 2020/21, pointing to the role of wider strain on the health system as an important feature in outcomes in people with Covid-19. While the Omicron variant has contributed to an increase in hospitalisations and emergency department presentations in England and elsewhere, its impact on staff absence has been particularly marked. At the peak of the Omicron wave in early January 2022, almost 50,000 NHS staff were absent due to Covid-19, almost a five-fold increase from the end of November 202120,21,22. Ensuring health systems possess the resilience to weather the dual shocks of an increased demand for care and decreased capacity to provide it, without adversely affecting the quality and safety of healthcare, is an ongoing area of concern.

Strengths and limitations

A strength of this study is the inclusion of routine national laboratory data for positive Covid-19 test results in adults in England with only 1.5% unable to be linked to EHR data, and as a result, has lower risk of sampling bias23. To our knowledge, this is the largest such study including individual level data at a national level. Previous studies in England on predictors of mortality are reported on a smaller cohort of patients with 40% national coverage6. The use of multiple imputation assumes that data are missing at random, and we cannot rule out non-random missing patterns, particularly for data on ethnicity and deprivation, where more marginalised groups are less likely to be registered in the primary care record. However, sensitivity analyses showed inferences were similar between the complete case analysis and imputed results, suggesting limited impact of the missing data on model estimates. Associations with risk factors may also be confounded by differential uptake of vaccinations among risk groups; for example, if those with co-morbidities or defined as CEV were more likely to be vaccinated, the odds ratios for hospitalisation and death may be under-estimated.

Data represented here include only those who died within 28 days of a positive test result, in line with estimates reported by PHE. Deaths mentioning Covid-19 on a death certificate are an alternative metric used widely in many countries as recommended by the World Health Organisation24 and have tended to give a larger estimate of deaths in England, due to those attributable to Covid-19 after 28 days4. Over 90% of deaths within 28 days in our study also had Covid-19 as a cause of death on the death certificate, but we did not have corresponding data for those cases recorded on a death certificate without a positive Covid-19 test. The associations found in our study might be different if using deaths recorded on death certificates, rather than deaths within 28 days of a positive Covid-19 test, particularly if there were changes to death certification practices over time.

Through use of linked EHR data, we were able to incorporate detailed medical factors for the study cohort. However, we were unable to explore the relationship with external factors such as Covid-19 variants. Geographical and time-varying system factors, such as proximity to a hospital and hospital capacity are likely to impact on a person’s health-seeking behaviour. Our study included people living in the community and given patients in England may attend any hospital, and the size of hospital markets vary considerably across the country, we could not reliably model the impact of nearby hospital bed availability at an individual level. However, our modelling showed only minimal residual variation accounted for by CCG level clustering (intraclass correlation coefficient <1%), suggesting these additional factors would have minimal impact on the findings. Access to testing may also impact the probability of having a positive test. Positivity rates in England peaked on 31st December 2020 at 18.3% and fell to 1.7% by 1st April 20214, but the extent to which this reflects increased incidence or a lack of test availability is uncertain. It is possible that if testing were limited during the peak in cases in December 2020–January 2021, those with more symptomatic disease may have been more likely to receive a test, compared to those who were asymptomatic or with mild symptoms. This may in turn lead to an apparent increase in risk of mortality due to changes in the severity of illness of those testing positive, rather than the severity of disease within the community as a whole. Furthermore, access to testing may be driven by sociodemographic factors, and the finding of lower hospitalisation and mortality risk in less deprived areas could reflect better availability of testing. Exploring mortality risk in patients admitted to hospital or to intensive care units and whether this changed over time was outside the scope of the current study but is an area for further research.

The risk of hospitalisation and death from Covid-19 varied significantly over time from October 2020 to April 2021 in all age groups, independent of the underlying risk in those infected. Time-varying risks should be considered by researchers and policymakers in assessing the risks of hospitalisation and mortality from Covid-19. People with severe mental illness and learning disability were amongst those with the highest odds of both admission and mortality, indicating the need for proactive care in these groups.

Methods

The work was conducted as part of a wider service evaluation, approved by Imperial College Healthcare Trust on December 3rd 2020. Data access was approved by the Independent Group Advising on the Release of Data (IGARD; DARS-NIC-421524-R0Y3P) on April 15th 2021.

