Cardiopulmonary Sequelae Research Articles

Long Neuro-COVID-19: Current Mechanistic Views and Therapeutic Perspectives.

Long-lasting COVID-19 (long COVID) diseases constitute a real life-changing burden for many patients around the globe and, overall, can be considered societal and economic issues. They include a variety of symptoms, such as fatigue, loss of smell (anosmia), and neurological-cognitive sequelae, such as memory loss, anxiety, brain fog, acute encephalitis, and stroke, collectively called long neuro-COVID-19 (long neuro-COVID). They also include cardiopulmonary sequelae, such as myocardial infarction, pulmonary damage, fibrosis, gastrointestinal dysregulation, renal failure, and vascular endothelial dysregulation, and the onset of new diabetes, with each symptom usually being treated individually. The main unmet challenge is to understand the mechanisms of the pathophysiologic sequelae, in particular the neurological symptoms. This mini-review presents the main mechanistic hypotheses considered to explain the multiple long neuro-COVID symptoms, namely immune dysregulation and prolonged inflammation, persistent viral reservoirs, vascular and endothelial dysfunction, and the disruption of the neurotransmitter signaling along various paths. We suggest that the nucleoprotein N of SARS-CoV-2 constitutes a "hub" between the virus and the host inflammation, immunity, and neurotransmission.

Two-year cardio-pulmonary follow-up after severe COVID-19: a prospective study

Short- and medium-term cardio-pulmonary sequelae after COVID-19 have been extensively studied. However, studies with longer follow-ups are required. This study aims to identify and characterise cardio-pulmonary sequelae, in patients hospitalised for SARS-CoV-2 pneumonia, at 24 months follow-up. This is a prospective, observational cohort study conducted on consecutive patients hospitalised for COVID-19 and acute respiratory failure. Patients were followed up at 24 months with complete pulmonary function tests (PFTs), 6-min walking test and a dyspnoea score (Modified Medical Research Council scale). A subgroup of patients with at least one clinical or functional sign suggestive of increased pulmonary pressures also underwent transthoracic echocardiography (TTE) to evaluate the presence of direct or indirect signs of pulmonary hypertension (PH). Ninety consecutive patients (74% men, median age 59.1 years) were enrolled in the study. In regard to PFTs, carbon monoxide diffusion capacity (DLCO) impairment was observed in 23 cases (26%), in all cases of mild entity. When considering the dyspnoea, 30 (34%) patients showed some degree of breathlessness. Forty patients underwent TTE. No patients had overt PH or chronic thromboembolic PH. However, all patients showed a hyperdynamic state of the right ventricle, and 8 (20%) patients had a decreased acceleration time on pulmonary valve, signs of increased pulmonary vasculature resistances and afterload elevation. At 24-month follow-up after severe COVID-19, DLCO and TTE prove to be the most sensitive tool to detect cardio-pulmonary sequelae. Dyspnoea is still present in about one-third of patients and requires a multidisciplinary approach.

Epidemiological and clinical perspectives of long COVID syndrome

Long COVID, or post-acute COVID-19 syndrome, is characterized by multi-organ symptoms lasting 2+ months after initial COVID-19 virus infection. This review presents the current state of evidence for long COVID syndrome, including the global public health context, incidence, prevalence, cardiopulmonary sequelae, physical and mental symptoms, recovery time, prognosis, risk factors, rehospitalization rates, and the impact of vaccination on long COVID outcomes. Results are presented by clinically relevant subgroups. Overall, 10–35% of COVID survivors develop long COVID, with common symptoms including fatigue, dyspnea, chest pain, cough, depression, anxiety, post-traumatic stress disorder, memory loss, and difficulty concentrating. Delineating these issues will be crucial to inform appropriate post-pandemic health policy and protect the health of COVID-19 survivors, including potentially vulnerable or underrepresented groups. Directed to policymakers, health practitioners, and the general public, we provide recommendations and suggest avenues for future research with the larger goal of reducing harms associated with long COVID syndrome.

Cardiopulmonary disease as sequelae of long-term COVID-19: Current perspectives and challenges.

