Delusional Thinking That COVID-19 Is Over

A couple recent articles indicate a lot of reasons for concern.

First of all, it is important to recognize that even among persons less than 55 years of age, COVID-19 was the leading cause of death in 2021. Inside Medicine: Open Access: The million US Covid dead are younger than you think.

Sadly, more than 300,000 deaths in the U.S. could have been averted (NPR: This is how many lives could have been saved with COVID vaccinations in each state)

There has been a culture shift to learn to live with the virus. This is evident almost everywhere from packed restaurants, crowded venues, etc. However, there is currently high transmission and variants that are evading vaccine protection as detailed by Eric Topol, Open Access: The Covid Capitulation

Key points:

  • The United States is now in the midst of a new wave related to Omicron variants BA.2 and BA.2.12.1 with over 90,000 confirmed new cases a day and a 20% increase in hospitalizations in the past 2 weeks…The real number of cases is likely at least 500,000 per day, far greater than any of the US prior waves except Omicron.
  • “Infections…beget more cases, …Long Covid, … sickness, hospitalizations and deaths. They are also the underpinning of new variants.”
  • CDC currently is vastly underestimating the number of cases leading many towards false confidence, “feeding the myth that the pandemic is over.”
  • “As of last week, 43% of new cases were attributable to BA.2.12.1 …. BA.2.12.1 is out-competing BA.2 with its 25% higher transmission rate, which foretells its further rise to dominance across the US in the days and weeks ahead.”
  • “This family of Omicron variants with functional impact indicates more rapid evolution of the virus than what we have seen previously.”
  • There has been a “reduction in vaccine effectiveness that we are now encountering…[Protection from severe disease] has declined to approximately 80%, particularly taking account the more rapid waning than previously seen.”
  • “It’s overly optimistic to think we’ll be done when Omicron variants run their course. Not only are they providing further seeding grounds for more variants of concern, but that path is further facilitated by tens of millions of immunocompromised people around the world, multiple and massive animal reservoirs, and increased frequency of recombinants.”
  • “Vaccinated individuals accounted for … 42 per cent [of the deaths] during the Omicron wave. This is attributable to waning of protection, lack of boosters, and the diminished protection against Omicron (BA.1).”
  • What needs to be done: More boosters/vaccines (“we rank 60th in the world’s countries for boosters”) along with more medicines, and nasal vaccines which could induce mucosal immunity

My take: Unfortunately, these articles indicate that we have a long way to go. High quality masks are going to be needed at health care settings for a while. For those trying to avoid COVID-19, it will remain important to avoid large indoor gatherings. For public policy/economic policy, we need to continue to fund COVID-19 resources.

Related blog posts:

Shifting of Infectious Diseases Due to Climate Change

CDC (January 2022): Open Access PDF: Our Risk of Infectious Diseases Is Increasing Because of Climate Change

“Between 2004 and 2018, the number of reported illnesses from mosquito, tick, and flea bites more than doubled, with more than 760,000 cases reported in the United States. Nine new germs spread by mosquitoes and ticks were discovered or introduced into the United States during this period. The geographic ranges where ticks spread Lyme disease, anaplasmosis, ehrlichiosis, and spotted fever rickettsiosis have expanded, and experts predict that tickborne diseases will continue to increase.”

EPA: Climate Change Indicators: Lyme Disease This EPA website has links to many other climate change indicators.

The lack of dots in Massachusetts in 2018 is due to a difference in
reporting standards, not an absence of Lyme disease

Related blog posts:

Understanding Rapid COVID-19 Testing Compared to PCR Testing

VT Chu et al. JAMA Intern MedPublished online April 29, 2022. doi:10.1001/jamainternmed.2022.1827. Open Access: Comparison of Home Antigen Testing With RT-PCR and Viral Culture During the Course of SARS-CoV-2 Infection

Background: This was a prospective cohort study of 225 adults and children comparing reverse transcription–polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 infection with antigen testing (QuickVue At-Home OTC COVID-19 Test) and viral culture (January to May 2021)

Key findings:

  • Rapid testing (antigen) sensitivity was 64% and viral culture sensitivity was 84% when compared with same-day RT-PCR and viral culture
  • Rapid testing (antigen) sensitivity peaked 4 days after illness onset (77%); a second test 1 to 2 days later showed improved sensitivity (81%-85%)

My take: This study shows that a single rapid test is NOT adequate to exclude SARS-CoV-2 infection, especially if they are symptomatic (need to recheck 1-2 days later if negative rapid test). The reliability/accuracy/sensitivity is likely to vary greatly between different rapid tests and may change significantly with different viral variants.