Study design and population

We conducted a retrospective cohort study including all adults (≥18 years) resident in England with a positive Covid-19 test result (polymerase chain reaction or lateral flow tests) from 1st October 2020 to 30th April 2021, excluding people resident in care homes. Study participants were followed-up for 28 days from the date of a first positive test. The two primary outcomes were (i) one or more emergency hospital admissions and (ii) death from any cause, each within 28 days from the date of the positive test.

Data sources and data processing

Several datasets were linked for this study and provided by NHS Digital as part of an evaluation of the NHS England Covid Oximetry @home programme25. Covid-19 testing data was sourced from the Public Health England (PHE) Second Generation Surveillance System26, the national laboratory reporting system for positive Covid-19 tests, covering the period from 1st October 2020 to 30th April 2021. Primary care data came from the General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR)27. CEV status was linked to GDPPR from the Shielded Patient List (see Supplementary Methods)28. Data on hospital admissions came from Hospital Episode Statistics (HES) data set up to 31st May 2021, linked to Office for National Statistics (ONS) data on death registrations up to 5th July 2021. Datasets were linked using a de-identified NHS patient ID. Participants who could not be linked from testing data to at least one of GDPPR or HES were excluded.

Patient demographics were derived from GDPPR, or  where missing, from HES. Lower layer super output area (LSOA) of residence was linked to indices of relative deprivation using deciles of Index of Multiple Deprivation (IMD) 201929. Residence in a care home, CEV status, body mass index (BMI), and smoking status were derived from GDPPR only. BMI was categorised as underweight (<18.5 kg/m2), healthy weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obese (≥30.0 kg/m2). Chronic conditions were extracted from GDPPR based on Systematised Nomenclature of Medicine Clinical Terms (SNOMED-CT) codes pertaining to relevant diagnosis code clusters. Only codes recorded prior to the date of a positive Covid-19 test were included, to exclude any diagnoses following Covid-19 infection. Where the latest code indicated resolution of a condition, the diagnosis was excluded for that individual. Further details on data curation are given in the Supplementary Methods.

Statistical analysis

Patients were followed from date of first positive Covid-19 test to emergency hospital admission or death within 28 days. Mixed effects logistic regression was conducted for each outcome, with a two-level hierarchical model incorporating Clinical Commissioning Group (CCG, of which there are 106 in England) of residence as a random intercept. Time, represented by the week of Covid-19 test, was modelled as a restricted cubic spline with five knots placed at equally spaced percentiles30. Two models were run for each outcome:

  1. 1.Model 1: incorporating age category and time splines along with their interaction.
  2. 2.Model 2: incorporating age category and time splines along with their interaction and including all additional patient level covariates: sex, ethnicity, IMD decile, BMI category, CEV status, smoking status, and presence of chronic conditions.

For model 2, multiple imputation using chained equations was used to impute missing values of covariates, under the assumption that values were missing at random. All variables included in the analysis model were included in the imputation model31. Fifteen imputations were created, with a burn-in of 10 iterations which gave adequate precision and convergence, respectively (Supplementary Methods). A sensitivity analysis was performed using complete cases only. Calibration was assessed using plots of predicted against observed probabilities for each decile of predicted probability.

For each outcome, the predicted probability of the outcome was computed within each age group and study week stratum to calculate age- and time-specific case hospitalisation risk (CHR) and case fatality risk (CFR). These were calculated using the fixed portion of the model (assuming zero random effects). The relative changes in the CHR and CFR over time were calculated as the predicted probability in each week relative to the week of 5th–11th October 2020 in each age group. In adjusted models (model 2), other model covariates were set to the population mean (or proportion for categorical variables) within each age group. For CEV status, an additional sub-analysis was conducted adjusting only for the age category and time splines (and their interaction), sex, ethnicity, and IMD decile. Further details of the statistical methods are given in Supplementary Methods.

Analyses were conducted in the Big Data and Analytics Unit Secure Environment, Imperial College, using Python version 3.9.5, Pandas version 1.2.3, and Stata version 17.0 (StataCorp).