COVID-19 infection primarily targets the lungs, which in severe cases progresses to cytokine storm, acute respiratory distress syndrome, multiorgan dysfunction, and shock. Survivors are now presenting evidence of cardiopulmonary sequelae such as persistent right ventricular dysfunction, chronic thrombosis, lung fibrosis, and pulmonary hypertension. This review will summarize the current knowledge on long-term cardiopulmonary sequelae of COVID-19 and provide a framework for approaching the diagnosis and management of these entities. We will also identify research priorities to address areas of uncertainty and improve the quality of care provided to these patients.

Comparing cardiac MRI and lung PET/CT after completion of tuberculosis treatment – preliminary findings of participants co-enrolled into the StatinTB trial and Cardiac Imaging After TB (CIA-TB) study

Abstract Introduction Mortality rates after successful tuberculosis (TB) treatment remain elevated and healthy survival is impaired by chronic pulmonary disease and persistent inflammation. Inflammation leads to a complex cascade of events and has been associated with cardiovascular disease (CVD). Recent epidemiological work described an increased risk of CVD in persons with history of TB. Aims and objectives In our ongoing StatinTB trial (NCT04147286), we evaluate safety and efficacy of 40 mg atorvastatin to reduce persistent lung inflammation (PLI) after TB treatment in HIV−/HIV+ adults measured by 18F-FDG-PET/CT. Participants are co-enrolled into the Cardiac Imaging After Tuberculosis (CIA-TB) study. Here we report preliminary findings of participants enrolled into the StatinTB trial and CIA-TB study with the aim to correlate PLI with cardiac magnetic resonance imaging (CMR) parameters. Methods Participants with clinical response to TB treatment and a negative sputum culture at 16 weeks were screened at the end of a 24-week course of treatment for drug-sensitive TB. PET/CT was performed on a Philips Gemini TF scanner and analysed using MIM®Software. PLI was defined as total lung glycolysis (TLG) ≥50 SUV·mL (Figure 1). CMR was performed using a 3T Siemens Magnetom Skyra scanner and parameters were derived from the following acquisitions: SSFP cine imaging of the short and long axes, T1 mapping (MOLLI, 5 (3) 3), T2 mapping and late gadolinium enhancement (LGE) imaging. StatinTB trial is conducted according to ICH-GCP. Results 26 participants (mean age 37.8±13.8 years, 38.5% women) underwent PET/CT and CMR. 23.1% were infected with HIV, 34.6% smokers, and 26.9% had a previous history of TB. Median BMI was 21.3 (IQR 19.7; 24.3). One participant reported hypertension. Common symptoms at enrollment were cough (26.9%), shortness of breath (11.5%), and chest pain (3.9%). On CT scan, 73.1% had pulmonary nodules, 57.7% scarring, 50.0% cavities, 42.3% bronchiectasis, 19.2% centrilobular disease, 19.2% distorted lung architecture, and 11.5% consolidations. On PET/CT, PLI was detected among 11 (42.3%) participants with a mean TLG of 216.0 (IQR 78.2; 384.0). In a multivariable regression analysis, left ventricular end systolic volume (LVESV) (−1.46; 95% CI: −2.89, −0.23; p=0.047) and distorted lung architecture (2.84; 95% CI: 1.17, 4.52; p=0.003) were significantly associated with TLG. Native T1 relaxation time showed a strong, but not significant association with TLG (15.01; 95% CI: −8.08, 38.10; p=184). Conclusion We present data of a young cohort at the end of TB treatment without significant cardiac risk factors. Structural lung disease is affecting at least half of participants, and many remain symptomatic. PLI is present in more than one-third of participants and our preliminary findings suggest an association with cardiac impairment. Further enrolment and ongoing laboratory studies will shed more light into post-TB cardio-pulmonary sequelae. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EDCTP

The cross-talk of lung and heart complications in COVID-19: Endothelial cells dysfunction, thrombosis, and treatment.

