Excess Mortality in the USA

Stuart SilvermanJustin LiChelsea Wang

The COVID-19 pandemic has caused approximately one million deaths in the United States and continues to impact our daily life. Since the beginning of the COVID-19 pandemic in early 2020, we now have much more insight into COVID-19 deaths in the US, including hopes for how the pandemic may wind down because of widespread vaccinations and protection generated from prior infections.

While the media has reported how COVID-19 impacts the elderly the most, the data provided by the Centers for Disease Control and Prevention (CDC) may be telling us a more insightful story for middle-aged and younger individuals on the relative to expected mortality rate basis. As such, the experience over the past two years may be instructive for the life insurance industry going forward.

Excess mortality vs. “normal”

To determine the excess mortality during the COVID-19 pandemic, we utilized the general population data provided by the CDC for our analysis. Currently, the CDC has provided the final official data for 20201 and the provisional data for 20212.

Mortality data used in our analysis are based on all causes of death (not just COVID-19), as the COVID-19 pandemic is impacting the population both directly and indirectly. Though some of these extra deaths were not directly linked to COVID-19 (i.e. not coded as COVID-19 deaths), they may be ascribed to the broader effects of the pandemic, including the societal stress from lockdowns and unemployment, and the pandemic stress both on hospitals’ ability to serve and on sick people’s willingness to go to the hospital.

For our analysis, we define “normal” mortality to be the average mortality of 2017-2019. The following graphs show the excess mortality in 2020 and 2021 versus the “normal” mortality by age group. We first show the deaths with COVID-19 listed as the underlying cause on the death certificate as a percentage of the normal mortality, and then remaining excess deaths are shown as non-COVID deaths.

2020 Male mortality increase (%) over “normal”

2020 Male mortality increase (%) over "normal" mortality

2020 Female mortality increase (%) over “normal”

2020 Female mortality increase (%) over "normal" mortality

2021 Male mortality increase (%) over “normal”

2021 Male mortality increase (%) over "normal" mortality

2021 Female mortality increase (%) over “normal”

2021 Female mortality increase (%) over "normal" mortality

The press may have reported that the majority of COVID-19 deaths were among the elderly (which is certainly true on an absolute count basis), but there has been limited discussion about the increased mortality risk relative to the expected level of mortality at all adult ages. Obviously, these relative increases are particularly important for insurers, which price for and hold reserves based on mortality rates that vary by age.

While the overall percentages of total mortality increase (vs. “normal”) were near 18% for 2020 and 20% for 2021, the percentage of total mortality increase for different age groups could be significantly different depending on the time elapsed since the pandemic, with a wide range of 4% to 54%. As shown in the above graphs, in both 2020 and 2021, the total relative mortality increase peaks in the 35-44 age group for both males and females. In general, smaller total relative mortality increases were experienced in the older age groups.

In 2020, the relative increase in mortality attributable to COVID-19 was fairly consistent for middle-aged people and the elderly. However, the relative increase in mortality attributable to COVID-19 in 2021 was materially higher for middle-aged people compared to the elderly.

While COVID-19 was one of the main medical causes of increased mortality during the pandemic, the impact of societal changes as a response to the pandemic (e.g. societal stress, delayed healthcare) should also be considered when evaluating the overall mortality impact from the pandemic. These deaths attributable to these societal changes have caused a significant relative increase in the mortality rates of the younger age groups. For example, deaths caused by drug overdose increased by more than 35% during the pandemic for the age group of 35-44.

While slightly higher for younger age groups, in 2020 the total relative mortality increase per age group is relatively steady across age groups. We suspect that there were fewer societal differences between the age groups contributing to the excess levels of mortality in 2020. However, in 2021, the differential is much higher. While the virus may have been similarly lethal by calendar year, there were significant societal differences.

  • In 2021, the vaccine became available, first to older-aged people, but then soon after to everyone. Vaccination rates for older-aged people are higher than for younger individuals.
  • By 2021, younger and middle-aged people were becoming more comfortable in public settings compared to elderly individuals. As such, younger and middle-aged people may have been more exposed to the virus (as per the comment above, with a lower chance of being vaccinated).
  • By 2021, we learned how to prevent catastrophic spreading in nursing homes, which was a significant contributor to the levels of elderly excess mortality in 2020. We also learned more about how to mitigate spreading in general (e.g. being outdoors).
  • The cumulative financial and social implications of the lockdowns may have also had a significant impact on the non-COVID relative mortality increase in young and middle-aged people compared to the elderly.
  • Medical treatment for the disease also improved by 2021, but it is not clear why that would lead to differences across age groups. One hypothesis is that older people were more inclined to be in communication with their medical professionals soon after being diagnosed with COVID-19 while there still was an opportunity for successful treatment.

Implications and considerations

While COVID-19 has not yet finished running its course, we now have more experience to assess the impact of the COVID-19 pandemic on the life insurance industry. There is no doubt that the COVID-19 pandemic has been impacting the insurance industry in many ways (e.g. product development, assumption setting, economic capital). It’s important to consider and understand the potential implications of the COVID-19 pandemic to the industry and the changes life insurers need to consider as a result of the COVID-19 pandemic.

