Tag: cardiac disorders

Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19

Abstract:

Background Cardiac risk rises during acute SARS-CoV-2 infection and in long COVID syndrome in humans, but the mechanisms behind COVID-19-linked arrhythmias are unknown. This study explores the acute and long term effects of SARS-CoV-2 on the cardiac conduction system (CCS) in a hamster model of COVID-19.

Methods Radiotelemetry in conscious animals was used to non-invasively record electrocardiograms and subpleural pressures after intranasal SARS-CoV-2 infection. Cardiac cytokines, interferon-stimulated gene expression, and macrophage infiltration of the CCS, were assessed at 4 days and 4 weeks post-infection. A double-stranded RNA mimetic, polyinosinic:polycytidylic acid (PIC), was used in vivo and in vitro to activate viral pattern recognition receptors in the absence of SARS-CoV-2 infection.

Results COVID-19 induced pronounced tachypnea and severe cardiac conduction system (CCS) dysfunction, spanning from bradycardia to persistent atrioventricular block, although no viral protein expression was detected in the heart. Arrhythmias developed rapidly, partially reversed, and then redeveloped after the pulmonary infection was resolved, indicating persistent CCS injury. Increased cardiac cytokines, interferon-stimulated gene expression, and macrophage remodeling in the CCS accompanied the electrophysiological abnormalities. Interestingly, the arrhythmia phenotype was reproduced by cardiac injection of PIC in the absence of virus, indicating that innate immune activation was sufficient to drive the response. PIC also strongly induced cytokine secretion and robust interferon signaling in hearts, human iPSC-derived cardiomyocytes (hiPSC-CMs), and engineered heart tissues, accompanied by alterations in electrical and Ca2+ handling properties. Importantly, the pulmonary and cardiac effects of COVID-19 were blunted by in vivo inhibition of JAK/STAT signaling or by a mitochondrially-targeted antioxidant.

Conclusions The findings indicate that long term dysfunction and immune cell remodeling of the CCS is induced by COVID-19, arising indirectly from oxidative stress and excessive activation of cardiac innate immune responses during infection, with implications for long COVID Syndrome.

Source: Deepthi Ashok, Ting Liu, Joseph Criscione, Meghana Prakash, Byunggik Kim, Julian Chow, Morgan Craney, Kyriakos N. Papanicolaou, Agnieszka Sidor, D. Brian Foster, Andrew Pekosz, Jason Villano, Deok-Ho Kim, Brian O’Rourke. Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19. bioRxiv 2024.01.05.574280; doi: https://doi.org/10.1101/2024.01.05.574280 https://www.biorxiv.org/content/10.1101/2024.01.05.574280v1.full (Full text)

Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis

Abstract:

The question of COVID-19 and long-COVID-19 course in children remains unsolved. This infection in children, which is associated with COVID-19, can vary from asymptomatic to systemic damage of various systems. Multisystem inflammatory syndrome in children, associated with SARS-CoV-2 (MIS-C), is a serious condition in children and adolescents after experiencing COVID-19.
Published data on MIS-C have indicated that the inflammation can be registered in the gastrointestinal tract (60–100%), as well as in cardiovascular (80%), nervous (29–58%), and respiratory (21–65%) systems. However, with the changing characteristics of SARS-CoV-2, the manifestations of COVID-19 and long-COVID-19 in children have also been changing. Currently, there is no clear understanding of the development of severe COVID-19 and MIS-C in children, especially after being exposed to patients with COVID-19.
We presented two new clinical courses of multisystem inflammatory syndrome in children with severe multisystem damage after close contact to relatives with COVID-19 or long-COVID-19. Thus, high-risk children, who are positive for SARS-CoV-2 infection after contact with COVID-19 patients, should be clinically managed during the first few months. The identification of the disease complexity requires the involvement of neurologists, cardiologists, and other specialists.
Source: Vasichkina E, Kofeynikova O, Fetisova S, Starshinova AY, Sheyanova E, Vershinina T, Ryzhkov A, Skripnik A, Alekseeva D, Nechaeva E, Glushkova A, Kudlay D, Pervunina T, Starshinova A. Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis. Life. 2023; 13(3):781. https://doi.org/10.3390/life13030781 https://www.mdpi.com/2075-1729/13/3/781 (Full text)

