The long-term effects of the Covid-19 infection on cardiac symptoms.

BACKGROUND: Besides the lungs, coronavirus disease 2019 (COVID-19) can affect the cardiovascular, digestive, urinary, hepatic, and central nervous systems. Other than its short-term effects, COVID-19 may also cause long-term complications. In this study, we assessed long-term COVID-19 cardiovascular symptoms among patients in a cardiovascular clinic. METHOD: A retrospective cohort was conducted between October 2020 to May 2021 on patients at an outpatient cardiovascular clinic in Shiraz, Iran. Patients with a history of COVID-19 at least one year before their referral were included. Baseline information was extracted from the clinic's database. Data were collected regarding symptoms like dyspnea, chest pain, fatigue, and palpitations after a year of COVID-19. We also noted any major adverse cardiac events (MACE). RESULTS: Most common symptoms after a year of COVID-19 were exertional dyspnea (51.2%), dyspnea at rest (41.6%), fatigue (39%), and chest pain (27.1%). The symptoms were more prevalent in hospitalized patients than in non-hospitalized patients. The prevalence of MACE was about 6.1% during the 12-month follow-up, with this rate being higher in those with a history of hospitalization or comorbid diseases. CONCLUSION: The prevalence of cardiovascular symptoms was fairly high in patients at our clinic a year after COVID-19, and the most common symptom was dyspnea. Hospitalized patients had more MACE. (Clinicaltrial.gov number: NCT05715879)(04/02/2023).

Silent Hypoxemia in COVID-19 Pneumonia.

In patients suffering from Coronavirus Disease 2019 (COVID-19), dyspnoea is less likely to occur despite hypoxemia. Even if the patient develops severe hypoxemia, it cannot be detected from subjective symptoms. In other words, it becomes more serious without the person or the surroundings noticing it. Initially less talked about, hypoxemia without dyspnoea (silent hypoxemia or happy hypoxia: hypoxemia that does not coincide with dyspnoea) is now experienced in many institutions. Dyspnoea is defined as "the unpleasant sensation that accompanies breathing." Dyspnoea occurs when afferent information is transmitted to the sensory area. Receptors involved in the development of dyspnoea include central and peripheral chemoreceptors, chest wall receptors, lung receptors, upper respiratory tract receptors and corollary discharge receptors. In the present study, we considered mechanisms mediating the silent hypoxemia through three cases experienced at our hospital as a dedicated coronavirus treatment hospital. We have treated about 600 people infected with COVID-19, of which about 10% were severe cases. In the present study, the patients' condition was retrospectively extracted and analysed. We investigated three typical cases of COVID-19 pneumonia admitted to our hospital (men and women between the ages of 58 and 86 with hypoxemia and tachypnoea). Silent hypoxemia is not entirely without dyspnoea, but hypoxemia does not cause dyspnoea commensurate with its severity. The virus may have specific effects on the respiratory control system. In our cases, respiratory rate significantly increased with hypoxemia, and hyperventilation occurred. Therefore, information about hypoxemia is transmitted from the carotid body. Since hyperventilation occurs, it is suggested that information is transmitted to effectors such as respiratory muscles. The fact that these patients did not feel the unpleasant sensation indicates that information is not accurately transmitted to the sensory area of the cerebral cortex. These cases suggest that there may be a problem somewhere in the path from the respiratory centre to the sensory area.

Natriuretic Peptides as Biomarkers: Narrative Review and Considerations in Cardiovascular and Respiratory Dysfunctions.

