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Severe COVID-19 increases risk of future cardiovascular events

Study: COVID-19 severity and risk of subsequent cardiovascular events. Image Credit: Yurchanka Siarhei / Shutterstock.com

To date, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus responsible for the coronavirus disease 2019 (COVID-19), has infected over 603 million individuals and claimed more than 6.4 million lives worldwide.

About 30% of COVID-19 survivors continue to experience a wide range of persistent symptoms for several weeks since their initial diagnosis. This condition is commonly referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) or “long COVID.”

Study: COVID-19 severity and risk of subsequent cardiovascular events. Image Credit: Yurchanka Siarhei / Shutterstock.com

Study: COVID-19 severity and risk of subsequent cardiovascular events. Image Credit: Yurchanka Siarhei / Shutterstock.com

Background

Even though multisystem inflammatory syndrome is the most common PASC syndrome in adults and children, a wide range of other symptoms, including sleep difficulties, persistent fatigue, type 1 diabetes, and neurological disorders, have been reported. The incidence of these symptoms varies from one person to another based on their demographic and clinical characteristics.

Several studies have indicated the manifestation of multiple cardiovascular complications, such as arrhythmia, hypertension, acute myocardial infarction, thromboembolism, and cerebrovascular accidents, in individuals who have recovered from COVID-19. However, a limited number of studies have confirmed that severe COVID-19 leads to a high risk of cardiovascular diseases.

A recent Clinical Infectious Diseases journal study determines the relationship between COVID-19 severity and risk of subsequent cardiovascular events (CVEs) in a large cohort.

Study findings

A retrospective cohort study was performed using nationwide health insurance claims data of adults from the United States Health Verity Real-Time Insights and Evidence database. Increased COVID-19 severity was found to enhance the risk of developing subsequent CVEs among individuals without a cardiac history in previous years. 

As compared to COVID-19 patients who required outpatient care, those who required hospital admission were more likely to experience CVEs. Among COVID-19 hospitalized patients, those admitted to the intensive care unit (ICU) were almost 80% more likely to develop CVEs than non-ICU hospitalized patients.

In fact, non-ICU hospitalized patients exhibited only a 28% possibility of experiencing CVEs thirty days after initial COVID-19 symptoms. Additionally, as compared to COVID-19 outpatients, hospitalized patients were more likely to be admitted for a CVE after recovering from COVID-19.

In younger adults, the incidence of cardiovascular sequelae was lower as compared to older adults. Aside from CVEs, other severe outcomes, such as thrombotic events and cerebrovascular accidents, were observed in patients who recovered from severe COVID-19. However, such observations were less likely in COVID-19 patients who required only outpatient care.

The study findings emphasize the importance of vaccination, as demonstrated by its ability to reduce severe disease. Similarly, prompt antiviral treatment of acute COVID-19 has been recommended, which would help reduce the possibility of transition to severe illness.

Both COVID-19 vaccination and timely therapeutic interventions would alleviate the risk of severe COVID-19 and subsequently decrease the possibility of experiencing CVEs.

The findings of the present study are consistent with previous research that has reported a higher incidence of myocarditis and pericarditis in patients who recovered from severe SARS-CoV-2 infection. Nevertheless, it was observed that elevated cardiovascular risk after acute infection may not be exclusive to COVID-19.

In fact, some other diseases that have been associated with an increased risk of long-term CVEs are influenza and pneumonia bacteremia. Additionally, 22-65% of sepsis survivors are at an increased risk of CVEs.

The underlying mechanism responsible for the increased risk of CVEs following SARS-CoV-2 infection has not been determined. SARS-CoV-2 infects cardiac myocytes through their interaction with the angiotensin-converting enzyme 2 (ACE-2) receptor, which might remain persistent; therefore, this interaction induces chronic inflammatory responses and subsequent tissue damage or fibrosis.

Another mechanism related to the development of CVEs following recovery from COVID-19 is an autoimmune response to cardiac antigens that causes delayed damage to cardiac tissues. Anti-heart antibodies also correlated with cardiovascular manifestation and COVID-19.

Viral toxicity is another possible mechanism that might cause long-term cardiac damage or thrombosis in vasculitis. However, in the future, more research is needed to confirm the mechanisms related to cardiac damage after SARS-CoV-2 infection.

Conclusions

Due to the lack of a COVID-19-negative control group, the authors failed to quantify the elevated risk of CVEs in COVID-19 patients. The unwanted inclusion of patients with a history of CVEs could have overestimated the result as well. The impact of vaccination status on the incidence of CVE was not studied.

Despite these limitations, the present study strongly emphasized that patients who recovered from severe COVID-19 were at a greater risk of developing CVEs. As compared to COVID-19 patients who required outpatient care, those who were admitted to the ICU were at a higher risk of experiencing CVEs.

The importance of COVID-19 vaccination in preventing severe infection was strongly emphasized in this study.

