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)

Vascular “Long COVID”: A New Vessel Disease?

Abstract:

Vascular sequelae following (SARS-CoV-2 coronavirus disease) (COVID)-19 infection are considered as “Long Covid (LC)” disease, when occurring 12 weeks after the original infection. The paucity of specific data can be obviated by translating pathophysiological elements from the original Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection (In a microcirculatory system, a first “endotheliitis,” is often followed by production of “Neutrophil Extracellular Trap,” and can evolve into a more complex leukocytoklastic-like and hyperimmune vasculitis.

In medium/large-sized vessels, this corresponds to endothelial dysfunction, leading to an accelerated progression of pre-existing atherosclerotic plaques through an increased deposition of platelets, circulating inflammatory cells and proteins. Associated dysregulated immune and pro-coagulant conditions can directly cause thrombo-embolic arterial or venous complications. In order to implement appropriate treatment, physicians need to consider vascular pathologies observed after SARS-Cov-2 infections as possible “LC” disease.

Source: Zanini G, Selleri V, Roncati L, Coppi F, Nasi M, Farinetti A, Manenti A, Pinti M, Mattioli AV. Vascular “Long COVID”: A New Vessel Disease? Angiology. 2023 Jan 18:33197231153204. doi: 10.1177/00033197231153204. Epub ahead of print. PMID: 36652923. https://pubmed.ncbi.nlm.nih.gov/36652923/

A Review of Long COVID With a Special Focus on Its Cardiovascular Manifestations

Abstract:

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been the cause of the century’s worst pandemic so far: coronavirus disease 2019 (COVID-19). It has led to unprecedented mortality and morbidity, resulting in devastating consequences worldwide. The acute manifestations of COVID-19 including respiratory as well as multisystem involvement have been causes of great concern among physicians. However, the long-term effects of the coronavirus have left many patients battling with chronic symptoms, ranging from extreme fatigue to cardiomyopathy. In this article, we review the chronic manifestations of COVID-19 with a focus on cardiovascular manifestations.

We discuss the pathophysiology, post-acute sequelae, clinical manifestations, approach to the laboratory diagnosis of cardiovascular manifestations of long COVID, and a proposed multidisciplinary treatment method. We also explore the relationship between vaccination and the long COVID syndrome.

Source: Yousif E, Premraj S. A Review of Long COVID With a Special Focus on Its Cardiovascular Manifestations. Cureus. 2022 Nov 27;14(11):e31933. doi: 10.7759/cureus.31933. PMID: 36582565; PMCID: PMC9793803. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793803/ (Full text)

Long-term cardiovascular outcomes of COVID-19

Abstract:

The cardiovascular complications of acute coronavirus disease 2019 (COVID-19) are well described, but the post-acute cardiovascular manifestations of COVID-19 have not yet been comprehensively characterized. Here we used national healthcare databases from the US Department of Veterans Affairs to build a cohort of 153,760 individuals with COVID-19, as well as two sets of control cohorts with 5,637,647 (contemporary controls) and 5,859,411 (historical controls) individuals, to estimate risks and 1-year burdens of a set of pre-specified incident cardiovascular outcomes.

We show that, beyond the first 30 d after infection, individuals with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease. These risks and burdens were evident even among individuals who were not hospitalized during the acute phase of the infection and increased in a graded fashion according to the care setting during the acute phase (non-hospitalized, hospitalized and admitted to intensive care).

Our results provide evidence that the risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial. Care pathways of those surviving the acute episode of COVID-19 should include attention to cardiovascular health and disease.

Source: Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022 Mar;28(3):583-590. doi: 10.1038/s41591-022-01689-3. Epub 2022 Feb 7. PMID: 35132265; PMCID: PMC8938267. ncbi.nlm.nih.gov/pmc/articles/PMC8938267/ (Full text)

 

Psycho-physiological impact on women with chronic fatigue syndrome in the context of their couple relationship

Abstract:

The quality of dyadic adjustment is likely to play an important role in patients’ relational problems and may also be associated with the clinical presentation of chronic fatigue syndrome (CFS) symptoms. The objective of this study was (1) to determine whether CFS patients and their partners have similar perceptions of their dyadic adjustment and (2) to evaluate whether the influence of dyadic satisfaction in women with CFS, as well as common psychological parameters such as anxiety, may correlate with physiological responses at rest and/or when performing very low intensity exercise.