Natriuretic peptides (NPs) encompass a family of structurally related hormone/paracrine factors acting through the natriuretic peptide system regulating cell proliferation, vessel tone, inflammatory processes, neurohumoral pathways, fluids, and electrolyte balance. The three most studied peptides are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-Type natriuretic peptide (CNP). ANP and BNP are the most relevant NPs as biomarkers for the diagnosis and prognosis of heart failure and underlying cardiovascular diseases, such as cardiac valvular dysfunction, hypertension, coronary artery disease, myocardial infarction, persistent arrhythmias, and cardiomyopathies. Cardiac dysfunctions related to cardiomyocytes stretching in the atria and ventricles are primary elicitors of ANP and BNP release, respectively. ANP and BNP would serve as biomarkers for differentiating cardiac versus noncardiac causes of dyspnea and as a tool for measuring the prognosis of patients with heart failure; nevertheless, BNP has been shown with the highest predictive value, particularly related to pulmonary disorders. Plasma BNP has been reported to help differentiate cardiac from pulmonary etiologies of dyspnea in adults and neonates. Studies have shown that COVID-19 infection also increases serum levels of N-terminal pro b-type natriuretic peptide (NT-proBNP) and BNP. This narrative review assesses aspects of ANP and BNP on their physiology, and predictive values as biomarkers. We present an overview of the NPs' synthesis, structure, storage, and release, as well as receptors and physiological roles. Following, considerations focus on ANP versus BNP, comparing their relevance in settings and diseases associated with respiratory dysfunctions. Finally, we compiled data from guidelines for using BNP as a biomarker in dyspneic patients with cardiac dysfunction, including its considerations in COVID-19.

COVID-19 disease severity to predict persistent symptoms: a systematic review and meta-analysis.

BACKGROUND: It is unclear, whether the initial disease severity may help to predict which COVID-19 patients at risk of developing persistent symptoms. AIM: The aim of this study was to examine whether the initial disease severity affects the risk of persistent symptoms in post-acute COVID-19 syndrome and long COVID. METHODS: A systematic search was conducted using PUBMED, Google Scholar, EMBASE, and ProQuest databases to identify eligible articles published after January 2020 up to and including 30 August 2021. Pooled odds ratio (OR) and confidence intervals (CIs) were calculated using random effects meta-analysis. FINDINGS: After searching a total of 7733 articles, 20 relevant observational studies with a total of 7840 patients were selected for meta-analysis. The pooled OR for persistent dyspnea in COVID-19 survivors with a severe versus nonsevere initial disease was 2.17 [95%CI 1.62 to 2.90], and it was 1.33 [95%CI 0.75 to 2.33] for persistent cough, 1.30 [95%CI 1.06 to 1.58] for persistent fatigue, 1.02 [95%CI 0.73 to 1.40] for persistent anosmia, 1.22 [95%CI 0.69 to 2.16] for persistent chest pain, and 1.30 [95%CI 0.93 to 1.81] for persistent palpitation. CONCLUSIONS: Contrary to expectations, we did not observe an association between the initial COVID-19 disease severity and common persistent symptoms except for dyspnea and fatigue. In addition, it was found that being in the acute or prolonged post-COVID phase did not affect the risk of symptoms. Primary care providers should be alert to potential most prevalent persistent symptoms in all COVID-19 survivors, which are not limited to patients with critical-severe initial disease.

Comparing research recruitment strategies to prospectively identify patients presenting with breathlessness in primary care.

Two recruitment strategies for research were compared to prospectively identify patients with breathlessness who are awaiting a diagnosis in primary care. The first method utilised searches of the electronic patient record (EPR), the second method involved an electronic template triggered during a consultation. Using an electronic template triggered at the point of consultation increased recruitment to prospective research approximately nine-fold compared with searching for symptom codes and study mailouts.

Prevalence, risk factors and treatments for post-COVID-19 breathlessness: a systematic review and meta-analysis.

Persistent breathlessness >28 days after acute COVID-19 infection has been identified as a highly debilitating post-COVID symptom. However, the prevalence, risk factors, mechanisms and treatments for post-COVID breathlessness remain poorly understood. We systematically searched PubMed and Embase for relevant studies published from 1 January 2020 to 1 November 2021 (PROSPERO registration number: CRD42021285733) and included 119 eligible papers. Random-effects meta-analysis of 42 872 patients with COVID-19 reported in 102 papers found an overall prevalence of post-COVID breathlessness of 26% (95% CI 23-29) when measuring the presence/absence of the symptom, and 41% (95% CI 34-48) when using Medical Research Council (MRC)/modified MRC dyspnoea scale. The pooled prevalence decreased significantly from 1-6 months to 7-12 months post-infection. Post-COVID breathlessness was more common in those with severe/critical acute infection, those who were hospitalised and females, and was less likely to be reported by patients in Asia than those in Europe or North America. Multiple pathophysiological mechanisms have been proposed (including deconditioning, restrictive/obstructive airflow limitation, systemic inflammation, impaired mental health), but the body of evidence remains inconclusive. Seven cohort studies and one randomised controlled trial suggested rehabilitation exercises may reduce post-COVID breathlessness. There is an urgent need for mechanistic research and development of interventions for the prevention and treatment of post-COVID breathlessness.

