Prospective Cohort Study

Background: Pulmonary rehabilitation is recognized as a core component of the management of individuals with chronic respiratory disease. Since the 2006 American Thoracic Society (ATS)/European Respiratory Society (ERS) Statement on Pulmonary Rehabilitation, there has been considerable growth in our knowledge of its efficacy and scope.

Purpose: The purpose of this Statement is to update the 2006 document, including a new definition of pulmonary rehabilitation and highlighting key concepts and major advances in the field.

Methods: A multidisciplinary committee of experts representing the ATS Pulmonary Rehabilitation Assembly and the ERS Scientific Group 01.02, “Rehabilitation and Chronic Care,” determined the overall scope of this update through group consensus. Focused literature reviews in key topic areas were conducted by committee members with relevant clinical and scientific expertise. The final content of this Statement was agreed on by all members.

Results: An updated definition of pulmonary rehabilitation is proposed. New data are presented on the science and application of pulmonary rehabilitation, including its effectiveness in acutely ill individuals with chronic obstructive pulmonary disease, and in individuals with other chronic respiratory diseases. The important role of pulmonary rehabilitation in chronic disease management is highlighted. In addition, the role of health behavior change in optimizing and maintaining benefits is discussed.

Conclusions: The considerable growth in the science and application of pulmonary rehabilitation since 2006 adds further support for its efficacy in a wide range of individuals with chronic respiratory disease

Read More: http://www.atsjournals.org/doi/abs/10.1164/rccm.201309-1634ST

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An official American thoracic society/European respiratory society statement: Key concepts and advances in pulmonary rehabilitation

According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003, and H1N1 influenza in 2009, have been recorded Most recently, the Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, 2019 Published literature can trace the beginning of symptomatic individuals back to the beginning of December 2019 As they were unable to identify the causative agent, these first cases were classified as "pneumonia of unknown etiology " The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family, COVID-19 On February 11, 2020, the WHO Director-General, Dr Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a "COVID-19," which is the acronym of "coronavirus disease 2019" In the past twenty years, two additional coronavirus epidemics have occurred  SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases This new virus seems to be very contagious and has quickly spread globally In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States Initially, the new virus was called 2019-nCoV Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs) The CoVs have become the major pathogens of emerging respiratory disease outbreaks They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species  For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS  Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the "very high" level, on February 28, 2020 Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving World governments are at work to establish countermeasures to stem possible devastating effects Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing Many uncertainties remain with regard to both the virus-host interac ion and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days In Italy, in geographic regions of the north of the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system In the midst of the crisis, the authors have chosen to use the "Statpearls" platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time  The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated

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Features, Evaluation and Treatment Coronavirus (COVID-19)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.
 We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.
 The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy.
 The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.

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Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)

https://www.thelancet.com/article/S2215036620302030/pdf

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.

Background and objective:  Severe acute respiratory syndrome (SARS) emerged in 2003 and its long-term sequelae remain largely unclear. This study examined the long-term outcome of pulmonary function, exercise capacity, health and work status among SARS survivors.



Methods:  A prospective cohort study of SARS patients at the Prince of Wales Hospital, Hong Kong was conducted, with serial assessments of lung function, 6MWD and 36 item Short Form General Health Survey at 3, 6, 12, 18 and 24 months after disease onset. The work status was also recorded.



Results:  Serial assessments were completed by 55 of the 123 (39.9%) subjects, of whom 27 were health-care workers (HCW). The mean age of the group was 44.4 (SD 13.2) years and 19 (34.5%) were males. At 24 months, 10 (18.2%), 9 (16.4%), 6 (10.9%) and 29 (52.7%) subjects had FEV1, FVC, TLC and DLCO < 80% of predicted values, respectively. The mean (SD) 6MWD increased significantly from 439.0 (89.1) m at 3 months to 460.1 (102.8) m at 6 months (P 0.016) and became steady after 6 months. However, 6MWD and 36 item Short Form General Health Survey scores were lower than the normal population throughout the study. Moreover, 29.6% of HCW and 7.1% of non-HCW had not returned to work 2 years after illness onset.



Conclusions:  This 2-year study of a selected population of SARS survivors, showed significant impairment of DLCO, exercise capacity and health status persisted, with a more marked adverse impact among HCW.

The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status.

Background High-flow nasal cannula (HFNC) is an emerging therapy for respiratory failure but the extent of exhaled air dispersion during treatment is unknown. We examined exhaled air dispersion during HFNC therapy versus continuous positive airway pressure (CPAP) on a human patient simulator (HPS) in an isolation room with 16 air changes·h−1. Methods The HPS was programmed to represent different severity of lung injury. CPAP was delivered at 5–20 cmH2O via nasal pillows (Respironics Nuance Pro Gel or ResMed Swift FX) or an oronasal mask (ResMed Quattro Air). HFNC, humidified to 37°C, was delivered at 10–60 L·min−1 to the HPS. Exhaled airflow was marked with intrapulmonary smoke for visualisation and revealed by laser light-sheet. Normalised exhaled air concentration was estimated from the light scattered by the smoke particles. Significant exposure was defined when there was ≥20% normalised smoke concentration. Results In the normal lung condition, mean±sd exhaled air dispersion, along the sagittal plane, increased from 186±34 to 264±27 mm and from 207±11 to 332±34 mm when CPAP was increased from 5 to 20 cmH2O via Respironics and ResMed nasal pillows, respectively. Leakage from the oronasal mask was negligible. Mean±sd exhaled air distances increased from 65±15 to 172±33 mm when HFNC was increased from 10 to 60 L·min−1. Air leakage to 620 mm occurred laterally when HFNC and the interface tube became loose. Conclusion Exhaled air dispersion during HFNC and CPAP via different interfaces is limited provided there is good mask interface fitting.

https://erj.ersjournals.com/content/erj/53/4/1802339.full.pdf

Exhaled air dispersion during high-flow nasal cannula therapy versus CPAP via different masks.