  • Mortality assumptions. Mortality rates across all adult ages have been significantly higher since the beginning of the COVID-19 pandemic. However, there may be a mixture of push-pull effects on the mortality from the near to long term:
    • There may be some chronic complications from COVID-19 infection (“Long COVID”), which may result in people “aging” faster than if they weren’t infected with COVID-19. Long COVID may turn out to be a substantive phenomenon and, in turn, may cause future mortality rates to be higher than otherwise expected.
    • Many people delayed elective healthcare, which may have led to reduced diagnoses of conditions (either delayed or missed entirely). This dynamic may cause future mortality rates to be higher than otherwise expected.
    • However, it is possible that COVID-19 may have mostly accelerated deaths from people in poor health already who may have otherwise died earlier than the average person in their age group. Colin Powell, former U.S. Secretary of State, may be a noteworthy example of this – he died with COVID-19, but was suffering from cancer, and COVID-19 may have accelerated his death, which otherwise may have been caused by his cancer within a year or two. We may see a scenario in which the “strong survived” may cause future mortality rates to be lower than expected, thus leading to higher levels of mortality improvement.
  • Pandemic modeling and economic capital. We had envisioned the 1918 influenza pandemic as approximately a one-in-400-year event, but now the COVID-19 pandemic has shown a level of excess mortality comparable to that from the 1918 influenza pandemic. Thus, we have had two pandemics with similar severity in the last 100 to 105 years, so frequency estimates may need to be updated. The question we must ask is whether we view it as one pandemic in each of the last two 100-year periods (suggesting a frequency around 1% per year), or could we consider two pandemics in the last 100 years (suggesting a frequency higher than 1% per year)? This could be an essential consideration in catastrophic modeling and capital requirements.
  • Mergers and acquisitions (M&A) and reinsurance. Buyers of life insurance and annuity blocks of business are considering the implications of the pandemic and how future experience may unfold. Further, life insurers are considering exposures to mortality risk in light of what was experienced under the pandemic.
  • Long-term care (LTC) and annuity living benefits. While the COVID-19 pandemic increased life insurance claims, at the same time, it may have reduced liabilities for payout annuities, long-term care and disability income claims, as well as the living benefit claims associated with fixed and variable annuities. While those types of business may have benefited over the last couple of years from higher levels of reserves released than expected, companies may want to examine the implications of higher levels of mortality improvement if we follow with a “strong survived” scenario.
  • Pricing, product development, and underwriting. Clearly, the implications on assumptions and economic capital will ultimately impact pricing. However, the industry should examine how changed attitudes from the pandemic may impact people’s views of insurance products, which in turn can have implications for effective product design. Also, the unknown long-term chronic complications from COVID-19 infections may create challenges for accurate underwriting – for example, should insurers begin to ask about potential insureds medical history with COVID-19?
  • Sales. Life insurance sales may have increased due to higher awareness of life insurance protection needs raised by the COVID-19 pandemic. According to LIMRA, 31% of consumers said they were more likely to buy insurance due to the pandemic3. The potential increased need for life insurance (especially among younger people) may have created an opportunity for insurers to boost sales. However, this dynamic may reverse as the impact of the pandemic lessens. If so, insurers will have to develop alternative strategies to drive sales growth.
  • Sensitivities. As more experience and data unfolds, companies may want to consider various sensitivities to assess the potential financial impacts from future pandemics.
  • Mental health. The COVID-19 pandemic not only impacted people’s physical health but also their mental health. While the pandemic increases the general population’s mortality rates, it may also increase mental health-related deaths caused by the stress from the COVID-19 pandemic, e.g., suicide, drug overdoses, etc. While the overall suicide rate declined during the pandemic, deaths caused by drug overdoses increased significantly. Consideration should be given to how a more anxious population may influence future mortality rates.

Conclusion

While the media has reported that the COVID-19 pandemic mostly affected older aged people, the data shows that there was an elevated level of relative mortality increase across all age groups, including the main age groups that own life insurance. As we look back on the last couple of years, we collectively have learned a lot about disease, pandemics, and the implications on society. Though insurers may have different experiences from the general population, it is important for the life insurance industry to learn from the experience and make sound decisions for the many implications of how COVID-19 will affect the industry going forward.

This article was first published at https://www.milliman.com/en/insight/How-does-COVID-19-impact-the-life-insurance-industry-going-forward#. Re-used with permission.

References

1 CDC. Multiple Cause of Death, 1999-2020 Request. Retrieved March 6, 2022, from https://wonder.cdc.gov/mcd-icd10.html.

2 CDC. Provisional Mortality Statistics, 2018 Through Last Month Request. Retrieved March 6, 2022, from https://wonder.cdc.gov/mcd-icd10-provisional.html.

3 LIMRA (March 23, 2022). LIMRA: Challenges Brought On by the Pandemic Highlight the Importance of Family. Retrieved May 19, 2022, from https://www.limra.com/en/newsroom/industry-trends/2022/limra-challenges-brought-on-by-the-pandemic-highlight-the-importance-of-family/#:~:text=According%20to%20LIMRA’s%20and%20Life,highest%20growth%20recorded%20since%201983.

Estimates of long Covid are startlingly high. Here’s how to understand them

Authors:  Elizabeth Cooney July 2022 STAT

Think about the adults you know who have had Covid: Does 1 out of every 5 have long Covid, as the CDC estimates?

Asking that question should in no way diminish the suffering of people who thought they were done with their infections, only to find their return to well-being still beyond reach. But knowing how many people are living with that bitter legacy of Covid-19, and who among working-age adults can’t work or care for their families, is critical to their care and to the health of our society.

It’s important to remember that long Covid is an evolving umbrella term for an array of symptoms that vary in both number and degree. Some housebound people are assailed by brain fog that completely robs them of concentration, while others find memory aids help them get through their workdays. Some former athletes can’t complete a 6-minute walk test, while others can gradually return to activity if they monitor their heart rate. Long Covid clinics that adapt techniques from rehabilitation medicine see people eventually get better. In a world transitioning away from bustling downtowns to hybrid work-from-home status, we may not see who’s missing.

Whatever long Covid’s toll turns out to be, it will be too many people. However you gather or analyze the data, experts told STAT, the proportion of people whose troublesome, sometimes disabling symptoms linger after their acute Covid-19 infections clear is sizable and worrying. It’s the cruelty of large numbers: Even if the actual prevalence of long Covid is much smaller than recent estimates, a small percentage of a large number is a large number.

And yet, the U.S. has for months been operating in a nearly normal fashion. What could explain this discrepancy between estimates and common experience? It’s eerily similar to the pandemic’s early days, when people asked one another if they knew anyone who had caught the coronavirus, followed more than two years later by the flip side: knowing few people who haven’t been infected and no one who hasn’t been exposed.

Here are some factors that make the current range of estimates easier to understand.

First, what are the numbers?

That 20% figure, from a recent CDC analysis of millions of health records, implies that tens of millions of Americans — a fifth of people infected with Covid — have at least one lingering post-infection symptom that is seriously affecting their daily life. Compared to other estimates, like an April meta-analysis that puts global long Covid at closer to 50% or a June household survey from CDC saying 1 in 3, it’s even on the low side.