Data availability

The patient level data used in this study are not publicly available but are available to applicants meeting certain criteria through application of a Data Access Request Service (DARS) and approval from the Independent Group Advising on the Release of Data. Further information is given below: https://digital.nhs.uk/about-nhs-digital/corporate-information-and-documents/independent-group-advising-on-the-release-of-data.

Code availability

The SNOMED terms used in defining chronic conditions are available in our GitHub repository: https://github.com/tbeaney/Imperial-COh-evaluation. Further analysis codes are available on request to the corresponding author.

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Covid deaths no longer overwhelmingly among unvaccinated as toll on elderly grows

Authors: Fenit Nirappil and Dan Keating, The Washington PostApril 29, 2022

Unvaccinated people accounted for the overwhelming majority of deaths in the United States throughout much of the coronavirus pandemic. But that has changed in recent months, according to a Washington Post analysis of state and federal data.

The pandemic’s toll is no longer falling almost exclusively on those who chose not to get shots, with vaccine protection waning over time and the elderly and immunocompromised – who are at greatest risk of succumbing to covid-19, even if vaccinated – having a harder time dodging increasingly contagious strains.

The vaccinated made up 42% of fatalities in January and February during the highly contagious omicron variant’s surge, compared with 23% of the dead in September, the peak of the delta wave, according to nationwide data from the Centers for Disease Control and Prevention analyzed by The Post. The data is based on the date of infection and limited to a sampling of cases in which vaccination status was known.

As a group, the unvaccinated remain far more vulnerable to the worst consequences of infection – and are far more likely to die – than people who are vaccinated, and they are especially more at risk than people who have received a booster shot.

“It’s still absolutely more dangerous to be unvaccinated than vaccinated,” said Andrew Noymer, a public health professor at the University of California at Irvine who studies covid-19 mortality. “A pandemic of – and by – the unvaccinated is not correct. People still need to take care in terms of prevention and action if they became symptomatic.”

A key explanation for the rise in deaths among the vaccinated is that covid-19 fatalities are again concentrated among the elderly.

Nearly two-thirds of the people who died during the omicron surge were 75 and older, according to a Post analysis, compared with a third during the delta wave. Seniors are overwhelmingly immunized, but vaccines are less effective and their potency wanes over time in older age groups.

Experts say they are not surprised that vaccinated seniors are making up a greater share of the dead, even as vaccine holdouts died far more often than the vaccinated during the omicron surge, according to the CDC. As more people are infected with the virus, the more people it will kill, including a greater number who are vaccinated but among the most vulnerable.

The bulk of vaccinated deaths are among people who did not get a booster shot, according to state data provided to The Post. In two of the states, California and Mississippi, three-quarters of the vaccinated senior citizens who died in January and February did not have booster doses. Regulators in recent weeks have authorized second booster doses for people over the age of 50, but administration of first booster doses has stagnated.

Even though the death rates for the vaccinated elderly and immunocompromised are low, their losses numbered in the thousands when cases exploded, leaving behind blindsided families. But experts say the rising number of vaccinated people dying should not cause panic in those who got shots, the vast majority of whom will survive infections. Instead, they say, these deaths serve as a reminder that vaccines are not foolproof and that those in high-risk groups should consider getting boosted and taking extra precautions during surges.

“Vaccines are one of the most important and longest-lasting tools we have to protect ourselves,” said California State Epidemiologist Erica Pan, citing state estimates showing vaccines have shown to be 85% effective in preventing death.

“Unfortunately, that does leave another 15,” she said.

– – –

Arianne Bennett recalled her husband, Scott Bennett, saying, “But I’m vaxxed. But I’m vaxxed,” from the Washington hospital bed where he struggled to fight off covid-19 this winter.

Friends had a hard time believing Bennett, co-founder of the Washington-based chain Amsterdam Falafelshop, was 70. The adventurous longtime entrepreneur hoped to buy a bar and planned to resume scuba-diving trips and 40-mile bike rides to George Washington’s Mount Vernon estate.

Bennett went to get his booster in early December after returning to Washington from a lodge he owned in the Poconos, where he and his wife hunkered down for fall. Just a few days after his shot, Bennett began experiencing covid-19 symptoms, meaning he was probably exposed before the extra dose of immunity could kick in. His wife suspects he was infected at a dinner where he and his server were unmasked at times.