The pandemic respiratory illness SARS-CoV-2 has increasingly been shown to be a systemic disease that can also have profound impacts on the cardiovascular system. Although associated cardiopulmonary sequelae can persist after infection, the link between viral infection and these complications remains unclear. There is now a recognized link between endothelial cell dysfunction and thrombosis. Its role in stimulating platelet activation and thrombotic inflammation has been widely reported. However, the procoagulant role of microparticles (MPs) in COVID-19 seems to have been neglected. As membrane vesicles released after cell injury or apoptosis, MPs exert procoagulant activity mainly by exposing phosphatidylserine (PS) on their lipid membranes. It can provide a catalytic surface for the assembly of the prothrombinase complex. Therefore, inhibiting PS externalization is a potential therapeutic strategy. In this paper, we describe the pathophysiological mechanism by which SARS-CoV-2 induces lung and heart complications through injury of endothelial cells, emphasizing the procoagulant effect of MPs and PS, and demonstrate the importance of early antithrombotic therapy. In addition, we will detail the mechanisms underlying hypoxia, another serious pulmonary complication related to SARS-CoV-2-induced endothelial cells injury and discuss the use of oxygen therapy. In the case of SARS-CoV-2 infection, virus invades endothelial cells through direct infection, hypoxia, imbalance of the RAAS, and cytokine storm. These factors cause endothelial cells to release MPs, form MPs storm, and eventually lead to thrombosis. This, in turn, accelerates hypoxia and cytokine storms, forming a positive feedback loop. Given the important role of thrombosis in the disease, early antithrombotic therapy is an important tool for COVID-19. It may maintain normal blood circulation, accelerating the clearance of viruses, waning the formation of MPs storm, and avoiding disease progression.

Long-term comprehensive cardiopulmonary phenotyping of COVID-19

BackgroundPersistent symptoms after initial COVID-19 infection are common and are frequently referred to by the umbrella terms “post-COVID syndrome” and “long COVID”. The sheer number of affected patients pose an increasing challenge to healthcare systems worldwide. To date, our understanding of the pathophysiology of the post-COVID syndrome remains poor and the extent to which persistent cardiopulmonary abnormalities contribute to the symptom complex is unclear. We sought to determine the presence and impact of cardiopulmonary sequelae after COVID-19 in longitudinal assessment.MethodsWe report on 71 patients who underwent comprehensive, longitudinal testing in regular intervals for up to 12 months after their initial COVID-19 diagnosis. Testing included pulmonary function testing, cardiopulmonary exercise testing, dedicated left and right heart echocardiography, lung ultrasonography, and cardiac MRI.ResultsOur results demonstrate that subjective quality of life after COVID-19 (EQ-5D visual acuity scale, VAS, 67.4 for patients treated as outpatient, 79.2 for patients admitted to the general floor, 71.8 for patients treated in an ICU) is not related to the severity of the initial infection. Maximal exercise capacity is also reduced (VO2max 79% predicted, SD ± 19%); however, this is driven in large parts by patients who had initially required ICU-level of care. The degree of objective reduction in exertion did not correlate with quality of life scores. Pulmonary function testing revealed mild and persistent reduction in DLCO over the first 12 months without significant restrictive or obstructive lung disease. Left and right heart function was intact with good RV function and intact RV/PA coupling, imaging findings suggestive of myocarditis were uncommon (7% of patients).ConclusionA reduction in exercise capacity after COVID-19 is common, but is most prominent in patients previously treated in the ICU and more likely related to deconditioning or fatigue than to cardiopulmonary impairment. Subjective quality of life scores are independent of the severity of initial infection and do not correlate with objective measures of cardiopulmonary function. In our cohort, persistent cardiopulmonary impairment after COVID-19 was uncommon. The post-COVID syndrome is unlikely to be the result of cardiopulmonary sequalae and may reflect a post-ICU syndrome in some.Trial registration Registered on clinicaltrials.gov (NCT04442789), Date: June 23, 2020

