Long post-COVID-19 postural tachycardia syndrome (PoTS): A novel case

Introduction

There are no established ESC/NICE guidelines for early risk preventive strategies for postural tachycardia syndrome following long COVID-19 infection.1 A lack of early multi-disciplinary input and risk preventive strategies for this population has led to significant cardiovascular implications such as postural tachycardia and syncope, contributing to long-term emotional distress in recent years.1,2

Case presentation

A previously fit 36-year-old woman was admitted to our tertiary centre with a 3-month history of palpitations, chest discomfort and dizziness that were prominent while standing and improved with recumbence. She also described her palpitations, which were sometimes associated with missed beats, and it took longer than expected (at least 10–15 minutes) to settle after postural changes. These symptoms had all significantly impacted on her daily physical activities and caused emotional distress. She gave a history of serious COVID-19 infection requiring hospital admission 4 months previously. She reported that she was treated as having COVID pneumonitis requiring antibiotics, oxygen and steroids but no intensive care admission. Since then, she had noticed frequent episodes of postural palpitations with chest tightness, which had led to her recent admission. On examination, she has normal cardiorespiratory findings and no features of systemic involvement. She has no other significant family and social history with regard to other cardiovascular risk factors.

Initially, she was enrolled into a postural assessment of resting heart rate and blood pressure when she had her symptoms of palpitations. Her resting heart rate was 100 bpm while standing. Interestingly, her resting heart rate returned to normal (54 bpm) after 10 minutes of supine position. Her blood pressure 100/60 while supine and 98/74 when standing, which had ruled out postural hypotension. Following this, an active stand test (tilt table test) was administered on subsequent day. Her electrocardiogram (Fig 1) revealed sinus tachycardia when she had episodes of palpitation but it returned to normal sinus rhythm with heart rate 60 bpm after 10 minutes of recumbent position from standing. All blood investigations, including full blood count, troponins, inflammatory markers and renal profile including electrolytes, revealed normal findings, which had ruled out other differentials.

Discussion

As a whole, these postural assessments (Tables 1 and 2) had met the criteria for definition of postural tachycardia syndrome2 (typical symptoms with significant heart rate increase of >30 beats per minute within 10 minutes of standing and without orthostatic hypotension). To support this, her echocardiogram showed no significant signs of structural heart disease and satisfactory blood investigations. Given her timing of her postural cardiovascular symptoms related to post-COVID-19 infection and criteria being met for postural assessment, she was finally diagnosed as having postural tachycardia syndrome as a cause for long-COVID-19 symptoms.3 Overall, she was advised to increase her fluid intake to 3 litres per day with increased salt intake, to use lower body compression garments and to take non-upright exercise.1 This was followed by early multidisciplinary team (MDT) input, including the recommendation of webinars on living with POTS and psychological counselling.2

Conclusion

It is well-recognised in recent literature that a diagnosis of PoTS post-COVID infection is easily overlooked as it does not associate with structural or arrhythmic heart disease and its specific aetiology is poorly defined apart from autonomic dysregulation.1,3 Therefore, more epidemiology study and detailed prospective research in long-COVID-19 patients are crucial for early recognition of this syndrome and long-term risk prevention.1,2

Source: Khin Kay Kay Kyaw. Long post-COVID-19 postural tachycardia syndrome (PoTS): A novel case. Clinical Medicine Nov 2023, 23 (Suppl 6) 48-49; DOI: 10.7861/clinmed.23-6-s48 https://www.rcpjournals.org/content/clinmedicine/23/Suppl_6/48 (Full text)

Long COVID is not a uniform syndrome: Evidence from person-level symptom clusters using latent class analysis

Abstract:

Background: The current study aims to enhance insight into the heterogeneity of long COVID by identifying symptom clusters and associated socio-demographic and health determinants.

Methods: A total of 458 participants (Mage 36.0 ± 11.9; 46.5% male) with persistent symptoms after COVID-19 completed an online self-report questionnaire including a 114-item symptom list. First, a k-means clustering analysis was performed to investigate overall clustering patterns and identify symptoms that provided meaningful distinctions between clusters. Next, a step-three latent class analysis (LCA) was performed based on these distinctive symptoms to analyze person-centered clusters. Finally, multinominal logistic models were used to identify determinants associated with the symptom clusters.

