Association of Congenital and Acquired Cardiovascular Conditions With COVID-19 Severity Among Pediatric Patients in the US

Abstract:

Importance: Identifying the associations between severe COVID-19 and individual cardiovascular conditions in pediatric patients may inform treatment.

Objective: To assess the association between previous or preexisting cardiovascular conditions and severity of COVID-19 in pediatric patients.

Design, setting, and participants: This retrospective cohort study used data from a large, multicenter, electronic health records database in the US. The cohort included patients aged 2 months to 17 years with a laboratory-confirmed diagnosis of COVID-19 or a diagnosis code indicating infection or exposure to SARS-CoV-2 at 85 health systems between March 1, 2020, and January 31, 2021.

Exposures: Diagnoses for 26 cardiovascular conditions between January 1, 2015, and December 31, 2019 (before infection with SARS-CoV-2).

Main outcomes and measures: The main outcome was severe COVID-19, defined as need for supplemental oxygen or in-hospital death. Mixed-effects, random intercept logistic regression modeling assessed the significance and magnitude of associations between 26 cardiovascular conditions and COVID-19 severity. Multiple comparison adjustment was performed using the Benjamini-Hochberg false discovery rate procedure.

Results: The study comprised 171 416 pediatric patients; the median age was 8 years (IQR, 2-14 years), and 50.28% were male. Of these patients, 17 065 (9.96%) had severe COVID-19. The random intercept model showed that the following cardiovascular conditions were associated with severe COVID-19: cardiac arrest (odds ratio [OR], 9.92; 95% CI, 6.93-14.20), cardiogenic shock (OR, 3.07; 95% CI, 1.90-4.96), heart surgery (OR, 3.04; 95% CI, 2.26-4.08), cardiopulmonary disease (OR, 1.91; 95% CI, 1.56-2.34), heart failure (OR, 1.82; 95% CI, 1.46-2.26), hypotension (OR, 1.57; 95% CI, 1.38-1.79), nontraumatic cerebral hemorrhage (OR, 1.54; 95% CI, 1.24-1.91), pericarditis (OR, 1.50; 95% CI, 1.17-1.94), simple biventricular defects (OR, 1.45; 95% CI, 1.29-1.62), venous embolism and thrombosis (OR, 1.39; 95% CI, 1.11-1.73), other hypertensive disorders (OR, 1.34; 95% CI, 1.09-1.63), complex biventricular defects (OR, 1.33; 95% CI, 1.14-1.54), and essential primary hypertension (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.

Conclusions and relevance: The findings suggest that some previous or preexisting cardiovascular conditions are associated with increased severity of COVID-19 among pediatric patients in the US and that morbidity may be increased among individuals children younger than 12 years with previous cardiac arrest.

Source: Ehwerhemuepha L, Roth B, Patel AK, Heutlinger O, Heffernan C, Arrieta AC, Sanger T, Cooper DM, Shahbaba B, Chang AC, Feaster W, Taraman S, Morizono H, Marano R. Association of Congenital and Acquired Cardiovascular Conditions With COVID-19 Severity Among Pediatric Patients in the US. JAMA Netw Open. 2022 May 2;5(5):e2211967. doi: 10.1001/jamanetworkopen.2022.11967. PMID: 35579899. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2792374 (Full text)

Persistent COVID-19 symptoms in a community study of 606,434 people in England

Abstract:

Long COVID remains a broadly defined syndrome, with estimates of prevalence and duration varying widely. We use data from rounds 3-5 of the REACT-2 study (n = 508,707; September 2020 – February 2021), a representative community survey of adults in England, and replication data from round 6 (n = 97,717; May 2021) to estimate the prevalence and identify predictors of persistent symptoms lasting 12 weeks or more; and unsupervised learning to cluster individuals by reported symptoms.

At 12 weeks in rounds 3-5, 37.7% experienced at least one symptom, falling to 21.6% in round 6. Female sex, increasing age, obesity, smoking, vaping, hospitalisation with COVID-19, deprivation, and being a healthcare worker are associated with higher probability of persistent symptoms in rounds 3-5, and Asian ethnicity with lower probability. Clustering analysis identifies a subset of participants with predominantly respiratory symptoms. Managing the long-term sequelae of COVID-19 will remain a major challenge for affected individuals and their families and for health services.

