#17,293
Very early in the COVID pandemic we began to see signs of post-infection sequelae which could - in some percentage of cases - be both serious, and permanent. Making matters worse, these risks now appear to increase with every infection (see Nature: Acute and Postacute Sequelae Associated with SARS-CoV-2 Reinfection).
While many report mild or moderate symptoms, many of which resolve over time, others are not so lucky.
We've seen dozens of reports of serious, sometimes even fatal, post-infection issues, including:
Neurology: Incidence of Epilepsy and Seizures Over the First 6 Months After a COVID-19 Diagnosis: A Retrospective Cohort Study
The Lancet: Neurological and Psychiatric Risk Trajectories After SARS-CoV-2 Infection
MMWR: Post–COVID-19 Symptoms and Conditions Among Children and Adolescents
Nature: Long-term Cardiovascular Outcomes of COVID-19
Nature: Long-term Neurologic Outcomes of COVID-19
One of the reoccurring themes has been an increased risk of Diabetes (see Diabetologia: Incidence of Newly Diagnosed Diabetes After Covid-19 and from the CDC Risk for Newly Diagnosed Diabetes >30 Days After SARS-CoV-2 Infection Among Persons Aged <18 Years).
Since diabetes is often a precursor for other, potentially serious cardiovascular diseases, any increase could have a profound impact on the public's overall health in the years to come.
Yesterday the JAMA Network published a research letter from scientists at the Smidt Heart Institute at Cedars-Sinai showing a 58% increased risk of developing diabetes after a recent COVID infection. They also present evidence that a prior COVID vaccination may help reduce those risks.
First, the abstract from the study, followed by some excerpts from a press release. I'll return with a postscript after the break.
Research Letter Infectious Diseases
February 14, 2023
Association of COVID-19 Vaccination With Risk for Incident Diabetes After COVID-19 InfectionAlan C. Kwan, MD, MSc1; Joseph E. Ebinger, MD1; Patrick Botting, MSPH1; et alJesse Navarrette, MPA1; Brian Claggett, PhD2; Susan Cheng, MD, MPH, MMSc1
Author Affiliations Article Information
JAMA Netw Open. 2023;6(2):e2255965. doi:10.1001/jamanetworkopen.2022.55965Introduction
In early phases of the COVID-19 pandemic, persons who recovered from infection had increased risks for new-onset cardiometabolic diseases, including diabetes, hypertension, and hyperlipidemia.1-3 In the current pandemic phase, which is dominated by less virulent Omicron variants,4 it remains unclear whether risks of cardiometabolic disease after COVID-19 infection persist or have become attenuated and whether vaccination status is associated with these risks.
MethodsThis large cohort study of adult patients with 1 or more COVID-19 infections treated within the Cedars-Sinai Health System in Los Angeles, California from March 2020 to June 2022 used International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes (eTable in Supplement 1) to identify cardiometabolic diagnoses (hypertension, hyperlipidemia, and diabetes) newly reported before or after a patient’s first COVID-19 infection.5 A self-controlled exposure-crossover design6 was used to estimate odds of a new cardiometabolic diagnosis occurring 90 days after vs 90 days before COVID-19 infection.
To account for temporal confounders arising from disruptions in health care use during the pandemic, we compared the odds of a new cardiometabolic diagnosis with those of a new benchmark diagnosis (ie, urinary tract infection and gastroesophageal reflux), representing a marker of health care engagement unrelated to COVID-19. In multivariable logistic regression models, we estimated the odds ratio (OR) for a new cardiometabolic vs new benchmark diagnosis occurring 90 days after vs before infection while adjusting for age, sex, timing of infection (before vs after emergence of Omicron variant), and COVID-19 vaccination status (eMethods in Supplement 1). The study was approved by the Cedars Sinai Medical Center Institutional Review Board, which waived the informed consent requirement given the study’s retrospective nature. We followed the STROBE reporting guideline.
Data were analyzed using R, version 4.2.1 (R Foundation for Statistical Computing). The threshold for statistical significance was a 2-tailed P <.05.
ResultsThe cohort of 23 709 patients (mean [SD] age, 47.4 [19.3] years) included 12 706 females (54%) and 10 981 males (46%) (22 patients of unknown sex) with 1 or more COVID infection. Rates of new-onset diabetes, hypertension, hyperlipidemia, and benchmark diagnoses occurring in the 90 days after COVID-19 infection were higher than those before infection (Figure). The highest odds postinfection were for diabetes (2.35; 95% CI, 1.94-2.89; P < .001), followed by hypertension (1.54; 95% CI, 1.35-1.76; P < .001), benchmark diagnoses (1.42; 95% CI, 1.25-1.61; P < .001), and hyperlipidemia (1.22; 95% CI, 1.03-1.47; P = .03). In adjusted multivariable models, risk of new-onset diabetes (vs benchmark) diagnosis occurring after vs before COVID-19 infection was significantly elevated (OR, 1.58; 95% CI, 1.24-2.02; P < .001); however, risks of hypertension and hyperlipidemia vs benchmark diagnoses were not (Table).
