Coronavirus Disease 2019 Respiratory Failure Research Articles

Human Genetic and Immunological Determinants of SARS-CoV-2 Infection and Multisystem Inflammatory Syndrome in Children.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces pneumonia and acute respiratory failure in Coronavirus Disease 2019 (COVID-19) patients with inborn errors of immunity to type I interferon (IFN-I). The impact of SARS-CoV-2 infection varies widely, ranging from mild respiratory symptoms to life-threatening illness and organ failure, with a higher incidence in men than in women. Approximately 3 to 5% of critical COVID-19 patients under 60 and a smaller percentage of elderly patients exhibit genetic defects in IFN-I production, including X-chromosome-linked TLR7 and autosomal TLR3 deficiencies. Around 15 to 20% of cases over 70 years old, and a smaller percentage of younger patients, present with preexisting autoantibodies neutralizing type I interferons. Additionally, innate errors affecting the control of the response to type I interferon have been associated with pediatric multisystem inflammatory syndrome (MIS-C). Several studies have described rare errors of immunity, such as XIAP deficiency, CYBB, SOCS1, OAS1/2, and RNASEL, as underlying factors in MIS-C susceptibility. However, further investigations in expanded patient cohorts are needed to validate these findings and pave the way for new genetic approaches to MIS-C. This review aims to present recent evidence from the scientific literature on genetic and immunological abnormalities predisposing individuals to critical SARS-CoV-2 infection through IFN-I. We will also discuss multisystem inflammatory syndrome in children (MIS-C). Understanding the immunological mechanisms and pathogenesis of severe COVID-19 may inform personalized patient care and population protection strategies against future serious viral infections.

Pneumomediastinum in COVID-19: Risk factors and outcomes from a multicentre case-control study

BackgroundAn increased incidence of pneumomediastinum has been observed among patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. The study aimed to identify risk factors for COVID-19-associated pneumomediastinum and investigate the impact of pneumomediastinum on clinical outcomes. MethodsIn this multicentre retrospective case-control study, we included consecutive patients with COVID-19 pneumonia and pneumomediastinum hospitalized from March 2020 to July 2020 at ten centres; then, we identified a similarly sized control group of consecutive patients hospitalized with COVID-19 pneumonia and respiratory failure who did not develop pneumomediastinum during the same period. Clinical, laboratory, and radiological characteristics, as well as respiratory support and outcomes, were collected and compared between the two groups. Risk factors of pneumomediastinum were assessed by multivariable logistic analysis. ResultsOverall 139 patients with pneumomediastinum and 153 without pneumomediastinum were analysed. Lung involvement ≥75 %, consolidations, body mass index (BMI) < 22 kg/m2, C-reactive protein (CRP) > 150 mg/L, D-dimer >3000 ng/mL FEUs, and smoking exposure >20 pack-year were all independently correlated with the occurrence of pneumomediastinum. Patients with pneumomediastinum had a longer hospital stay (mean ± SD 31.2 ± 20.2 days vs 19.6 ± 14.2, p < 0.001), higher intubation rate (73/139, 52.5 % vs 27/153, 17.6 %, p < 0.001), and in-hospital mortality (68/139, 48.9 % vs 36/153, 23.5 %, p < 0.001) compared to controls. ConclusionsExtensive lung parenchyma involvement, consolidations, low BMI, high inflammatory markers, and tobacco exposure are associated with a greater risk of pneumomediastinum in COVID-19 pneumonia. This complication significantly worsens the outcomes.