Long COVID Syndrome and Cardiovascular Manifestations: A Systematic Review and Meta-Analysis

Abstract:

Background: Long COVID syndrome is a significant cause of morbidity in COVID-19 patients who remain symptomatic with varied clinical presentations beyond three weeks. Furthermore, the relevance of considering cardiovascular outcomes in post-COVID-19 syndrome is important in the current COVID-19 pandemic.
Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for this systematic review and meta-analysis. Systematic searches were conducted from multiple databases without language restrictions until October 8, 2022, to find studies evaluating cardiovascular outcomes such as arrhythmias, myocardium and pericardium diseases, coronary vessel disease, and thromboembolic disorders in post-COVID cases. The pooled odds ratio (OR), and standard mean difference (SMD) with their corresponding 95% confidence intervals (CI) were computed to find the association.
Results: Altogether, seven studies with a total of 8,126,462 (cases: 1,321,305; controls: 6,805,157) participants were included in the meta-analysis. Pooled odds ratios of cardiovascular outcomes were significantly higher in post-COVID cases (OR > 1, p < 0.05) than in controls. However, the mortality (OR: 4.76, p = 0.13), and heart rate variability (SMD: −0.06, p = 0.91) between cases and controls were not statistically significant.
Conclusions: Significant cardiovascular sequelae in long COVID syndrome highlight the importance of careful cardiac monitoring of COVID-19 patients in the post-COVID phase to address cardiovascular complications as soon as possible; larger-scale prospective studies are required for accurate estimation.
Source: Shrestha AB, Mehta A, Pokharel P, Mishra A, Adhikari L, Shrestha S, Yadav RS, Khanal S, Sah R, Nowrouzi-Kia B, Padhi BK, Chattu VK. Long COVID Syndrome and Cardiovascular Manifestations: A Systematic Review and Meta-Analysis. Diagnostics. 2023; 13(3):491. https://doi.org/10.3390/diagnostics13030491 https://www.mdpi.com/2075-4418/13/3/491 (Full text)

Mid- and Long-Term Atrio-Ventricular Functional Changes in Children after Recovery from COVID-19

Abstract:

Background: Although most children may experience mild to moderate symptoms and do not require hospitalization, there are little data on cardiac involvement in COVID-19. However, cardiac involvement is accurately demonstrated in children with MISC. The objective of this study was to evaluate cardiac mechanics in previously healthy children who recovered from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a long-term follow-up by means of two-dimensional speckle-tracking echocardiography (STE).
Methods: We analyzed a cohort of 157 paediatric patients, mean age 7.7 ± 4.5 years (age range 0.3–18 years), who had a laboratory-confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or mildly symptomatic for COVID-19. Patients underwent a standard transthoracic echocardiogram and STE at an average time of 148 ± 68 days after diagnosis and were divided in three follow-up groups (<180 days, 180–240 days, >240 days). Patients were compared with 107 (41 females—38%) age- and BSA-comparable healthy controls (CTRL).
Results: Left ventricular (LV) global longitudinal strain (post-COVID-19: −20.5 ± 2.9%; CTRL: −21.8 ± 1.7%; p < 0.001) was significantly reduced in cases compared with CTRLs. No significant differences were seen among the three follow-up groups (p = NS). Moreover, regional longitudinal strain was significantly reduced in LV apical-wall segments of children with disease onset during the second wave of the COVID-19 pandemic compared to the first wave (second wave: −20.2 ± 2.6%; first wave: −21.2 ± 3.4%; p = 0.048). Finally, peak left atrial systolic strain was within the normal range in the post-COVID-19 group with no significant differences compared to CTRLs.
Conclusions: Our study demonstrated for the first time the persistence of LV myocardial deformation abnormalities in previously healthy children with an asymptomatic or mildly symptomatic (WHO stages 0 or 1) COVID-19 course after an average follow-up of 148 ± 68 days. A more significant involvement was found in children affected during the second wave. These findings imply that subclinical LV dysfunction may also be a typical characteristic of COVID-19 infection in children and are concerning given the predictive value of LV longitudinal strain in the general population.
Source: Sabatino J, Di Chiara C, Di Candia A, Sirico D, Donà D, Fumanelli J, Basso A, Pogacnik P, Cuppini E, Romano LR, Castaldi B, Reffo E, Cerutti A, Biffanti R, Cozzani S, Giaquinto C, Di Salvo G. Mid- and Long-Term Atrio-Ventricular Functional Changes in Children after Recovery from COVID-19. Journal of Clinical Medicine. 2023; 12(1):186. https://doi.org/10.3390/jcm12010186 https://www.mdpi.com/2077-0383/12/1/186 (Full text)