Nathan Praschan, a psychiatry researcher at Massachusetts General Hospital, trusts it, calling the more rigorous CDC study’s epidemiology among the best he’s seen because for over a year it used a control group to tease out Covid effects. Still, he thinks it might have missed some people who don’t show up in medical records. Long Covid is defined by symptoms — psychiatric disorders and cognitive problems, to name two — that could make finding care more difficult, as would the same social determinants of health that mean Covid infection is more likely in some populations in the first place. “So, 1 in 5 may be an underestimate.”

What about different definitions?

CDC’s vs. WHO’s, for instance. The CDC defines long Covid, which it calls Post-Covid Conditions, as symptoms lasting four weeks after first infection. The World Health Organization starts the clock ticking after three months. Praschan said it makes sense to be inclusive, as in on the earlier side, while data are still being collected to avoid missing important information from these patients.

There may be differences in the data.

While some U.K. studies relied on records a national health system provides, others culled responses from a smartphone app asking people about their post-Covid symptoms. That limits the respondents to people who have smartphones and are also motivated to report how they are feeling.

The CDC report’s large numbers give power to the analysis, senior epidemiologist Lara Bull-Otterson told STAT. “While all studies have limitations, we believe the strengths of the data and the analysis are solid and are also supported by prior research,” she said. “Future research is always needed to support and expand on the findings of this study.”

Bruce Levy, chief of pulmonary and critical care medicine at Brigham and Women’s Hospital, doesn’t think the 20% estimate is rock solid, noting how studies have varied widely in the U.S. and in other parts of the world. “Even if it’s in single digits at the end of the day, once a formal case definition and a true prevalence study can be accomplished, it’s still a lot of people. But it’s very hard to pinpoint a solid number.”

If the size of the CDC study is impressive, the source of the data has limits, epidemiologist Priya Duggal of Johns Hopkins Bloomberg School of Public Health said. Patient records reflect only the people who sought care and whose symptoms were coded in their charts. Such data don’t include people who didn’t have access to health care, didn’t seek it, or gave up, thinking there was no help for their crazy quilt of symptoms.

“It doesn’t mean the data’s not right. It doesn’t mean that what we’re looking at isn’t important,” she told STAT. “It just means that that’s a different group of people that you might be looking at.”

Even with caveats, she finds the data pretty consistent for a range of 20% to 30% of people experiencing long Covid symptoms “It’s still a substantial number of people. To me, that’s the take-home point,” she said. “The second point is that it’s real.”

Long Covid is a constellation of diseases that manifest differently.

Symptoms linked to long Covid hit bodies from head to toe: brain fog, fatigue, shortness of breath, digestive problems, muscle weakness. The symptoms vary in severity and number, depending on the study. But most patients don’t necessarily have all of them. Some patients don’t have debilitating fatigue, but might report persistent digestive problems they didn’t have before getting Covid.

Some long Covid may be something else.

With long Covid so disparate and common, it’s possible that some doctors are misattributing symptoms to long Covid and missing the diagnosis of a different disease. Or, because lifesaving measures in intensive care units can be like a train wreck for the body, it’s hard to tease out the treatment from the disease.

Some long Covid is hidden to bystanders.

“Some of it is going to be visible like, oh, they’re weak, they’re sickly, they can’t walk, they can’t go upstairs,” Duggal said. “Then there’s also long Covid where you have kidney damage now, and the average person walking down the street doesn’t know that.”

She’s heard people say they don’t know anyone who has long Covid. “I’m like, you probably do.”

Long Covid isn’t all debilitating.

The CDC definitions capture thousands who fit the worst-case image of long Covid: formerly healthy people who can no longer function. But its prevalence estimate also includes anyone reporting at least one symptom, Bruce Walker, director of the Ragon Institute of Massachusetts General Hospital, MIT and Harvard, reminded reporters on a recent call. Estimates may also capture a worsening pre-Covid condition like asthma, an important consideration for the many people with underlying conditions before they caught Covid.

What’s next?

Bull-Otterson of the CDC urged routine screening for long Covid and better defining it so risk factors could be identified and treatments devised. The impact of vaccination and the wild card of variants also need to be understood.

Long Covid has the potential to widen existing gaps in health, Linda Sprague Martinez of the Boston University School of Social Work said on a video call with reporters, pointing to a map of counties with high case numbers but few long Covid clinics. “We don’t want to wait,” she said. “Getting ahead of it will be really important for us,” she said.

OK, what can we say now?

Estimates of long Covid will certainly evolve, and perhaps be refined into the systems they affect: cardiopulmonary, digestive, musculoskeletal, or neurological, including autonomic powers that control breathing, heart rate, and other unconscious functions. If, as experts say, there is an inevitability to catching Covid now, or catching it again, long Covid will likely follow in some proportion of cases, disabling some further fraction of those people. Recent studies suggest that Covid infections precede the risk of certain other chronic diseases like type 2 diabetes, but the mechanism isn’t clear. Even if the world wasn’t ready for one pandemic, it has to deal with its aftereffects somehow.

“We see people still two years out having long-term symptoms, so if that’s true and people can continue to get infected, this is going to be with us for quite a while,” Duggal said.

The CDC Is Breaking Trust in Childhood Vaccination

With its unscientific push to vaccinate all infants and toddlers against COVID, the agency will harm vaccine uptake for more significant diseases

Authors: LESLIE BIENEN, TRACY BETH HØEG JULY 05, 2022 Tablet

On June 18, the U.S. Centers for Disease Control and Prevention (CDC) officially recommended Pfizer and Moderna COVID-19 vaccines for all children between the ages of 6 months and 5 years. While the Food and Drug Administration (FDA) is the agency responsible for authorizing emergency use of vaccines, it’s the CDC that crafts subsequent messaging, makes specific recommendations, and prioritizes who can, should, or should not get vaccinated. In her briefing, CDC Director Rochelle Walensky strongly urged all parents of the nearly 20 million American children in this age group to vaccinate them as soon as possible.

For some parents, Walensky’s briefing came as a huge relief. But if polling from May is anything to go by, a larger number of parents likely greeted the recommendation with skepticism. Even before the underwhelming trial results came out, only 18% of surveyed parents reported that they planned to vaccinate their babies and toddlers. Nationally, uptake in minors between the ages of 5 and 11 as of June 22, 2022, was 29% receiving two doses, and 36% receiving one, but vaccine requirements for sports, camps, and other activities likely drove an unknown percentage of vaccination in this age group.

