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This year's headlines on COVID-19 featured new research on COVID-related mortality, post-acute sequelae of infection, vaccine safety, and potential therapeutics.

COVID Deaths Are Down, but...

After being in the top five leading causes of death in the U.S. since the start of the pandemic, COVID-19 dropped to tenth in 2023, according to provisional CDC data.

Notably, the mortality rate for COVID-19 deaths was 68.9% lower in 2023 than in 2022, CDC researchers reported. Although that change was dramatic, COVID still remains a leading cause of death, the study authors pointed out.

In a related JAMA Viewpoint, the authors noted that COVID-19 peaked in 2020 and 2021 as the third highest cause of mortality and fell to fourth in 2022 before dropping to tenth in 2023.

Meanwhile, an analysis of VA data found that although COVID-19 is becoming less deadly, hospitalized cases are still associated with a higher risk of death than influenza. Among over 11,000 patients hospitalized for either illness during the fall and winter of 2023-2024, 5.7% of patients with COVID-19 died within 30 days of admission versus 4.24% of patients with the flu.

After adjusting for variables, the risk of death in people hospitalized for COVID-19 was 35% higher (adjusted HR [aHR] 1.35, 95% CI 1.10-1.66), the authors detailed in a research letter in JAMA.

Wegovy for COVID?

In a subanalysis of the pivotal SELECT trial, weekly injections with the weight-loss formulation of semaglutide (Wegovy) not only significantly reduced all-cause deaths but also mortality related to COVID-19 (HR 0.66, 95% CI 0.44-0.96) among people with overweight and obesity and pre-existing cardiovascular disease.

It is unknown if effects of weight loss or another pathway might have played a role in the GLP-1 receptor agonist reducing deaths among this population with COVID-19. The authors of the study conjectured that the decreased risk could somehow be associated with weight loss, which was 5 kg greater in patients assigned to semaglutide compared to placebo by 1 year.

The initial results of the SELECT trial revealed that semaglutide reduced mortality from a composite of cardiovascular causes, leading to its FDA approval for reducing the risk of cardiovascular death, heart attack, and stroke in this population earlier this year.

Type 2 Diabetes Emerges in Teens Months After COVID

Adolescents 10 to 19 years old had a 55% higher risk for a new diagnosis of type 2 diabetes 1 month after a COVID diagnosis compared with peers diagnosed with a non-COVID respiratory virus (risk ratio [RR] 1.55, 95% CI 1.28-1.89), according to a study published in JAMA Network Open.

The risk of a new type 2 diabetes diagnosis remained elevated at 3 months (RR 1.48, 95% CI 1.24-1.76) and 6 months (RR 1.58, 95% CI 1.35-1.85) after COVID infection, researchers detailed.

"SARS-CoV-2 may have the ability to selectively infect human pancreatic β cells, and if this triggers apoptosis, the ability of the pancreas to secrete insulin may be impaired," the researchers wrote.

COVID Vaccine Safety in Young Kids

Data gathered from over 4 million children revealed that myocarditis or pericarditis occurred at higher rates than before the vaccines were introduced among 12- to 17-year-olds after receiving the original monovalent Pfizer-BioNTech BNT162b2 vaccine (Comirnaty), according to a study appearing in JAMA Network Open.

Researchers also detected a statistical signal for seizures after vaccination with the BNT162b2 vaccine among children ages 2 to 4 years and with the Moderna mRNA-1273 vaccine (Spikevax) among children ages 2 to 5 years. They found a total of 72 cases of seizures among these children, the majority of which were febrile seizures (71%). The median time between vaccination and seizure diagnosis was 2 days (range 1-5).

"The new statistical signal for seizure observed in our study should be interpreted with caution," the study authors wrote. "Because febrile seizures can be common in young children for a variety of reasons, the analysis may have identified febrile seizures unrelated to the vaccination."

The observational analysis did not establish a causal relationship between vaccines and health outcomes, they noted.

Severe COVID Linked to Mental Illness

Severe COVID-19 was associated with elevated risks for depression and serious mental illness months after infection, especially among unvaccinated people, a cohort study involving more than 18 million individuals in the U.K. found.

Compared to the period before a COVID infection or to individuals without an infection, those hospitalized for COVID had substantially higher risks for depression in the 4 weeks after admission, both in the pre-vaccine era (aHR 16.3, 95% CI 15.6-17.0) and among unvaccinated (aHR 15.6, 95% CI 13.9-17.4) and vaccinated (aHR 12.9, 95% CI 12.0-14.0) individuals in the vaccine era. In all three groups, the risk for depression remained elevated up to a year later.

Similarly, elevated risks for serious mental illness were observed among hospitalized patients in the 4 weeks after a COVID diagnosis, researchers reported in JAMA Psychiatry:

• Pre-vaccine era: aHR 9.71 (95% CI 8.80-10.7)
• Unvaccinated: aHR 8.75 (95% CI 7.01-10.9)
• Vaccinated: aHR 6.52 (95% CI 5.36-7.93)

Serious mental illness was a composite of schizophrenia, schizoaffective disorder, bipolar disorder, and psychotic depression.

Rates of most mental illnesses examined -- including anxiety, post-traumatic stress disorder, eating disorders, addiction, and self-harm -- were higher in the first 4 weeks after a COVID hospitalization. There was little association between COVID-19 that did not lead to hospitalization with subsequent mental illness.

Vaccination may attenuate adverse effects of COVID on mental illnesses, the authors posited. "Potential mechanisms include reduced systemic inflammation and psychological benefits of vaccination, such as reduced concern about COVID-19 and increased social engagement," they wrote.

Other COVID-Related News for 2024:

ACIP Backs Extra COVID Vaccine Dose for Seniors

Asthma Drug Did Not Reduce Symptom Duration in Mild to Moderate COVID

Kids' Neurodevelopment Appears Unharmed by Maternal COVID Infection

Excess Deaths Highest Among Younger Minorities During COVID Pandemic

Obesity May Raise Risk of Long COVID in Youth

CDC: Latest COVID Vax Cuts Hospitalization Risk in Immunocompromised People

Long COVID Risk Has Fallen, Largely Attributable to Vaccine Rollout

Paxlovid After a COVID Exposure Fails to Reduce Household Transmission

Don't Try ARBs for Severe COVID, Trial Indicates

Trust in Doctors Crashed During the COVID Pandemic -- And Remains Low

Did COVID Vax Mandates for Health Workers Increase Uptake?

番茄社区app writers Rachael Robertson, Nicole Lou, and Kristen Monaco also contributed to this report.

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