“Crossing Lines” and Why Firearm Deaths are The Leading Cause of Death in Children

LK Lee et al. N Engl J Med 2022; 386:1485-1487. Open Access: Crossing Lines — A Change in the Leading Cause of Death among U.S. Children

This short commentary explains how the childhood deaths due to motor vehicle accidents have improved. “The crossing of these trend lines demonstrates how a concerted approach to injury prevention can reduce injuries and deaths — and, conversely, how a public health problem can be exacerbated in the absence of such attention.”

Omicron More Severe for Unvaccinated Children

NY Times: Omicron Was More Severe for Unvaccinated Children in 5-to-11 Age Group, Study Shows

  • “The C.D.C. study covered the period from mid-December to late February, during which about 400 children were hospitalized with Covid at the select hospitals participating in the study.”
  • “Among the children who tested positive for the virus before or during their hospitalization, three-quarters of them were admitted primarily for Covid, rather than other illnesses, the C.D.C. said.”

CDC MMWR (4/19/22): Hospitalizations of Children Aged 5–11 Years with Laboratory-Confirmed COVID-19 — COVID-NET, 14 States, March 2020–February 2022

Related blog post: COVID-19 Hospitalization Data from CDC on UnVax, Vax, and Vax + Boosted

Firearms: #1 Cause of Pediatric Deaths & Households with Guns =More Deaths

AL Andrews et al. Pediatrics (2022) 149 (3): e2021052739. Pediatric Firearm Injury Mortality Epidemiology

Key points:

  • In 2019, firearm injuries surpassed motor vehicle collisions to become the leading cause of death for youth aged 0 to 19 years in the United States.
  • Approximately 60% of firearm-related deaths are homicides, 35% are suicides, and 4% are due to unintentional injuries
  • In 2015, the U.S. accounted for over 90% of all firearm deaths among children ages 0-14 years in high income countries.

DS Studdert et al. Annals Intern Med 2022; https://doi.org/10.7326/M21-3762. Open Access: Homicide Deaths Among Adult Cohabitants of Handgun Owners in California, 2004 to 2016

This retrospective cohort study followed 17.6 million adult residents of California for up to 12 years.

Key findings:

  • Overall rates of homicide were more than twice as high among cohabitants of handgun owners than among cohabitants of nonowners (adjusted hazard ratio, 2.33).
  • These elevated rates were driven largely by higher rates of homicide by firearm (adjusted hazard ratio, 2.83).
  • Among homicides occurring at home, cohabitants of gun owners had sevenfold higher rates of being fatally shot by a spouse or intimate partner (adjusted hazard ratio, 7.16); 84% of these victims were female.

My take: Gun ownership increases the likelihood of firearm-related deaths.

AAP Website: Gun Violence Prevention Advocacy Toolkit

Related blog posts:

Latest Research: Modest Drinking Does NOT Confer Cardiac Benefits

KR Biddinger et al. JAMA Netw Open. 2022;5(3):e223849. doi:10.1001/jamanetworkopen.2022.3849. Open Access: Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease

NY Times Analysis of This Study: Does Moderate Drinking Protect Your Heart? A Genetic Study Offers a New Answer.

An excerpt:

“There is no level of drinking that does not confer heart disease risk. The risk is small if people have an average of seven drinks a week when compared with none. But it increases quickly as the level of alcohol consumption rises”

“The study, which may help resolve medical disputes over the effects of alcohol on the heart, involved sophisticated analyses of the genes and medical data of nearly 400,000 people who participate in the U.K. Biobank”

“Some researchers have reported that drinking modestly protects the heart because moderate drinkers as a group have less heart disease than those who drink heavily or those who abstain. Dr. Aragam and his colleagues also saw that effect. But the reason, they report, is not that alcohol protects the heart. It is that light to moderate drinkers — those who consume up to 14 drinks a week — tend to have other characteristics that decrease their risk, like smoking less, exercising more and weighing less than those who drink more heavily and those who do not drink.

“Many earlier studies of alcohol consumption and heart health were observational, meaning the subjects were followed over time to see if the amount of drinking was linked to heart health. Such studies are only able to find correlation but not causation, researchers say. But the Biobank study’s use of Mendelian randomization is more suggestive of causality, and so its results might carry more weight.”