There remains, moreover, no solid consensus among physicians about the importance of vaccinating healthy children against COVID-19. A survey from December 2021 indicates that as many as 30%-40% may not be recommending COVID vaccination for children ages 5 to 17, to say nothing of infants. A recent editorial in The Lancet expressed uncertainty about whether the benefits of vaccinating healthy 5- to 11-year-olds outweigh the risks, especially in those with a history of infection.

The gap between the CDC’s enthusiasm for vaccinating all children against COVID and that of parents and health care providers is unlikely to be bridged by approval under Emergency Use Authorization. Approval for the COVID vaccines in infants and toddlers is based on two trials that used changes in antibody levels as an estimate of efficacy, but did not assess protection from severe disease, hospitalization, or multisystem inflammatory syndrome in children (MIS-C), important outcomes that parents worry about. In a Food and Drug Administration (FDA) meeting on June 28, Pfizer Vice President for Viral Vaccines Kena Swanson even acknowledged that “there is no established correlate” between antibody levels and protection from disease.

In the Pfizer trial, the confidence interval—which shows the possible range of protection level—was alarmingly wide, with the lower bound suggesting the possibility of a 380% increase in the chance of infection after the third dose. Additionally, neither trial met the 50% efficacy requirement established by the FDA for approval of adult COVID vaccines. Peter Marks, the FDA’s top vaccine official, told Congress in May that the efficacy requirement would be lowered for the pediatric vaccine simply because vaccine efficacy against the omicron variant was lower in general.

With rates of severe disease now much lower in children than at the start of the pandemic—due to higher levels of natural immunity and lower rates of severe disease caused by omicron—trials would have needed to enroll hundreds of thousands of children, if not over a million, in order to detect a significant impact of the pediatric vaccine against severe disease. Vaccine companies could have conducted such time-consuming and costly trials, especially if there had been interest in international collaboration. But there was no economic incentive to do so, and every economic incentive not to: Speed, not providing meaningful information to parents and physicians about safety and efficacy, was the priority of U.S. regulatory agencies.

Because Pfizer and Moderna were permitted to seek approval for pediatric COVID vaccines under the emergency use pathway, Moderna only enrolled 6,300 total children in trials (4,700 in the vaccine group and 1,600 in the placebo group), and Pfizer only enrolled 4,526 total (2,750 in the vaccine group and 1,776 in the placebo), with two-thirds dropping out before the third dose. The trials, in other words, enrolled only a fraction of the number of participants that would have been required to determine efficacy against end points like severe disease, hospitalization, and rare adverse events such as myocarditis, which has been linked to COVID vaccination in males in the 12- to 17-year-old age group at a rate of up to 1 in 2,700.

Furthermore, the follow-up time after the second dose of Moderna and the third dose of Pfizer was only 1-3 months. Data from adults show protection against infection is transient, though protection against severe disease so far seems longer lasting. For the Moderna vaccine, efficacy against infection was not statistically significant for children between 6 months and 2 years, according to one of the company’s two analyses. In the Pfizer trial, there was no evidence of efficacy for the first two doses against omicron for this age group; the “effect” seen after the third dose was so uncertain that it is impossible to draw firm conclusions about how well the vaccine worked to prevent cases.

Still more puzzling is the fact that neither Pfizer nor Moderna—despite continued assurances that mRNA vaccines are uniquely flexible, allowing manufacturers to quickly tweak vaccines to match new variants—has released an updated version of their product: The pediatric vaccines now being administered target an outdated variant. In addition, the infant and toddler trials were mostly limited to children who had not been previously infected with COVID (estimates based on blood work showed less than 15% of children enrolled had previously been infected). With 75% of children nationally having already been infected by February 2022, the immune-naïve children enrolled in the trial were not representative of their age group at large.

Even in the already troubled context of the last two years, the CDC’s unqualified recommendation to vaccinate every young child against COVID may further contribute to the profound chasm of trust between U.S. citizens and their public health agencies. In January, a Hart poll found that only 44% of respondents said they believe what the CDC says; a March Gallup poll put it at 32%. Evidence of trust slippage can be seen even in highly vaccinated places like Portland, Oregon, where CDC recommendations were for the most part embraced unquestioningly during the pandemic. Despite the CDC’s recommendation that all children 5 and up should receive a booster, as of June 26 only 8.7% of children ages 5-11 in the Portland area are boosted, compared to 3.9% in the entire state of Oregon. (The CDC and American Academy of Pediatrics have not made nationwide data available.)

The general trust deficit is more troubling than skepticism toward this particular vaccine, because it could conceivably drive down uptake of other childhood vaccines that we know are more important to children’s health, such as those against measles, mumps, rubella, diphtheria, polio, and Haemophilus influenza type b (Hib). This is not an alarmist or trivial concern, as vaccinations are one of the most lifesaving medical interventions in human history, rivaled perhaps only by antibiotics. In 1800, 46% of American children did not make it to age 5, and the majority died from what are now vaccine-preventable diseases. The smallpox vaccine alone is estimated to have saved 150 million to 200 million lives. Rates of diseases such as tetanus, rubella, polio, Haemophilus influenza type b (Hib) have declined by 99% since widespread childhood vaccination became commonplace in the 20th century.

It is therefore worth our attention when, for example, a recent letter in the New England Journal of Medicine noted that flu shot uptake has decreased over the pandemic, which the authors suspect may be due to growing vaccine hesitancy in general. The CDC published a study in April showing that childhood vaccination rates fell by only 1% in 2021, a small proportion of the total when spread over 70 million children. But given that many of these vaccines require two or three doses for full coverage, this still translates to several million missing doses, and could threaten herd immunity for diseases such as measles, which require very high percentages of the population to be vaccinated. It is also difficult to separate out the factors behind this drop in coverage, because schools and local clinics—where many low-income children receive vaccines—were closed for much of the last two years. But it is reasonable to at least assume that low trust in the CDC, the agency responsible for making evidence-based recommendations about vaccines, is not helping.

