Hypoxemic Pneumonia Research Articles

Effect of noninvasive ventilation on mortality and clinical outcomes among patients with severe hypoxemic COVID-19 pneumonia after high-flow nasal oxygen failure: a multicenter retrospective French cohort with propensity score analysis

BackgroundWe assessed the effect of noninvasive ventilation (NIV) on mortality and length of stay after high flow nasal oxygenation (HFNO) failure among patients with severe hypoxemic COVID-19 pneumonia.MethodsIn this multicenter, retrospective study, we enrolled COVID-19 patients admitted in intensive care unit (ICU) for severe COVID-19 pneumonia with a HFNO failure from December 2020 to January 2022. The primary outcome was to compare the 90-day mortality between patients who required a straight intubation after HFNO failure and patients who received NIV after HFNO failure. Secondary outcomes included ICU and hospital length of stay. A propensity score analysis was performed to control for confounding factors between groups. Exploratory outcomes included a subgroup analysis for 90-day mortality.ResultsWe included 461 patients with HFNO failure in the analysis, 233 patients in the straight intubation group and 228 in the NIV group. The 90-day mortality did not significantly differ between groups, 58/228 (25.4%) int the NIV group compared with 59/233 (25.3%) in the straight intubation group, with an adjusted hazard ratio (HR) after propensity score weighting of 0.82 [95%CI, 0.50–1.35] (p = 0.434). ICU length of stay was significantly shorter in the NIV group compared to the straight intubation group, 10.0 days [IQR, 7.0-19.8] versus 18.0 days [IQR,11.0–31.0] with a propensity score weighted HR of 1.77 [95%CI, 1.29–2.43] (p < 0.001). A subgroup analysis showed a significant increase in mortality rate for intubated patients in the NIV group with 56/122 (45.9%), compared to 59/233 (25.3%) for patients in the straight intubation group (p < 0.001).ConclusionsIn severely hypoxemic COVID-19 patients, no significant differences were observed on 90-day mortality between patients receiving straight intubation and those receiving NIV after HFNO failure. NIV strategy was associated with a significant reduction in ICU length of stay, despite an increase in mortality in the subgroup of patients finally intubated.

Clinical predictors of hypoxic pneumonia in children from the Eastern Highlands Province, Papua New Guinea: secondary analysis of two prospective observational studies

BackgroundPneumonia is the leading cause of death in young children globally and is prevalent in the Papua New Guinea highlands. We investigated clinical predictors of hypoxic pneumonia to inform local treatment guidelines in this resource-limited setting. MethodsBetween 2013 and 2020, two consecutive prospective observational studies were undertaken enrolling children 0-4 years presenting with pneumonia to health-care facilities in Goroka Town, Eastern Highlands Province. Logistic regression models were developed to identify clinical predictors of hypoxic pneumonia (oxygen saturation <90% on presentation). Model performance was compared against established criteria to identify severe pneumonia. FindingsThere were 2067 cases of pneumonia; hypoxaemia was detected in 36·1%. The strongest independent predictors of hypoxic pneumonia were central cyanosis on examination (adjusted odds ratio [aOR] 5·14; 95%CI 3·47-7·60), reduced breath sounds (aOR 2·92; 95%CI 2·30-3·71), and nasal flaring or grunting (aOR 2·34; 95%CI 1·62-3·38). While the model developed to predict hypoxic pneumonia outperformed established pneumonia severity criteria, it was not sensitive enough to be clinically useful at this time. InterpretationGiven signs and symptoms are unable to accurately detect hypoxia, all health care facilities should be equipped with pulse oximeters. However, for the health care worker without access to pulse oximetry, consideration of central cyanosis, reduced breath sounds, nasal flaring or grunting, age-specific tachycardia, wheezing, parent-reported drowsiness, or bronchial breathing as suggestive of hypoxaemic pneumonia, and thus severe disease, may prove useful in guiding management, hospital referral and use of oxygen therapy.