The effect of antifibrotic agents on acute respiratory failure in COVID-19 patients: a retrospective cohort study from TriNetX US collaborative networks

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global health and economies, resulting in millions of infections and deaths. This retrospective cohort study aimed to investigate the effect of antifibrotic agents (nintedanib and pirfenidone) on 1-year mortality in COVID-19 patients with acute respiratory failure.MethodsData from 61 healthcare organizations in the TriNetX database were analyzed. Adult patients with COVID-19 and acute respiratory failure were included. Patients with a pre-existing diagnosis of idiopathic pulmonary fibrosis before their COVID-19 diagnosis were excluded. The study population was divided into an antifibrotic group and a control group. Propensity score matching was used to compare outcomes, and hazard ratios (HR) for 1-year mortality were calculated.ResultsThe antifibrotic group exhibited a significantly lower 1-year mortality rate compared to the control group. The survival probability at the end of the study was 84.42% in the antifibrotic group and 69.87% in the control group. The Log-Rank test yielded a p-value of less than 0.001. The hazard ratio was 0.434 (95% CI: 0.264–0.712), indicating a significant reduction in 1-year mortality in the antifibrotic group. Subgroup analysis demonstrated significantly improved 1-year survival in patients receiving nintedanib treatment and during periods when the Wuhan strain was predominant.DiscussionThis study is the first to demonstrate a survival benefit of antifibrotic agents in COVID-19 patients with acute respiratory failure. Further research and clinical trials are needed to confirm the efficacy of these antifibrotic agents in the context of COVID-19 and acute respiratory failure.

Frailty in Critically Ill Patients with COVID-19: The Lessons Learned.

The coronavirus disease 2019 (COVID-19) pandemic has unquestionably transformed the field of intensive care medicine. Never have we witnessed millions of patients develop acute respiratory failure in such a short span of time. This led to extensive resource constraints and difficulty in treating patients. However, this also gave rise to several innovations that have spurred the development and progress of intensive care medicine as a specialty. In this chapter, we explore an overview of frailty, the impact of frailty in patients with severe COVID-19 respiratory failure, and the available supports, by summarising the current literature. This chapter also discusses the lessons learnt from each of the sections that can be applied to daily clinical practice. The chapter also proposes insights into future research.

Comparison of High Flow Nasal Cannula and Continuous Positive Airway Pressure in COVID-19 Patients With Acute Respiratory Distress Syndrome in Critical Care Unit: A Randomized Control Study.

Background and objective Acute hypoxic respiratory failure in coronavirus disease 2019 (COVID-19) pneumonia has been treated with oxygen delivered by oxygen masks and non-invasive ventilation (NIV) with continuous positive airway pressure (CPAP), and more recently with high-flow nasal cannula (HFNC) devices. There is a paucity of randomized controlled trials to compare the efficacy of CPAP with HFNC in COVID-19 pneumonia. We conceptualized a randomized control study to compare the efficacy of HFNC and CPAP in reducing the need for invasive mechanical ventilation, estimation of mechanical ventilation-free days, and risk of intubation in COVID-19 patients with hypoxic respiratory failure. Methodology One hundred consecutive patients who satisfied the inclusion criteria were included in the trial. The patients were then randomly allocated to receive either CPAP or HFNC with settings as per the study protocol. The patients were deemed to have achieved the study endpoint when they were intubated due to any reason or successfully weaned from NIV to conventional oxygen therapies. The number of patients who required invasive ventilation and the number of invasive ventilation-free days were recorded and analyzed. Results Nineteen (38%) patients in the CPAP group and 30 (60%) patients in the HFNC group required invasive mechanical ventilation and the difference was statistically significant (p = 0.03, 95%CI: 0.1829-0.9129). The median number of days free of invasive mechanical ventilation in the CPAP group (median=5 (interquartile range (IQR(=5,6)) was more than in the HFNC group (median=4 (IQR=3,4)) and this difference was statistically significant (p<0.000). The secondary analysis of risk evaluation for intubation done using the Cox regression model showed no significant factors that could have contributed to intubation in the study population. The Kaplan-Meyer curve was used to express the probability of a patient getting intubated and the calculated hazard ratio was 2.29. Conclusion The administration of CPAP significantly reduced the intubation rate and prolonged invasive mechanical ventilation-free period in COVID-19 patients with hypoxic respiratory failure. We also inferred a two-fold increase in the risk of intubation in patients receiving HFNC compared to CPAP.