Journal reference:

  • Wiemken, L. T., McGrath, L. J., Andersen, K. M., et al. (2022). COVID-19 severity and risk of subsequent cardiovascular events. Clinical Infectious Diseases. doi:10.1093/cid/ciac661.
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‘1 in 10-year event’: Experts react to severe flash rain events in the Okanagan – Kelowna Capital News

‘1 in 10-year event’: Experts react to severe flash rain events in the Okanagan - Kelowna Capital News

Monday afternoon’s rainfall in the Okanagan was so significant that meteorologists say such an event may not happen for at least another 10 years.

Within 45 minutes between 2 p.m. to 3 p.m. on July 4, more than 12 millimetres of rain fell to the ground in Penticton, prompting the evacuation of 16 homes, 86 structures flooded and the activation of a local state of emergency.

But Environment Canada meteorologist Doug Lundquist says the focus of the event should be more on the “return rate” of the rain, as opposed to overall precipitation statistics.

“All the way from the U.S. border at Osoyoos and to the suburbs of Kelowna, there were storms that recorded a return rate of 10 years, at the minimum,” he explained. “That’s just based on where our weather stations are, though. In all likelihood, the return period is probably even longer than that.”

Though it was Penticton’s emergency operations centre who responded to 86 flood-related calls from residents on Monday, Lundquist says that Summerland actually experienced the heaviest rainfall in the South Okanagan.

Based on the location of the local Environment Canada weather centre, Summerland set its own all-time precipitation record for the day of July 4, experiencing more than eight millimetres of rain in one hour with 15.7 mm in total.

Lundquist added that Osoyoos also broke its own daily precipitation record on Monday (14.1 mm).

While Penticton fell short of setting a daily record, what set the city apart compared to other Okanagan communities was the number of different neighbourhoods that were affected by the heavy amounts of rain.

“What’s unique about this is for Penticton that the most severe weather hit right where people live,” Lundquist said. “There have been storms like this in the high terrain, which is why Mission Creek in Kelowna has peaked out a couple of times in the last month or so.

“But we haven’t seen something like that this year and it seems as though it affected people in Penticton the most.”

Before the anticipated heatwave next week — where temperatures are expected to reach up to 32 C — Lundquist says that people in the Okanagan should still be on guard for severe storms until Thursday.

“We’re not out of the woods just yet,” he said. “‘There’s another storm that may be coming on Thursday, and we’re worried about that, too.”

Environment Canada weatherNewsOkanagan

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Corticosteroid exposure associated with hospitalization for severe pain event among patients with sickle cell disease

Corticosteroid exposure associated with hospitalization for severe pain event among patients with sickle cell disease

People with sickle cell disease (SCD) who were recently prescribed a corticosteroid – a medicine frequently used to treat asthma or inflammation – were found to be significantly more likely to be hospitalized for a severe pain event, according to a paper published today in the journal Blood. The research also found that older adults, women, and people who were not taking the drug hydroxyurea to manage their underlying SCD symptoms were the most likely to be hospitalized.

SCD is the most common inherited red blood cell disorder in the United States, affecting an estimated 100,000 people. According to the Centers for Disease Control and Prevention (CDC), SCD affects one out of every 365 Black or African American births and one out of every 16,300 Hispanic American births. Pain events, also known as vaso-occlusive episodes (VOE), are the most common complications of SCD and can result in intense pain and potentially irreversible organ damage.

Apart from case reports, researchers say this is the first study to systematically evaluate the association between corticosteroid exposure and hospitalization for VOE.

Individuals living with SCD often suffer crippling episodes of pain, which can greatly impair their quality of life. Based on our data, corticosteroids are commonly prescribed for conditions unrelated to their underlying SCD. Vaso-occlusive events and related hospitalization appear to follow corticosteroid prescription fairly quickly. This evidence suggests corticosteroids may be contributing to the events and should be avoided as much as possible in these patients.”


Ondine Walter, MD, Study Author, Toulouse University Hospital in France

Notably, the median time between filling a prescription for a corticosteroid and hospitalization was just five days. Also striking was the fact that nearly half (46%) of patients with SCD had been prescribed at least one systemic corticosteroid during the study period. Dr. Walter said the results underscore the need for widespread education of clinicians and patients alike about the potential risks of using corticosteroids, especially when there isn’t a clear indication to use them.

“Corticosteroids are mostly easy to avoid, and in circumstances when they are necessary, it’s important to start them in collaboration with an SCD expert and to take all appropriate precautionary measures to administer them safely,” said Dr. Walter.

The study used data from a total of 5,151 patients with SCD drawn from the French National Health Insurance Database between 2010 and 2018. Patients had to have at least one hospitalization for VOE to be included, and corticosteroid exposure was identified using outpatient prescribing records.

The study found that those who had exposure to a corticosteroid – defined in the month leading up to the event – were significantly more likely to be hospitalized for VOE. People who were also taking hydroxyurea seem to have less risk of hospitalization compared with those not taking the drug, which may signal a potential protective effect of hydroxyurea on the occurrence of VOE, Dr. Walter explained. Hydroxyurea is often prescribed to reduce the number of pain events caused by SCD as well as the need for blood transfusions. The risk of admission was also lower in men compared to women and in children compared to adults.

“Some factors such as hydroxyurea use, male gender, and younger age were associated with a lower risk of hospitalization for VOE after corticosteroid exposure in our study. Still, based on these results, we still need to think twice about using corticosteroids when treating patients with SCD,” said Dr. Walter.