Results: From a 5-cluster solution obtained from k-means clustering, 30 distinctive symptoms were selected. Using LCA, six symptom classes were identified: moderate (20.7%) and high (20.7%) inflammatory symptoms, moderate malaise-neurocognitive symptoms (18.3%), high malaise-neurocognitive-psychosocial symptoms (17.0%), low-overall symptoms (13.3%) and high overall symptoms (9.8%). Sex, age, employment, COVID-19 suspicion, COVID-19 severity, number of acute COVID-19 symptoms, long COVID symptom duration, long COVID diagnosis, and impact of long COVID were associated with the different symptom clusters.

Conclusions: The current study’s findings characterize the heterogeneity in long COVID symptoms and underscore the importance of identifying determinants of different symptom clusters.

Source: van den Houdt SCM, Slurink IAL, Mertens G. Long COVID is not a uniform syndrome: Evidence from person-level symptom clusters using latent class analysis. J Infect Public Health. 2023 Dec 29;17(2):321-328. doi: 10.1016/j.jiph.2023.12.019. Epub ahead of print. PMID: 38183882. https://www.sciencedirect.com/science/article/pii/S1876034123004616 (Full text)

The Multisystem Impact of Long COVID: A Comprehensive Review

Abstract:

Background: COVID-19 was responsible for the latest pandemic, shaking and reshaping healthcare systems worldwide. Its late clinical manifestations make it linger in medical memory as a debilitating illness over extended periods.
Methods: Recent literature was systematically analyzed to categorize and examine the symptomatology and pathophysiology of Long COVID across various bodily systems, including pulmonary, cardiovascular, gastrointestinal, neuropsychiatric, dermatological, renal, hematological, and endocrinological aspects.
Results: The review outlines the diverse clinical manifestations of Long COVID across multiple systems, emphasizing its complexity and challenges in diagnosis and treatment. Factors such as pre-existing conditions, initial COVID-19 severity, vaccination status, gender, and age were identified as influential in the manifestation and persistence of Long COVID symptoms. This condition is highlighted as a debilitating disease capable of enduring over an extended period and presenting new symptoms over time.
Conclusions: Long COVID emerges as a condition with intricate multi-systemic involvement, complicating its diagnosis and treatment. The findings underscore the necessity for a nuanced understanding of its diverse manifestations to effectively manage and address the evolving nature of this condition over time.
Source: Negrut, N.; Georgios, M.; Kampioti, S.; Bourelou, M.; Kopanyi, F.; Hassan, F.D.; Asowed, A.; Taleouine, F.Z.; Ferician, A.; Marian, P. The Multisystem Impact of Long COVID: A Comprehensive Review. Preprints 2024, 2024010099. https://doi.org/10.20944/preprints202401.0099.v1 https://www.preprints.org/manuscript/202401.0099/v1 (Full text available as PDF file)

Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection

Abstract:

Introduction: Emotional apathy has recently been identified as a common symptom of long COVID. While recent meta-analyses have demonstrated generalized EEG slowing with the emergence of delta rhythms in patients hospitalized for severe SARS-CoV-2 infection, no EEG study or dopamine transporter scintigraphy (DaTSCAN) has been performed in patients with long COVID presenting with apathy. The objective of this case report was to explore the pathophysiology of neuropsychological symptoms in long COVID.

Case presentation: A 47-year-old patient who developed a long COVID with prominent apathy following an initially clinically mild SARS-CoV-2 infection underwent neuropsychological assessment, cerebral MRI, DaTSCAN, and resting-state high-density EEG 7 months after SARS-CoV-2 infection. The EEG data were compared to those of 21 healthy participants. The patient presented with apathy, cognitive difficulties with dysexecutive syndrome, moderate attentional and verbal episodic memory disturbances, and resolution of premorbid mild gaming disorder, mild mood disturbances, and sleep disturbances. His MRI and DaTSCAN were unremarkable. EEG revealed a complex pattern of oscillatory abnormalities compared to the control group, with a strong increase in whole-scalp delta and beta band activity, as well as a decrease in alpha band activity. Overall, these effects were more prominent in the frontal-central-temporal region.