Lung transplantation for COVID-2019 respiratory failure in the United States: Outcomes 1-year posttransplant and the impact of preoperative extracorporeal membrane oxygenation support

ObjectivePatients with end-stage respiratory failure after severe coronavirus disease 2019 (COVID-19) infection may benefit from lung transplant; however, data on transplant outcomes and the impact of prolonged circulatory support before transplant in these patients are limited. MethodsWe assessed survival, postoperative complications, and the impact of pretransplant extracorporeal membrane oxygenation (ECMO) in patients undergoing lung transplant in the United States from August 2020 through March 2022 using records validated by United Network for Organ Sharing experts and extracted from the United Network for Organ Sharing database. ResultsIn 305 patients with COVID-19–related respiratory failure and validated data, survival for up to 1-year posttransplant did not differ between 188 patients with COVID-19–related acute respiratory distress syndrome and 117 patients with post-COVID-19 pulmonary fibrosis (P = .8). Pretransplant ECMO support (median 66 days) was required in 191 patients (63%), and venovenous ECMO was used in 91.2% of patients. One-, 6-, and 12-month survival was not significantly different between patients requiring ECMO and patients without ECMO (95.8% vs 99.1%, 93.1% vs 96.4%, 84.8% vs 90.9%, P = .2) In addition, 1-year survival was similar in recipients requiring ECMO for COVID-19 lung failure and recipients requiring ECMO for non-COVID-19 restrictive lung failure (84.8% vs 78.0%, P = .1). ConclusionsThese findings suggest that lung transplant in patients with COVID-19 respiratory failure yields acceptable 1-year outcomes. Despite an often more complex postoperative course, prolonged ECMO pretransplant in well-selected patients was associated with adequate clinical and functional status.

Remdesivir and corticosteroids in the treatment of hospitalized COVID-19 patients

Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by the newly discovered severe acute respiratory syndrome coronavirus 2. Remdesivir (RDV) and corticosteroids are used mainly in COVID-19 patients with acute respiratory failure. The main objective of the study was to assess the effectiveness of remdesivir with and without corticosteroids in the treatment of COVID-19 patients. We conducted a prospective observational study, including adult patients consecutively hospitalized with confirmed COVID-19 and acute respiratory failure. Patients were divided according to treatment strategy: RDV alone versus RDV with corticosteroids. The primary outcome was the time to recovery in both treatment groups. We included 374 COVID-19 adult patients, 184 were treated with RDV, and 190 were treated with RDV and corticosteroid. Patients in the RDV group had a shorter time to recovery in comparison with patients in the RDV plus corticosteroids group at 28 days after admission [11 vs. 16 days (95% confidence Interval 9.7–12.8; 14.9–17.1; p = .016)]. Patients treated with RDV alone had a shorter length of hospital stay. The use of corticosteroids as adjunctive therapy of RDV was not associated with improvement in mortality of COVID-19 patients.

The effects of high-flow oxygen therapy on mortality in patients with COVID-19.

High-flow oxygen therapy (HFOT) has been successful in treating acute hypoxic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS). Successful treatment with noninvasive ventilation and avoidance of mechanical ventilation (MV) has been associated with decreased mortality and positive patient outcomes. It is unclear whether the evidence supports the use of HFOT to treat coronavirus disease 2019 (COVID-19)-induced AHRF and ARDS. To determine whether the use of HFOT decreases the need for intubation or decreases mortality compared with MV in patients with AHRF due to COVID-19. A literature search was conducted in March 2022 using CINAHL, Embase, PubMed, and Scopus bibliographic databases. Ten studies comparing HFOT and MV in COVID-19 respiratory failure met inclusion criteria. Nine studies found a statistically significant reduction in the need for intubation; eight studies found significantly decreased morality in patients who received HFOT. Study design and methodologies limited the findings. Based on the available evidence, the use of HFOT positively affected mortality and incidence of the need for intubation and MV. Further research needs to be conducted before HFOT is adopted as the standard of care for COVID-19-induced AHRF and ARDS. Nurse practitioners should be informed regarding the various respiratory support modalities and evaluate risk versus benefit when caring for patients with COVID-19-induced AHRF and ARDS.