This study is limited in that it can only show an association between corticosteroids and VOE-related hospitalizations and not prove causation. Because corticosteroid exposure was based on dispensing data, it is also not possible to confirm that patients took the medicine, only that the prescription was filled.

With future research, investigators aim to understand how corticosteroids may prompt VOE. Studies have shown that the cessation of corticosteroids, in particular, has been associated with rebound pain. ASH’s Clinical Practice Guidelines on SCD recommend against using corticosteroids for acute pain management in patients with SCD. This study adds important data about the association of corticosteroid use with subsequent VOE to a growing body of evidence that suggests corticosteroids should be used only when needed, and under the guidance of an SCD expert.

Source:

Journal reference:

Walter, O., et al. (2022) Risk of vaso-occlusive episode after exposure to corticosteroids in patients with sickle cell disease. Blood. doi.org/10.1182/blood.2021014473.

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Female Patients More Likely Than Males to Experience Severe Adverse Events During Cancer Treatment, Study Finds

Female Patients More Likely Than Males to Experience Severe Adverse Events During Cancer Treatment, Study Finds

Women are known to experience more adverse events with chemotherapy, but a recent study found an increased risk across therapy types, especially immunotherapy.

Women receiving chemotherapy are likely to have more adverse events (AEs) than men undergoing the treatment, but very little research has assessed the differences between men and women’s experiences with immunotherapy or targeted therapy. A recent study explored the role of patient sex in symptomatic and objective AEs with cytotoxic, immune, and targeted therapies for cancer.

The study, published in the Journal of Clinical Oncology, used SWOG Cancer Research Network phase 2 and 3 clinical trial data from trials between 1980 and 2019. Sex-specific cancers were excluded from the analysis.

In total, 13 symptomatic AEs and 14 objective and measurable AEs were analyzed. Symptomatic AEs included those in the Patient-Reported Outcome Common Terminology Criteria for Adverse Events given past evidence that clinician reports may under-report symptomatic AEs. Objective AEs were laboratory-based or measurable and were also categorized as either hematologic or nonhematologic.

Overall, 23,296 patients including 8838 women (37.9%) from 202 trials were included in the study. Of the patients included, 17,417 received chemotherapy, 2319 received immunotherapy, and 3560 received targeted therapy. Collectively, patients experienced 274,688 AEs, with 15,051 (64.6%) experiencing AEs of grade 3 or higher. Chemotherapy was especially prevalent in trials between 1989 and 1999. Immunotherapy and targeted therapies were more common from 2010 to 2019.

“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies,” study author Joseph Unger, PhD, associate professor, biostatistician, and health sciences researcher at Fred Hutchinson Cancer Center, said in a statement. “We found similar large differences, especially for immune treatments.”

While 64.6% of all patients experienced 1 or more severe AE, women had a 34% greater risk of severe toxicity than men (odds ratio [OR], 1.34; 95% CI, 1.27 to 1.42; P < .001). Women were at an increased risk across treatment types, especially immunotherapy (OR, 1.49; 95% CI, 1.24 to 1.78; P < .001).

Women were at a 33.3% greater risk of experiencing symptomatic AEs (OR, 1.33; 95% CI, 1.26 to 1.41; P < .001) compared with men (27.9%). They also had an increased risk of hematologic AEs compared with men (45.2% vs. 39.1%) and objective nonhematologic AEs (30.9% vs 29.0%). Women treated with immunotherapy were at an especially higher risk of severe symptomatic and hematologic AEs than men who received immunotherapy (33.7% vs 25.4%). Severe objective, nonhematologic AEs occurred at similar rates in men and women across treatment types.

These findings suggest that, in addition to the typical patient and tumor characteristics considered in cancer treatment decisions, patient sex may be a key factor in maximizing treatment efficacy while limiting toxicity. This is especially relevant with immunotherapy, during which women were at the greatest risk for severe AEs in this study.

The authors presented several possible explanations for the sex-related differences in AEs. They could be related to body size differences and relative dosing, differences in medication adherence for oral therapies, bias in the interpretation and reporting of AEs, or different reporting habits in men and women. However, the authors noted that objective hematologic AEs were also more common in women in these trials.

One study limitation is the population, which is limited to clinical trials and therefore likely includes younger, healthier patients than the general patient population, study authors said. The study also only included the worst toxicity grade in each category, so there was no observation of toxicity patterns over time.

Despite limitations, these findings suggest that sex could be an important factor in individualizing cancer treatment and maximizing efficacy.

“If confirmed, our findings suggest that underlying mechanisms may result in generalized worse toxicity outcomes for women, with or without corresponding survival improvements or detriments,” the authors wrote. “Therefore, more awareness of symptom differences or reporting differences in women versus men is needed.”

Reference

Unger JM, Vaidya R, Albain KS, et al. Sex differences in risk of severe adverse events in patients receiving immunotherapy, targeted therapy, or chemotherapy in cancer clinical trials. J Clin Oncol. Published online February 4, 2022. doi:10.1200/JCO.21.02377

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February 2022 severe weather event: Council updates and impacts