Conclusion: These results suggest widespread changes in EEG oscillatory patterns in a patient with long COVID characterized by neuropsychological complications with prominent apathy. Despite the inherent limitations of a case report, these results suggest dysfunction in the cortical networks involved in motivation and emotion.

Source: Benis D, Voruz P, Chiuve SC, Garibotto V, Assal F, Krack P, Péron J, Fleury V. Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection. Case Rep Neurol. 2023 Dec 5;16(1):6-17. doi: 10.1159/000535241. PMID: 38179211; PMCID: PMC10764086. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764086/ (Full text)

Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden

Abstract:

Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction.

Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD. For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever.

In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition.

Key points:

  • Cardiovascular autonomic dysfunction (CVAD), in particular postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia, are among the most frequent and distinct phenotypes of post-COVID-19 syndrome; one-third of highly symptomatic patients can be affected.
  • CVAD arises from a malfunction of the autonomic control of the circulation, and can involve failure or inadequate or excessive activation of the sympathetic and parasympathetic components of the autonomic nervous system.
  • As well as global circulatory disturbances, CVAD in post-COVID-19 syndrome can manifest as microvascular and endothelial dysfunction, with local symptoms such as headache, brain fog, chest pain, dyspnoea and peripheral circulatory symptoms, including skin discolouration, oedema, Raynaud-like phenomena, and heat and cold intolerance.
  • A structured diagnostic work-up based on a detailed patient history, cardiovascular autonomic testing, long-term electrocardiogram and blood-pressure monitoring, and ancillary cardiac and peripheral vascular tests will lead to an appropriate diagnosis.
  • Management of CVAD in post-COVID-19 syndrome should involve a correct diagnosis, patient education, and both non-pharmacological and pharmacological methods; a tailored exercise training programme, blood volume expansion and compression garments are especially effective.
  • Pharmacological approaches target heart rate control, blood volume expansion, promotion of vasoconstriction and venoconstriction, and reduction of hyperadrenergic drive.

Source: Fedorowski, A., Fanciulli, A., Raj, S.R. et al. Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden. Nat Rev Cardiol (2024). https://doi.org/10.1038/s41569-023-00962-3 https://www.nature.com/articles/s41569-023-00962-3

New Alcohol Sensitivity in Patients With Post-acute Sequelae of SARS-CoV-2 (PASC): A Case Series

Abstract:

Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID, is characterized by persistent symptoms after acute SARS-CoV-2 infection that can vary from patient to patient. Here, we present a case series of four patients with a history of SARS-CoV-2 infection referred to the Post-Acute COVID-19 Syndrome (PACS) Clinic at Stanford University for evaluation of persistent symptoms, who also experienced new-onset alcohol sensitivity.

Alcohol reactions and sensitivity are not well characterized in the literature as it relates to post-viral illness. While there have been some anecdotal reports of new alcohol sensitivity in PASC patients in the media, there is a paucity of published data in the medical literature about this topic. During their medical consultation, the patients self-reported new changes in their symptoms or behaviors following the use of alcohol. A new onset of alcohol sensitivities should be assessed along with other post-COVID-19 symptoms and may provide novel avenues to explore the pathobiology of illness and potential interventions.

Source: Eastin E F, Tiwari A, Quach T C, et al. (December 29, 2023) New Alcohol Sensitivity in Patients With Post-acute Sequelae of SARS-CoV-2 (PASC): A Case Series. Cureus 15(12): e51286. doi:10.7759/cureus.51286 https://www.cureus.com/articles/152512-new-alcohol-sensitivity-in-patients-with-post-acute-sequelae-of-sars-cov-2-pasc-a-case-series#!/ (Full text)

Dermatologic Changes in Experimental Model of Long-COVID

Abstract:

The COVID-19 pandemic, declared in early 2020, is an unprecedented global health crisis, causing over 7.0 million deaths and ongoing challenges. While the pharmaceutical industry expedited vaccine development, mutant SARS-CoV-2 strains remain a major fear. Moreover, concerns regarding the long-term health repercussions of COVID-19-affected individuals persist since individuals affected by mild and moderate to severe SARS-CoV-2 infection experience long-term cardiovascular complications, liver dysfunction, pulmonary afflictions, kidney impairments, and most importantly neurocognitive deficits.
In recent studies, we documented pathophysiological changes in various organs following the post-acute infection of mice with murine hepatitis virus-1 (MHV-1), a coronavirus, at both 7 days and 12 months after infection. One part of the body that can be drastically affected by SARS-CoV-2 is the skin. Studies have shown major changes in the skin post-acute SARS CoV-2 infection in humans. However, long-term dermatologic changes post-COVID have never been explored.
For the first time, we show several cutaneous findings both at the acute stages and long-term post-infection of mice with MHV-1 coronavirus (a promising experimental model to study acute and long-COVID). Precisely, we found destruction of the epidermal layer, an increase in the number of hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of the sebaceous glands at the acute stages, along with thinning of the panniculus carnosus, as well as the adventitial layer, which corresponds well with studies in humans.
In contrast, the cutaneous investigation in the long-COVID phase shows the absence of hair follicles from both the epidermal and dermal layers, the destruction of adipose tissues, and the devastation of the epidermal layer. Further, treatment of these mice with a 15 amino acid synthetic peptide, SPIKENET (SPK), which was effective in preventing Spike glycoprotein-1 binding with host receptors, as well as has a potent anti-inflammatory response to severe inflammatory stimulus) restored the loss of hair follicles and re-architected the epidermal and dermal layers.
Additionally, destruction in fatty tissue in the infected mice was successfully restored post-treatment with SPK. These findings suggest that SARS-CoV-2 initiates the changes early post-infection, leading to devastating skin alterations in the long term which can be prevented by our newly identified peptide drug SPK.
Source: Hussain, H.; Paidas, M.J.; Rajalakshmi, R.; Fadel, A.; Ali, M.; Chen, P.; Jayakumar, A.R. Dermatologic Changes in Experimental Model of Long-COVID. Preprints 2023, 2023122339. https://doi.org/10.20944/preprints202312.2339.v1 https://www.preprints.org/manuscript/202312.2339/v1 (Full text available as PDF file)

Smartphone-based evaluation of static balance and mobility in long-lasting COVID-19 patients

Abstract:

Background: SARS-CoV-2 infection can lead to a variety of persistent sequelae, collectively known as long COVID-19. Deficits in postural balance have been reported in patients several months after COVID-19 infection. The purpose of this study was to evaluate the static balance and balance of individuals with long COVID-19 using inertial sensors in smartphones.

Methods: A total of 73 participants were included in this study, of which 41 had long COVID-19 and 32 served as controls. All participants in the long COVID-19 group reported physical complaints for at least 7 months after SARS-CoV-2 infection. Participants were evaluated using a built-in inertial sensor of a smartphone attached to the low back, which recorded inertial signals during a static balance and mobility task (timed up and go test). The parameters of static balance and mobility obtained from both groups were compared.

Results: The groups were matched for age and BMI. Of the 41 participants in the long COVID-19 group, 22 reported balance impairment and 33 had impaired balance in the Sharpened Romberg test. Static balance assessment revealed that the long COVID-19 group had greater postural instability with both eyes open and closed than the control group. In the TUG test, the long COVID-19 group showed greater acceleration during the sit-to-stand transition compared to the control group.

Conclusion: The smartphone was feasible to identify losses in the balance motor control and mobility of patients with long-lasting symptomatic COVID-19 even after several months or years. Attention to the balance impairment experienced by these patients could help prevent falls and improve their quality of life, and the use of the smartphone can expand this monitoring for a broader population.

Source: Corrêa BDC, Santos EGR, Belgamo A, Pinto GHL, Xavier SS, Silva CC, Dias ÁRN, Paranhos ACM, Cabral ADS, Callegari B, Costa E Silva AA, Quaresma JAS, Falcão LFM, Souza GS. Smartphone-based evaluation of static balance and mobility in long-lasting COVID-19 patients. Front Neurol. 2023 Dec 11;14:1277408. doi: 10.3389/fneur.2023.1277408. PMID: 38148981; PMCID: PMC10750373. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10750373/ (Full text)

Analysis of post-COVID symptoms and predisposing factors for chronic post-COVID syndrome

Abstract:

Introduction: While there is sufficient information about acute COVID-19, which can cause a multisystemic and fatal disease, post-COVID syndrome and risk factors for this condition remain poorly known. We aimed to identify postCOVID symptoms and risk factors for chronic post-COVID syndrome through this study.