Conservative oxygen supplementation during helmet continuous positive airway pressure therapy in patients with COVID-19 and respiratory failure: a pilot study.

Respiratory failure is a severe complication in coronavirus disease 2019 (COVID-19) pneumonia that, in addition to oxygen therapy, may require continuous positive airway pressure (CPAP) support. It has been postulated that COVID-19 lung injury may share some features with those observed in hyperoxic acute lung injury. Thus, a correct target arterial oxygen tension (P aO2 ) during oxygen supplementation may be crucial to protect the lung from further tissue damage. The aims of this study were: 1) to evaluate the effects of conservative oxygen supplementation during helmet CPAP therapy on mortality and intensive care unit (ICU) admission in patients with COVID-19 and respiratory failure, and 2) to evaluate the effect of conservative oxygen supplementation on new-onset organ failure and secondary pulmonary infections. This was a single-centre, historically controlled study of patients with severe respiratory failure due to COVID-19 pneumonia, receiving either conservative or nonconservative oxygen supplementation during helmet CPAP. A cohort receiving conservative oxygen supplementation was studied prospectively in which oxygen supplementation was administered with a target P aO2 <100 mmHg. Results of this cohort were compared with those of a cohort who had received liberal oxygen supplementation. 71 patients were included in the conservative cohort and 75 in the nonconservative cohort. Mortality rate was lower in the conservative cohort (22.5% versus 62.7%; p<0.001). Rates of ICU admission and new-onset organ failure were lower in the conservative cohort (14.1% versus 37.3%; p=0.001 and 9.9% versus 45.3%; p<0.001, respectively). In patients with COVID-19 and severe respiratory failure, conservative oxygen supplementation during helmet CPAP was associated with improved survival, lower ICU admission rate and less new-onset organ failure.

Retrospective Analysis of Arterial Carbon Dioxide Level and Arterial pH Level at the Time of Initiation of Respiratory ECMO and Outcome

AbstractIntroduction Respiratory extracorporeal membrane oxygenation (ECMO) is well established and its popularity has increased during coronavirus disease 2019 (COVID-19) time. The efficacy of ECMO has been proved in refractory respiratory failure with varied etiology. More than 85,000 respiratory ECMO cases (neonatal, pediatric, adult) registered as per Extracorporeal Life support Organization (ELSO) statistics April 2022 report, with survived to discharge or transfer ranging from 58 to 73%. Early initiation of ECMO is usually associated with shorter ECMO run and better outcome. Many patient factors have been associated with mortality while on ECMO. Pre-ECMO patient pH and arterial partial pressure of carbon dioxide (paCO2) have been associated with poor outcome. We designed a retrospective study from a single tertiary care center and analyzed our data of all respiratory ECMO (neonatal, pediatric, and adult) to understand the effect of pre ECMO, paCO2, and arterial pH to ECMO outcome.Methods It is a retrospective analysis of data collected of patients with acute respiratory failure managed on ECMO from January 2010 to December 2021. Pre-ECMO (1–6 hours before initiation), paCO2, and arterial pH level were noted and analyzed with primary and secondary outcome. Primary outcome goal was survivor and discharged home versus nonsurvivor, while secondary goal was the number of ECMO days and incidence of neurological complications. The statistical analysis was done for primary outcome and incidences of neurological complications and p-value obtained by using chi-squared method. Meta-analysis was done by classifying the respiratory ECMO cases in three major category—COVID-19, H1N1 non-COVID-19, and H1N1 respiratory failure.Results The total 256 patients of respiratory failure were treated with ECMO during specified period by Riddhi Vinayak Multispecialty Hospital ECMO team. Data analysis of 251 patients (5 patients were transferred for lung transplant, hence been not included in study) done. Patients were divided on the basis of pH level less than 7.2 and more than 7.2 and analyzed for primary and secondary outcome. Similarly, patients were divided on the basis of paCO2 level of less than 45 and more than 45.Patient with pre-ECMO pH level more than 7.2 has statistically better survived extracorporeal life support (ECLS) (p-value: 0.008) and survival to discharge home (p-value: 0.038) chances. Pre-ECMO paCO2 level of less than 45 also showed better survival chance of survived ECLS (46.67 vs. 36.02) and survived to discharge home (42.22 vs. 31.06) but not statistically significant (p-value: 0.15 and 0.18, respectively). There was no significant difference in average number of ECMO days in patient survived to discharge home with paCO2 less than 45 and more than 45 (15.7 vs. 11.1 days), and also in pH more than 7.2 and pH less than 7.2 (15.8 vs. 11.6). The incidence of neurological complications was also found lower in patient with pH more than 7.2 (7.5 vs. 17.3%, p-value: 0.034) and in paCO2 level of less than 45 (4.4 vs. 12.65, p-value: 0.15).Conclusion Pre-ECMO arterial pH of more than 7.2 (statistically significant) and paCO2 of less than 45 (statistically not significant) have definitely better survival chances and have lesser incidences of neurological complications. There was no significance difference in the number of ECMO days in either group. Authors recommends early initiation of ECMO for mortality and morbidity benefits.