Compare the CDC’s response to vaccine hesitancy during COVID to a similar challenge in the late 1990s and early 2000s: rotavirus. Only a year after Andrew Wakefield’s false claims in 1998 that the MMR vaccines caused autism—leading to one of the most disastrous setbacks for vaccination uptake in history—Wyeth’s RotaShield vaccine was pulled off the market due to evidence it caused a rare and serious intestinal malfunction (intussusception) in babies. The effect of the RotaShield withdrawal so hard on the heels of the Wakefield disaster is hard to isolate, but CDC officials acknowledged that the combined events led to “a particularly turbulent period” for U.S. vaccine programs. Referring to vaccine hesitancy that might result from the RotaShield adverse events, the CDC’s Dr. John Livengood remarked at the time that the CDC “shouldn’t be seen as withholding information right now.”

The original trial for RotaShield had enrolled 10,054 vaccine recipients and 4,633 placebo recipients. During a February 1998 meeting of the CDC’s Advisory Committee on Immunization Practices (the same body that recently met to discuss the pediatric COVID vaccines), an FDA panel member, Dr. Margaret Rennels, noted that more babies in the vaccine group experienced intestinal intussusception than in the placebo group by about 2.5-fold, with a rate of 1/2011 (0.05%) in the vaccine group compared with 1/4633 (0.02%) in the placebo. But because the absolute numbers were small, and the trial was also relatively small, intestinal intussusception did not achieve statistical significance. RotaShield was licensed by the FDA in 1998, widely rolled out, and championed by the CDC in the spring of 1999. Intussusception was not mentioned further, and the issue was buried in a 19-page document where it was listed as a side effect that did not occur significantly more often in vaccinated babies than in the control group.

By summer, however, officials at the CDC grew concerned about a growing number of intussusception reports from the Vaccine Adverse Event Reporting System (VAERS), and were anxious not to lose gains made during the Carter and Clinton administrations in raising general childhood vaccination rates. By the end of President Clinton’s first term, toddler immunization rates had achieved what was then an all-time high, thanks to Vaccines for Children, a program that expanded access to free and low-cost vaccination.

The CDC was also cognizant that Wakefield’s false claims were continuing to spur a growing movement of vaccine hesitancy. As a result, the CDC—then under the direction of Dr. Jeffrey Koplan—immediately launched a large-scale investigation into the RotaShield VAERS reports. The investigation concluded that one additional case of intussusception was attributable to the vaccine for every 5,000-10,000 infants vaccinated—lower than rates of myocarditis due to vaccine injury in COVID-vaccinated adolescent males age 12-17.

RotaShield was pulled off the market that October. To justify the decision to pull a vaccine that was 85% effective at preventing hospitalization from a viral infection that had killed hundreds of thousands of infants worldwide, CDC personnel wrote the following:

At a time when many parents express concerns about the safety of vaccines and vaccine adverse events are the focus of increasing attention by the public, media, and U.S. Congress, the wisdom of recommending a vaccine that causes a severe adverse reaction in an estimated 1 in 10,000 infants must be considered.

The next vaccine against rotavirus—RotaTeq, made by Merck and released in 2004—was only released after the Rotavirus Efficacy and Safety Trial (REST) trial, which was notable for its “[randomized] design, large sample size, detailed execution, continuous safety monitoring, and lengthy duration,” and was undertaken in direct response to the perceived failures of the RotaShield trial. The authors of a paper describing its execution wrote, “The design and conduct of this study may serve as a useful tool for planning other future clinical trials, especially those evaluating uncommon adverse events.” The REST trial was conducted in 11 countries at more than 500 study sites and enrolled 70,000 subjects (including over 35,000 infants from the United States), making it one of the largest vaccine clinical trials ever conducted pre-approval. Post-approval, Merck conducted an additional study enrolling more than 85,000 infants.

The obvious drawback of a trial like REST is that it took four years to complete (though today it could almost certainly be completed faster due to advances in recruitment methods). A multiyear trial was simply not an option during COVID, which is why the notably small and short COVID vaccine trials were allowed to serve as the basis for approval under the emergency use provision. But because COVID so rarely causes severe disease in children, and current COVID vaccines do not reliably prevent transmission, especially after a few months, it is difficult to understand how such small trials could be justified without meaningful endpoints for this age group.

Consider the case of rotavirus again. Prior to vaccination, rotavirus was a significant cause of morbidity and mortality in infants in the United States (and still is globally). Until 15 years ago, it was the leading cause of gastrointestinal hospitalization in babies in the United States and, prior to rotavirus vaccines, caused an estimated 50,000-70,000 hospitalizations per year in infants. Compare this figure with the number of children age 0-4 hospitalized with COVID: The CDC places the cumulative total during the entire pandemic at approximately 130 in 100,000, or about 26,000 children. The CDC estimates that during omicron, at least 14% of COVID hospitalizations for children ages 6 months to 4 years were incidental (meaning the need for hospitalization was due to something other than COVID itself), though this is likely an underestimate, as 63% of current COVID hospitalizations in the U.K. for all ages are “incidental.” Thus, at the time rotavirus vaccines were being trialed, there were 2-4 times more hospitalizations for rotavirus in this age group than there have been for COVID since the pandemic began. (The CDC estimates the death rate from COVID in 6-month- to 4-year-olds to be 86 per year, compared with 20-60 per year from rotavirus, but the COVID estimate does not separate out deaths primarily due to another cause, nor does it adjust for the reduction in severity associated with omicron for children in this age group.)

The rotavirus experience taught the CDC a hard-earned lesson: Speaking in absolutes about vaccine safety and efficacy regardless of trial standards can backfire. In nearly every dimension by which trial data are measured—proper endpoints, size, rigorous randomization, and other factors—the RotaShield trial was far more robust than the Pfizer and Moderna infant and toddler COVID vaccine trials. Furthermore, if the identification of safety signals is not quickly acknowledged, it becomes even harder to recover trust. More and more Americans are wondering, for example, why Canada and several European countries have advised against the Moderna vaccine for people under 30 due to myocarditis risks, while the U.S. government still won’t even acknowledge the higher risk of myocarditis.

Clinical trial data expert and Tablet contributor Dr. Vinay Prasad has pointed out many times that “expedited pathways do not always benefit people, but they always benefit companies.” This might help explain why no other country in the world has started vaccinating infants against COVID, and only a handful have vaccinated toddlers. (In addition to the United States, the only countries vaccinating 2- to 3-year-olds against COVID right now are Cuba, China, Argentina, Bahrain, Venezuela, Colombia, Hong Kong, and Chile, none of which are using mRNA vaccines.) It is perhaps especially damning that no other country collaborated with the United States on the mRNA COVID-19 vaccine trials for infants and toddlers, which could have quickly enabled enough trial participation to study effects of the vaccines against severe disease, as was done in the RotaTeq trial. Tellingly, the Danish minister of health recently claimed that it was a “mistake” to vaccinate children under 16 against COVID at all, saying, “we’ve gotten smarter and would not recommend the same today.”

