Tag: long covid complications

Long COVID: An approach to clinical assessment and management in primary care

Abstract:

Long COVID is an emerging public health threat, following swiftly behind the surges of acute infection over the course of the COVID-19 pandemic. It is estimated that there are already approximately 100 million people suffering from Long COVID globally, 0.5 million of whom are South African, and for whom our incomplete understanding of the condition has forestalled appropriate diagnosis and clinical care. There are several leading postulates for the complex, multi-mechanistic pathogenesis of Long COVID. Patients with Long COVID may present with a diversity of clinical phenotypes, often with significant overlap, which may exhibit temporal heterogeneity and evolution.

Post-acute care follow-up, targeted screening, diagnosis, a broad initial assessment and more directed subsequent assessments are necessary at the primary care level. Symptomatic treatment, self-management and rehabilitation are the mainstays of clinical care for Long COVID. However, evidence-based pharmacological interventions for the prevention and treatment of Long COVID are beginning to emerge. This article presents a rational approach for assessing and managing patients with Long COVID in the primary care setting.

Source: Perumal R, Shunmugam L, Naidoo K. Long COVID: An approach to clinical assessment and management in primary care. S Afr Fam Pract (2004). 2023 Jun 23;65(1):e1-e10. doi: 10.4102/safp.v65i1.5751. PMID: 37427773; PMCID: PMC10331047. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10331047/ (Full text)

Long COVID and its cardiovascular consequences: What is known?

Abstract:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity and mortality and has been a source of substantial challenges for healthcare systems globally. Despite a full recovery, a significant proportion of patients demonstrate a broad spectrum of cardiovascular, pulmonary and neurological symptoms that are believed to be caused by long-term tissue damage and pathological inflammation, which play a vital role in disease development. Microvascular dysfunction also causes significant health problems.

This review aimed to critically appraise the current data on the long-term cardiovascular sequelae of coronavirus disease 2019 (COVID-19), with a primary focus on cardiovascular symptoms such as chest pain, fatigue, palpitations, and breathlessness, and more significant disease entities including myocarditis, pericarditis and postural tachycardia syndrome. Potential risk factors identified in recent studies that contribute towards the development of long COVID are also included alongside a summary of recent advances in diagnostics and putative treatment options.

Source: Składanek JA, Leśkiewicz M, Gumiężna K, Baruś P, Piasecki A, Klimczak-Tomaniak D, Sygitowicz G, Kochman J, Grabowski M, Tomaniak M. Long COVID and its cardiovascular consequences: What is known? Adv Clin Exp Med. 2023 Jun 30. doi: 10.17219/acem/167482. Epub ahead of print. PMID: 37386857. https://advances.umw.edu.pl/en/ahead-of-print/167482/ (Full text)

The impact of acute SARS-CoV-2 on testicular function including insulin-like factor 3 [INSL3] in men with mild COVID-19: A longitudinal study

Abstract:

Background: SARS-CoV-2 may affect the male reproductive system as it uses angiotensin-converting enzyme [ACE]2, which is expressed in testicular tissue, as an entry point into the cell. Few studies have evaluated the long-term effects of mild COVID-19 on testicular function, and INSL3 levels have not previously been assessed during acute SARS-CoV-2 infection.

Objectives: To assess the impact of acute SARS-CoV-2 infection on testicular function including INSL3 and the presence of SARS-CoV-2 RNA in semen in non-hospitalised men with mild COVID-19.

Materials and methods: This longitudinal study included 36 non-hospitalised SARS-CoV-2-positive men (median age 29 years). Inclusion was within seven days following a positive SARS-CoV-2 RT-PCR test. Reproductive hormone levels, semen parameters, and the presence of SARS-CoV-2 RNA in oropharyngeal and semen samples were assessed during acute SARS-CoV-2 infection (baseline) and at three- and six-month follow-up. Wilcoxon matched-pair signed-rank (two samples) test was used to assess time-related alterations in reproductive hormone levels and semen parameters.