Successful kidney transplantation from a deceased donor with severe COVID-19 respiratory illness with undetectable SARS-CoV-2 in donor kidney and aorta

To the Editor: Kidney transplantation (KT) from coronavirus disease 2019 (COVID-19) donors were avoided due to concerns for donor-derived transmission.1Kates OS Fisher CE Rakita RM Reyes JD Limaye AP. Use of SARS-CoV-2-infected deceased organ donors: should we always "just say no?".Am J Transplant. 2020; 20 (doi:10.1111/ajt.16000): 1787-1794Crossref PubMed Scopus (0) Google Scholar,2Shah MB Lynch RJ El-Haddad H Doby B Brockmeier D Goldberg DS. Utilization of deceased donors during a pandemic: argument against using SARS-CoV-2-positive donors.Am J Transplant. 2020; 20 (doi:10.1111/ajt.15969): 1795-1799Crossref PubMed Scopus (43) Google Scholar There have been no data on the long-term safety, and sensitive molecular testing for SARS-CoV-2 in donor kidney is not routinely performed. We report a successful KT from a deceased donor who died with severe COVID-19 respiratory failure with a detailed investigation of the donor kidney and aorta tissue for SARS-CoV-2. A 30-year-old female was admitted to a hospital due to severe COVID-19 pneumonia with a positive nasopharyngeal RT-PCR for SARS-CoV-2. With clinical worsening, she was placed on extracorporeal membrane oxygenation, but developed hypoxic brain injury and progressed to brain death. Renal function was stable during her hospital course with a serum creatinine concentration of 0.7 mg/dl. SARS-CoV-2 PCR for bronchoalveolar lavage and nasopharyngeal swab re-tested 3 days prior to donation was negative. A 55-year-old male recipient with an end-stage renal disease secondary to hypertension underwent a transplant with the left kidney from this donor. The donor kidney was studied using pre-implantation surgical biopsy samples to investigate the presence of SARS-CoV-2 RNA using in situ hybridization (ISH) and quantitative RT-PCR (qRT-PCR). Aorta tissue dissected with the kidney during the organ procurement was also studied given high expression of angiotensin-converting enzyme 2 receptors in vasculature. Kidney hematoxylin and eosin staining showed acute tubular injury without any glomerular damage or inflammation (Figure 1A). ISH analyses lacked a positive signal for SARS-CoV-2 RNA in the donor kidney sample (Figure 1B) compared to the SARS-CoV-2 positive lung control (Figure 1C). All samples for qRT-PCR were negative for SARS-CoV-2. We found no evidence of SARS-CoV-2 in donor tissues. The recipient has tested negative for SARS-CoV-2 by nasopharyngeal swab RT-PCR on days 20, 30, and 90 following transplantation, and there have been no signs or symptoms of COVID-19. After an initial period of delayed graft function requiring hemodialysis, the recipient now has excellent renal recovery over 9 months following the transplant, and the most recent creatinine is 1.3 mg/dl. Evidence supporting the use of deceased donors who died due to catastrophic COVID-19-related respiratory illness is limited, and these cases do not fit in any categories of the most up-to-date guideline for COVID-19 donors.3Summary of current evidence and information–donor SARS-CoV-2 testing & organ recovery from donors with a history of COVID-19. https://optn.transplant.hrsa.gov/media/kkhnlwah/sars-cov-2-summary-of-evidence.pdf. Published September 22, 2021. Accessed December 20, 2021.Google Scholar As such, the decision of whether to accept nonlung organs from those donors has been decided on a case-by-case basis. Based on recent observations of successful KT outcomes from mild or asymptomatic SARS-CoV-2 positive donors,4Koval CE Poggio ED Lin YC Kerr H Eltemamy M Wee A. Early success transplanting kidneys from donors with new SARS-CoV-2 RNA positivity: a report of 10 cases.Am J Transplant. 2021; 21 (doi:10.1111/ajt.16765): 3743-3749Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar and a short-term safety report of KT from a donor similar to this case,5Meshram HS Kute VB Patel H Desai S Chauhan S Dave RB. A case report of successful kidney transplantation from a deceased donor with terminal COVID-19-related lung damage: ongoing dilemma between discarding and accepting organs in COVID-19 era!.Transpl Infect Dis. 2021; 23 (doi:10.1111/tid.13683)Crossref Scopus (10) Google Scholar the transmission risk of SARS-CoV-2 through KT is likely very low. In conclusion, the use of deceased donors who died after severe COVID-19 can be individually considered for KT, and these organs should not be routinely discarded. We acknowledge that our case may not be representative of many possible COVID-19 donors since the donor was negative for SARS-CoV-2 PCR at the time of transplantation. Larger scale studies are warranted to confirm our findings, and long-term graft outcomes from COVID-19 donors should be studied. We thank all the JH kidney transplant and COVID-19 research team members.