In June, the CDC had the chance to help rebuild public trust: In the absence of trials and data that would have met the gold standard for scientific rigor, the CDC could have made a softer recommendation based on the data it does have. It could have been honest about the trials’ shortcomings and what these data do and do not show. It could have told the public that the data are preliminary, do not establish efficacy against severe disease or long COVID, and do not rule out the possibility of a rare adverse event. Perhaps it could have recommended COVID vaccines for high-risk children, and remained cautious about the benefits for healthy children who have already had COVID infections. The CDC and FDA together could have insisted that blanket approval and recommendations would only come after a properly conducted vaccination trial—one that would give pediatricians and public health officials the confidence to make the evidence-based recommendations parents are seeking.

In 1999, the CDC, working closely with the FDA, took such steps to shore up parents’ confidence in their recommendations. After the RotaShield withdrawal, the FDA requested that future trials of any rotavirus vaccine enroll at least 60,000 children. This level of accountability and collaboration between the two agencies responsible for vaccines in the United States resulted in the delivery of a widely trusted vaccine against a virus that posed a similar or greater danger to young children than COVID-19. This level of accountability was what the American public reasonably expected of its public health agencies two decades ago. It’s not too much to expect today.

Israel sees 70% spike in number of seriously ill COVID patients within a week

‘It’s an unpredictable and unstable situation,’ says immune system expert Prof. Cyrille Cohen, urging lawmakers to ‘actively encourage herd immunity among the vulnerable’

Authors:  Times of Israel June 2022

The number of coronavirus patients in serious condition in Israel reached 140 on Friday, marking a near 70% rise since last week, with health experts warning that the current situation was “unstable.”

While Israel has seen rising infection numbers for a few weeks, a rise in seriously ill patients marks a real concern as the country deals with the spread of the new variant BA.5, with experts warning that hospitals may need to reopen COVID wards. The number was up from 85 seriously ill patients on Friday last week.

Some 7,313 Israelis tested positive for the virus on Friday, the Health Ministry said. The reproduction number (R) stood at 1.31 as of Friday. The figure measures how many people each coronavirus carrier infects on average, with any number above 1 meaning the spread of COVID-19 is increasing. It first began to rise above 1 in mid-May, having stayed below that threshold for nearly two months.

The death toll stood at 10,882, including six fatalities over the past week.

“The data definitely indicates that the disease is active in the community,” immune system expert Prof. Cyrille Cohen of Bar Ilan University told the Ynet news site.

“The real indication is the number of patients in serious condition because we know much of the morbidity is not detected as people don’t go and get tested, and that should also be taken into account,” he said.

“The thing that determines the policy is not necessarily the number of confirmed patients but the condition of seriously ill patients. We need to understand whether they are experiencing the disease in a more severe way — and whether we will need to get ready to reopen COVID wards this summer,” he added.

Despite the warning, Cohen said it’s too early to know the severity of the variant that mutated from Omicron, known as BA.5, and whether or not it will develop into a new wave.

“We don’t know exactly what this wave will look like and whether we can call it a wave at all,” he said. “We are following the events in Portugal because variant BA.5 is the dominant one there and because its population is similar to Israel in size with many people vaccinated, even more so than in Israel.”

Cohen noted that morbidity and mortality rates rose in Portugal at the same time the BA5 variant started spreading.

“We need to realize that’s going to happen here as well,” he said, urging lawmakers to take action. “It’s an unpredictable and unstable situation regarding COVID. It will take months and even years before there is a significant decrease and we reach a more predictable scenario. But one must also be careful with making estimations,” he added.

Cohen said the effort should be concentrated on “actively encouraging herd immunity among the vulnerable and older population” by “calling people who haven’t received the vaccine and encouraging them to get it.”

He also advised wearing masks in crowded places like on buses and at shopping centers.

On Wednesday, coronavirus czar Prof. Salman Zarka said the new variant BA.5 is quickly gaining traction and is more resistant to vaccines than previous strains.

“The BA.5 strain currently accounts for about 50 percent of patients,” he said. “The strain caused relatively mild illness among young people, but we can see a rise in hospitalizations.”

He said BA.5 was replacing Omicron as the dominant variant, and that it will continue to gain ground.

Israel scrapped its indoor mask requirement in April as infection numbers dropped off sharply. Outdoor masks have not been required since April of last year.

Salman Zarka also said Israelis may soon be able to be officially recognized as COVID-19 patients based solely on a home test, under certain conditions, while at the same time the Health Ministry was working to expand test facilities.

COVID-19 was deadly to working-class Americans in 2020, researcher says

Authors: Sam Ogozalek June 3, 2022 Tampa Bay Times

Working-class Americans died of COVID-19 at five times the rate of those in higher socioeconomic positions during the first year of the pandemic, according to a study.

The staggering disparity was revealed in a study of roughly 69,000 U.S. coronavirus victims ages 25 to 64 who died in 2020. It was conducted by a group of researchers including University of South Florida epidemiologist Jason Salemi.

The study’s authors found that 68% of the deaths they studied were among people considered to be in a low socioeconomic position, defined as workers whose education stopped at high school. Only about 12% of deaths occurred among people in high socioeconomic positions, defined as those with at least a bachelor’s degree.

The researchers said the majority of working-class adults in the U.S. were employed in blue collar, service or retail jobs and couldn’t work remotely in the first year of the virus, before vaccines became widely available in 2021.

“Our results support the hypothesis that hazardous conditions of work were a primary driver of joint socioeconomic, gender, and racial/ethnic disparities in COVID-19 mortality,” the researchers wrote.

Working-class employees faced “elevated infection risks,” according to a USF summary of the study, compared to higher-paid workers who were “more likely to have fewer exposure risks, options to work remotely, paid sick leave and better access to quality health care.”

The report comes as Florida and several parts of the nation grapple with high levels of COVID-19 transmission driven by contagious omicron subvariants. The Tampa Bay region is considered to be at “high” risk of infection, according to the Centers for Disease Control and Prevention, which recommends wearing masks in indoor public spaces.