Results: Lower plasma testosterone [T] (total and calculated free [c-fT]) and higher LH concentrations were observed during acute SARS-CoV-2 infection (baseline) compared to three- and six-month follow-up. Consequently, ratios of c-fT/LH were lower at baseline compared to three- and six-month follow-up (P < 0.001 and P = 0.003, respectively). Concomitantly, lower INSL3 concentrations were observed at baseline compared to three-month follow-up (P = 0.01). The total number of motile spermatozoa was also lower at baseline compared to six-month follow-up (P = 0.02). The alterations were detected irrespective of whether the men had experienced SARS-CoV-2-related fever episodes or not. No SARS-CoV-2 RNA was detected in semen at any time point.

Discussion and conclusion: This study showed a reduction in testicular function, which was for the first time confirmed by INSL3, in men mildly affected by SARS-CoV-2 infection. The risk of transmission of SARS-CoV-2 RNA via semen seems to be low. Febrile episodes may impact testicular function, but a direct effect of SARS-CoV-2 cannot be excluded. This article is protected by copyright. All rights reserved.

Source: Lauritsen MP, Kristensen TL, Bo Hansen C, Schneider UV, Talbot AL, Skytte AB, Petersen JH, Johannsen TH, Zedeler A, Albrethsen J, Juul A, Priskorn L, Jørgensen N, Westh H, Freiesleben NC, Nielsen HS. The impact of acute SARS-CoV-2 on testicular function including insulin-like factor 3 [INSL3] in men with mild COVID-19: A longitudinal study. Andrology. 2023 Jul 8. doi: 10.1111/andr.13494. Epub ahead of print. PMID: 37421657. https://pubmed.ncbi.nlm.nih.gov/37421657/

Unsuspected Subclinical Left Ventricular Dysfunction in Post-COVID Patients: A Real-world Observation

Abstract:

Background: Subclinical myocardial dysfunction may exist in post-COVID-19 patients and may carry significance in long term.

Methodology: Subjects of long-COVID-19 with historically and radiologically significant pulmonary involvement (without documented cardiac involvement) were evaluated on outpatient follow-up echocardiographically when they had disproportionate shortness of breath (SOB), fatigue, or high pulse rate as perceived by the physicians. The common acute-phase symptoms were noted and scored retrospectively. The assessment included spirometry and measurement of chronic obstructive pulmonary disease (COPD) assessment test (CAT) score with measurement of the left ventricular (LV) and right ventricular (RV) free wall global longitudinal strain as an adjunct to routine two-dimensional and Doppler echocardiography and spirometry. The results were evaluated statistically with respect to the history of hospitalization.

Results: The hospitalized (n = 15) and nonhospitalized (n = 10) patients were demographically similar. However, the nonhospitalized patients had higher total symptom score (p = 0.03), anosmia (p = 0.017), and ageusia (p = 0.0019). At follow-up (&gt;3 months of acute illness), the nonhospitalized patients had a better CAT score (p = 0.04), higher change in max pulse rate (p = 0.03), and higher forced expiratory volume in 1 second (FEV1) (p = 0.002), tricuspid annular plane systolic excursion (TAPSE) (p = 0.02), and left ventricular global longitudinal strain (LVGLS) (-17.15 ± 1.19 vs -13.11 ± 1.91) (p = 0.0001). Overall, the two groups formed distinct clusters. The LVGLS and the maximum pulse rate difference in the two chair test (2CT) seem to contribute maximally to the variance between the two groups in multivariate analysis.

Conclusion: The subclinical myocardial dysfunction persisting in post-COVID patients (without suspected cardiac affection and lower neuroinflammatory symptoms in the acute phase) with significant pulmonary affection needs further evaluation. They demonstrate a higher max pulse rate difference in the 2CT. This real-world observation demands further investigations.

Source: Bhattacharyya P, Sengupta S, De A, Mukherjee S, Paul M, Dey D. Unsuspected Subclinical Left Ventricular Dysfunction in Post-COVID Patients: A Real-world Observation. J Assoc Physicians India. 2022 Nov;70(11):11-12. doi: 10.5005/japi-11001-0147. PMID: 37355939. https://japi.org/article/files/JAPI0147_p18-22_compressed.pdf (Full text)

Exploring potential biomarkers and therapeutic targets of long COVID-associated inflammatory cardiomyopathy

Background: The negative impact of long COVID on social life and human health is increasingly prominent, and the elevated risk of cardiovascular disease in patients recovering from COVID-19 has also been fully confirmed. However, the pathogenesis of long COVID-related inflammatory cardiomyopathy is still unclear. Here, we explore potential biomarkers and therapeutic targets of long COVID-associated inflammatory cardiomyopathy.

