Clinical Utility of Midregional Proadrenomedullin in Patients with COVID-19.

OBJECTIVE: The aim of the study was to assess the role of midregional proadrenomedullin (MR-proADM) in patients with COVID-19. METHODS: We included 110 patients hospitalized for COVID-19. Biochemical biomarkers, including MR-proADM, were measured at admission. The association of plasma MR-proADM levels with COVID-19 severity, defined as a requirement for mechanical ventilation or in-hospital mortality, was evaluated. RESULTS: Patients showed increased levels of MR-proADM. In addition, MR-proADM was higher in patients who died during hospitalization than in patients who survived (median, 2.59 nmol/L; interquartile range, 2.3-2.95 vs median, 0.82 nmol/L; interquartile range, 0.57-1.03; P <.0001). Receiver operating characteristic curve analysis showed good accuracy of MR-proADM for predicting mortality. A MR-proADM value of 1.73 nmol/L was established as the best cutoff value, with 90% sensitivity and 95% specificity (P <.0001). CONCLUSION: We found that MR-proADM could represent a prognostic biomarker of COVID-19.

Is COVID Evolution Due to Occurrence of Pulmonary Vascular Thrombosis?

In this hypothesis paper, we suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce intravascular pulmonary thrombosis, which may result in the rapid worsening of clinical conditions and, eventually, exitus. Previously published papers have demonstrated that increased levels of D-dimer at hospital admission correlate with a more severe disease (0.5 mg/L) or occurrence of death (1 mg/L). The potential prothrombotic action of the SARS-CoV-2 is supported by the topographical involvement of the lung regions with a predilection for the lower lobe with peripheral involvement. If this hypothesis is demonstrated, this could suggest the benefit of using antithrombotic/coagulation regimens for SARS-CoV-2 and, at the same time, the urgency to identify drugs that could alter the inflammatory storm, thus protecting the vessel wall.

Validation of the Withings ScanWatch as a Wrist-Worn Reflective Pulse Oximeter: Prospective Interventional Clinical Study.

BACKGROUND: A decrease in the level of pulse oxygen saturation as measured by pulse oximetry (SpO2) is an indicator of hypoxemia that may occur in various respiratory diseases, such as chronic obstructive pulmonary disease (COPD), sleep apnea syndrome, and COVID-19. Currently, no mass-market wrist-worn SpO2 monitor meets the medical standards for pulse oximeters. OBJECTIVE: The main objective of this monocentric and prospective clinical study with single-blind analysis was to test and validate the accuracy of the reflective pulse oximeter function of the Withings ScanWatch to measure SpO2 levels at different stages of hypoxia. The secondary objective was to confirm the safety of this device when used as intended. METHODS: To achieve these objectives, we included 14 healthy participants aged 23-39 years in the study, and we induced several stable plateaus of arterial oxygen saturation (SaO2) ranging from 100%-70% to mimic nonhypoxic conditions and then mild, moderate, and severe hypoxic conditions. We measured the SpO2 level with a Withings ScanWatch on each participant's wrist and the SaO2 from blood samples with a co-oximeter, the ABL90 hemoximeter (Radiometer Medical ApS). RESULTS: After removal of the inconclusive measurements, we obtained 275 and 244 conclusive measurements with the two ScanWatches on the participants' right and left wrists, respectively, evenly distributed among the 3 predetermined SpO2 groups: SpO2≤80%, 80%

Direct and indirect evidence of efficacy and safety of rapid exercise tests for exertional desaturation in Covid-19: a rapid systematic review.

