Identification of factors impairing exercise capacity after severe COVID-19 pulmonary infection: a 3-month follow-up of prospective COVulnerability cohort.

BACKGROUND: Patient hospitalized for coronavirus disease 2019 (COVID-19) pulmonary infection can have sequelae such as impaired exercise capacity. We aimed to determine the frequency of long-term exercise capacity limitation in survivors of severe COVID-19 pulmonary infection and the factors associated with this limitation. METHODS: Patients with severe COVID-19 pulmonary infection were enrolled 3 months after hospital discharge in COVulnerability, a prospective cohort. They underwent cardiopulmonary exercise testing, pulmonary function test, echocardiography, and skeletal muscle mass evaluation. RESULTS: Among 105 patients included, 35% had a reduced exercise capacity (VO2peak < 80% of predicted). Compared to patients with a normal exercise capacity, patients with reduced exercise capacity were more often men (89.2% vs. 67.6%, p = 0.015), with diabetes (45.9% vs. 17.6%, p = 0.002) and renal dysfunction (21.6% vs. 17.6%, p = 0.006), but did not differ in terms of initial acute disease severity. An altered exercise capacity was associated with an impaired respiratory function as assessed by a decrease in forced vital capacity (p < 0.0001), FEV1 (p < 0.0001), total lung capacity (p < 0.0001) and DLCO (p = 0.015). Moreover, we uncovered a decrease of muscular mass index and grip test in the reduced exercise capacity group (p = 0.001 and p = 0.047 respectively), whilst 38.9% of patients with low exercise capacity had a sarcopenia, compared to 10.9% in those with normal exercise capacity (p = 0.001). Myocardial function was normal with similar systolic and diastolic parameters between groups whilst reduced exercise capacity was associated with a slightly shorter pulmonary acceleration time, despite no pulmonary hypertension. CONCLUSION: Three months after a severe COVID-19 pulmonary infection, more than one third of patients had an impairment of exercise capacity which was associated with a reduced pulmonary function, a reduced skeletal muscle mass and function but without any significant impairment in cardiac function.

Clinical outcomes in patients with COPD hospitalized with SARS-CoV-2 versus non- SARS-CoV-2 community-acquired pneumonia.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have poor outcomes in the setting of community-acquired pneumonia (CAP) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary objective is to compare outcomes of SARS-CoV-2 CAP and non-SARS-CoV-2 CAP in patients with COPD. The secondary objective is to compare outcomes of SARS-CoV-2 CAP with and without COPD. METHODS: In this analysis of two observational studies, three cohorts were analyzed: (1) patients with COPD and SARS-CoV-2 CAP; (2) patients with COPD and non-SARS-CoV-2 CAP; and (3) patients with SARS-CoV-2 CAP without COPD. Outcomes included length of stay, ICU admission, cardiac events, and in-hospital mortality. RESULTS: Ninety-six patients with COPD and SARS-CoV-2 CAP were compared to 1129 patients with COPD and non-SARS-CoV-2 CAP. 536 patients without COPD and SARS-CoV-2 CAP were analyzed for the secondary objective. Patients with COPD and SARS-CoV-2 CAP had longer hospital stay (15 vs 5 days, p < 0.001), 4.98 higher odds of cardiac events (95% CI: 3.74-6.69), and 7.31 higher odds of death (95% CI: 5.36-10.12) in comparison to patients with COPD and non-SARS-CoV-2 CAP. In patients with SARS-CoV-2 CAP, presence of COPD was associated with 1.74 (95% CI: 1.39-2.19) higher odds of ICU admission and 1.47 (95% CI: 1.05-2.05) higher odds of death. CONCLUSION: In patients with COPD and CAP, presence of SARS-CoV-2 as an etiologic agent is associated with more cardiovascular events, longer hospital stay, and seven-fold increase in mortality. In patients with SARS-CoV-2 CAP, presence of COPD is associated with 1.5-fold increase in mortality.

Comparison of the Epidemiological and Clinical Characteristics of Hospitalized Children With Pneumonia Caused by SARS-CoV-2, Influenza A, and Human Adenoviruses: A Case-Control Study.