Methods: Datasets that met the study requirements were identified in Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) were obtained by the algorithm. Then, functional enrichment analysis was performed to explore the basic molecular mechanisms and biological processes associated with DEGs. A protein–protein interaction (PPI) network was constructed and analyzed to identify hub genes among the common DEGs. Finally, a third dataset was introduced for validation.

Results: Ultimately, 3,098 upregulated DEGs and 1965 downregulated DEGs were extracted from the inflammatory cardiomyopathy dataset. A total of 89 upregulated DEGs and 217 downregulated DEGs were extracted from the dataset of convalescent COVID patients. Enrichment analysis and construction of the PPI network confirmed VEGFA, FOXO1, CXCR4, and SMAD4 as upregulated hub genes and KRAS and TXN as downregulated hub genes. The separate dataset of patients with COVID-19 infection used for verification led to speculation that long COVID-associated inflammatory cardiomyopathy is mainly attributable to the immune-mediated response and inflammation rather than to direct infection of cells by the virus.

Conclusion: Screening of potential biomarkers and therapeutic targets sheds new light on the pathogenesis of long COVID-associated inflammatory cardiomyopathy as well as potential therapeutic approaches. Further clinical studies are needed to explore these possibilities in light of the increasingly severe negative impacts of long COVID.

Source: Peng Qi, Mengjie Huang and Haiyan Zhu. Exploring potential biomarkers and therapeutic targets of long COVID-associated inflammatory cardiomyopathy. Front. Med., 29 June 2023. Sec. Infectious Diseases: Pathogenesis and Therapy. Volume 10 – 2023 | https://doi.org/10.3389/fmed.2023.1191354 https://www.frontiersin.org/articles/10.3389/fmed.2023.1191354/full (Full text)

Cardiac MRI Findings in Patients Clinically Referred for Evaluation of Post-Acute Sequelae of SARS-CoV-2 Infection

Abstract:

Persistent or recurrent cardiovascular symptoms have been identified as one of the hallmarks of long-COVID or post-acute sequelae of SARS-CoV-2 infection (PASC). The purpose of this study was to determine the prevalence and extent of cardiac abnormalities in patients referred for cardiac MRI due to clinical evidence of PASC. To investigate this, two tertiary care hospitals identified all patients who were referred for cardiac MRI under the suspicion of PASC in a 2-year period and retrospectively included them in this study.
Patients with previously known cardiac diseases were excluded. This resulted in a total cohort of 129 patients (63, 51% female; age 41 ± 16 years). The majority of patients (57%) showed normal cardiac results. No patient had active myocarditis or an acute myocardial infarction. However, 30% of patients had evidence of non-ischemic myocardial fibrosis, which exceeds the prevalence in the normal adult population and suggests that a possible history of myocarditis might explain persistent symptoms in the PASC setting.
Source: Halfmann MC, Luetkens JA, Langenbach IL, Kravchenko D, Wenzel P, Emrich T, Isaak A. Cardiac MRI Findings in Patients Clinically Referred for Evaluation of Post-Acute Sequelae of SARS-CoV-2 Infection. Diagnostics. 2023; 13(13):2172. https://doi.org/10.3390/diagnostics13132172 https://www.mdpi.com/2075-4418/13/13/2172 (Full text)

Clinical Features of Post-Covid Syndrome

Abstract:

There is no common understanding of the clinical picture of post-covid syndrome. The US regulator CDC proposes to highlight:

(A) persistent symptoms and conditions that begin during acute COVID-19 illness;

B) new onset late complications after asymptomatic disease or a period of acute symptomatic relief or remission;

(C) the evolution of symptoms and conditions that include some persistent symptoms (eg, shortness of breath) with the addition of new symptoms or conditions over time (eg, cognitive difficulties).

Some manifestations may resemble other postviral syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome, dysautonomia (eg, postural orthostatic tachycardia syndrome), or mast cell activation syndrome.