BACKGROUND: Even when resting pulse oximetry is normal in the patient with acute Covid-19, hypoxia can manifest on exertion. We summarise the literature on the performance of different rapid tests for exertional desaturation and draw on this evidence base to provide guidance in the context of acute Covid-19. MAIN RESEARCH QUESTIONS: 1. What exercise tests have been used to assess exertional hypoxia at home or in an ambulatory setting in the context of Covid-19 and to what extent have they been validated? 2. What exercise tests have been used to assess exertional hypoxia in other lung conditions, to what extent have they been validated and what is the applicability of these studies to acute Covid-19? METHOD: AMED, CINAHL, EMBASE MEDLINE, Cochrane and PubMed using LitCovid, Scholar and Google databases were searched to September 2020. Studies where participants had Covid-19 or another lung disease and underwent any form of exercise test which was compared to a reference standard were eligible. Risk of bias was assessed using QUADAS 2. A protocol for the review was published on the Medrxiv database. RESULTS: Of 47 relevant papers, 15 were empirical studies, of which 11 described an attempt to validate one or more exercise desaturation tests in lung diseases other than Covid-19. In all but one of these, methodological quality was poor or impossible to fully assess. None had been designed as a formal validation study (most used simple tests of correlation). Only one validation study (comparing a 1-min sit-to-stand test [1MSTST] with reference to the 6-min walk test [6MWT] in 107 patients with interstitial lung disease) contained sufficient raw data for us to calculate the sensitivity (88%), specificity (81%) and positive and negative predictive value (79% and 89% respectively) of the 1MSTST. The other 4 empirical studies included two predictive studies on patients with Covid-19, and two on HIV-positive patients with suspected pneumocystis pneumonia. We found no studies on the 40-step walk test (a less demanding test that is widely used in clinical practice to assess Covid-19 patients). Heterogeneity of study design precluded meta-analysis. DISCUSSION: Exertional desaturation tests have not yet been validated in patients with (or suspected of having) Covid-19. A stronger evidence base exists for the diagnostic accuracy of the 1MSTST in chronic long-term pulmonary disease; the relative intensity of this test may raise safety concerns in remote consultations or unstable patients. The less strenuous 40-step walk test should be urgently evaluated.

sFasL-The Key to a Riddle: Immune Responses in Aging Lung and Disease.

By dint of the aging population and further deepened with the Covid-19 pandemic, lung disease has turned out to be a major cause of worldwide morbidity and mortality. The condition is exacerbated when the immune system further attacks the healthy, rather than the diseased, tissue within the lung. Governed by unremittingly proliferating mesenchymal cells and increased collagen deposition, if inflammation persists, as frequently occurs in aging lungs, the tissue develops tumors and/or turns into scars (fibrosis), with limited regenerative capacity and organ failure. Fas ligand (FasL, a ligand of the Fas cell death receptor) is a key factor in the regulation of these processes. FasL is primarily found in two forms: full length (membrane, or mFasL) and cleaved (soluble, or sFasL). We and others found that T-cells expressing the mFasL retain autoimmune surveillance that controls mesenchymal, as well as tumor cell accumulation following an inflammatory response. However, mesenchymal cells from fibrotic lungs, tumor cells, or cells from immune-privileged sites, resist FasL+ T-cell-induced cell death. The mechanisms involved are a counterattack of immune cells by FasL, by releasing a soluble form of FasL that competes with the membrane version, and inhibits their cell death, promoting cell survival. This review focuses on understanding the previously unrecognized role of FasL, and in particular its soluble form, sFasL, in the serum of aged subjects, and its association with the evolution of lung disease, paving the way to new methods of diagnosis and treatment.

C-reactive protein levels in the early stage of COVID-19.

BACKGROUND: COVID-19 is a new infectious disease, for which there is currently no treatment. It is therefore necessary to explore biomarkers to determine the extent of lung lesions and disease severity. OBJECTIVE: We aimed to assess the usefulness of CRP levels in the early stage of COVID-19 and to correlate them with lung lesions and severe presentation. METHODS: Confirmed cases of COVID-19 were selected at the Fever Unit in two regions of Guizhou, China. On admission CRP levels were collected, and the diameter of the largest lung lesion was measured in the most severe lung lesion by lung CT scan. Differences in the diameter and CRP levels were compared in the following groups of patients: mild group, moderate group, severe group, and critical group. RESULT: CRP levels and the diameter of the largest lung lesion in the moderate group were higher than those in the mild group (Mann-Whitney test=-2.647, -2.171, P˂0.05), those in the severe group were higher than those in the moderate group (Mann-Whitney test=0.693, -2.177, P˂0.05), and those in the critical group were higher than those in the severe group (Mann-Whitney test=-0.068, -1.549, P˂0.05). The difference was statistically significant. CRP levels were positively correlated with the diameter of lung lesion and severe presentation (correlation coefficient=0.873, 0.734, P˂0.001). CONCLUSION: In the early stage of COVID-19 CRP levels were positively correlated with lung lesions and could reflect disease severity.