Background. This case-control study aims to investigate the clinical characteristics in pediatric patients with pneumonia infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A, and human adenoviruses (HAdVs). Methods. Hospitalized pediatric patients with pneumonia infected with SARS-CoV-2 at Wuhan Children's Hospital and pneumonia infected with influenza A, and HAdVs at Qilu Children's Hospital were compared. Clinical manifestations, laboratory examinations, and imaging characteristics were analyzed. Results. The proportions of hyperpyrexia (54.3%, 33.9%), cough (100%, 99.2%), wheezing (45.7%, 53.7%), diarrhea (31.4%, 14.9%), and fever (100%, 75.2%) in patients with influenza A and HAdVs were higher than those of patients with SARS-CoV-2 (9.4%, P < .001; 48.5%, P < .001; 0%, P < .001; 8.8%, P = .002; 41.5%, P < .001; respectively). Laboratory examinations revealed the proportions of leukocytosis (37.1%, 52.9%), abnormal rates of neutrophils (40%, 40.5%), and lymphocytosis (42.9%, 65.3%) in influenza A and HAdV pneumonia groups were significantly higher than coronavirus disease 2019 (COVID-19) group (0%, P < .001; 0%, P < .001; 0%, P < .001; respectively). The proportion of elevated procalcitonin (5.7%, 14%) in patients with influenza A and HAdVs was significantly lower than those in patients with SARS-CoV-2 (64%, P < .001). In chest computed tomography, ground-glass opacities near the pleura were more common in patients with COVID-19 than those in patients with influenza A and HAdVs (32.7% vs 0% vs 0%, P < .001). Conclusion. Fever, cough, and wheezing are more common in the influenza A and HAdVs groups, whereas procalcitonin and computed tomography findings are likely to be pronounced in COVID-19 pneumonia. It provides a variety of methods except polymerase chain reaction for differentiating COVID-19 pneumonia from influenza A and HAdVs pneumonia.

Pulmonary function and six-minute-walk test in patients after recovery from COVID-19: A prospective cohort study.

OBJECTIVES: To study abnormality of spirometry, six-minute walk distance, and chest radiograph among patients recovered from Coronavirus Disease 2019 (COVID-19). METHODS AND STUDY DESIGN: A prospective cohort study was conducted in 87 COVID-19 confirmed cases who recovered and discharged from a medical school hospital in Thailand. At the follow-up visit on day 60 after onset of symptoms, patients underwent an evaluation by spirometry (FVC, FEV1, FEV1/FVC, FEF25-75, and PEF), a six-minute-walk test (6MWT), and a chest radiograph. RESULTS: There were 35 men and 52 women, with a mean age of 39.6±11.8 years and the mean body mass index (BMI) was 23.8±4.3 kg/m2. Of all, 45 cases had mild symptoms; 35 had non-severe pneumonia, and 7 had severe pneumonia. Abnormality in spirometry was observed in 15 cases (17.2%), with 8% of restrictive defect and 9.2% of obstructive defect. Among the patients with an abnormal spirometry, the majority of the cases were in the severe pneumonia group (71.4%), compared with 15.6% in the non-severe pneumonia group, and 10.2% in the mild symptom group (p = 0.001). The mean six-minute-walk distance (6MWD) in the mild symptom and non-severe pneumonia groups was 538±56.8 and 527.5±53.5 meters, respectively. Although the severe pneumonia group tended to have a shorter mean 6-min walking distance, but this was not statistically significant (p = 0.118). Twelve patients (13.8%) had abnormal chest radiographs that showed residual fibrosis. This abnormality was more common in the severe pneumonia group (85.7%) and in others (7.5%) (p<0.001). CONCLUSIONS: Abnormal spirometry was noted in 17.2% of COVID-19 survivors with both restrictive and obstructive defects. Severe COVID-19 pneumonia patients had higher prevalence rates of abnormal spirometry and residual fibrosis on the chest radiographs when compared to patients in the mild symptom and non-severe pneumonia groups.

E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR α7 receptor: role of nAChR α7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation.

Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has been conducted to understand the possible mechanisms that mediate toxicity and pulmonary health effects of e-cigs. We hypothesized that sub-chronic e-cig exposure induces inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChRα7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lung tissues were collected to determine e-cig induced inflammatory response and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased inflammatory cellular influx of macrophages and T-lymphocytes including increased pro-inflammatory cytokines in BALF and increased SARS-Cov-2 Covid-19 ACE2 receptor, whereas nAChRα7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8 and MMP9, were altered both at the protein and mRNA transcript levels in female and male KO mice, but WT mice exposed to PG alone showed a sex-dependent phenotype. Moreover, MMP12 was increased significantly in male mice exposed to PG with or without nicotine in a nAChRα7-dependent manner. Additionally, sub-chronic e-cig exposure with or without nicotine altered the abundance of ECM proteins, such as collagen and fibronectin, significantly in a sex-dependent manner, but without the direct role of nAChRα7 gene. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChRα7 in a sex-dependent manner.