Source: Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, Ward H, Elliott P. Persistent COVID-19 symptoms in a community study of 606,434 people in England. Nat Commun. 2022 Apr 12;13(1):1957. doi: 10.1038/s41467-022-29521-z. PMID: 35413949; PMCID: PMC9005552. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005552/ (Full text)

Differences in clinical presentation with long covid following community and hospital infection, and associations with all-cause mortality: English sentinel network database study

Abstract:

Background: Most studies of long covid (symptoms of COVID-19 beyond 4 weeks) have focused on people hospitalised in their initial illness. Long covid is thought to be under-recorded in UK primary care electronic records.

Objective: We sought to determine which symptoms people present to primary care following COVID-19, and whether presentation differs in people who were not hospitalised, and post-long covid mortality.

Methods: We used routine data from the nationally representative Primary Care Sentinel Cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7.4million), applying a pre-defined long covid phenotype and grouped by whether the illness index was in hospital or community. We included COVID-19 cases between 1st-March-2020 and 1st-April-2021. We conducted a before and after analysis of pre-specified long covid symptoms identified by the Office of National Statistics, comparing symptoms presented between one and six months after their index infection matched with the same months one year previously. We conducted logistic regression analysis, quoting odds ratios with 95% confidence intervals, reporting differences between those with an index community infection compared to those who had been hospitalised, and separately associations with all-cause mortality.

Results: 5.6% (416,505/7,396,702) and 1.8% (7,623/416,505) of patients respectively had a coded diagnosis of COVID-19 and diagnosis or referral for long covid. People coded as having long covid were significantly more likely to have presented the pre-specified symptoms after vs before COVID-19 infection (odds ratios 2.66 [2.46-2.88] for those with index community infection and 2.42 [2.03-2.89] for those hospitalised). Following an index community infection, patients were more likely to present with non-specific symptoms (odds ratio 3.44 [3.00-3.95], P<.001) than following a hospital admission (odds ratio 2.09 [1.56-2.80], P<.001). Mental health sequelae were more commonly associated with hospital admission index infections (odds ratio 2.21 [1.64-2.96]) compared to community (odds ratio 1.36 [1.21-1.53], P<.001). People presenting to primary care following hospital infection were more likely to be male (odds ratio 1.43 [1.25-1.64], P<.001), more socioeconomically deprived (odds ratio 1.42 [1.24-1.63], P<.001); and to have multi-morbidity (odds ratio 1.41 [1.26-1.57], P<.001) than those presenting after an index community infection. All-cause mortality in people with long covid was associated with increasing age; male gender (odds ratio 3.32 [1.34-9.24], P<.01) and higher multi-morbidity score (odds ratio 2.11 [1.34-3.29], P<.001). One or more vaccine doses was associated with reduced odds of mortality (odds ratio 0.10 [0.03-0.35], P<.001).

Conclusions: The low percentage of people recorded as having long covid following COVID-19 reflects either low prevalence or under-recording. The characteristics and comorbidities of those presenting with long covid following a community infection are different from those who were hospitalised with their index infection. This study provides insights into the presentation of long covid in primary care and implications for workload.

Source: Meza-Torres B, Delanerolle G, Okusi C, Mayer N, Anand S, McCartney J, Gatenby P, Glampson B, Chapman M, Curcin V, Mayer E, Joy M, Greenhalgh T, Delaney B, de Lusignan S. Differences in clinical presentation with long covid following community and hospital infection, and associations with all-cause mortality: English sentinel network database study. JMIR Public Health Surveill. 2022 May 17. doi: 10.2196/37668. Epub ahead of print. PMID: 35605170.  https://preprints.jmir.org/preprint/37668/accepted (Full text)

Predictors of Post-Acute Sequelae of COVID-19 Development and Rehabilitation: A Retrospective Study

Abstract:

Objective: Clinical and demographic factors associated with the development, severity, and rehabilitation utilization of patients with Post-Acute Sequelae of COVID-19 (PASC) are not well defined. We examined the frequency of PASC, and the factors associated with rehabilitation utilization in a large adult population with PASC.

Design: Retrospective study SETTING: Hospital health system PARTICIPANTS: All COVID-19 patients from March 10, 2020 to January 17, 2021 INTERVENTION: Not applicable.