Vitamin D: A Role Also in Long COVID-19?

Coronavirus disease 2019 (COVID-19) has quickly become a global pandemic. Reports from different parts of the world indicate that a significant proportion of people who have recovered from COVID-19 are suffering from various health problems collectively referred to as “long COVID-19”. Common symptoms include fatigue, shortness of breath, cough, joint pain, chest pain, muscle aches, headaches, and so on. Vitamin D is an immunomodulatory hormone with proven efficacy against various upper respiratory tract infections. Vitamin D can inhibit hyperinflammatory reactions and accelerate the healing process in the affected areas, especially in lung tissue. Moreover, vitamin D deficiency has been associated with the severity and mortality of COVID-19 cases, with a high prevalence of hypovitaminosis D found in patients with COVID-19 and acute respiratory failure. Thus, there are promising reasons to promote research into the effects of vitamin D supplementation in COVID-19 patients. However, no studies to date have found that vitamin D affects post-COVID-19 symptoms or biomarkers. Based on this scenario, this review aims to provide an up-to-date overview of the potential role of vitamin D in long COVID-19 and of the current literature on this topic.

Survival benefit of extracorporeal membrane oxygenation in severe COVID-19: a multi-centre-matched cohort study.

PurposeExtracorporeal membrane oxygenation (ECMO) has become an established therapy for severe respiratory failure in coronavirus disease 2019 (COVID-19). The added benefit of receiving ECMO in COVID-19 remains uncertain. The aim of this study is to analyse the impact of receiving ECMO at specialist centres on hospital mortality.MethodsA multi-centre retrospective study was conducted in COVID-19 patients from 111 hospitals, referred to two specialist ECMO centres in the United Kingdom (UK) (March 2020 to February 2021). Detailed covariate data were contemporaneously curated from electronic referral systems. We analysed added benefit of ECMO treatment in specialist centres using propensity score matching techniques.Results1363 patients, 243 receiving ECMO, were analysed. The best matching technique generated 209 matches, with a marginal odds ratio (OR) for mortality of 0.44 (95% CI 0.29–0.68, p < 0.001) and absolute mortality reduction of 18.2% (44% vs 25.8%, p < 0.001) for treatment with ECMO in a specialist centre.ConclusionWe found ECMO provided at specialist centres conferred significant survival benefit. Where resources and specialism allow, ECMO should be widely offered.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00134-022-06645-w.