264 Cardiac and pulmonary sequelae after COVID-19 pneumonia: a case series

AimsAlthough the new coronavirus (SARS-CoV-2) may cause an acute multiorgan syndrome (COVID-19), data are emerging on mid- and long-term sequelae of COVID-19 pneumonia. Since no study has hitherto investigated the role of both cardiac and pulmonary ultrasound techniques in detecting such sequelae, this study aimed at evaluating these simple diagnostic tools to appraise the cardiopulmonary involvement occurring after COVID-19 pneumonia.Methods and resultsTwenty-nine patients fully recovered from COVID-19 pneumonia were considered at our centre. On admission, all patients underwent 12-lead electrocardiogram (ECG) and transthoracic echocardiography (TTE) evaluation. Compression ultrasound (CUS) and lung ultrasound (LUS) were also performed. Finally, in each patient, pathological findings detected on LUS were correlated with the pulmonary involvement occurring after COVID-19 pneumonia as assessed on thoracic computed tomography (CT). Out of 29 patients (mean age 70 ± 10 years old; M 69%), prior cardiovascular and pulmonary comorbidities were recorded in 22 (76%). Twenty-seven patients (93%) were in sinus rhythm and two (7%) in atrial fibrillation. ECG repolarization abnormalities were extremely common (93%) and reflected the high prevalence of pericardial involvement on TTE (86%). Likewise, pleural abnormalities were frequently observed (66%). TTE signs of left and right ventricular dysfunction were reported in two patients only, but values of systolic pulmonary artery pressure were abnormal in 16 (55%) despite absence of prior comorbidities in 44% of them. Regarding LUS evaluation, most patients displayed abnormal values of diaphragmatic thickness and excursion (93%) which well correlated with the high prevalence (76%) of on pathological findings on CT scan. CUS ruled out deep vein thrombosis in all patients.ConclusionsData on cardiopulmonary sequelae after COVID-19 pneumonia are scarce. In our study, simple diagnostic tools (TTE and LUS) proved clinically useful for detection of cardiopulmonary involvement after COVID-19 pneumonia.

Evidence for impaired chronotropic responses to and recovery from 6-minute walk test in women with post-acute COVID-19 syndrome.

New Findings What is the central question of this study? Are chronotropic responses to a 6‐minute walk test different in women with post‐acute coronavirus disease 2019 (COVID‐19) syndrome compared with control subjects? What is the main finding and its importance? Compared with control subjects, the increase in heart rate was attenuated and recovery delayed after a 6‐minute walk test in participants after infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Women reporting specific symptoms at time of testing had greater impairments compared with control subjects and SARS‐CoV‐2 participants not actively experiencing these symptoms. Such alterations have potential to constrain not only exercise tolerance but also participation in free‐living physical activity in women during post‐acute recovery from COVID‐19. The short‐term cardiopulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are well defined. However, the implications of cardiopulmonary sequelae, persisting beyond acute illness, on physical function are largely unknown. Herein, we characterized heart rate responses to and recovery from a 6‐minute walk test (6MWT) in women ∼3 months after mild‐to‐moderate SARS‐CoV‐2 infection compared with non‐infected control subjects. Forty‐five women (n = 29 SARS‐CoV‐2; n = 16 controls; age = 56 ± 11 years; body mass index = 25.8 ± 6.0 kg/m2) completed pulmonary function testing and a 6MWT. The SARS‐CoV‐2 participants demonstrated reduced total lung capacity (84 ± 8 vs. 93 ± 13%; P = 0.006), vital capacity (87 ± 10 vs. 93 ± 10%; P = 0.040), functional residual capacity (75 ± 16 vs. 88 ± 16%; P = 0.006) and residual volume (76 ± 18 vs. 93 ± 22%; P = 0.001) compared with control subjects. No between‐group differences were observed in 6MWT distance (P = 0.194); however, the increase in heart rate with exertion was attenuated among SARS‐CoV‐2 participants compared with control subjects (+52 ± 20 vs. +65 ± 18 beats/min; P = 0.029). The decrease in heart rate was also delayed for minutes 1–5 of recovery among SARS‐CoV‐2 participants (all P < 0.05). Women reporting specific symptoms at the time of testing had greater impairments compared with control subjects and SARS‐CoV‐2 participants not actively experiencing these symptoms. Our findings provide evidence for marked differences in chronotropic responses to and recovery from a 6MWT in women several months after acute SARS‐CoV‐2 infection.

Long COVID: Distinction between Organ Damage and Deconditioning.