Forty females with CFS and their partners completed the Dyadic Adjustment Scale, the State-Trait Anxiety Inventory, and the Hospital Anxiety and Depression scale. The cardiovascular adaptation of patients was evaluated during resting conditions and on a precalibrated cycle ergometer while performing very low intensity exercise. Patients and partners had similar perceptions of their marital relationship.

Both at rest and during very low workload, various physiological parameters in the patient group showed statistical correlations with certain psychological parameters. Several psychological variables, such as anxiety and dyadic adjustment, were associated with the cardioventilatory response monitored at rest and during very low intensity exercise. Further studies are needed to determine the nature of this association.

 

Source: Blazquez A, Guillamó E, Alegre J, Ruiz E, Javierre C. Psycho-physiological impact on women with chronic fatigue syndrome in the context of their couple relationship. Psychol Health Med. 2012;17(2):150-63. doi: 10.1080/13548506.2011.582124. Epub 2011 Jul 11. https://www.ncbi.nlm.nih.gov/pubmed/21745025

 

Usefulness of an abnormal cardiovascular response during low-grade head-up tilt-test for discriminating adolescents with chronic fatigue from healthy controls

Abstract:

Hemodynamic dysfunction is documented in chronic fatigue syndrome (CFS). This study was conducted to investigate cardiovascular responses to orthostatic stress in adolescents with CFS, using a novel procedure for tilt-table testing.

A total of 27 adolescents with CFS and 33 healthy control subjects with equal age and gender distribution underwent 15 minutes of 20 degrees head-up tilt testing. Heart rate, systolic blood pressure (BP), mean BP, diastolic BP, stroke index, total peripheral resistance index, end-diastolic volume index, and acceleration index were continuously and noninvasively recorded.

At rest, patients with CFS had higher total peripheral resistance index values (p<0.01) and lower stroke index and end-diastolic volume index values (p<0.05) than controls. During 20 degrees head-up tilt testing, patients with CFS had greater increases in heart rate, diastolic BP (p<0.001), mean BP (p<0.01), and total peripheral resistance index (p<0.05) than controls and greater decreases in stroke index (p<0.05). Syncope or near syncope was not observed.

In conclusion, this study found that adolescents with CFS have significant abnormalities of cardiovascular regulation in response to mild orthostatic stress, differentiating them from healthy controls.

 

Source: Wyller VB, Due R, Saul JP, Amlie JP, Thaulow E. Usefulness of an abnormal cardiovascular response during low-grade head-up tilt-test for discriminating adolescents with chronic fatigue from healthy controls. Am J Cardiol. 2007 Apr 1;99(7):997-1001. Epub 2007 Feb 16. https://www.ncbi.nlm.nih.gov/pubmed/17398200

 

Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome

Abstract:

PURPOSE: To evaluate the aerobic power (as maximum volume of oxygen consumed [VO2 max]) of women with chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: Twenty-one women with CFS and 22 sedentary healthy controls (CON) were studied at the CFS Cooperative Research Center Exercise Laboratory at the VA Medical Center, East Orange, New Jersey. Performance was measured on an incremental treadmill protocol walking to exhaustion. Expired gases were analyzed by a metabolic system, heart rate was recorded continuously, and ratings of perceived exertion (RPE) were taken at each workload. The groups were divided into those who achieved VO2 max (CFS-MAX and CON-MAX) and those who stopped at a submaximal level (CFS-NOMAX and CON-NOMAX) by using standard criteria.

RESULTS: Seventeen CON and 10 CFS subjects achieved VO2 max. The VO2 max (mL/kg/min) of the CFS-MAX (28.1 +/- 5.1) was lower than that of the CON-MAX (32.1 +/- 4.3, P = 0.05). The CFS-MAX achieved 98 +/- 11% of predicted VO2 max. The CFS group had a higher RPE at the same absolute workloads as controls (P < 0.01) but not the same relative workloads.

CONCLUSION: Compared with normal controls, women with CFS have an aerobic power indicating a low normal fitness level with no indication of cardiopulmonary abnormality. Our CFS group could withstand a maximal treadmill exercise test without a major exacerbation in either fatigue or other symptoms of their illness.

Comment in:

Exercise limits in chronic fatigue syndrome. [Am J Med. 1997]

Graded exercise testing and chronic fatigue syndrome. [Am J Med. 1997]

 

Source: Sisto SA, LaManca J, Cordero DL, Bergen MT, Ellis SP, Drastal S, Boda WL, Tapp WN, Natelson BH. Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome. Am J Med. 1996 Jun;100(6):634-40. http://www.ncbi.nlm.nih.gov/pubmed/8678084