Though the research is based on deaths that occurred in 2020 — before vaccines reduced COVID-19 mortality across the board — Salemi said he believes working-class people are still at higher risk of sickness and death.

He said the study’s findings offer a warning about how the pathogen can deeply impact vulnerable communities.

Talk of “getting back to normal,” he said, means “very different things” to different people in the U.S.

“Some people are still going to be in the line of fire,” Salemi said.

The question facing the country, he said, is what can be done to help working-class employees stay safe?

His solutions: Improve ventilation in buildings to reduce indoor transmission; wear high-quality masks indoors to reduce infections; and institute paid sick leave so the infected can stay home instead of spreading the virus.

The study was published in April in the peer-reviewed International Journal of Environmental Research and Public Health. The research team collected provisional COVID-19 death data from the U.S. National Center for Health Statistics. Deaths were included if COVID-19 was listed as an underlying or contributing cause of death. The center uses educational levels to measure socioeconomic status.

The study found that the age-adjusted COVID-19 death rate for working-class adults was 72.2 deaths per 100,000. For those in high socioeconomic positions, the rate was 14.6 deaths per 100,000.

The researchers discovered other disparities:

  • The age-adjusted COVID-19 death rate of working-class Hispanic men was more than 27 times higher than the death rate for white women in higher socioeconomic jobs.
  • Working-class Black men had a death rate that was nearly 20 times higher than the death rate for white women who graduated from a four-year college.
  • The death rate for working-class Black women was about 13 times higher than the rate for white women with at least a bachelor’s degree.
  • Working-class white men had a death rate roughly four times higher than the rate for white men in high socioeconomic positions.

Another Hidden Covid Risk: Lingering Kidney Problems

September 1, 2021in News

Since the beginning of the pandemic, doctors have found that people who become very ill with Covid-19 often experience kidney problems, not just the lung impairments that are the hallmark of the illness.

Now, a large study suggests that kidney issues can last for months after patients recover from the initial infection, and may lead to a serious lifelong reduction of kidney function in some patients.

The study, published Wednesday in the Journal of the American Society of Nephrology, found that the sicker Covid patients were initially, the more likely they were to experience lingering kidney damage.

But even people with less severe initial infections could be vulnerable.

“You see really, across the board, a higher risk of a bunch of important kidney-associated events,” said Dr. F. Perry Wilson, a nephrologist and associate professor of medicine at Yale, who was not involved in the study. “And what was particularly striking to me was that these persisted.”

Kidneys play a vital role in the body, clearing toxins and excess fluid from the blood, helping maintain a healthy blood pressure, and keeping a balance of electrolytes and other important substances. When the kidneys are not working properly or efficiently, fluids build up, leading to swelling, high blood pressure, weakened bones and other problems.

The heart, lungs, central nervous system and immune system can become impaired. In end-stage kidney disease, dialysis or an organ transplant may become necessary. The condition can be fatal.

The new study, based on records of patients in the Department of Veterans Affairs health system, analyzed data from 89,216 people who tested positive for the coronavirus between March 1, 2020, and March 15, 2021, as well as data from 1,637,467 people who were not Covid patients.

Between one and six months after becoming infected, Covid survivors were about 35 percent more likely than non-Covid patients to have kidney damage or substantial declines in kidney function, said Dr. Ziyad Al-Aly, chief of the research and development service at the V.A. St. Louis Health Care System and senior author of the study.

“People who have survived the first 30 days of Covid are at risk of developing kidney disease,” Dr. Al-Aly, a nephrologist, said.

Because many people with reduced kidney function do not experience pain or other symptoms, “what’s really important is that people realize that the risk is there and that physicians caring for post-Covid patients really pay attention to kidney function and disease,” he said.

The two sets of patients in the study differed, in that members of one group had all been infected with Covid and members of the other group may have had a variety of other health conditions. Experts cautioned that there were limitations to the comparisons.

The researchers tried to minimize the differences with detailed analyses that adjusted for a long list of demographic characteristics, pre-existing health conditions, medication usage and whether people were in nursing homes.

Another limitation is that patients in the V.A. study were largely male and white, with a median age of 68, so it is unclear how generalizable the results are.

One strength of the research, experts said, is that it involves over 1.7 million patients with detailed electronic medical records, making it the largest study so far on Covid-related kidney problems.

While the results most likely would not apply to all Covid patients, they show that for those in the study, “there’s a pretty notable impact on kidney health in survivors of Covid-19 over the long term, particularly those who were very sick during their acute illness,” said Dr. C. John Sperati, a nephrologist and associate professor of medicine at Johns Hopkins, who was not involved in the study.

Other researchers have found similar patterns, “so this is not the only study suggesting that these events are transpiring after Covid-19 infection,” he added.

He and other experts said that if even a small percentage of the millions of Covid survivors in the United States developed lasting kidney problems, the impact on health care would be great.

To assess kidney function, the research team evaluated levels of creatinine, a waste product that kidneys are supposed to clear from the body, as well as a measure of how well the kidneys filter the blood called the estimated glomerular filtration rate.

Healthy adults gradually lose kidney function over time, about 1 percent or less a year, starting in their 30s or 40s, Dr. Wilson said. Serious illnesses and infections can cause more profound or permanent loss of function that may lead to chronic kidney disease or end-stage kidney disease.

The new study found that 4,757 Covid survivors had lost at least 30 percent of kidney function in the year after their infection, Dr. Al-Aly said.

That is equivalent to roughly “30 years of kidney function decline,” Dr. Wilson said.

Covid patients were 25 percent more likely to reach that level of decline than people who had not had the illness, the study found.

Smaller numbers of Covid survivors had steeper declines. But Covid patients were 44 percent more likely than non-Covid patients to lose at least 40 percent of kidney function and 62 percent more likely to lose at least 50 percent.

End-stage kidney disease, which occurs when at least 85 percent of kidney function is lost, was detected in 220 Covid patients, Dr. Al-Aly said. Covid survivors were nearly three times as likely to receive the diagnosis as patients without Covid, the study found.

Dr. Al-Aly and his colleagues also looked at a type of sudden renal failure called acute kidney injury, which other studies have found in up to half of hospitalized Covid patients. The condition can heal without causing long-term loss of kidney function.