My take: Light alcohol consumption is NOT beneficial for your heart.

Distant Kite Boarder, Isle of Palms, SC

Shiny New Object: Gene Therapy in Gastroenterology

It’s hard not to be fascinated by the emerging treatments in gene therapy. A great summary of this topic as it relates to gastroenterology:

RL Kruse et al. Gastroenterol 2022; 162: 1019-1023. Open Access: How to Embrace Gene Therapy in Gastroenterology

Key points:

  • Researcher’s have utilized viruses to introduce exogenous DNA in efforts to correct defects in genetic diseases. Adeno-associated virus (AAV) vectors are the most common vectors used. In addition, AAV have a natural tropism to the liver following intravenous infusion
  • “Highlighting programs with the most advanced efficacy, hemophilia gene therapies in the liver have advanced into phase 2/3 and have shown promising efficacy based on factor VIII or IX levels achieved and reduction in bleeding events, with the main questions being long-term expression and safety of the approach”

Limitations:

  • “Integrated AAV have been associated with an increased incidence of hepatocellular carcinoma in mice”
  • Antibodies to AAV may be present or develop after infusion…” this factor has precluded any redosing in trials because antibodies would neutralize all incoming vectors”
  • In hemophilia trials, in the liver there has been a slow decrease in the levels of expression over time 6 which indicates that years into the future patients will need to be redosed to maintain efficacy
  • “Practically, AAV can only achieve delivery in a fraction of cells within an organ”

Newer Approaches for Gene Delivery:

  • mRNA delivery: mRNA is being explored as a tool for gene therapy, because mRNA only requires cytoplasmic delivery for expression.
  • “mRNA can also express gene-editing enzymes like Cas9….However, gene editing presents inherent risks of off-targeting cutting or base editing that would occur in millions of hepatocytes, potentially leading to cancer”
  • “Nonviral approaches of DNA delivery could drop the costs of vector production at least 100-fold versus AAV…delivery of DNA through LNPs [lipid nanoparticles] has largely yielded inefficient gene expression”
  • “Hydrodynamic injection is a process where fluid pressure is used to deliver naked DNA directly into cell…injection into the biliary system through endoscopic retrograde cholangiopancreatography”

The authors note that gene delivery could be important in modifying more common disorders including nonalcoholic steatohepatitis, diabetes and autoimmune diseases.

My take: While this field of study is quite exciting, to me it is definitely a shiny object, like all of precision medicine, in that it may distract researchers and physicians away from more pressing common problems.

Related blog posts:

For Policy Wonks: Bayh-Dole Act and Reducing Pharmaceutical Costs

AB Engelberg et al. NEJM 2022; 386: 1104-1106 (Commentary). A New Way to Contain Unaffordable Medication Costs — Exercising the Government’s Existing Rights

This commentary notes that the National Institutes of Health (NIH) spends more than $40 billion each year to fund biomedical research. “We believe that medicines discovered at public expense should be affordable.”

A Few Excerpts:

  • “Existing laws provide two paths for achieving this result. First, the Bayh–Dole Act of 1980 gives the government a royalty-free license to use patented inventions that were discovered using federal funding. The government has never exercised its Bayh–Dole license”
  • “Second, 28 U.S. Code §1498, which dates to 1910, gives the government immunity from being sued for patent infringement in federal courts, while giving patent owners the right to receive reasonable compensation when the government makes or uses a patent-protected product”
  • Case in point: “Recently, the government signed a contract with Merck to purchase molnupiravir (Lagevrio), an oral antiviral drug that reduces the severity of Covid-19. The contract price of $712 per treatment is estimated to be more than 35 times the cost of producing the drug at a reasonable profit. Molnupiravir was discovered at Emory University using government funding, and Emory’s patent applications acknowledge the government’s Bayh–Dole license.5 Molnupiravir payments for Medicare, Medicaid, and VHA patients could cost the government billions in 2022. This amount could be reduced by more than 90% if the government exercised its license and allowed a generic manufacturer to supply the drug for patients in government-supported programs.”

My take: U.S. taxpayers should get a return on their investment when new medications are developed with government funding rather than paying more for these medications than any other country.

Related blog posts:

Ravenel Bridge, Charleston SC (blue skies -no filter)