Although the diabetes risk after infection was higher among unvaccinated (OR, 1.78; 95% CI, 1.35-2.37; P < .001) than vaccinated (OR, 1.07; 95% CI, 0.64-1.77; P = .80) patients, the interaction term between vaccination status and diabetes diagnosis was not statistically significant (OR, 0.59; 95% CI, 0.34-1.06; P = .08). There was no evidence of interaction by age, sex, or preexisting cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any model (Table).
DiscussionIn this cohort study, COVID-19 infection was associated with increased risk of diabetes, consistent findings of a meta-analysis.1 Our results suggest that this risk persisted as the Omicron variant became predominant, and the association remained even after accounting for temporal confounders. Diabetes risk after COVID-19 infection was higher in unvaccinated than vaccinated patients, suggesting a benefit of vaccination. Mechanisms contributing to postinfection diabetes risk remain unclear, although persistent inflammation contributing to insulin resistance is a proposed pathway. Study limitations include reliance on diagnostic coding, unaccounted confounders (infection severity indices), and insufficient sample size and statistical power for testing multiple interactions. Additional studies are needed to understand cardiometabolic sequelae of COVID-19 and whether COVID-19 vaccination attenuates risk of cardiometabolic disease.
Los Angeles, Feb 14, 2023
Verified: COVID-19 Infection Increases Diabetes Risk
Study Verifies COVID-19 Infection Increases Diabetes Risk | Cedars-Sinai
Results Also Suggest the Diabetes Risk Persists Across COVID-19 Variants, and That Upfront Vaccination May Help to Reduce Risk of Post-Infection Diabetes
Investigators in the Smidt Heart Institute at Cedars-Sinai have confirmed that people who have had COVID-19 have an increased risk for new-onset diabetes—the most significant contributor to cardiovascular disease.
“Our results validate early findings revealing a risk of developing Type 2 diabetes after a COVID-19 infection and indicate that this risk has, unfortunately, persisted through the Omicron era,” said Alan Kwan, MD, first and corresponding author of the study and a cardiovascular physician in the Smidt Heart Institute at Cedars-Sinai.
The trend, Kwan says, is concerning because most people in the United States will eventually experience a COVID-19 infection. “This research study helps us understand—and better prepare for—the post-COVID-19 era of cardiovascular risk,” Kwan said.
The findings, published today in the journal JAMA Network Open, also suggest that the risk of Type 2 diabetes appears lower in individuals who were already vaccinated against COVID-19 by the time they were infected.
To determine the rising rates of diabetes, investigators evaluated medical records from 23,709 adult patients who had at least one documented COVID-19 infection and were treated within the Cedars-Sinai Health System in Los Angeles from 2020-2022. The average patient was 47 years old, and 54% of subjects were female.
Within the study time frame:
“These results suggest that COVID-19 vaccination prior to infection may provide a protective effect against diabetes risk,” said Kwan. “Although further studies are needed to validate this hypothesis, we remain steadfast in our belief that COVID-19 vaccination remains an important tool in protecting against COVID-19 and the still-uncertain risks that people may experience during the post-infection period.”
- The combined risk of Type 2 diabetes after COVID-19 exposure—accounting for both vaccinated and unvaccinated patients—was 2.1%, with 70% occurring after COVID-19 infection versus 30% happening prior to COVID-19 exposure.
- The risk of Type 2 diabetes after COVID-19 exposure for unvaccinated patients was 2.7%, with 74% occurring after COVID-19 infection versus 26% happening prior to COVID-19 exposure.
- The risk of Type 2 diabetes after COVID-19 exposure for vaccinated patients was 1.0%, with 51% occurring after COVID-19 infection versus 49% happening prior to COVID-19 exposure.
This isn't the first study to suggest that COVID infection could lead to an increased incidence of cardiovascular disease.
One of the earliest warnings came in the summer of 2020, when JAMA published an original investigation which found a substantial increase in out-of-hospital cardiac arrests in New York City during the peak of their first COVID-19 wave, finding:
From March 1 to April 25, 2020, New York City, New York (NYC), reported 17 118 COVID-19–related deaths. On April 6, 2020, out-of-hospital cardiac arrests peaked at 305 cases, nearly a 10-fold increase from the prior year.
Also that summer, in JAMA: Two Studies Linking SARS-CoV-2 Infection To Cardiac Injury, we examined the results of 39 autopsies on COVID cases, that showed that even when pneumonia was the presumed cause of death - and even without overt histopathic evidence of acute myocarditis - the heart often shows a high viral load of SARS-COV-2.
An accompanying editorial (see Coronavirus Disease 2019 (COVID-19) and the Heart—Is Heart Failure the Next Chapter? by Clyde W. Yancy, MD, MSc1,2; Gregg C. Fonarow, MD3,4) raised serious concerns over the long-term impact of COVID on public health.
But the evidence continues to suggest that normalizing COVID infection (and reinfections) will come at a cost, one that will be measured both in lives lost and the quality of life.
But just how big of a cost be may not be truly known for another 5 or 10 years.
