Exercise Pathophysiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-Acute Sequelae of SARS-CoV-2: More in Common Than Not?

TOPIC IMPORTANCE: Postacute sequelae of SARS-CoV-2 (PASC) is a long-term consequence of acute infection from COVID-19. Clinical overlap between PASC and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has been observed, with shared symptoms, including intractable fatigue, postexertional malaise, and orthostatic intolerance. The mechanistic underpinnings of such symptoms are poorly understood. REVIEW FINDINGS: Early studies suggest deconditioning as the primary explanation for exertional intolerance in PASC. Cardiopulmonary exercise testing reveals perturbations related to systemic blood flow and ventilatory control associated with acute exercise intolerance in PASC, which are not typical of simple detraining. Hemodynamic and gas exchange derangements in PASC have substantial overlap with those observed with ME/CFS, suggestive of shared mechanisms. SUMMARY: This review illustrates exercise pathophysiological commonalities between PASC and ME/CFS that will help guide future diagnostics and treatment.

Proteomic profiling demonstrates inflammatory and endotheliopathy signatures associated with impaired cardiopulmonary exercise hemodynamic profile in Post Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome.

Approximately 50% of patients who recover from the acute SARS-CoV-2 experience Post Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome. The pathophysiological hallmark of PASC is characterized by impaired system oxygen extraction (EO2) on invasive cardiopulmonary exercise test (iCPET). However, the mechanistic insights into impaired EO2 remain unclear. We studied 21 consecutive iCPET in PASC patients with unexplained exertional intolerance. PASC patients were dichotomized into mildly reduced (EO2peak-mild) and severely reduced (EO2peak-severe) EO2 groups according to the median peak EO2 value. Proteomic profiling was performed on mixed venous blood plasma obtained at peak exercise during iCPET. PASC patients as a group exhibited depressed peak exercise aerobic capacity (peak VO2; 85 ± 18 vs. 131 ± 45% predicted; p = 0.0002) with normal systemic oxygen delivery, DO2 (37 ± 9 vs. 42 ± 15 mL/kg/min; p = 0.43) and reduced EO2 (0.4 ± 0.1 vs. 0.8 ± 0.1; p < 0.0001). PASC patients with EO2peak-mild exhibited greater DO2 compared to those with EO2peak-severe [42.9 (34.2-41.2) vs. 32.1 (26.8-38.0) mL/kg/min; p = 0.01]. The proteins with increased expression in the EO2peak-severe group were involved in inflammatory and fibrotic processes. In the EO2peak-mild group, proteins associated with oxidative phosphorylation and glycogen metabolism were elevated. In PASC patients with impaired EO2, there exist a spectrum of PASC phenotype related to differential aberrant protein expression and cardio-pulmonary physiologic response. PASC patients with EO2peak-severe exhibit a maladaptive physiologic and proteomic signature consistent with persistent inflammatory state and endothelial dysfunction, while in the EO2peak-mild group, there is enhanced expression of proteins involved in oxidative phosphorylation-mediated ATP synthesis along with an enhanced cardiopulmonary physiological response.

Persistent Exertional Intolerance After COVID-19: Insights From Invasive Cardiopulmonary Exercise Testing.

BACKGROUND: Some patients with COVID-19 who have recovered from the acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that often is unexplained by conventional investigative studies. RESEARCH QUESTION: What is the pathophysiologic mechanism of exercise intolerance that underlies the post-COVID-19 long-haul syndrome in patients without cardiopulmonary disease? STUDY DESIGN AND METHODS: This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 patients who recovered from COVID-19 and were without cardiopulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results with those from 10 age- and sex-matched control participants. These data then were used to define potential reasons for exertional limitation in the cohort of patients who had recovered from COVID-19. RESULTS: The patients who had recovered from COVID-19 exhibited markedly reduced peak exercise aerobic capacity (oxygen consumption [VO2]) compared with control participants (70 ± 11% predicted vs 131 ± 45% predicted; P < .0001). This reduction in peak VO2 was associated with impaired systemic oxygen extraction (ie, narrow arterial-mixed venous oxygen content difference to arterial oxygen content ratio) compared with control participants (0.49 ± 0.1 vs 0.78 ± 0.1; P < .0001), despite a preserved peak cardiac index (7.8 ± 3.1 L/min vs 8.4±2.3 L/min; P > .05). Additionally, patients who had recovered from COVID-19 demonstrated greater ventilatory inefficiency (ie, abnormal ventilatory efficiency [VE/VCO2] slope: 35 ± 5 vs 27 ± 5; P = .01) compared with control participants without an increase in dead space ventilation. INTERPRETATION: Patients who have recovered from COVID-19 without cardiopulmonary disease demonstrate a marked reduction in peak VO2 from a peripheral rather than a central cardiac limit, along with an exaggerated hyperventilatory response during exercise.

Physicians' Reactions to COVID-19: The Results of a Preliminary International Internet Survey.

OBJECTIVES: Physicians across the world have been disproportionately affected by the COVID-19 pandemic. This study was designed and conducted to assess the emotional and behavioural reactions of physicians to the initial phase of the COVID-19 pandemic. SUBJECTS AND METHODS: An online survey questionnaire using the google forms platform was constructed by the authors. The items in the questionnaire were based on clinical experience, relevant literature review and discussion with peers. A list of issues that were deemed as essential components of the experience of the pandemic relevant to physicians was arrived at. Thereafter these issues were operationalized into question form and hosted on the google forms platform. The link to this questionnaire was circulated by the authors among their peer groups in the month of April 2020. RESULTS: We received 295 responses and 3 were unusable. Most of the responses were from India, the United States of America, Australia, Canada and the United Kingdom. About 60% of the respondents identified themselves as frontline and had a decade of clinical experience. Most respondents reported being anxious due to the pandemic and also observed the same in their peers and families. A majority also observed changes in behaviour in self and others and advanced a variety of reasons and concerns. A sense of duty was the most commonly employed coping mechanism. CONCLUSION: Physicians are not immune from information and misinformation, or cues in the environment. Behavioural choices are not always predicted by knowledge but by a combination of knowledge, emotional state, personality and environment. Healthcare settings need to be ready for emergencies and should focus on reducing uncertainty in physicians. These factors may also be gainfully used in the mental health promotion of physicians in COVID-19 care roles.