Long-term cardiac pathology in individuals with mild initial COVID-19 illness

Abstract:

Cardiac symptoms are increasingly recognized as late complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in previously well individuals with mild initial illness, but the underlying pathophysiology leading to long-term cardiac symptoms remains unclear.

In this study, we conducted serial cardiac assessments in a selected population of individuals with Coronavirus Disease 2019 (COVID-19) with no previous cardiac disease or notable comorbidities by measuring blood biomarkers of heart injury or dysfunction and by performing magnetic resonance imaging. Baseline measurements from 346 individuals with COVID-19 (52% females) were obtained at a median of 109 days (interquartile range (IQR), 77–177 days) after infection, when 73% of participants reported cardiac symptoms, such as exertional dyspnea (62%), palpitations (28%), atypical chest pain (27%) and syncope (3%). Symptomatic individuals had higher heart rates and higher imaging values or contrast agent accumulation, denoting inflammatory cardiac involvement, compared to asymptomatic individuals. Structural heart disease or high levels of biomarkers of cardiac injury or dysfunction were rare in symptomatic individuals.

At follow-up (329 days (IQR, 274–383 days) after infection), 57% of participants had persistent cardiac symptoms. Diffuse myocardial edema was more pronounced in participants who remained symptomatic at follow-up as compared to those who improved. Female gender and diffuse myocardial involvement on baseline imaging independently predicted the presence of cardiac symptoms at follow-up. Ongoing inflammatory cardiac involvement may, at least in part, explain the lingering cardiac symptoms in previously well individuals with mild initial COVID-19 illness.

Source: Puntmann, V.O., Martin, S., Shchendrygina, A. et al. Long-term cardiac pathology in individuals with mild initial COVID-19 illness. Nat Med (2022). https://doi.org/10.1038/s41591-022-02000-0 https://www.nature.com/articles/s41591-022-02000-0 (Full text)

Cardiac impairments in postacute COVID-19 with sustained symptoms: A review of the literature and proof of concept

Abstract:

Although acute COVID-19 is known to cause cardiac damage in some cases, there is still much to learn about the duration and relative permanence of the damage that may occur. Long COVID is a condition that can occur when COVID-19 symptoms remain in the postviral acute period. Varying accounts of long COVID have been described across the literature, however, cardiac impairments are sustained in many individuals and cardiovascular assessment is now considered to be an expected follow-up examination.

The purpose of this review and proof of concept is to summarize the current research related to the assessment of cardiac function, including echocardiography and blood biomarker data, during the follow-up period in patients who recovered from COVID-19. Following a literature review, it was found that right ventricular dysfunction along with global longitudinal strain and diastolic dysfunction are common findings.

Finally, more severe acute myocardial injury during the index hospitalization appears to exacerbate cardiac function. The available literature implies that cardiac function must be monitored in patients recovered from COVID-19 who remain symptomatic and that the impairments and severity vary from person-to-person.

The proof-of-concept analysis of patients with cardiac disease and respiratory disease in comparison to those with sustained symptoms from COVID-19 suggests elevated systolic time interval in those with sustained symptoms from COVID-19, thus reducing heart performance indices. Future research must consider the details of cardiac complications during the acute infection period and relate this to the cardiac function in patients with long COVID during mid- and long-term follow-up.

Source: Singh J, Bhagaloo L, Sy E, Lavoie AJ, Dehghani P, Bardutz HA, Mang CS, Buttigieg J, Neary JP. Cardiac impairments in postacute COVID-19 with sustained symptoms: A review of the literature and proof of concept. Physiol Rep. 2022 Aug;10(16):e15430. doi: 10.14814/phy2.15430. PMID: 35993433; PMCID: PMC9393908.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393908/ (Full text)

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)