Materials and methods: This prospective cross-sectional study was conducted on 254 out of 384 COVID-19 patients admitted to our COVID-19 polyclinic between February and April 2021. The patients were questioned with a list of 37 symptoms at the fifth and twelfth weeks after disease onset via phone review, and their acute post-COVID (APC) and chronic post-COVID (CPC) symptoms were recorded. Data on risk factors were collected from the hospital’s medical records system. Associations between symptom count in the CPC phase and age, sex, hospitalization, RT-PCR result, specific radiological findings, comorbidities, and long-term medications were evaluated.

Result: Two hundred twenty-one patients had APC symptoms, and 138 patients had CPC symptoms. While the most common symptom was fatigue at week five, it was hair loss at week 12. Symptoms were observed significantly less in the CPC phase than in the APC phase (Z= -12.301, p= 0.00). Female sex and the presence of specific radiological findings were significantly associated with the occurrence of CPC symptoms (p= 0.03, p= 0.00, respectively). Long-term use of angiotensin-2 receptor blockers (ARBs) was correlated with a low symptom count in the CPC phase (p= 0.00).

Conclusions: Female sex and the presence of specific radiological findings were risk factors for developing CPC. Long-term use of ARBs was associated with a low chronic post-COVID symptom burden. A substantial cluster of multisystemic symptoms was observed in both phases, and this condition highlights the requirement for customized outpatient management that includes long-term follow-up and treatment of COVID-19 patients. Identifying the high-risk patients that will develop persistent symptoms can guide this management.

Source: Abalı H, Demir D, Gül Ş, Şimşek Veske N, Tural Onur S. Analysis of post-COVID symptoms and predisposing factors for chronic post-COVID syndrome. Tuberk Toraks. 2023 Dec;71(4):378-389. English. doi: 10.5578/tt.20239606. PMID: 38152008. https://pubmed.ncbi.nlm.nih.gov/38152008/ (Full text available as PDF file)

Persistence of post-COVID symptoms in the general population two years after SARS-CoV-2 infection: A systematic review and meta-analysis

Abstract:

Objective: This meta-analysis investigated the prevalence of post-COVID symptoms two-years after SARS-CoV-2 infection.

Methods: Electronic literature searches on PubMed, MEDLINE, CINAHL, EMBASE, Web of Science databases, and on medRxiv/bioRxiv preprint servers were conducted up to October 1, 2023. Studies reporting data on post-COVID symptoms at two-years after infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. Random-effects models were used for meta-analytical pooled prevalence of each symptom.

Results: From 742 studies identified, twelve met inclusion criteria. The sample included 7912 COVID-19 survivors (50.7% female; age: 59.5, SD: 16.3). Post-COVID symptoms were assessed at a follow-up of 722.9 (SD: 51.5) days after. The overall methodological quality of studies was moderate (mean: 6/10, SD: 1.2 points). The most prevalent post-COVID symptoms two-years after SARS-CoV-2 infection were fatigue (28.0%, 95%CI 12.0-47.0), cognitive impairments (27.6%, 95%CI 12.6-45.8), and pain (8.4%, 95%CI 4.9-12.8). Psychological disturbances such as anxiety (13.4%, 95%CI 6.3-22.5) and depressive (18.0%, 95%CI 4.8-36.7) levels as well as sleep problems (20.9%, 95%CI 5.25-43.25) were also prevalent. Pooled data showed high heterogeneity (I2 ≥ 75%).

Conclusion: This meta-analysis shows the presence of post-COVID symptoms in 30% of patients two-years after COVID-19. Fatigue, cognitive disorders, and pain were the most prevalent post-COVID symptoms. Psychological disturbances as well as sleep problems were still present two-years after COVID-19.

Source: Fernandez-de-Las-Peñas C, Notarte KI, Macasaet R, Velasco JV, Catahay JA, Ver AT, Chung W, Valera-Calero JA, Navarro-Santana M. Persistence of post-COVID symptoms in the general population two years after SARS-CoV-2 infection: A systematic review and meta-analysis. J Infect. 2023 Dec 13:S0163-4453(23)00590-X. doi: 10.1016/j.jinf.2023.12.004. Epub ahead of print. PMID: 38101521. https://www.journalofinfection.com/article/S0163-4453(23)00590-X/fulltext (Full text)