Hospital pharmacy response to COVID-19 at two UK teaching hospitals: a departmental review of actions implemented to inform future strategy.

OBJECTIVES: To determine the views of pharmacy staff on a departmental response to wave 1 of the UK COVID-19 pandemic in order to inform a strategy for a second wave at two large UK National Health Service (NHS) hospitals. METHODS: This study was undertaken at two large teaching hospitals in the UK. Pharmacy staff attended local departmental focus groups. Staff attendance included pharmacists, pharmacy technicians and pharmacy assistants representing all pharmacy services including aseptics, ward-based services, dispensary/distribution and procurement. Responses were transcribed and analysed using thematic analysis. RESULTS: A total of 138 pharmacy staff attended the departmental focus groups. This study identified which pharmacy-related changes implemented in the first wave will be beneficial to take forward into a second wave. These included extending the hours of the pharmacy service to critical care, retaining the competence of pharmacists and pharmacy technicians redeployed to critical care during wave 1, development of standard operating procedures for changes in practice, delivering/posting of dispensed outpatient medication to patients' place of residence, maintenance of ward-based pharmacy services, use of the healthcare app PANDO to aid team communication, utilisation of remote-controlled drug ordering, deployment of a COVID-19 ward stocklist, procurement of ready-made bags/prefilled syringes of critical care medications, aligning the central intravenous additive service with critical care demand to reduce waste and establishment of a pharmacy response in line with the hospital's implementation plan. CONCLUSIONS: This study has provided a number of recommendations for how hospital pharmacy departments may respond to a global pandemic. These experiences derived from the pharmacy departments at two large UK NHS Trusts may be used by other healthcare providers to help inform the pharmacy response to a global pandemic.

A Clinic Blueprint for Post-Coronavirus Disease 2019 RECOVERY: Learning From the Past, Looking to the Future.

The severe acute respiratory syndrome coronavirus 2 pandemic poses extraordinary challenges. The tremendous number of coronavirus disease 2019 (COVID-19) cases in the United States has resulted in a large population of survivors with prolonged postinfection symptoms. The creation of multidisciplinary post-COVID-19 clinics to address both persistent symptoms and potential long-term complications requires an understanding of the acute disease and the emerging data regarding COVID-19 outcomes. Experience with severe acute respiratory syndrome and Middle East respiratory syndrome, post-acute respiratory distress syndrome complications, and post-intensive care syndrome also informs anticipated sequelae and clinical program design. Post-COVID-19 clinical programs should be prepared to care for individuals previously hospitalized with COVID-19 (including those who required critical care support), nonhospitalized individuals with persistent respiratory symptoms following COVID-19, and individuals with preexisting lung disease complicated by COVID-19. Effective multidisciplinary collaboration models leverage lessons learned during the early phases of the pandemic to overcome the unique logistical challenges posed by pandemic circumstances. Collaboration between physicians and researchers across disciplines will provide insight into survivorship that may shape the treatment of both acute disease and chronic complications. In this review, we discuss the aims, general principles, elements of design, and challenges of a successful multidisciplinary model to address the needs of COVID-19 survivors.

Investigating the challenges and opportunities for medicines management in an NHS field hospital during the COVID-19 pandemic.

INTRODUCTION: Hospital admissions from COVID-19 initially increased rapidly within the UK. National Health Service (NHS) field hospitals are part of a capacity building response built at great scale and speed to respond to the anticipated increased demand the NHS faces during this time. NHS Nightingale Hospital Birmingham (NHB) is modelled to treat mild to moderate (non-critical care) COVID-19 disease, to provide step-down capacity for patients in recovery, or for palliating patients in the dying phase of their disease in the Midlands. Opportunities and challenges presented for optimal medicines management (MM) during the development of the NHB are investigated, and a framework developed to support future NHS field hospitals of this model. METHODS: A team, comprised of an associate medical director, trust chief pharmacist and senior pharmacists iteratively developed a framework to convert the large non-hospital setting into a functioning NHS field hospital with standardised MM processes adjusted appropriately to cope with operational constraints in the pandemic situation. NHB has, because of its repurposing, both challenges and advantages affecting MM that influence development of the framework. Throughout implementation, a 7-week period between announcement and opening, there was continuous evaluation, external stakeholder validation and peer review. RESULTS: The PESTLE model, a mechanism of analysis to identify elements of a project environment (Political, Environmental, Social, Technological, Legal and Economic), was applied to identify influencing factors and support detailed project planning. Compliance with medicines legislation was at the forefront of all MM process development for the NHB field hospital. Internal factors were identified by the core MM team, resulting in a workforce, education & training and clinical pharmacy MM plan. DISCUSSION: MM processes are extensive and integral to NHS field hospitals. The presented framework of influencing factors may support future NHS field hospital development. It is pertinent to have a broad team working approach to any large-scale project such as outlined here, and suggest the identified factors be used as a core framework for development of any future MM processes in NHS field hospitals.