Secondary organizing pneumonia associated with protracted COVID: A case series

ObjectivesImmunocompromised B-cell-depleted patients are at risk of developing protracted COVID-19, a clinical syndrome characterized by prolonged viral shedding and respiratory symptoms that can lead to hypoxemic pneumonia. Our aim is to describe this unusual condition and its treatment. Patients and methodsThis monocentric retrospective study reports six cases of severe organizing pneumonia that developed during the clinical course of protracted COVID-19. ResultsAll patients developed organizing pneumonia (OP) in the setting of protracted COVID. Clinical improvement was obtained after several treatment lines including specific antiviral agents and occurred simultaneously with control of the viral load. ConclusionAs it was the most frequent presentation of protracted COVID-19 in our survey, we believe that this specific form of organizing pneumonia warrants increased awareness. Furthermore, specific antiviral therapy seems to control this condition.

Clinical hypoxemia score for outpatient child pneumonia care lacking pulse oximetry in Africa and South Asia.

Pulse oximeters are not routinely available in outpatient clinics in low- and middle-income countries. We derived clinical scores to identify hypoxemic child pneumonia. This was a retrospective pooled analysis of two outpatient datasets of 3-35 month olds with World Health Organization (WHO)-defined pneumonia in Bangladesh and Malawi. We constructed, internally validated, and compared fit & discrimination of four models predicting SpO2 < 93% and <90%: (1) Integrated Management of Childhood Illness guidelines, (2) WHO-composite guidelines, (3) Independent variable least absolute shrinkage and selection operator (LASSO); (4) Composite variable LASSO. 12,712 observations were included. The independent and composite LASSO models discriminated moderately (both C-statistic 0.77) between children with a SpO2 < 93% and ≥94%; model predictive capacities remained moderate after adjusting for potential overfitting (C-statistic 0.74 and 0.75). The IMCI and WHO-composite models had poorer discrimination (C-statistic 0.56 and 0.68) and identified 20.6% and 56.8% of SpO2 < 93% cases. The highest score stratum of the independent and composite LASSO models identified 46.7% and 49.0% of SpO2 < 93% cases. Both LASSO models had similar performance for a SpO2 < 90%. In the absence of pulse oximeters, both LASSO models better identified outpatient hypoxemic pneumonia cases than the WHO guidelines. Score external validation and implementation are needed.

Cidofovir in Severe Hypoxemic Adenoviral Pneumonia.

The authors present a 16-mo-old boy with flu like symptoms, not responding to supportive management and progressed to severe hypoxemic pneumonia. Adenovirus was detected in the nasopharyngeal aspirate. He showed rapid improvement after intravenous cidofovir administration.

Predictive Factors and Impact of Secondary Pulmonary Infection on Mortality in Patients with Hypoxemic COVID-19 Pneumonia: A Retrospective Cohort Study

Background: Secondary pulmonary infection (SPI) is a severe complication in patients with COVID-19. Objective: To investigate the risk factors, mortality rates, and complications associated with SPI in hypoxemic COVID-19 pneumonia patients. Materials and Methods: A retrospective cohort study was conducted at Saraburi Hospital, analyzing medical records of 512 hospitalized COVID-19 patients. The Fine-Gray model identified risk factors for SPI. Results: SPI was diagnosed in 25.4% of hypoxemic COVID-19 pneumonia patients. SPI patients (mean age of 65.9±15.1 years) had higher inflammation biomarkers, increased in-hospital mortality (IHM), and more complications than non-SPI patients. The primary pathogens causing IHM were gram-negative bacteria in 59.23%. Risk factors for SPI included age of 65 years or older (sHR 1.52; 95% CI 1.03 to 2.25; p=0.032), obesity (sHR 1.52; 95% CI 1.04 to 2.23; p=0.028), invasive mechanical ventilation (sHR 2.87; 95% CI 1.64 to 5.02; p&lt;0.001), lactate dehydrogenase (LDH) level of 520 U/L or more (sHR 2.37; 95% CI 1.69 to 3.33; p=0.027), and catheter-related bloodstream infection (sHR 2.74; 95% CI 1.71 to 4.40; p&lt;0.001). SPI patients had an IHM rate of 74.62%. Multivariable analysis showed higher IHM in SPI patients (aOR 5.29; 95% CI 2.70 to 10.36) compared to non-SPI patients. Conclusion: SPI is a common and harmful complication in hypoxemic COVID-19 pneumonia. Older age, obesity, invasive mechanical ventilation, elevated LDH levels, and catheter-related bloodstream infection are significant risk factors for SPI. Early detection and prevention strategies are crucial to mitigate the short-term consequences of SPI in COVID-19 patients. Keywords: COVID-19; Secondary pulmonary infection; Mortality; Risk factors