A fever-stricken Bennett limped into the hospital alongside his wife, who was also infected, a week before Christmas. He died Jan. 13, among the 125,000 Americans who succumbed to covid-19 in January and February.

“He was absolutely shocked. He did not expect to be sick. He really thought he was safe,'” Arianne Bennett recalled. “And I’m like, ‘But baby, you’ve got to wear the mask all the time. All the time. Up over your nose.'”

Jason Salemi, an epidemiologist at the University of South Florida College of Public Health, said the deaths of vaccinated people are among the consequences of a pandemic response that emphasizes individuals protecting themselves.

“When we are not taking this collective effort to curb community spread of the virus, the virus has proven time and time again it’s really good at finding that subset of vulnerable people,” Salemi said.

While experts say even the medically vulnerable should feel assured that a vaccine will probably save their lives, they should remain vigilant for signs of infection. As more therapeutics become available, early detection and treatment is key.

When Wayne Perkey, 84, first started sneezing and feeling other cold symptoms in early February, he resisted his physician daughter’s plea to get tested for the coronavirus.

The legendary former morning radio host in Louisville had been boosted in October. He diligently wore a mask and kept his social engagements to a minimum. It must have been the common cold or allergies, he believed. Even the physician who ordered a chest X-ray and had no coronavirus tests on hand thought so.

Perkey relented, and the test came back positive. He didn’t think he needed to go to the hospital, even as his oxygen levels declined.

“In his last voice conversation with me, he said, ‘I thought I was doing everything right,'” recalled Lady Booth Olson, another daughter, who lives in Virginia. “I believe society is getting complacent, and clearly somebody he was around was carrying the virus. … We’ll never know.”

From his hospital bed, Perkey resumed a familiar role as a high-profile proponent for vaccines and coronavirus precautions. He was familiar to many Kentuckians who grew up hearing his voice on the radio and watched him host the televised annual Crusade for Children fundraiser. He spent much of the pandemic as a caregiver to his ex-wife who struggled with chronic fatigue and other long-haul covid symptoms.

“It’s the 7th day of my Covid battle, the worst day so far, and my anger boils when I hear deniers talk about banning masks or social distancing,” Perkey wrote on Facebook on Feb. 16, almost exactly one year after he posted about getting his first shot. “I remember times we cared about our neighbors.”

In messages to a family group chat, he struck an optimistic note. “Thanks for all the love and positive energy,” he texted on Feb. 23. “Wear your mask.”

As is often the case for covid-19 patients, his condition rapidly turned for the worse. His daughter Rebecca Booth, the physician, suspects a previous bout with leukemia made it harder for his immune system to fight off the virus. He died March 6.

“Really and truly his final days were about, ‘This virus is bad news.’ He basically was saying: ‘Get vaccinated. Be careful. But there is no guarantee,'” Rebecca Booth said. “And, ‘If you think this isn’t a really bad virus, look at me.’ And it is.”

Hospitals, particularly in highly vaccinated areas, have also seen a shift from covid wards filled predominantly with the unvaccinated. Many who end up in the hospital have other conditions that weakens the shield afforded by the vaccine.

Vaccinated people made up slightly less than half the patients in the intensive care units of Kaiser Permanente’s Northern California hospital system in December and January, according to a spokesman.

Gregory Marelich, chair of critical care for the 21 hospitals in that system, said most of the vaccinated and boosted people he saw in ICUs were immunosuppressed, usually after organ transplants or because of medications for diseases such as lupus or rheumatoid arthritis.

“I’ve cared for patients who are vaccinated and immunosuppressed and are in disbelief when they come down with covid,” Marelich said.

– – –

Jessica Estep, 41, rang a bell celebrating her last treatment for follicular lymphoma in September. The single mother of two teenagers had settled into a new home in Michigan, near the Indiana border. After her first marriage ended, she found love again and got married in a zoo in November.

As an asthmatic cancer survivor, Estep knew she faced a heightened risk from covid-19, relatives said. She saw only a tight circle of friends and worked in her own office in her electronics repair job. She lived in an area where around 1 in 4 residents are fully vaccinated. She planned to get a booster shot in the winter.

“She was the most nonjudgmental person I know,” said her mother, Vickie Estep. “It was OK with her if people didn’t mask up or get vaccinated. It was okay with her that they exercised their right of choice, but she just wanted them to do that away from her so that she could be safe.”