But the V.A. study found that months after their infection, 2,812 Covid survivors suffered acute kidney injury, nearly twice the rate in non-Covid patients, Dr. Al-Aly said.

Dr. Wilson said the new data supported results of a study of 1,612 patients that he and colleagues conducted that found that Covid patients with acute kidney injury had significantly worse kidney function in the months after leaving the hospital than people with acute kidney injuries from other medical conditions.

In the new study, researchers did not directly compare Covid survivors with people infected with other viruses, like the flu, making it hard to know “are you really any sicker than if you just had another bad infection,” Dr. Sperati said.

In a previous study by Dr. Al-Aly’s team, however, which looked at many post-Covid health issues, including kidney problems, people hospitalized with Covid-19 were at significantly greater risk of developing long-term health problems in virtually every medical category, including cardiovascular, metabolic and gastrointestinal conditions, than were people hospitalized with the flu.

Every type of kidney impairment measured in the new study was much more common in Covid patients who were sicker initially — those in intensive care or who experienced acute kidney injury in the hospital.

People who were less ill during their Covid hospitalization were less likely to have lingering kidney problems, but still considerably more likely than non-Covid patients.

“People who are at highest risk are the people who really had it bad to start with,” Dr. Al-Aly said. “But really, no one is spared the risk.”

The study also found that even Covid patients who never needed hospitalization had slightly higher risk of kidney trouble than the general V.A. patient population. But the risk seemed so small, Dr. Sperati said, that “I don’t know that I would hang my hat on” those results.

Dr. Wilson noted that some Covid patients who did not need hospitalization were nonetheless quite ill, needing to stay in bed for days. He said it’s possible that those were the ones who developed long-term kidney dysfunction, rather than people at the mildest end of the Covid spectrum.

Doctors are unsure why Covid can cause kidney damage. Kidneys might be especially sensitive to surges of inflammation or immune system activation, or blood-clotting problems often seen in Covid patients may disturb kidney function, experts said.

Dr. Sperati said Covid patients in the hospital seemed to have greater need for dialysis, and more protein and blood in their urine, than patients hospitalized with other severe illnesses.

“Covid is probably a little more of a kidney-toxic virus,” Dr. Wilson said. “I do think that the Covid syndrome has some long-term adverse effects on the kidney.”

The post Another Hidden Covid Risk: Lingering Kidney Problems appeared first on New York Times.

Neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives

Authors:

  1. Jonathan P Rogers1,2, Cameron J Watson3, et.al

Abstract

There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations.

We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence.

13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n=15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n=221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n=21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n=13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n=66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n=43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n=64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n=42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n=49 326, 19 studies). Heterogeneity for most clinical manifestations was high.

Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic’s early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

For More Information: https://jnnp.bmj.com/content/92/9/932

Age-Adjusted Associations Between Comorbidity and Outcomes of COVID-19: A Review of the Evidence From the Early Stages of the Pandemic

Authors: Kate E. Mason*Gillian MaudsleyPhilip McHaleAndy PenningtonJennifer Day and Ben Barr

Objectives: Early in the COVID-19 pandemic, people with underlying comorbidities were overrepresented in hospitalised cases of COVID-19, but the relationship between comorbidity and COVID-19 outcomes was complicated by potential confounding by age. This review therefore sought to characterise the international evidence base available in the early stages of the pandemic on the association between comorbidities and progression to severe disease, critical care, or death, after accounting for age, among hospitalised patients with COVID-19.

Methods: We conducted a rapid, comprehensive review of the literature (to 14 May 2020), to assess the international evidence on the age-adjusted association between comorbidities and severe COVID-19 progression or death, among hospitalised COVID-19 patients – the only population for whom studies were available at that time.

Results: After screening 1,100 studies, we identified 14 eligible for inclusion. Overall, evidence for obesity and cancer increasing risk of severe disease or death was most consistent. Most studies found that having at least one of obesity, diabetes mellitus, hypertension, heart disease, cancer, or chronic lung disease was significantly associated with worse outcomes following hospitalisation. Associations were more consistent for mortality than other outcomes. Increasing numbers of comorbidities and obesity both showed a dose-response relationship. Quality and reporting were suboptimal in these rapidly conducted studies, and there was a clear need for additional studies using population-based samples.

Conclusions: This review summarizes the most robust evidence on this topic that was available in the first few months of the pandemic. It was clear at this early stage that COVID-19 would go on to exacerbate existing health inequalities unless actions were taken to reduce pre-existing vulnerabilities and target control measures to protect groups with chronic health conditions.

For More Information: https://www.frontiersin.org/articles/10.3389/fpubh.2021.584182/full

The Age-Related Risk of Severe Outcomes Due to COVID-19 Infection: A Rapid Review, Meta-Analysis, and Meta-Regression

Authors: Karla Romero Starke 1Gabriela Petereit-Haack 2Melanie Schubert 1Daniel Kämpf 1Alexandra Schliebner 1Janice Hegewald 1Andreas Seidler 1

Abstract

Increased age appears to be a strong risk factor for COVID-19 severe outcomes. However, studies do not sufficiently consider the age-dependency of other important factors influencing the course of disease. The aim of this review was to quantify the isolated effect of age on severe COVID-19 outcomes. We searched Pubmed to find relevant studies published in 2020. Two independent reviewers evaluated them using predefined inclusion and exclusion criteria. We extracted the results and assessed seven domains of bias for each study. After adjusting for important age-related risk factors, the isolated effect of age was estimated using meta-regression. Twelve studies met our inclusion criteria: four studies for COVID-19 disease severity, seven for mortality, and one for admission to ICU. The crude effect of age (5.2% and 13.4% higher risk of disease severity and death per age year, respectively) substantially decreased when adjusting for important age-dependent risk factors (diabetes, hypertension, coronary heart disease/cerebrovascular disease, compromised immunity, previous respiratory disease, renal disease). Adjusting for all six comorbidities indicates a 2.7% risk increase for disease severity (two studies), and no additional risk of death per year of age (five studies). The indication of a rather weak influence of age on COVID-19 disease severity after adjustment for important age-dependent risk factors should be taken in consideration when implementing age-related preventative measures (e.g., age-dependent work restrictions).

For More Information: https://pubmed.ncbi.nlm.nih.gov/32824596/