Autoantibodies Neutralizing Type I IFNs in the Bronchoalveolar Lavage of at Least 10% of Patients During Life-Threatening COVID-19 Pneumonia

Autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) are found in the blood of at least 15% of unvaccinated patients with life-threatening COVID-19 pneumonia. We report here the presence of auto-Abs neutralizing type I IFNs in the bronchoalveolar lavage (BAL) of 54 of the 415 unvaccinated patients (13%) with life-threatening COVID-19 pneumonia tested. The 54 individuals with neutralizing auto-Abs in the BAL included 45 (11%) with auto-Abs against IFN-α2, 37 (9%) with auto-Abs against IFN-ω, 54 (13%) with auto-Abs against IFN-α2 and/or ω, and five (1%) with auto-Abs against IFN-β, including three (0.7%) with auto-Abs neutralizing IFN-α2, IFN-ω, and IFN-β, and two (0.5%) with auto-Abs neutralizing IFN-α2 and IFN-β. Auto-Abs against IFN-α2 also neutralize the other 12 subtypes of IFN-α. Paired plasma samples were available for 95 patients. All seven patients with paired samples who had detectable auto-Abs in BAL also had detectable auto-Abs in plasma, and one patient had auto-Abs detectable only in blood. Auto-Abs neutralizing type I IFNs are, therefore, present in the alveolar space of at least 10% of patients with life-threatening COVID-19 pneumonia. These findings suggest that these auto-Abs impair type I IFN immunity in the lower respiratory tract, thereby contributing to hypoxemic COVID-19 pneumonia.

Human Genomics of COVID-19 Pneumonia: Contributions of Rare and Common Variants.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is silent or benign in most infected individuals, but causes hypoxemic COVID-19 pneumonia in about 10% of cases. We review studies of the human genetics of life-threatening COVID-19 pneumonia, focusing on both rare and common variants. Large-scale genome-wide association studies have identified more than 20 common loci robustly associated with COVID-19 pneumonia with modest effect sizes, some implicating genes expressed in the lungs or leukocytes. The most robust association, on chromosome 3, concerns a haplotype inherited from Neanderthals. Sequencing studies focusing on rare variants with a strong effect have been particularly successful, identifying inborn errors of type I interferon (IFN) immunity in 1-5% of unvaccinated patients with critical pneumonia, and their autoimmune phenocopy, autoantibodies against type I IFN, in another 15-20% of cases. Our growing understanding of the impact of human genetic variation on immunity to SARS-CoV-2 is enabling health systems to improve protection for individuals and populations.

Early Discharge, Outpatient Evaluation, and Home Management of Acute Respiratory Failure from COVID-19 in Martinique.

A worldwide pandemic of viral infection due to SARS-CoV-2 (and its resultant disease, COVID-19) has been ongoing since 2019. Martinique was affected by a major wave in summer 2021, with saturation of the health system forcing the implementation of home care management. We conducted a retrospective, observational study that included patients treated in the KOVIDHOM 972 program. We included adult patients with SARS-CoV2 hypoxemic pneumonia and requiring 4 L per minute or less of oxygen. In total, 418 were discharged to home with oxygen therapy after hospitalization for SARS-CoV-2 hypoxemic acute pneumonia, and 416 were analyzed. Half (50.2%) were women. Mean age was 58.8 ± 13.0 years. Time from onset of symptoms to hospitalization was 9.1 ± 3.5 days, and average length of stay was 10.5 ± 7.4 days. Maximum oxygen flow during hospitalization was 6.9 ± 4.5 L/min in patients who did not require intensive care. Average oxygen flow at discharge was 1.8 ± 07 L/min. At 30 days after discharge, the readmission rate was 0.5% (95% CI: 0-1.18), and the death rate was 0.5% (95% CI 0-1.18). Our study shows a very low rate of readmission or death in COVID-19 patients discharged to home with oxygen therapy. These results highlight the possibility of safe home care in carefully selected patients. Such programs could be useful in pandemic or wide-scale emergency situations.

Inherited deficiency of the OAS-RNase L pathway in children with MIS-C

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2ʹ-5ʹ-linked oligoadenylates (2–5A) that activate the ssRNA-degrading RNase L. Consistent with the absence of pneumonia in these patients, epithelial cells and fibroblasts defective for this pathway restricted SARS-CoV-2 normally. This contrasted with IFNAR1-deficient cells from patients prone to hypoxemic pneumonia without MIS-C. Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV- 2 stimulation. Exogenous 2–5A suppresses cytokine production in OAS1-but not RNase L- deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by MAVS deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.