Analysis of Early Biomarkers Associated with the Development of Critical Respiratory Failure in Coronavirus Disease 2019 (COVID-19).

Certain biomarkers predict death due to acute respiratory distress syndrome in COVID-19 patients. We retrospectively analyzed biomarkers associated with time to mechanical ventilation for respiratory failure due to COVID-19 (time-to-mechanical ventilation) in 135 consecutive patients in our hospital. We analyzed biomarkers that were elevated immediately (at admission) and later (3 days after admission) using Cox proportional hazards regression analysis. Independent biomarkers of time-to-mechanical ventilation were high C-reactive protein (CRP), interleukin (IL)-6, and Krebs von den Lungen-6 (KL-6) concentrations at admission and elevated CRP, high-mobility group box-1 protein (HMGB-1), and d-dimer levels and low platelets 3 days after admission. Receiver operating characteristic analysis for detecting the association between independent biomarkers associated with time-to-event in multivariate analyses and the start of mechanical ventilation revealed that these biomarkers had area under the curve values higher than 0.700. The present study suggests that CRP was the only biomarker associated with time-to-mechanical ventilation both at admission and 3 days after admission. Moreover, IL-6 (an inflammatory cytokine), HMGB-1 (a late inflammatory mediator), and KL-6 (reflecting injury and/or remodeling of type II pneumocytes) were associated with outcomes in COVID-19 as reported previously. In conclusion, increased CRP, IL-6, KL-6, HMGB-1, and d-dimer levels and decreased platelet counts were associated with the start of mechanical ventilation due to COVID-19.

Acute Respiratory Failure and Mechanical Ventilation in Women With COVID-19 During Pregnancy: Best Clinical Practices.

Symptomatic pregnant women with coronavirus disease-2019 (COVID-19) are at increased risk of severe disease and death compared with symptomatic nonpregnant females of reproductive age. Among those who become critically ill, profound acute hypoxemic respiratory failure is the dominant finding. Significant morbidity and mortality from COVID-19 are largely due to acute viral pneumonia that evolves to acute respiratory distress syndrome. Admission of these patients with critical disease to an intensive care unit and initiation of invasive mechanical ventilation may be indicated. Effective ventilatory support can be challenging in the COVID-19 patient population, even more so when the need occurs in a woman during pregnancy. Key respiratory changes during pregnancy are reviewed. Principles related to maternal-fetal oxygen transport, assessment of ventilation and oxygenation status, and oxygenation goals are also reviewed. Selected concepts related to mechanical ventilatory support for the woman with COVID-19 and acute respiratory failure during pregnancy are presented including indications for ventilatory support, noninvasive support, and invasive ventilator management. Challenges in providing care to this patient population are identified as well as strategies to address them going forward.

Interleukin-1RA Mitigates SARS-CoV-2-Induced Inflammatory Lung Vascular Leakage and Mortality in Humanized K18-hACE-2 Mice.

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Impact of prone position on outcomes of COVID-19 patients with spontaneous breathing.

Background In this study, we explored whether early application of the prone position (PP) can improve severe hypoxemia and respiratory failure in coronavirus disease 2019 (COVID-19) patients with spontaneous breathing.Methods This is a prospective observational study of severe, critically ill adult COVID-19 patients admitted to the intensive care unit. All vital parameters were recorded in real time for all patients. Moreover, the results of chest computed tomography (CT), when available, were analyzed.Results PP was applied in 21 patients who were breathing spontaneously. The application of PP was associated with a significant increase in oxygen saturation measured by pulse oximetry (SpO2) from 82%±12% to 96%±3% (P<0.001) 1 hour later. Moreover, PP was associated with a significant reduction in respiratory rate from 31±10 to 21±4 breaths/min (P<0.001). Furthermore, the number of patients who exhibited signs of respiratory distress after PP was reduced from 10 (47%) to 3 (14%) (P=0.04). Early PP application also led to a clear improvement on CT imaging. It was not, however, associated with a reduction in mortality rate or in the use of invasive mechanical ventilation (P>0.05 for both).Conclusions Our study confirmed that the early application of PP can improve hypoxemia and tachypnea in COVID-19 patients with spontaneous breathing. Randomized controlled trials are needed to confirm the beneficial effects of PP in COVID-19 patients with spontaneous breathing.