Low dose of morphine to relieve dyspnea in acute respiratory failure (OpiDys): protocol for a double-blind randomized controlled study.

BACKGROUND: Dyspnea is common and severe in intensive care unit (ICU) patients managed for acute respiratory failure. Dyspnea appears to be associated with impaired prognosis and neuropsychological sequels. Pain and dyspnea share many similarities and previous studies have shown the benefit of morphine on dyspnea in patients with end-stage onco-hematological disease and severe heart or respiratory disease. In these populations, morphine administration was safe. Here, we hypothesize that low-dose opioids may help to reduce dyspnea in patients admitted to the ICU for acute respiratory failure. The primary objective of the trial is to determine whether the administration of low-dose titrated opioids, compared to placebo, in patients admitted to the ICU for acute respiratory failure with severe dyspnea decreases the mean 24-h intensity of dyspnea score. METHODS: In this single-center double-blind randomized controlled trial with 2 parallel arms, we plan to include 22 patients (aged 18-75 years) on spontaneous ventilation with either non-invasive ventilation, high flow oxygen therapy or standard oxygen therapy admitted to the ICU for acute respiratory failure with severe dyspnea. They will be assigned after randomization with a 1:1 allocation ratio to receive in experimental arm administration of low-dose titrated morphine hydrochloride for 24 h consisting in an intravenous titration relayed subcutaneously according to a predefined protocol, or a placebo (0.9% NaCl) administered according to the same protocol in the control arm. The primary endpoint is the mean 24-h dyspnea score assessed by a visual analog scale of dyspnea. DISCUSSION: To our knowledge, this study is the first to evaluate the benefit of opioids on dyspnea in ICU patients admitted for acute respiratory failure. TRIAL REGISTRATION: ClinicalTrials.gov NCT04358133 . Registered on 24 April 2020.

The effects of COVID-19 on respiratory muscle performance: making the case for respiratory muscle testing and training.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in multiorgan damage primarily mediated by viral infiltration via angiotensin-converting enzyme-2 receptors on the surface of cells. A primary symptom for many patients is exertional dyspnoea which may persist even beyond recovery from the viral infection. Respiratory muscle (RM) performance was hypothesised as a contributing factor to the severity of coronavirus disease 2019 (COVID-19) symptoms, such as dyspnoea, and outcomes. This was attributed to similarities between patient populations at elevated risk for severe COVID-19 symptoms and those with a greater likelihood of baseline RM weakness and the effects of prolonged mechanical ventilation. More recent evidence suggests that SARS-CoV-2 infection itself may cause damage to the RM, and many patients who have recovered report persistent dyspnoea despite having mild cases, normal lung function or undamaged lung parenchyma. These more recent findings suggest that the role of RM in the persistent dyspnoea due to COVID-19 may be more substantial than originally hypothesised. Therefore, screening for RM weakness and providing interventions to improve RM performance appears to be important for patients with COVID-19. This article will review the impact of SARS-CoV-2 infection on RM performance and provide clinical recommendations for screening RM performance and treatment interventions.

Cardiopulmonary Exercise Testing Distinguishes between Post-COVID-19 as a Dysfunctional Syndrome and Organ Pathologies.