With Michigan battling back-to-back surges of the delta and omicron variants, Jessica Estep wasn’t able to dodge the virus any longer – she fell ill in mid-December. After surviving a cancer doctors described as incurable, Estep died Jan. 27. Physicians said the coronavirus essentially turned her lungs into concrete, her mother said.

Estep’s 14-year-old daughter now lives with her grandparents. Her widower returned to Indianapolis just months after he moved to Michigan to be with his new wife.

Her family shared her story with a local television station in hopes of inspiring others to get vaccinated, to protect people such as Estep who could not rely on their own vaccination as a foolproof shield. In response to the station’s Facebook post about the story, several commenters shrugged off their pleas and insinuated it was the vaccines rather than covid causing deaths.

Immunocompromised people and those with other underlying conditions are worth protecting, Vickie Estep said. “There’s life potential in those people.”

– – –

As Arianne Bennett navigates life without her husband, she hopes the lesson people heed from his death is to take advantage of all tools available to mitigate a virus that still finds and kills the vulnerable, including by getting boosters.

Bennett wore a music festival shirt her husband gave her as she walked into a grocery store to get her third shot in March. Her husband urged her to get one when they returned to Washington, but she became sick at the same time he did. She scheduled the appointment for the earliest she could get the shot: 90 days after receiving monoclonal antibodies to treat the disease.

“My booster! Yay!” Bennett exclaimed in her chair as the pharmacist presented an updated vaccine card.

“It’s been challenging, but we got through it,” the pharmacist said, unaware of Scott Bennett’s death.

Tears welled in Bennett’s eyes as the needle went in her left arm, just over a year after she and her husband received their first shots.

“Last time we got it, we took selfies: ‘Look, we had vaccines,'” Bennett said, beginning to sob. “This one leaves me crying, missing him so much.”

The pharmacist leaned over and gave Bennett a hug in her chair.

“He would want you to do this,” the pharmacist said. “You have to know.”

– – –

The Washington Post’s Lenny Bernstein contributed to this report.

– – –

Death rates compare the number of deaths in various groups with an adjustment for the number of people in each group. The death rates listed for the fully vaccinated, the unvaccinated and those vaccinated with boosters were calculated by the CDC using a sample of deaths from 23 health departments in the country that record vaccine status, including boosters, for deaths related to covid-19. The CDC study assigns deaths to the month when a patient contracted covid-19, not the month of death. The latest data published in April reflected deaths of people who contracted covid as of February. The CDC study of deaths among the vaccinated is online, and the data can be downloaded.

The death rates for fully vaccinated people, unvaccinated people and fully vaccinated people who received an additional booster are expressed as deaths per 100,000 people. The death rates are also called incidence rates. The CDC estimated the population sizes from census data and vaccination records. The study does not include partially vaccinated people in the deaths or population. CDC adjusted the population sizes for inaccuracies in the vaccination data. The death data is provisional and subject to change. The study sample includes the population eligible for boosters, which was originally 18 and older, and now is 12 and older.

To compare death rates between groups with different vaccination status, the CDC uses incidence rate ratios. For example, if one group has a rate of 10 deaths per 100,000 people, the death incidence rate would be 10. Another group may have a death incidence rate of 2.5. The ratio between the first group and the second group is the rate of 10 divided by the rate of 2.5, so the incidence rate ratio would be 4 (10 ÷ 2.5 = 4). That means the first group dies at a rate four times that of the second group.

The CDC calculates the death incidence rates and incidence rate ratios by age groups. It also calculates a value for the entire population adjusted for the size of the population in each age group. The Post used those age-adjusted total death incidence rates and incidence rate ratios.

The Post calculated the share of deaths by vaccine status from the sample of death records the CDC used to calculate death incidence rates by vaccine status. As of April, that data included 44,000 deaths of people who contracted covid in January and February.

The share of deaths for each vaccine status does not include deaths for partially vaccinated people because they are not included in the CDC data.

The Post calculated the share of deaths in each age group from provisional covid-19 death records that have age details from the CDC’s National Center for Health Statistics. That data assigns deaths by the date of death, not the date on which the person contracted covid-19. That data does not include any information on vaccine status of the people who died.

SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis

Authors: RALPH TURCHIANO    • 

Abstract

Establishing the rate of post-vaccination cardiac myocarditis in the 12-15 and 16-17-year-old population in the context of their COVID-19 hospitalization risk is critical for developing a vaccination recommendation framework that balances harms with benefits for this patient demographic. Design, Setting and Participants: Using the Vaccine Adverse Event Reporting System (VAERS), this retrospective epidemiological assessment reviewed reports filed between January 1, 2021, and June 18, 2021, among adolescents ages 12-17 who received mRNA vaccination against COVID-19. Symptom search criteria included the words myocarditis, pericarditis, and myopericarditis to identify children with evidence of cardiac injury. The word troponin was a required element in the laboratory findings. Inclusion criteria were aligned with the CDC working case definition for probable myocarditis. Stratified cardiac adverse event (CAE) rates were reported for age, sex and vaccination dose number. A harm-benefit analysis was conducted using existing literature on COVID-19-related hospitalization risks in this demographic. Main outcome measures: 1) Stratified rates of mRNA vaccine-related myocarditis in adolescents age 12-15 and 16-17; and 2) harm-benefit analysis of vaccine-related CAEs in relation to COVID-19 hospitalization risk. Results: A total of 257 CAEs were identified. Rates per million following dose 2 among males were 162.2 (ages 12-15) and 94.0 (ages 16-17); among females, rates were 13.0 and 13.4 per million, respectively. For boys 12-15 without medical comorbidities receiving their second mRNA vaccination dose, the rate of CAE is 3.7-6.1 times higher than their 120-day COVID-19 hospitalization risk as of August 21, 2021 (7-day hospitalizations 1.5/100k population) and 2.6-4.3-fold higher at times of high weekly hospitalization risk (2.1/100k), such as during January 2021. For boys 16-17 without medical comorbidities, the rate of CAE is currently 2.1-3.5 times higher than their 120-day COVID-19 hospitalization risk, and 1.5-2.5 times higher at times of high weekly COVID-19 hospitalization. Conclusions: Post-vaccination CAE rate was highest in young boys aged 12-15 following dose two. For boys 12-17 without medical comorbidities, the likelihood of post vaccination dose two CAE is 162.2 and 94.0/million respectively. This incidence exceeds their expected 120-day COVID-19 hospitalization rate at both moderate (August 21, 2021 rates) and high COVID-19 hospitalization incidence. Further research into the severity and long-term sequelae of post-vaccination CAE is warranted. Quantification of the benefits of the second vaccination dose and vaccination in addition to natural immunity in this demographic may be indicated to minimize harm.

Millennials Experienced the “Worst-Ever Excess Mortality in History” – An 84% Increase In Deaths After Vaccine Mandates

The most recent data from the CDC shows that U.S. millennials, aged 25-44, experienced a record-setting 84% increase in excess mortality during the final four months of 2021, according to the analysis of financial expert and Blackrock whistleblower, Edward Dowd,

Dowd, with the assistance of an insurance industry expert, compiled data from the CDC showing that, in just the second half of 2021, the total number of excess deaths for millennials was higher than the number of Americans who died in the entirety of the Vietnam War. Between August and December, there were over 61,000 deaths in this age group, compared to 58,000 over the course of 10 years in Vietnam.

In all, excess death among those who are traditionally the healthiest Americans is up by 84%.

Does this enzyme raise the chance of COVID-related death?

Researchers discovered an enzyme that is genetically related to a key enzyme in snake venom and was found in COVID-19 fatalities in doses 20 times the safe amount.