(1) Background: Long COVID syndrome refers to long-term sequelae of the novel viral disease, which occur even in patients with initially mild disease courses. However, there is still little evidence of the actual organic consequences and their frequency, and there is no standardized workup to diagnose long COVID syndrome yet. In this study, we aim to determine the efficiency of a stepwise diagnostic approach for reconvalescent COVID-19 patients with cardiopulmonary symptoms. (2) Methods: The diagnostic workup for long COVID syndrome included three steps. In the first step, the focus was on broad applicability (e.g., blood tests and body plethysmography). In the second step, cardiopulmonary exercise testing (CPET) and cardiac MRI (CMR) were used. The third step was tailored to the individual needs of each patient. The observation period lasted from 22 February to 14 May 2021. (3) Results: We examined 231 patients in our long COVID unit (mean [SD] age, 47.8 [14.9], 132 [57.1%] women). Acute illness occurred a mean (SD) of 121 (77) days previously. Suspicious findings in the first visit were seen in 80 (34.6%) patients, prompting further diagnostics. Thirty-six patients were further examined with CPET and CMR. Of those, 16 (44.4%) had pathological findings. The rest had functional complaints without organ damage (“functional long COVID”). Cardiopulmonary sequelae were found in asymptomatic as well as severe courses of the initial COVID-19 disease. (4) Conclusions: A structured diagnostic pathway for the diagnosis of long COVID syndrome is practicable and rational in terms of resource allocation. With this approach, manifest organ damage can be accurately and comprehensively diagnosed and distinguished from functional complaints.

Return to High Altitude After Recovery from Coronavirus Disease 2019.

Luks, Andrew M. and Colin K. Grissom. Return to high altitude after recovery from coronavirus disease 2019. High Alt Med Biol. 22: 119-127, 2021.-With the increasing availability of coronavirus disease 2019 (COVID-19) vaccines and the eventual decline in the burden of the disease, it is anticipated that all forms of tourism, including travel to high altitude, will rebound in the near future. Given the physiologic challenges posed by hypobaric hypoxia at high altitude, it is useful to consider whether high-altitude travel will pose risks to those previously infected with severe acute respiratory syndrome coronavirus 2, particularly those with persistent symptoms after resolution of their infection. Although no studies have specifically examined this question as of yet, available data on the cardiopulmonary sequelae of COVID-19 provide some sense of the problems people may face at high altitude and who warrants evaluation before such endeavors. On average, most individuals who have recovered from COVID-19 have normal or near normal gas exchange, pulmonary function testing, cardiovascular function, and exercise capacity, although a subset of individuals have persistent functional deficits in some or all of these domains when examined up to 5 months after infection. Evaluation is warranted before planned high-altitude travel in individuals with persistent symptoms at least 2 weeks after a positive test or hospital discharge as well as in those who required care in an intensive care unit or suffered from myocarditis or arterial or venous thromboembolism. Depending on the results of this testing, planned high-altitude travel may need to be modified or even deferred pending resolution of the identified abnormalities. As more people travel to high altitude after the pandemic and further studies are conducted, additional data should become available to provide further guidance on these issues.

Resumption of Sport at the United States Olympic and Paralympic Training Facilities During the COVID-19 Pandemic.

In this brief report, we describe the safety of reopening US Olympic and Paralympic Training facilities (USOPTFs) during the coronavirus disease 2019 (COVID-19) pandemic from July 2020 through October 2020. We evaluated the prevalence of COVID-19 infection at the time of reentry and cardiopulmonary sequelae of COVID-19 in elite athletes. All athletes returning to a USOPTF were required to go through a reentry protocol consisting of an electronic health history, a 6-day quarantine including twice-daily symptom surveys, COVID-19 polymerase chain reaction and antibody testing, physical examination, 12-lead electrocardiogram, high-sensitivity cardiac troponin I, and pulmonary function testing. Athletes with current or prior COVID-19 infection also underwent an echocardiogram, cardiology consultation, and additional testing as indicated. All athletes followed rigorous infection prevention measures and minimized contact with the outside community following reentry. At the time of this report, 301 athletes completed the reentry protocol among which 14 (4.7%) tested positive for active (positive polymerase chain reaction test, n = 3) or prior (positive antibody test, n = 11) COVID-19 infection. During the study period, this cohort accrued 14,916 days living and training at USOPTFs. Only one (0.3%) athlete was subsequently diagnosed with a new COVID-19 infection. No cardiopulmonary pathology attributable to COVID-19 was detected. Our findings suggest that residential elite athlete training facilities can successfully resume activity during the COVID-19 pandemic when strict reentry and infection prevention measures are followed. Dissemination of our reentry quarantine and screening protocols with COVID-19 mitigation measures may assist the global sports and medical community develop best practices for reopening of similar training centers.