(1) Background: Dyspnea is one of the most frequent symptoms among post-COVID-19 patients. Cardiopulmonary exercise testing (CPET) is key to a differential diagnosis of dyspnea. This study aimed to describe and classify patterns of cardiopulmonary dysfunction in post-COVID-19 patients, using CPET. (2) Methods: A total of 143 symptomatic post-COVID-19 patients were included in the study. All patients underwent CPET, including oxygen consumption, slope of minute ventilation to CO2 production, and capillary blood gas testing, and were evaluated for signs of limitation by two experienced examiners. In total, 120 patients reached a satisfactory level of exertion and were included in further analyses. (3) Results: Using CPET, cardiovascular diseases such as venous thromboembolism or ischemic and nonischemic heart disease were identified as either cardiac (4.2%) or pulmonary vascular (5.8%) limitations. Some patients also exhibited dysfunctional states, such as deconditioning (15.8%) or pulmonary mechanical limitation (9.2%), mostly resulting from dysfunctional breathing patterns. Most (65%) patients showed no signs of limitation. (4) Conclusions: CPET can identify patients with distinct limitation patterns, and potentially guide further therapy and rehabilitation. Dysfunctional breathing and deconditioning are crucial factors for the evaluation of post-COVID-19 patients, as they can differentiate these dysfunctional syndromes from organic diseases. This highlights the importance of dynamic (as opposed to static) investigations in the post-COVID-19 context.

A Man With Malaise, Myalgia, and Rapidly Progressive Interstitial Lung Disease.

CASE PRESENTATION: A 45-year-old man sought treatment at the ED during the third wave of the COVID-19 pandemic with a month-long history of fatigue, cough, myalgia, and hand stiffness. He did not report dyspnea. He had no past medical history and previously was fit and active, working as a farmer. He was a lifelong nonsmoker and had no family history of lung disease.

A 54-Year-Old Man With Migratory Pulmonary Consolidation and Progressive Dyspnea.

CASE PRESENTATION: A 54-year-old man with chronic hepatitis B was admitted to the hospital with progressive dyspnea on exertion. He reported experiencing intermittent fever, dyspnea on exertion, and relapsing pleuritic chest pain starting 6 months prior, after his first dose of the ChAdOx1 nCoV-19 vaccine. In the past 2 months, he had been admitted to the hospital twice and diagnosed with recurrent pneumonia. Under antibiotic treatment, his dyspnea and low-grade fever demonstrated waxing and waning behaviors. Migratory pulmonary consolidation, which moved from the left lower lobe to the right middle lobe, was identified and diagnosed as relapsing pneumonia. Chest CT scan was performed in a previous admission 2 months earlier that revealed multifocal peripheral consolidation in the left lower lobe and right middle lobe. His occupation required the maintenance of overall fitness, and he denied immunosuppressant use, illicit drug abuse, cigarette smoking, suspicious travel, suspicious contact, or family history. No recent history of trauma, surgery, or air travel was reported.

Diaphragm dysfunction as a potential determinant of dyspnea on exertion in patients 1 year after COVID-19-related ARDS.

Some COVID-19 patients experience dyspnea without objective impairment of pulmonary or cardiac function. This study determined diaphragm function and its central voluntary activation as a potential correlate with exertional dyspnea after COVID-19 acute respiratory distress syndrome (ARDS) in ten patients and matched controls. One year post discharge, both pulmonary function tests and echocardiography were normal. However, six patients with persisting dyspnea on exertion showed impaired volitional diaphragm function and control based on ultrasound, magnetic stimulation and balloon catheter-based recordings. Diaphragm dysfunction with impaired voluntary activation can be present 1 year after severe COVID-19 ARDS and may relate to exertional dyspnea.This prospective case-control study was registered under the trial registration number NCT04854863 April, 22 2021.

A Young Man With Dyspnea.

CASE PRESENTATION: A 27-year-old accountant came to the ED with difficulty walking and progressive weakness of both lower limbs for 4 days' duration. He did not report a history of trauma or fall. He demonstrated no vertigo, headache, neck or back pain, disturbed vision, loss of weight, or weakness in upper limbs. He also reported difficulty breathing, fever, severe abdominal pain, and loose stools of 1 day's duration. His recorded maximum temperature at home was 38.3 °C. The fever subsided with oral paracetamol 500 mg. He did not report having weakness in any limb before the current presentation. He did not have comorbid diabetes mellitus or hypertension. Thirty days before presentation, he experienced fever, cough, and rhinorrhea and received a diagnosis of COVID-19 after reverse-transcriptase polymerase chain reaction testing. At that time, symptoms had been minimal, vitals signs and chest radiography findings were normal, and he had undergone home isolation. He had maintained an oxygen saturation of 98% to 99% as measured on pulse oximetry. He had not received any treatment at that time. His symptoms had lasted for 7 days, and he remained asymptomatic up to the current presentation with paraparesis.