Main outcome measure: Descriptive analyses were conducted across the entire cohort along with an adult subgroup analysis. A logistic regression was performed to assess factors associated with PASC development and rehabilitation utilization.

Results: In an analysis of 19,792 patients, the frequency of PASC was 42.8% in the adult population. Patients with PASC compared to those without had a higher utilization of rehabilitation services (8.6% vs 3.8%, p<0.001). Risk factors for rehabilitation utilization in patients with PASC included younger age (OR 0.99, 95% CI 0.98-1.00; p=0.01). In addition to several comorbidities and demographics factors, risk factors for rehabilitation utilization solely in the inpatient population included male sex (OR 1.24, 95% CI 1.02-1.50; p=0.03) with patients on angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers three months prior to COVID-19 infections having a decreased risk of needing rehabilitation (OR 0.80, 95% CI 0.64-0.99; p=0.04).

Conclusion: Patients with PASC had higher rehabilitation utilization. We identified several clinical and demographic factors associated with the development of PASC and rehabilitation utilization.

Source: Abdelwahab N, Ingraham NE, Nguyen N, Siegel L, Silverman G, Sahoo HS, Pakhomov S, Morse LR, Billings J, Usher MG, Melnik TE, Tignanelli CJ, Ikramuddin F. Predictors of Post-Acute Sequelae of COVID-19 Development and Rehabilitation: A Retrospective Study. Arch Phys Med Rehabil. 2022 May 12:S0003-9993(22)00397-5. doi: 10.1016/j.apmr.2022.04.009. Epub ahead of print. PMID: 35569640; PMCID: PMC9098397. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098397/ (Full text)

Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol

Abstract:

Background: Emerging evidence shows that both adults and children may develop post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this study is to characterise and compare long-term post-SARS-CoV-2 infection outcomes in adults and children in a defined region in Italy.

Methods: A prospective cohort study including children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection and their household members. Participants were assessed via telephone and face-to-face visits up to 12 months post-SARS-CoV-2 diagnosis of household index case, using the ISARIC COVID-19 follow-up survey.

Results: Of 507 participants from 201 households, 56.4% (286/507) were children, 43.6% (221/507) adults. SARS-CoV-2 positivity was 87% (249/286) in children, and 78% (172/221) in adults. The mean age of PCR positive children was 10.4 (SD = 4.5) and of PCR positive adults was 44.5 years (SD = 9.5), similar to the PCR negative control groups [children 10.5 years (SD = 3.24), adults 42.3 years (SD = 9.06)]. Median follow-up post-SARS-CoV-2 diagnosis was 77 days (IQR 47-169). A significantly higher proportion of adults compared to children reported at least one persistent symptom (67%, 68/101 vs. 32%, 57/179, p < 0.001) at the first follow up. Adults had more frequently coexistence of several symptom categories at both follow-up time-points. Female gender was identified as a risk factor for PASC in adults (p 0.02 at 1-3 months and p 0.01 at 6-9 months follow up), but not in children. We found no significant correlation between adults and children symptoms. In the paediatric group, there was a significant difference in persisting symptoms between those with confirmed SARS-CoV-2 infection compared to controls at 1-3 months follow up, but not at 6-9 months. Conversely, positive adults had a higher frequency of persisting symptoms at both follow-up assessments.

Conclusion: Our data highlights that children can experience persistent multisystemic symptoms months after diagnosis of mild acute SARS-CoV-2 infection, although less frequently and less severely than co-habitant adults. There was no correlation between symptoms experienced by adults and children living in the same household. Our data highlights an urgent need for studies to characterise PASC in whole populations and the wider impact on families.

Source: Buonsenso D, Munblit D, Pazukhina E, Ricchiuto A, Sinatti D, Zona M, De Matteis A, D’Ilario F, Gentili C, Lanni R, Rongai T, Del Balzo P, Fonte MT, Valente M, Zampino G, De Rose C, Sigfrid L, Valentini P; FIMP-Roma. Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol. Front Pediatr. 2022 Apr 21;10:834875. doi: 10.3389/fped.2022.834875. PMID: 35529336; PMCID: PMC9070551.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070551/ (Full text)