Heteromeric TRP Channels in Lung Inflammation.

Activation of Transient Receptor Potential (TRP) channels can disrupt endothelial barrier function, as their mediated Ca2+ influx activates the CaM (calmodulin)/MLCK (myosin light chain kinase)-signaling pathway, and thereby rearranges the cytoskeleton, increases endothelial permeability and thus can facilitate activation of inflammatory cells and formation of pulmonary edema. Interestingly, TRP channel subunits can build heterotetramers, whereas heteromeric TRPC1/4, TRPC3/6 and TRPV1/4 are expressed in the lung endothelium and could be targeted as a protective strategy to reduce endothelial permeability in pulmonary inflammation. An update on TRP heteromers and their role in lung inflammation will be provided with this review.

Clinical presentation of COVID-19 / Cuadro clínico del COVID-19

El Coronavirus SARS-CoV-2 produce la enfermedad COVID-19, cuya manifestación más grave y potencialmente letal es la neumonía. En este artículo revisaremos las manifestaciones clínicas del COVID-19, la fisiopatología de la neumonía, el manejo intrahospitalario previo al ingreso a Unidades de Cuidados Intensivos, la embolia pulmonar que es una complicación muy frecuente de esta enfermedad y el seguimiento de los pacientes posterior al alta. Para esta publicación nos hemos basado en publicaciones médicas y en estudios que hemos hecho durante esta pandemia en nuestro Centro de Enfermedades Respiratorias. i:es

The SARS-CoV-2 Coronavirus causes the COVID-19 disease, the most severe and potentially fatal manifestation of which is pneumonia. In this article, we will review the clinical manifestations of COVID-19, the pathophysiology of pneumonia, in-hospital management prior to admission to Intensive Care Units, pulmonary embolism, which is a very frequent complication of this disease, and the follow-up of patients after hospitalization. For this publication we have relied on medical publications and studies that we have done during this pandemic at our Center for Respiratory Diseases. i:en

Cardiorespiratory Fitness, Inflammation, and the Incident Risk of Pneumonia.

INTRODUCTION: Both inflammation and cardiorespiratory fitness (CRF) are associated with the risk of respiratory infections. To clarify the hypothesis that CRF attenuates the incident risk of pneumonia due to inflammation, we conducted a prospective study examining the independent and joint associations of inflammation and CRF on the risk of pneumonia in a population sample of 2041 middle-aged men. METHODS: Cardiorespiratory fitness was directly measured as peak oxygen uptake (V˙o2peak) during progressive exercise testing to volitional fatigue, and categorized into tertiles. Inflammation was defined by high-sensitivity C-reactive protein (hsCRP). Pneumonia cases were identified by internal medicine physicians using the International Classification of Diseases codes in clinical practice. RESULTS: During a median follow-up of 27 yr, 432 pneumonia cases were recorded. High hsCRP and CRF were associated with a higher risk (HR = 1.38; 95% CI, 1.02-1.88) and a lower risk of pneumonia (HR = 0.55; CI, 0.39-0.76) after adjusting for potential confounders, respectively. Compared with normal hsCRP-Fit, moderate to high hsCRP-Unfit had an increased risk of pneumonia (HR = 1.63; CI, 1.21-2.20), but moderate to high hsCRP-Fit was not associated with an increased risk of pneumonia (HR = 1.25; CI, 0.93-1.68). CONCLUSIONS: High CRF attenuates the increased risk of pneumonia due to inflammation. These findings have potential implications for the prevention of respiratory infection characterized by systemic inflammation, such as coronavirus disease-2019 (COVID-19).

Probable positive effects of the photobiomodulation as an adjunctive treatment in COVID-19: A systematic review.