A 51-Year-Old Woman With Interstitial Lung Disease and Subsequent COVID-19 Presenting With Worsening Dyspnea.

CASE PRESENTATION: A 51-year-old Puerto Rican woman, with a known but inconclusive diagnosis of interstitial lung disease (ILD) since 2002 and recent moderate COVID-19, is now presenting with subacute worsening dyspnea on exertion. The patient had sporadic medical care over the years for her ILD (Table 1). Prior workup included chest CT imaging with a "crazy-paving" pattern of lung disease, as defined by ground-glass opacity with superimposed interlobular septal thickening and visible intralobular lines. Bronchoscopy showed normal airway examination, and BAL revealed clear fluid with foamy macrophages and negative cultures. Video-assisted thoracoscopic surgery and transbronchial biopsy specimens both showed foamy macrophages. Results of pulmonary function testing (PFT) revealed an isolated gas transfer defect on diffusing capacity of the lungs for carbon monoxide (Dlco). She had lived with mild yet nonprogressive functional impairment and stable exercise intolerance over these years. She was then hospitalized for COVID-19 in August 2020 and for recurrent shortness of breath in September 2020. She now presented 4 months following her September 2020 hospitalization.

Platypnea-orthodeoxia syndrome in SARS-CoV-2 related ARDS: a case report.

Platypnea-Orthodeoxia Syndrome (POS) is an often misdiagnosed clinical condition characterized by dyspnea and hypoxia in sitting or semi-sitting position, reversible in supine position. Although POS is typically associated with intracardiac shunts, it seems frequent also in SARS-CoV-2 related Acute Respiratory Distress Syndrome (ARDS). In fact, the prevalent involvement of the lung bases due to interstitial pneumonia can determine refractory positional hypoxemia, with marked desaturation in the sitting position and regression or improvement in the supine position, configuring the clinical picture of the POS. We present a clinical case of POS associated with acute respiratory distress from SARS-CoV-2 pneumonia in which refractory hypoxia would have required support by invasive mechanical ventilation if the syndrome had not been identified.

A 31-Year-Old Man With Fever, Atypical Chest Pain, and Mediastinal Mass.

CASE PRESENTATION: A 31-year-old Asian male never-smoker living in the upper Midwest with a past medical history of congenital bilateral hearing loss sought treatment with a 1-week history of fever, fatigue, right-sided pleuritic chest pain, shortness of breath, productive cough with mild intermittent hemoptysis, night sweats, and unintentional 10-lb weight loss over 4 weeks. He was adopted from South Korea as an infant, and thus the family history was unknown. He worked in the heating, ventilation, and air conditioning business, performing installations and repairs. There was no known exposure to animals, caves, rivers, lakes, or wooded areas. He travelled to South Korea and New Hampshire approximately 9 months previously. He did not take any medication.

[Dyspnea: neurobiological and clinical aspects].

An analysis of the results of studies carried out by specialists of the Russian Respiratory Society over the past 15 years is given. The article also includes the main provisions set out in the III Guidelines for dyspnea. A significant part of the manual is devoted to the recent achievements in studying neurophysiological processes in the brain structures during the development of dyspnea. These achievements were driven by image-diagnosis methods. An important aspect of this series of works for the clinical practice was identifying dyspnea domains and developing the instruments to assess severity. Analysis of the data on dyspnea from the clinical practice showed a highly heterogenic clinical picture, which must be taken into account in the management of individual patients. A diagnostic algorithm for long-term follow-up of patients with dyspnea syndrome is also discussed. The attention of doctors is drawn to the features of dyspnea during COVID-19; the disproportion between the sensory perception of respiratory discomfort and the degree of oxygen desaturation is emphasized. It was concluded that in the Russian-speaking environment of patients, doctors should actively use a verbal characteristic of dyspnea the language of dyspnea.