Source: Sayfulloyevich, P. S. ., & Musayevich, U. R. . (2023). Clinical Features of Post-Covid Syndrome. EUROPEAN JOURNAL OF INNOVATION IN NONFORMAL EDUCATION, 3(6), 34–36. Retrieved from http://inovatus.es/index.php/ejine/article/view/1786 http://inovatus.es/index.php/ejine/article/view/1786/1794 (Full text)

Long COVID: Complications, Underlying Mechanisms, and Treatment Strategies

Abstract:

Long Covid is one of the most prevalent and puzzling conditions that arose with the Covid pandemic. Covid-19 infection generally resolves within several weeks but some experience new or lingering symptoms. Though there is no formal definition for such lingering symptoms the CDC boadly describes long Covid as persons having a wide range of new, recurring or sustained health issues four or more weeks after first being infected with SARS-CoV2. The WHO defines long Covid as the manifestation of symptoms from a “probable or confirmed” Covid-19 infection that start approximately 3 months after the onset of the acute infection and last for more than 2 months.

Numerous studies have looked at the implications of long Covid on various organs. Many specific mechanisms have been proposed for such changes. In this article, we provide an overview of some of the main mechanisms by which long Covid induces end-organ damage proposed in recent research studies. We also review various treatment options, current clinical trials, and other potential therapeutic avenues to control long Covid followed by the information about the effect of vaccination on long Covid.

Lastly, we discuss some of the questions and knowledge gaps in the present understanding of long Covid. We believe more studies of the effects long Covid has on quality of life, future health and life expectancy are required to better understand and eventually prevent or treat the disease. We acknowledge the effects of long Covid are not limited to those in this article but as it may affect the health of future offspring and therefore, we deem it important to identify more prognostic and therapeutic targets to control this condition.

Source: Farigol Hakem Zadeh, Daniel R. Wilson, Devendra K. Agrawal. Long COVID: Complications, Underlying Mechanisms, and Treatment Strategies. Archives of Microbiology and Immunology. 7 (2023): 36-61. http://www.fortunejournals.com/articles/long-covid-complications-underlying-mechanisms-and-treatment-strategies.html (Full text)

New-onset type 1 diabetes in children and adolescents as postacute sequelae of SARS-CoV-2 infection: A systematic review and meta-analysis of cohort studies

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents may increase risk for a variety of post-acute sequelae including new-onset type 1 diabetes mellitus (T1DM). Therefore, this meta-analysis aims to estimate the risk of developing new-onset type 1 diabetes in children and adolescents as post-acute sequelae of SARS-CoV-2 infection.

PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to March 20, 2023. A systematic review and subsequent meta-analyses were performed to calculate the pooled effect size, expressed as risk ratio (RR) with corresponding 95% confidence interval (CI) of each outcome based on a one-stage approach and the random-effects estimate of the pooled effect sizes of each outcome were generated with the use of the DerSimonian-Laird method. Eight reports from seven studies involving 11 220 530 participants (2 140 897 patients with a history of diagnosed SARS-CoV-2 infection and 9 079 633 participants in the respective control groups) were included. The included studies reported data from four U.S. medical claims databases covering more than 503 million patients (IQVIA, HealthVerity, TriNetX, and Cerner Real-World Data), and three national health registries for all children and adolescents in Norway, Scotland, and Denmark.

It was shown that the risk of new-onset T1DM following SARS-CoV-2 infection in children and adolescents was 42% (95% CI 13%-77%, p = 0.002) higher compared with non-COVID-19 control groups. The risk of developing new-onset T1DM following SARS-CoV-2 infection was significantly higher (67%, 95% CI 32 %-112%, p = 0.0001) in children and adolescents between 0 and 11 years, but not in those between 12 and 17 years (RR = 1.10, 95% CI 0.54-2.23, p = 0.79). We also found that the higher risk for developing new-onset T1DM following SARS-CoV-2 infection only exists in studies from the United States (RR = 1.70, 95% CI 1.37-2.11, p = 0.00001) but not Europe (RR = 1.02, 95% CI 0.67-1.55, p = 0.93). Furthermore, we found that SARS-CoV-2 infection was associated with an elevation in the risk of diabetic ketoacidosis (DKA) in children and adolescents compared with non-COVID-19 control groups (RR = 2.56, 95% CI 1.07-6.11, p = 0.03).