BACKGROUND: COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea in half of the patients and acute respiratory distress syndrome (ARDS) in up to one -third of the cases. Pulmonary edema, neutrophilic infiltration, and inflammatory cytokine release are the pathologic signs of this disease. The anti-inflammatory effect of the photobiomodulation (PBM) has been confirmed in many previous studies. Therefore, this review study was conducted to evaluate the direct effect of PBM on the acute lung inflammation or ARDS and also accelerating the regeneration of the damaged tissues. The indirect effects of PBM on modulation of the immune system, increasing the blood flow and oxygenation in other tissues were also considered. METHODOLOGY: The databases of PubMed, Cochrane library, and Google Scholar were searched to find the relevant studies. Keywords included the PBM and related terms, lung inflammation, and COVID-19 -related signs. Studies were categorized with respect to the target tissue, laser parameters, and their results. RESULTS: Seventeen related papers were included in this review. All of them were in animal models. They showed that the PBM could significantly decrease the pulmonary edema, neutrophil influx, and generation of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), intracellular adhesion molecule (ICAM), reactive oxygen species (ROS), isoform of nitric oxide synthase (iNOS), and macrophage inflammatory protein 2 (MIP-2)). CONCLUSION: Our findings revealed that the PBM could be helpful in reducing the lung inflammation and promoting the regeneration of the damaged tissue. PBM can increase the oxygenation indirectly in order to rehabilitate the affected organs. Thus, the infra-red lasers or light-emitting diodes (LEDs) are recommended in this regard.

Factors Associated with a Positive Severe Acute Respiratory Syndrome Coronavirus 2 Testing in Suspected Cases Presenting with Pneumonia: A Retrospective Cohort Study in a Single Medical Center.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global emerging infectious disease. OBJECTIVES: To analyze the initial clinical characteristics of COVID-19 suspected and confirmed patients on admission in order to find out which kinds may be more likely to get positive nucleic acid testing results, and to explore the risk factors associated with all-cause death. METHODS: Medical records from 309 highly suspected cases with pneumonia were collected from February 13, 2020, to March 14, 2020, in a COVID-19-designated hospital of Wuhan. The majority of the clinical data were collected on the first day of hospital admission. RESULTS: Of 309 patients with median age 64 years (interquartile ranges [IQR], 53-72 years), 111 patients (35.9%) were confirmed by nucleic acid testing (median age 64 years, IQR: 56-71 years; 48 males). Of those 111 patients, 13 (11.7%) patients died. In multivariate analysis, factors associated with positive testing included fatigue (odds ratios [OR] = 3.14; 95% confidence interval [CI]: 1.88-5.24, p < 0.001), cough (OR = 0.55; 95% CI: 0.32-0.95, p = 0.032), no less than 1 comorbidity (OR = 1.77; 95% CI: 1.06-2.98, p = 0.030), and severe pneumonia (OR = 2.67; 95% CI: 1.20-5.97, p = 0.016). Furthermore, age, dyspnea, noneffective antibiotic treatment, white blood cell, lymphocyte, platelets, and organ dysfunction (e.g., higher lactate dehydrogenase) were significantly associated with all-cause in-hospital death in patients with COVID-19. CONCLUSION: Patients with severe forms of this disease were more likely to get positive results. Age and organ dysfunction were associated with a greater risk of death.

Chest Computed Tomography Scoring in Patients With Novel Coronavirus-infected Pneumonia: Correlation With Clinical and Laboratory Features and Disease Outcome.

BACKGROUND/AIM: This study investigated the correlation of chest computed tomography (CT), findings, graded using two different scoring methods, with clinical and laboratory features and disease outcome, including a novel clinical predictive score, in patients with novel coronavirus-infected pneumonia (NCIP). PATIENTS AND METHODS: In this retrospective, observational study, CT scan of 92 NCIP patients admitted to Policlinico Tor Vergata, were analyzed using a quantitative, computed-based and a semiquantitative, radiologist-assessed scoring system. Correlations of the two radiological scores with clinical and laboratory features, the CALL score, and their association with a composite adverse outcome were assessed. RESULTS: The two scores correlated significantly with each other (ρ=0.637, p<0.0001) and were independently associated with age, LDH, estimated glomerular filtration rate, diabetes, and with the composite outcome, which occurred in 24 patients. CONCLUSION: In NCIP patients, two different radiological scores correlated with each other and with several clinical, laboratory features, and the CALL score. The quantitative score was a better independent predictor of the composite adverse outcome than the semiquantitative score.

Temporal changes of CT findings between non-severe and severe cases of COVID-19 pneumonia: a multi-center, retrospective, longitudinal Study.

