Covid-19: Kids with CVD Susceptible to More Severe Disease

Children with preexisting or congenital cardiovascular conditions appear to be at increased risk for contracting severe Covid-19, a finding that underscores the importance of Covid-19 vaccination in this population, according to a retrospective cohort study published in JAMA Network Open. "Although the magnitude of the associations found in this study differed considerably across the 26 cardiovascular conditions studied, the results suggest a high overall cardiovascular burden associated with severe Covid-19," Rachel Marano, MD, of Children’s Health of Orange County, Orange, California, and colleagues wrote. "History of cardiac arrest had the highest [odds ratio] OR among all variables in the model. Despite the high rate of mortality (27.91%) among pediatric patients with a history of cardiac arrest and severe Covid-19 in this study, only one-third of individuals younger than 12 years were eligible to receive a Covid-19 vaccine or monoclonal antibodies based on recommendations as of September 2021."

For their analysis, Marano and colleagues looked at electronic health records of 171,416 pediatric patients, of whom 17,065 (9.96%) contracted severe Covid-19, and found that the following conditions were most associated with increased risk severe Covid-19:

• Cardiac arrest: 892% increased risk (odds ratio [OR], 9.92; 95% CI, 6.93-14.20).
• Cardiogenic shock: 207% (OR, 3.07; 95% CI, 1.90-4.96).
• Heart surgery: 204% (OR, 3.04; 95% CI, 2.26-4.08).
• Cardiopulmonary disease: 91% (OR, 1.91; 95% CI, 1.56-2.34).
• Heart failure: 82% (OR, 1.82; 95% CI, 1.46-2.26).
• Hypotension: 57% (OR, 1.57; 95% CI, 1.38-1.79).
• Nontraumatic cerebral hemorrhage: 54% (OR, 1.54; 95% CI, 1.24-1.91).
• Pericarditis: 50% (OR, 1.50; 95% CI, 1.17-1.94).
• Simple biventricular defects: 45% (OR, 1.45; 95% CI, 1.29-1.62).
• Venous embolism and thrombosis: 39% (OR, 1.39; 95% CI, 1.11-1.73).
• Other hypertensive disorders (not including essential primary hypertension): 34% (OR, 1.34; 95% CI, 1.09-1.63).
• Complex biventricular defects: 33% (OR, 1.33; 95% CI, 1.14-1.54).
• Essential primary hypertension: 22% (OR, 1.22; 95% CI, 1.08-1.38).

"Furthermore, 194 of 258 patients (75.19%) with a history of cardiac arrest were younger than 12 years," Marano and colleagues pointed out.

The study participants were selected using the large, multicenter data base, Cerner Real-World Data, from which Marano and colleagues identified patients with confirmed Covid-19 either by lab-confirmed diagnoses or the diagnosis code for infection or exposure. Eighty-five health systems were involved in the trial, which took place from March 1, 2020 to Jan. 31, 2021.

The median age of the participants was 8 years old, 64.04% White, 44.38% were Hispanic or Latino, and 14.45% were Black. Less than 2% were American Indian/Alaska Native or Asian/Pacific Islander.

Marano and colleagues were seeking to ascertain 26 cardiovascular conditions diagnosed before a SARS-CoV-2 infections from Jan. 1, 2015 to Dec. 31, 2019. Severe Covid-19 was defined as needing supplemental oxygen or the patient dying in hospital.

"The study population included 8,544 patients (4.98%) requiring a nasal cannula, 170 (0.10%) receiving bilevel or continuous positive airway pressure, 11,500 (6.71%) requiring a high-flow nasal cannula, 4,116 (2.40%) receiving mechanical ventilation, and 29 (0.02%) receiving extracorporeal membrane oxygenation; 197 patients (0.11%) died," Marano and colleagues wrote. "Overlap between these groups used to define severe Covid-19 resulted in 17,065 severe cases (9.96%). Data on BMI were found for 67.29% of patients; ICD-10-CM diagnosis codes were scanned for the remaining 32.71%. We estimated that less than 1% of patients may have had multisystem inflammatory syndrome in children (MIS-C) during the first Covid-19–related encounter because 0.34% of these patients received intravenous immunoglobulin therapy or a biologic agent such as rituximab or tocilizumab…"

The study authors pointed out that the cardiovascular conditions looked at in their study "may not occur independent of each other, indicating potential additive risk because of the overlapping effects of multiple conditions," they wrote. "For example, cardiogenic shock may result from heart failure, which was associated with increased odds of severe Covid-19 in our study. The presence of other chronic conditions may also be associated with increased morbidity from Covid-19. These considerations are important considering our findings that cardiomyopathy and atrioventricular and conduction blocks were associated with reduced odds of severe Covid-19. This finding must be interpreted with caution, and more granular analyses will be necessary to determine the underlying mechanism and whether angiotensin converting enzyme II (ACE2) may play a role. Of note, all cardiovascular conditions considered were associated with increased odds of severe disease in the unadjusted (univariable) analysis. Patients with cardiomyopathy and/or atrioventricular and conduction blocks may have comorbidities associated with risk of severe disease."

Limitations of the study include the study authors’ definition of severe Covid-19, which might not have caught those patients who developed cardiovascular complications during hospitalization. Other variants of Covid-19 have developed since the study was performed, "and systematic analyses must be performed to identify the factors associated with the severe disease caused by a given variant," they noted. Also, very young patients may have not yet been diagnosed with preexisting conditions.

Marano disclosed no relevant relationships.

Marano R, et al "Association of congenital and acquired cardiovascular conditions with Covid-19 severity among pediatric patients in the US" JAMA Netw Open 2022; 5(5):e2211967.