Risk and accuracy of outpatient-identified hypoxaemia for death among suspected child pneumonia cases in rural Bangladesh: a multifacility prospective cohort study

Hypoxaemic pneumonia mortality risk in low-income and middle-income countries is high in children who have been hospitalised, but unknown among outpatient children. We sought to establish the outpatient burden, mortality risk, and prognostic accuracy of death from hypoxaemia in children with suspected pneumonia in Bangladesh. We conducted a prospective community-based cohort study encompassing three upazila (subdistrict) health complex catchment areas in Sylhet, Bangladesh. Children aged 3-35 months participating in a community surveillance programme and presenting to one of three upazila health complex Integrated Management of Childhood Illness (IMCI) outpatient clinics with an acute illness and signs of difficult breathing (defined as suspected pneumonia) were enrolled in the study; because lower respiratory tract infection mortality mainly occurs in children younger than 1 year, the primary study population comprised children aged 3-11 months. Study physicians recorded WHO IMCI pneumonia guideline clinical signs and peripheral arterial oxyhaemoglobin saturations (SpO2) in room air. They treated children with pneumonia with antibiotics (oral amoxicillin [40 mg/kg per dose twice per day for 5-7 days, as per local practice]), and recommended oxygen, parenteral antibiotics, and hospitalisation for those with an SpO2 of less than 90%, WHO IMCI danger signs, or severe malnutrition. Community health workers documented the children's vital status and the date of any vital status changes during routine household surveillance (one visit to each household every 2 months). The primary outcome was death at 2 weeks after enrolment in children aged 3-11 months (primary study population) and 12-35 months (secondary study population). Primary analyses included estimating the outpatient prevalence, mortality risk, and prognostic accuracy of hypoxaemia for death in children aged 3-11 months with suspected pneumonia. Risk ratios were produced by fitting a multivariable model that regressed predefined SpO2 ranges (<90%, 90-93%, and 94-100%) on the primary 2-week mortality outcome (binary outcome) using Poisson models with robust variance estimation. We established the prognostic accuracy of WHO IMCI guidelines for death with and without varying SpO2 thresholds. Participants were recruited between Sept 1, 2015, to Aug 31, 2017. During the study period, a total of 7440 children aged 3-35 months with the first suspected pneumonia episode were enrolled, of whom 3848 (54·3%) with an attempted pulse oximeter measurement and 2-week outcome were included in our primary study population of children aged 3-11-months. Among children aged 3-11 months, an SpO2 of less than 90% occurred in 102 (2·7%) of 3848 children, an SpO2 of 90-93% occurred in 306 (8·0%) children, a failed SpO2 measurement occurred in 67 (1·7%) children, and 24 (0·6%) children with suspected pneumonia died. Compared with an SpO2 of 94-100% (3373 [87·7%] of 3848), the adjusted risk ratio for death was 10·3 (95% CI 3·2-32·3; p<0·001) for an SpO2 of less than 90%, 4·3 (1·5-11·8; p=0·005) for an SpO2 of 90-93%, and 11·4 (3·1-41·4; p<0·001) for a failed measurement. When not considering pulse oximetry, of the children who died, WHO IMCI guidelines identified only 25·0% (95% CI 9·7-46·7; six of 24 children) as eligible for referral to hospital. For identifying deaths, in children with an SpO2 of less than 90% WHO IMCI guidelines had a 41·7% sensitivity (95% CI 22·1-63·4) and 89·7% specificity (88·7-90·7); for children with an SpO2 of less than 90% or measurement failure the guidelines had a 54·2% sensitivity (32·8-74·4) and 88·3% specificity (87·2-89·3); and for children with an SpO2 of less than 94% or measurement failure the guidelines had a 62·5% sensitivity (40·6-81·2) and 81·3% specificity (80·0-82·5). These findings support pulse oximeter use during the outpatient care of young children with suspected pneumonia in Bangladesh as well as the re-evaluation of the WHO IMCI currently recommended threshold of an SpO2 less than 90% for hospital referral. Fogarty International Center of the National Institutes of Health (K01TW009988), The Bill & Melinda Gates Foundation (OPP1084286 and OPP1117483), and GlaxoSmithKline (90063241).