Percardiac closure of large apical ventricular septal defects in infants: Novel modifications and mid-term results.

Background/AimBoth open heart surgery and percutaneous approaches retain several limitations in closing large apical muscular ventricular septal defects (AmVSD) in infants. We present probe‐assisted percardiac device closure (PDC), an exclusively transoesophageal‐echocardiography guided technique, as an alternative with midterm results.MethodsThirty‐six infants with large AmVSDs (single or multiple‐holed) underwent PDC in our department. Mean AmVSD for single and multiple‐holed measured 7.2 ± 2.4 mm and 6.3 ± 3.4 mm, respectively. Subjects presented with a spectrum of cardiopulmonary sequelae and growth retardation, either alone or combined. Some were ventilator dependent and re‐do cases. In addition, AmVSDs were categorized: cylindrical, tunnel and cave‐like shaped as per color Doppler interrogation. Pursuant to cardiac access and deployment technique, subjects were apportioned: group A; inferior median sternotomy (perventricular), B; right mini‐thoracotomy (peratrial) and C; complete median sternotomy (perventricular). Under exclusive echocardiography, the Z‐ or J probe‐assisted delivery system was utilized to access AmVSDs and implant device(s) via aforementioned techniques.ResultsForty‐two muscular ventricular septal devices (8.4 ± 2.6 mm) were implanted in 36 subjects uneventfully. Seventeen “complex,” and 10 cylindrical or straight tunnel‐shapedAmVSDs (including 2 re‐do patients) suited perventricular and peratrial techniques respectively. Comparatively, group B exhibited shorter procedural indices than A (p < .01). Five of 15 multiple‐holed AmVSDs (four Swiss cheese) required two or three devices for a satisfactory occlusion. Nevertheless, post occlusion insignificant residual shunts( ≤ 2 mm) seldom achieved spontaneous closure, and at 36‐month follow‐up complete closure was 67%. Residual shunt persisted amongst multiple‐holed. All patients improved during follow up.ConclusionPDC is feasible, safe and effective alternative technique for AmVSD in infants.

Cardio-Pulmonary Sequelae in Recovered COVID-19 Patients: Considerations for Primary Care.

Background:Current literature lacks characterization of the post-recovery sequelae among COVID-19 patients. This review characterizes the course of clinical, laboratory, radiological findings during the primary infection period, and the complications post-recovery. Primary care findings are presented for long-COVID care.Methods:Adhering to PRISMA guidelines, 4 databases were searched (PubMed, Embase, CINAHL Plus, Scopus) through December 5, 2020, using the keywords “COVID-19 and/or recovered and/or cardiovascular and/or long-term and/or sequelae and/or sub-acute and/or complication.” We included published peer-reviewed case reports, case series, and cross-sectional studies providing the clinical course of COVID-19 infection, and cardiopulmonary complications of patients who recovered from COVID-19, while making healthcare considerations for primary care workers.Results:We identified 29 studies across 9 countries including 37.9% Chinese and 24.1% U.S. studies, comprising 655 patients (Mean Age = 45) with various ethnical backgrounds including Asian and European. Based on the WHO COVID-19 severity classification scale, initial disease severity was mild for 377 patients and severe for 52 patients. Treatments during primary infection included corticosteroids, oxygen support, and antivirals. The mean value (in days) for complication onset after acute recovery was 28 days. Complete blood counts and RT-PCR tests were the most common laboratory results described. In 22 of the studies, patients showed signs of clinical improvement and were prescribed medications such as anticoagulants or corticosteroids.Conclusion:Post-recovery infectious complications are common in long-COVID-19 patients ranging from mild infections to life-threatening conditions. International thoracic and cardiovascular societies need to develop guidelines for patients recovering from COVID-19 pneumonia, while focused patient care by the primary care physician is crucial to curb preventable adverse events. Recommendations for real-time and lab-quality diagnostic tests are warranted to establish point-of-care testing, detect early complications, and provide timely treatment.