Combined Noninvasive Respiratory Support Therapies to Treat COVID-19.

The roles of high-flow nasal cannula (HFNC) and CPAP in coronavirus disease 2019 (COVID-19) are controversial. The objective of the study was to evaluate the impact of the application of a noninvasive respiratory support algorithm on clinical outcomes in subjects with COVID-19 and with acute respiratory failure. We performed a single-center prospective observational study of subjects with respiratory failure from COVID-19 managed with HFNC and with CPAP plus HFNC (combined therapy). The main outcome was the intubation rate, which defined failure of therapy. We also analyzed the role of the ROX index ([[Formula: see text]/[Formula: see text]]/breathing frequency) to predict the need for intubation. From June to December 2020, 113 subjects with COVID-19 respiratory failure were admitted to our respiratory intermediate care unit. HFNC was applied in 65 subjects (57.52%) and combined therapy in 48 subjects (42.47%). A total of 83 subjects (73.45%) were successfully treated with noninvasive respiratory support. The intubation rate was 26.54%, and the overall mortality rate was 14.15%. The mortality rate in subjects who were intubated was 55.2%. An ROX index of 6.28 at 12 h predicted noninvasive respiratory support failure, with 97.6% sensitivity and 51.8% specificity. Data from our cohort managed in a respiratory intermediate care unit showed that combined noninvasive respiratory support was feasible, with favorable outcomes. Further prospective studies are required.

Development and Validation of ARC, a Model for Anticipating Acute Respiratory Failure in Coronavirus Disease 2019 Patients.

To evaluate factors predictive of clinical progression among coronavirus disease 2019 patients following admission, and whether continuous, automated assessments of patient status may contribute to optimal monitoring and management. Retrospective cohort for algorithm training, testing, and validation. Eight hospitals across two geographically distinct regions. Two-thousand fifteen hospitalized coronavirus disease 2019-positive patients. None. Anticipating Respiratory failure in Coronavirus disease (ARC), a clinically interpretable, continuously monitoring prognostic model of acute respiratory failure in hospitalized coronavirus disease 2019 patients, was developed and validated. An analysis of the most important clinical predictors aligns with key risk factors identified by other investigators but contributes new insights regarding the time at which key factors first begin to exhibit aberrency and distinguishes features predictive of acute respiratory failure in coronavirus disease 2019 versus pneumonia caused by other types of infection. Departing from prior work, ARC was designed to update continuously over time as new observations (vitals and laboratory test results) are recorded in the electronic health record. Validation against data from two geographically distinct health systems showed that the proposed model achieved 75% specificity and 77% sensitivity and predicted acute respiratory failure at a median time of 32 hours prior to onset. Over 80% of true-positive alerts occurred in non-ICU settings. Patients admitted to non-ICU environments with coronavirus disease 2019 are at ongoing risk of clinical progression to severe disease, yet it is challenging to anticipate which patients will develop acute respiratory failure. A continuously monitoring prognostic model has potential to facilitate anticipatory rather than reactive approaches to escalation of care (e.g., earlier initiation of treatments for severe disease or structured monitoring and therapeutic interventions for high-risk patients).

An Eight-week Follow-up Study in Patients With COVID-19 Respiratory Failure: Delayed Recovery or Lung Sequel

In recent months, coronavirus disease 2019 (COVID-19) is a significant global health problem that has a tremendous negative impact on the human being, and almost all countries of the world have been affected by the disease. CT imaging techniques have an important role in the primary diagnosis of pneumonia secondary to COVID-19; moreover, the level of pulmonary involvement in CT scan is one of the criteria for disease severity in the acute phase of COVID-19 pneumonia. Still, the role of CT scan in the follow-up period is unknown.