Our findings mainly obtained from US medical claims databases, suggest that SARS-CoV-2 infection is associated with higher risk of developing new-onset T1DM and diabetic ketoacidosis in children and adolescents. These findings highlight the need for targeted measures to raise public health practitioners and physician awareness to provide intervention strategies to reduce the risk of developing T1DM in children and adolescents who have had COVID-19.

Source: Rahmati M, Yon DK, Lee SW, Udeh R, McEVoy M, Kim MS, Gyasi RM, Oh H, López Sánchez GF, Jacob L, Li Y, Koyanagi A, Shin JI, Smith L. New-onset type 1 diabetes in children and adolescents as postacute sequelae of SARS-CoV-2 infection: A systematic review and meta-analysis of cohort studies. J Med Virol. 2023 Jun;95(6):e28833. doi: 10.1002/jmv.28833. PMID: 37264687. https://onlinelibrary.wiley.com/doi/10.1002/jmv.28833

Analysis of tumor progression among patients with glioma after COVID-19 infection

Background: As of January 2023, there have been 6.7 million worldwide deaths attributed to SARS-CoV-2 COVID-19, which has impacted outcomes and medical care for all patients. Relatively little is known about the direct effects mediated by the virus on CNS tumor biology, despite the fact that viral neurotropism is well described, various coronavirus receptors have been observed in glioblastoma (GBM) tissues, and differential monocytic infiltration has been proposed to dysregulate the immune microenvironment. We detected a trend of rapid progression following COVID-19 infection among several patients with primary brain tumor patients and sought to systematically evaluate the pace of progression among infected patients in our institution.

Methods: A single-institutional database of COVID-19 patients and an electronic medical record (EMR) search tool were used to identify a total cohort of 67 patients with glioma for retrospective analysis. This included 38 GBMs, 18 IDH-mutant gliomas, 5 ependymomas, 2 pilocytic astrocytomas, 1 diffuse midline glioma, 1 diffuse hemispheric glioma, and 1 ganglioglioma patients, each of whom had a documented COVID-19 infection between June 2020-December 2022. Hyperprogression was defined as tumor increase ≥40% compared to previous scan using RECIST size criteria.

Results: Thirty-nine (58%) patients experienced tumor progression following COVID-19 infection at a median of 34 days (range=1-734 days) after testing positive for COVID-19. Twenty-two (56%) had received COVID-19 vaccine before their infection and 5 (13%) had asymptomatic infections. Twenty-two patients had measurably increased tumor area by a median of 63% (range=10-2,900%), 18 of which constituted hyperprogression;16 patients developed multifocal disease, 8 developed new nodular enhancement, 3 developed leptomeningeal disease (LMD), and 2 experienced increased infiltrative disease alone. Ten patients’ presentation with new glioma was preceded by COVID-19 infection by a median of 31 days. GBM patients represented the majority of progression events, among whom 59% progressed within 60 days of documented infection (median 25 days). This subgroup of GBM with rapid progression within 60 days had a mOS from infection of 5.2 months; 89% had TERT promotor mutations and 42% had MGMT promoter methylation.

Conclusions: Glioma patients appear to have disease progression at an accelerated pace in the first two months after COVID-19 infection. This suggests that glioma patients should continue observing strict precautions to prevent infection and should be clinically monitored vigilantly after infection, with consideration for short interval imaging during treatment. These preliminary data warrant further investigation exploring changes of immune cell infiltration in the tumor microenvironment and the possible correlation between tumor progression and COVID-19.

Source: Tim Gregory, Stephanie Knight, Ashley Aaroe, Barbara Jane O’Brien, Chirag B Patel, Shiao-Pei S. Weathers, Nazanin Majd, Vinay K. Puduvalli, and Carlos Kamiya-Matsuoka. Analysis of tumor progression among patients with glioma after COVID-19 infection.
Journal of Clinical Oncology 2023 41:16_suppl, 2041-2041 https://ascopubs.org/action/showCitFormats?doi=10.1200/JCO.2023.41.16_suppl.2041