Long-term sequelae following previous coronavirus epidemics

Before the current pandemic, there had been two global epidemics from major coronavirus outbreaks since the turn of the century: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Both epidemics left survivors with fatigue, persistent shortness of breath, reduced quality of life and a significant burden of mental health problems.It is likely that some of the chronic problems encountered by survivors of SARS and MERS may be relevant for medical planning of the services required for survivors of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2. Given the similarities between the diseases, the recovery and rehabilitation of the survivors of COVID-19 is likely to be focused around cardiopulmonary sequelae, fatigue and the psychological burden of COVID-19, but in a much larger population.

Protective effect of unilateral vasospasm in the setting of HHH-associated posterior reversible encephalopathy syndrome: case report, review of the literature, and treatment considerations

BackgroundHyperdynamic therapy, also called triple-H therapy, is the standard treatment and prophylaxis for aneurysmal-associated vasospasm. In patients who are able to tolerate cardiopulmonary stressors induced by this therapy, it is of benefit as a modality for prevention and treatment of delayed ischemic neurologic deficit. However, it can be a cause of significant cardiopulmonary or neurologic sequelae. In rare cases, it can be associated with posterior reversible encephalopathy syndrome (PRES), secondary to prolonged vasopressor and hypertensive therapies.Case presentationWe present the case of a patient with right-sided aneurysmal-associated vasospasm who, after 10 days of triple-H therapy, experienced a seizure and was found to have left-sided PRES. Right-sided vasospasm served as a protective mechanism from triple-H therapy-associated PRES. It presented a treatment conundrum due to contradictory perfusion requirements. Hypertensive therapy was curtailed and in efforts to preserve local cerebral perfusion and vasodilation, local therapy with intrathecal nicardipine was initiated. We present our case, a review of the literature, and management considerations.ConclusionsTherapies that have conventionally functioned as second line treatments for aneurysmal subarachnoid hemorrhage (intra-arterial vasodilators and intrathecal vasodilators) may be beneficial as earlier treatments in the setting of vasospasm given the systemic difficulties and complications associated with HHH therapy in patients with PRES.

Circadian Dysregulation: The Next Frontier in Obstructive Sleep Apnea Research.

To review the effects of the circadian clock on homeostasis, the functional interaction between the circadian clock and hypoxia-inducible factors, and the role of circadian dysregulation in the progression of cardiopulmonary disease in obstructive sleep apnea (OSA). The MEDLINE database was accessed through PubMed. A general review is presented on molecular pathways disrupted in OSA, circadian rhythms and the role of the circadian clock, hypoxia signaling, crosstalk between the circadian and hypoxia systems, the role of the circadian clock in cardiovascular disease, and implications for practice. Studies included in this State of the Art Review demonstrate the potential contribution of the circadian clock and hypoxia in animal models or human disease. Molecular crosstalk between the circadian clock and hypoxia-inducible factors has not been evaluated in disease models of OSA. Pediatric OSA is highly prevalent and, if left untreated, may lead to cardiopulmonary sequelae. Changes in inflammatory markers that normally demonstrate circadian rhythmicity are also seen among patients with OSA. Hypoxia-inducible transcription factors interact with core circadian clock transcription factors; however, the interplay between these pathways has not been elucidated in the cardiopulmonary system. This gap in knowledge hinders our ability to identify potential biomarkers of OSA and develop alternative therapeutic strategies. A deeper understanding of the mechanisms by which OSA impinges on clock function and the impact of clock dysregulation on the cardiopulmonary system may lead to future advancements for the care of patients with OSA. The aim of this review is to shed light on this important clinical topic.