By JERUSALEM POST STAFF   SEPTEMBER 4, 2021 19:37

A study from the University of Arizona discovered that an enzyme with a key role in severe inflammation may be a vital mechanism in COVID-19 severity and could provide a new target for medicine development.The researchers collaborated with Stony Brook University and Wake Forest School of Medicine to analyze blood samples from two COVID-19 patients and discovered that the circulation of the sPLA2-11A enzyme may be an important method in predicting which patients would die of COVID-19.At high levels, the enzyme has the ability to “shred” the membranes of vital organs. “It’s a bell-shaped curve of disease resistance versus host tolerance,” said Floyd (ski) Chilton, senior author on the paper and director of the U Arizona Precision Nutrition and Wellness Initiative at the university. “In other words, this enzyme is trying to kill the virus, but at a certain point it is released in such high amounts that things head in a really bad direction, destroying the patient’s cell membranes and thereby contributing to multiple organ failure and death.” “The idea to identify a potential prognostic factor in COVID-19 patients originated from Dr. Chilton,” said Maurizio Del Poeta, a co-author of the study. “He first contacted us last fall with the idea to analyze lipids and metabolites in blood samples of COVID-19 patients.” The research team analyzed thousands of patient data points. The team focused on traditional risk factors like age, body mass index and preexisting conditions, but they also focused on biochemical enzymes and patients’ levels of lipid metabolites.

“In this study, we were able to identify patterns of metabolites that were present in individuals who succumbed to the disease,” said Justin Snider, an assistant research professor at the University of Arizona and lead study author. “The metabolites that surfaced revealed cell energy dysfunction and high levels of the sPLA2-11A enzyme. The former was expected but not the latter.”The analysis showed that most healthy people have approximately half a nanogram of the enzyme per milliliter, 63% of people who had severe COVID-19 and died had more than 10 nanograms per milliliter.”Some of the patients who died from COVID-19 had some of the highest levels of this enzyme that have ever been reported,” said Chilton.Previous research into the enzyme shows that it has similar genetic ancestry to a key enzyme contained in snake venom. “Like venom coursing through the body, [the enzyme] has the capacity to bind to receptors at neuromuscular junctions and potentially disable the function of these muscles,” said Chilton.”Roughly a third of people develop long COVID, and many of them were active individuals who now cannot walk 100 yards,” he added. “The question we are investigating now is: if this enzyme is still relatively high and active, could it be responsible for part of the long COVID outcomes that we’re seeing?”

First case of postmortem study in a patient vaccinated against SARS-CoV-2

Author:TorstenHansenaUlfTitzeaNidhi Su AnnKulamadayil-HeidenreichbSabineGlombitzacJohannes, et. al.

Highlights

• We report on a patient with a single dose of vaccine against SARS-CoV-2.

• He developed relevant serum titer levels but died 4 weeks later.

• By postmortem molecular mapping, we found viral RNA in nearly all organs examined.

• However, we did not observe any characteristic morphological features of COVID-19.

Immunogenicity might be elicited, while sterile immunity was not established.

Abstract

A previously symptomless 86-year-old man received the first dose of the BNT162b2 mRNA COVID-19 vaccine. He died 4 weeks later from acute renal and respiratory failure. Although he did not present with any COVID-19-specific symptoms, he tested positive for SARS-CoV-2 before he died. Spike protein (S1) antigen-binding showed significant levels for immunoglobulin (Ig) G, while nucleocapsid IgG/IgM was not elicited. Acute bronchopneumonia and tubular failure were assigned as the cause of death at autopsy; however, we did not observe any characteristic morphological features of COVID-19. Postmortem molecular mapping by real-time polymerase chain reaction revealed relevant SARS-CoV-2 cycle threshold values in all organs examined (oropharynx, olfactory mucosa, trachea, lungs, heart, kidney and cerebrum) except for the liver and olfactory bulb. These results might suggest that the first vaccination induces immunogenicity but not sterile immunity.

Keywords

SARS-CoV-2VaccineAutopsyHistologyRT-PCR

We report on an 86-year-old male resident of a retirement home who received vaccine against SARS-CoV-2. Past medical history included systemic arterial hypertensionchronic venous insufficiencydementia and prostate carcinoma. On January 9, 2021, the man received lipid nanoparticle-formulated, nucleoside-modified RNA vaccine BNT162b2 in a 30 μg dose. On that day and in the following 2 weeks, he presented with no clinical symptoms (Table 1). On day 18, he was admitted to hospital for worsening diarrhea. Since he did not present with any clinical signs of COVID-19, isolation in a specific setting did not occur. Laboratory testing revealed hypochromic anemia and increased creatinine serum levels. Antigen test and polymerase chain reaction (PCR) for SARS-CoV-2 were negative.

For More Information: https://www.sciencedirect.com/science/article/pii/S1201971221003647