Background and aim: To perform a longitudinal analysis of serial CT findings over time in patients with COVID-19 pneumonia. Methods: From February 5 to March 8, 2020, 73 patients (male to female, ratio of 43:30; mean age, 51 years) with COVID-19 pneumonia were retrospectively enrolled and followed up until discharge from three institutions in China. The patients were divided into the severe and non-severe groups according to treatment option. The patterns and distribution of lung abnormalities, total CT scores, single ground-glass opacity (GGO) CT scores, single consolidation CT scores, single reticular CT scores and the amounts of zones involved were reviewed by 2 radiologists. These features were analyzed for temporal changes. Results: In non-severe group, total CT scores (median, 9.5) and the amounts of zones involved were slowly increased and peaked in disease week 2. In the severe group, the increase was faster, with scores also peaking at 2 weeks (median, 20). In both groups, the later parameters began to decrease in week 4 (median values of 9 and 19 in the non-severe and severe groups, respectively). In the severe group, the dominant residual lung lesions were reticular (median single reticular CT score, 10) and consolidation (median single consolidation CT score, 7). In the non-severe group, the dominant residual lung lesions were GGO (median single GGO CT score, 7) and reticular (median single reticular CT score, 4). In both non-severe and severe groups, the GGO pattern was dominant in week 1, with a higher proportion in the severe group compared with the non-severe group (72% vs. 65%). The consolidation pattern peaked in week 2, with 9 (32%) and 19 (73%) in the non-severe and severe groups, respectively; the reticular pattern became dominant from week 4 (both group >40%). Conclusion: The extent of CT abnormalities in the severe and non-severe groups peaked in disease week 2. The temporal changes of CT manifestations followed a specific pattern, which might indicate disease progression and recovery.

Clinical characteristics and longitudinal chest CT features of healthcare workers hospitalized with coronavirus disease 2019 (COVID-19).

Rationale: The clinical data and corresponding dynamic CT findings were investigated in detail to describe the clinical and imaging profiles of COVID-19 pneumonia disease progression. Methods: Forty HCWs with COVID-19 were included in this study and 30 enrolled for imaging assessment. Disease was divided into four stages based on time from onset: stage 1 (1-6 days), stage 2 (7-13 days), stage 3 (14-22 days), and stage 4 (> 22 days). Clinical wand imaging data were analyzed retrospectively. Results: The cohort included 33 female and 7 male cases, with a median age of 40 years. Six had underlying comorbidities. More than half of the cases were nurses (22, 55%). Each stage included 39, 37, 34 and 32 CTs, respectively. Bilateral lesions, multifocal lesions and lesions with GGO pattern occurred in both lower lobes at all stages. The crazy-paving pattern (20, 54%), air bronchogram (13, 35%), and pleural effusion (2, 5%) were the most common CT features in stage 2. Consolidation score peaked in stage 2 whereas total lesions score peaked in stage 3. Conclusions: COVID-19 pneumonia in HCWs has a potential predilection for younger female workers. Stage 2 of COVID-19 pneumonia may be the key period for controlling progression of the disease, and consolidation scores may be an objective reflection of the severity of lung involvement.

COVID-19: comparative clinical features and outcome in 114 patients with or without pneumonia (Nord Franche-Comte Hospital, France).

COVID-19 patients (n = 114) were included (55 patients with pneumonia (group P) and 59 without pneumonia (group NP). Patients in group P were older (69 (±17) years vs 46 (±16); p < 0.001) with a male predominance (58.2% vs 27.1%; p < 0.001). The symptoms which were statistically more frequents in patients with pneumonia were fever ≥ 38 °C (93% vs 70%; p = 0.002) and dyspnea (73% vs 22%; p < 0.001). Symptoms such as facial headache (42% vs 15%; p = 0.001), sore throat (39% vs 16%; p = 0.007), dysgeusia (61% vs 33%; p = 0.003), anosmia (63% vs 31%; p = 0.001) were statistically more frequents in patients without pneumonia.

Infection as a Stroke Risk Factor and Determinant of Outcome After Stroke.

Understanding the relationship between infection and stroke has taken on new urgency in the era of the coronavirus disease 2019 (COVID-19) pandemic. This association is not a new concept, as several infections have long been recognized to contribute to stroke risk. The association of infection and stroke is also bidirectional. Although infection can lead to stroke, stroke also induces immune suppression which increases risk of infection. Apart from their short-term effects, emerging evidence suggests that poststroke immune changes may also adversely affect long-term cognitive outcomes in patients with stroke, increasing the risk of poststroke neurodegeneration and dementia. Infections at the time of stroke may also increase immune dysregulation after the stroke, further exacerbating the risk of cognitive decline. This review will cover the role of acute infections, including respiratory infections such as COVID-19, as a trigger for stroke; the role of infectious burden, or the cumulative number of infections throughout life, as a contributor to long-term risk of atherosclerotic disease and stroke; immune dysregulation after stroke and its effect on the risk of stroke-associated infection; and the impact of infection at the time of a stroke on the immune reaction to brain injury and subsequent long-term cognitive and functional outcomes. Finally, we will present a model to conceptualize the many relationships among chronic and acute infections and their short- and long-term neurological consequences. This model will suggest several directions for future research.

Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia.

BACKGROUND: In December 2019, novel coronavirus (SARS-CoV-2) pneumonia (COVID-19) was reported in Wuhan and has since rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19. METHODS: The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. RESULTS: Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells, and natural killer (NK) cells decreased in COVID-19 patients, and severe cases had a lower level than mild cases. The subsets showed a significant association with inflammatory status in COVID-19, especially CD8+ T cells and CD4+/CD8+ ratio. After treatment, 37 patients (67%) showed clinical response, with an increase in CD8+ T cells and B cells. No significant change in any subset was detected in nonresponsive cases. In multivariate analysis, posttreatment decrease in CD8+ T cells and B cells and increase in CD4+/CD8+ ratio were indicated as independent predictors of poor efficacy. CONCLUSIONS: Peripheral lymphocyte subset alteration was associated with clinical characteristics and treatment efficacy of COVID-19. CD8+ T cells tended to be an independent predictor for COVID-19 severity and treatment efficacy.

Understanding the renin-angiotensin-aldosterone-SARS-CoV axis: a comprehensive review.

IMPORTANCE: Coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic with significant morbidity and mortality since first appearing in Wuhan, China, in late 2019. As many countries are grappling with the onset of their epidemics, pharmacotherapeutics remain lacking. The window of opportunity to mitigate downstream morbidity and mortality is narrow but remains open. The renin-angiotensin-aldosterone system (RAAS) is crucial to the homeostasis of both the cardiovascular and respiratory systems. Importantly, SARS-CoV-2 utilises and interrupts this pathway directly, which could be described as the renin-angiotensin-aldosterone-SARS-CoV (RAAS-SCoV) axis. There exists significant controversy and confusion surrounding how anti-hypertensive agents might function along this pathway. This review explores the current state of knowledge regarding the RAAS-SCoV axis (informed by prior studies of SARS-CoV), how this relates to our currently evolving pandemic, and how these insights might guide our next steps in an evidence-based manner. OBSERVATIONS: This review discusses the role of the RAAS-SCoV axis in acute lung injury and the effects, risks and benefits of pharmacological modification of this axis. There may be an opportunity to leverage the different aspects of RAAS inhibitors to mitigate indirect viral-induced lung injury. Concerns have been raised that such modulation might exacerbate the disease. While relevant preclinical, experimental models to date favour a protective effect of RAAS-SCoV axis inhibition on both lung injury and survival, clinical data related to the role of RAAS modulation in the setting of SARS-CoV-2 remain limited. CONCLUSION: Proposed interventions for SARS-CoV-2 predominantly focus on viral microbiology and aim to inhibit viral cellular injury. While these therapies are promising, immediate use may not be feasible, and the time window of their efficacy remains a major unanswered question. An alternative approach is the modulation of the specific downstream pathophysiological effects caused by the virus that lead to morbidity and mortality. We propose a preponderance of evidence that supports clinical equipoise regarding the efficacy of RAAS-based interventions, and the imminent need for a multisite randomised controlled clinical trial to evaluate the inhibition of the RAAS-SCoV axis on acute lung injury in COVID-19.

Features of anosmia in COVID-19.

BACKGROUND: Medical publications about anosmia with COVID-19 are scarce. We aimed to describe the prevalence and features of anosmia in COVID-19 patients. METHODS: We retrospectively included COVID-19 patients with anosmia between March 1st and March 17th, 2020. We used SARS-CoV-2 real time PCR in respiratory samples to confirm the cases. RESULTS: Fifty-four of 114 patients (47%) with confirmed COVID-19 reported anosmia. Mean age of the 54 patients was 47 (±16) years; 67% were females and 37% were hospitalised. The median Charlson comorbidity index was 0.70 (±1.6 [0-7]). Forty-six patients (85%) had dysgeusia and 28% presented with pneumonia. Anosmia began 4.4 (±1.9 [1-8]) days after infection onset. The mean duration of anosmia was 8.9 (±6.3 [1-21]) days and 98% of patients recovered within 28 days. CONCLUSIONS: Anosmia was present in half of our European COVID-19 patients and was often associated with dysgeusia.