Cor pulmonale in an unusual case of obstructive adenoid enlargement

Enlargement and infection of the adenoids and tonsils are associated with problems of otitis media, sinusitis, obstructive sleep disordered breathing, and alterations of facial growth. In addition, they may also lead to cardiopulmonary disorders in children. This report aims to highlight the cardiopulmonary sequelae in a child with obstructive adenoid enlargement and temporomandibular joint ankylosis in our practice. The child presented at 6 years of age with complaints of noisy breathing, blocked nose, mouth breathing, and loud snoring. Her condition deteriorated with frequent apneic attacks, easy fatigability, and swelling of the legs. The blood pressure was 100/60 mmHg, the jugular venous pressure was elevated, with displaced apex beat at the sixth left intercostal space, anterior axillary line, with parasternal heave. There were first and second heart sounds with a loud P2. The findings on electrocardiogram and echocardiogram confirmed a diagnosis of cor pulmonale secondary to severe obstructive adenotonsillar disease. A flexible nasopharyngoscopy revealed a bilateral grade IV adenoidal obstruction of the choanae. She was managed for heart failure and had emergency tracheostomy. Subsequently, she had endoscopic transnasal microdebrider-assisted adenoidectomy. She has improved remarkably and on follow-ups at the ENT, pediatric, and MFU clinics. In conclusion, pulmonary hypertension and cor pulmonale, even though rare, are possible complications of untreated adenotonsillar hypertrophy in children.

Complications of Emerging Oncology Therapies Requiring Treatment in the Pediatric Intensive Care Unit

The development of immunotherapies has resulted in significant improvements in survival for children with cancer and congenital blood disorders. The purpose of this review is to guide the recognition and treatment of significant side of effects three increasingly used immunotherapies—T cell-mediated therapies, immune checkpoint inhibitors, and anti-GD2 antibodies. Cytokine release syndrome (CRS) is a cytokine-induced systemic inflammatory state secondary to chimeric antigen receptor T cells (CAR–T cells), a therapy used for relapsed and refractory leukemia. CRS can range from fever and mild flu-like symptoms to cardiopulmonary collapse and neurologic sequelae including encephalitis, seizures, and cerebral edema. Immune check point inhibitors work to redirect the T cell response towards cancer cells and have shown a survival advantage for patients with advanced melanoma. These agents also activate an immune response which can mimic autoimmune disease and cause organ failure and neurologic complications like Guillain–Barre and posterior reversible encephalopathy. Children with high-risk and chemotherapy-resistant neuroblastoma have seen improved survival with the use of anti-GD2, an immunotherapy directed at the highly abundant and conserved GD2 antigen expressed on neuroblastoma cells. Severe pain is the consistently reported side effect of anti-GD2, occurring in an estimated 50% of patients and often requiring narcotic and sedative agents for the duration of therapy. Immunotherapy has become critical to the treatment of previously irremediable diseases like relapsed leukemia and refractory neuroblastoma. The survival advantage offered by these therapies requires an understanding of diagnosis and treatment of their life-threatening toxicities.

Dysfunction of the foetal arterial duct results in a wide spectrum of cardiovascular pathology

Objective: Foetal ductal problems may have various cardiopulmonary consequences. This study aimed to identify the spectrum of ductus arteriosus (DA) dysfunction (closure, constriction, kinking, aneurysm and thrombosis) and the resultant clinical and echocardiographic presentation in foetuses and neonates.Methods and results: This is a retrospective analysis of serial pre- and post-natal data of 27 cases of foetal ductal dysfunction diagnosed at a median gestational age of 33 weeks (range 20–39). The most common abnormalities observed were premature closure of the DA in 56% (15/27) and constriction in 29% (8/27). Right ventricular hypertrophy was present in 75% (n = 11/15) of foetuses with premature DA closure, while ventricular dilation (4/7, 57%) was a more common feature in foetuses with ductal constriction. After birth, 63% (17/27) of new borns presented with cyanosis and pulmonary hypertension that required active treatment. Three infants died after birth. Abnormalities resolved spontaneously after birth in about 50% of patients. In some children, pulmonary valve stenosis and regurgitation was progressive and required further treatment.Conclusions: An abnormal right heart on foetal four-chamber ultrasound view should alert the sonographer to the possible presence of foetal ductal dysfunction. Ductal occlusion, transient or fixed constriction, kinking and aneurysm formation are associated with foetal cardiopulmonary sequelae. Symptoms and pathology is probably related to the type, foetal age, rapidity of progression and duration of intrauterine ductal dysfunction. Correspondingly, clinical outcomes vary ranging from little or no symptoms to severe respiratory distress and even foetal or neonatal death.