The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or vaccinated individuals to understand potential loss of protection against infection by Omicron. We previously established that a 50% plaque reduction neutralization antibody titer (PRNT50) ≥25.6 in our live virus assay corresponded to the threshold for 50% protection from infection against wild-type (WT) SARS-CoV-2. Here we show markedly reduced serum antibody titers against the Omicron variant (geometric mean titer (GMT) < 10) compared to WT virus 3–5 weeks after two doses of BNT162b2 (GMT = 218.8) or CoronaVac vaccine (GMT = 32.5). A BNT162b2 booster dose elicited Omicron PRNT50 titers ≥25.6 in 88% of individuals (22 of 25) who previously received 2 doses of BNT162b2 and 80% of individuals (24 of 30) who previously received CoronaVac. However, few (3%) previously infected individuals (1 of 30) or those vaccinated with three doses of CoronaVac (1 of 30) met this threshold. Our findings suggest that countries primarily using CoronaVac vaccines should consider messenger RNA vaccine boosters in response to the spread of Omicron. Studies evaluating the effectiveness of different vaccines against the Omicron variant are urgently needed. Serum neutralizing antibody titers against the SARS-CoV-2 Omicron variant markedly increase after a third dose of BNT162b2 vaccine in individuals who previously received either two doses of the BNT162b2 vaccine or two doses of the CoronaVac vaccine. 

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Neutralizing antibodies against the SARS-CoV-2 Omicron variant BA.1 following homologous and heterologous CoronaVac or BNT162b2 vaccination

Background Long-term complications after COVID-19 are common, but the potential cause for persistent symptoms after viral clearance remains unclear. Objective To investigate whether gut microbiome composition is linked to post-acute COVID-19 syndrome (PACS), defined as at least one persistent symptom 4 weeks after clearance of the SARS-CoV-2 virus. Methods We conducted a prospective study of 106 patients with a spectrum of COVID-19 severity followed up from admission to 6 months and 68 non-COVID-19 controls. We analysed serial faecal microbiome of 258 samples using shotgun metagenomic sequencing, and correlated the results with persistent symptoms at 6 months. Results At 6 months, 76% of patients had PACS and the most common symptoms were fatigue, poor memory and hair loss. Gut microbiota composition at admission was associated with occurrence of PACS. Patients without PACS showed recovered gut microbiome profile at 6 months comparable to that of non-COVID-19 controls. Gut microbiome of patients with PACS were characterised by higher levels of Ruminococcus gnavus, Bacteroides vulgatus and lower levels of Faecalibacterium prausnitzii. Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including Clostridium innocuum and Actinomyces naeslundii (all p<0.05). Butyrate-producing bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii showed the largest inverse correlations with PACS at 6 months. Conclusion These findings provided observational evidence of compositional alterations of gut microbiome in patients with long-term complications of COVID-19. Further studies should investigate whether microbiota modulation can facilitate timely recovery from post-acute COVID-19 syndrome.

https://gut.bmj.com/content/gutjnl/early/2022/01/05/gutjnl-2021-325989.full.pdf

Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome

Objectives: We compared the expelled air dispersion distances during coughing from a human patient simulator (HPS) lying at 45u with and without wearing a surgical mask or N95 mask in a negative pressure isolation room. Methods: Airflow was marked with intrapulmonary smoke. Coughing bouts were generated by short bursts of oxygen flow at 650, 320, and 220L/min to simulate normal, mild and poor coughing efforts, respectively. The coughing jet was revealed by laser light-sheet and images were captured by high definition video. Smoke concentration in the plume was estimated from the light scattered by smoke particles. Significant exposure was arbitrarily defined where there was $ 20% of normalized smoke concentration. Results: During normal cough, expelled air dispersion distances were 68, 30 and 15 cm along the median sagittal plane when the HPS wore no mask, a surgical mask and a N95 mask, respectively. In moderate lung injury, the corresponding air dispersion distances for mild coughing efforts were reduced to 55, 27 and 14 cm, respectively, p , 0.001. The distances were reduced to 30, 24 and 12 cm, respectively during poor coughing effort as in severe lung injury. Lateral dispersion distances during normal cough were 0, 28 and 15 cm when the HPS wore no mask, a surgical mask and a N95 mask, respectively. Conclusions: Normal cough produced a turbulent jet about 0.7 m towards the end of the bed from the recumbent subject. N95 mask was more effective than surgical mask in preventing expelled air leakage during coughing but there was still significant sideway leakage.

Susanna S.S. Ng

Papers

The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status.

Exhaled air dispersion during high-flow nasal cannula therapy versus CPAP via different masks.

Neutralizing antibodies against the SARS-CoV-2 Omicron variant BA.1 following homologous and heterologous CoronaVac or BNT162b2 vaccination

Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome

Exhaled air dispersion during coughing with and without wearing a surgical or N95 mask.