Human genetic and immunological determinants of SARS-CoV-2 and Epstein-Barr virus diseases in childhood: Insightful contrasts.

There is growing evidence to suggest that severe disease in children infected with common viruses that are typically benign in other children can result from inborn errors of immunity or their phenocopies. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a cytolytic respiratory RNA virus, can lead to acute hypoxemic COVID-19 pneumonia in children with inborn errors of type I interferon (IFN) immunity or autoantibodies against IFNs. These patients do not appear to be prone to severe disease during infection with Epstein-Barr virus (EBV), a leukocyte-tropic DNA virus that can establish latency. By contrast, various forms of severe EBV disease, ranging from acute hemophagocytosis to chronic or long-term illnesses, such as agammaglobulinemia and lymphoma, can manifest in children with inborn errors disrupting specific molecular bridges involved in the control of EBV-infected B cells by cytotoxic T cells. The patients with these disorders do not seem to be prone to severe COVID-19 pneumonia. These experiments of nature reveal surprising levels of redundancy of two different arms of immunity, with type I IFN being essential for host defense against SARS-CoV-2 in respiratory epithelial cells, and certain surface molecules on cytotoxic T cells essential for host defense against EBV in B lymphocytes.

Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia

Given the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative. To determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies. The ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis-114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023. Patients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days. A hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death). Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, -14.7 [95% CI -6.2 to -23.2] and -14.7 [95% CI -6.2 to -23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, -13.5; 95% CI -2.6 to -24.3). This randomized clinical trial found that compared with SD-PA, neither HD-PA nor TA use improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemic COVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis. ClinicalTrials.gov Identifier: NCT04808882.

Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia.

X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8-207.8, P < 0.001). The patients' susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.

Clinical and biochemical short-term effects of hyperbaric oxygen therapy on SARS-Cov-2+ hospitalized patients with hypoxemic respiratory failure

BackgroundHyperbaric oxygen therapy (HBOT) has been proposed to address COVID-19- associated respiratory failure. However, its biochemical effects are poorly known. Method50 patients with hypoxemic COVID-19 pneumonia were divided into C group (standard care) and H group (standard care plus HBOT). Blood was obtained at t = 0 and t = 5 days. Oxygen saturation (O2 Sat) was followed up. White blood cell (WC) count, lymphocytes (L) and platelets(P) and serum analysis (glucose, urea, creatinine, sodium, potassium, ferritin, D dimer, LDH and CRP) were carried out. Plasma levels of sVCAM, sICAM, sPselectin, SAA and MPO, and of cytokines (IL-1β, IL-1RA, IL-6, TNFα, IFNα, IFNγ, IL-15, VEGF, MIP1α, IL-12p70, IL-2 and IP-10) were measured by multiplex assays. Angiotensin Converting Enzyme 2 (ACE-2) levels were determined by ELISA. ResultsThe average basal O2 Sat was 85 ± 3%. The days needed to reach O2 Sat >90% were: H: 3 ± 1 and C: 5 ± 1 (P < 0,01). At term, H increased WC, L and P counts (all, H vs C: P < 0,01). Also, H diminished D dimer levels (H vs C, P < 0,001) and LDH concentration (H vs C, P < 0.01]. At term, H showed lower levels of sVCAM, sPselectin and SAA than C with respect to basal values (H vs C: ΔsVCAM: P < 0,01; ΔsPselectin: P < 0,05; ΔSAA: P < 0,01). Similarly, H showed diminished levels of TNFα (ΔTNFα: P < 0,05) and increased levels of IL-1RA and VEGF than C respect to basal values (H vs C: ΔIL-1RA and ΔVEGF: P < 0,05). ConclusionPatients underwent HBOT improved O2 Sat with lower levels of severity markers (WC and platelets count, D dimer, LDH, SAA). Moreover, HBOT reduced proinflammatory agents (sVCAM, sPselectin, TNFα) and increased anti-inflammatory and pro-angiogenic ones (IL-1RA and VEGF).

USING THE RATIO OF OXYGEN SATURATION (ROX) INDEX TO PREDICT TREATMENT OUTCOME FOR HIGH-FLOW NASAL CANNULA AND/OR NONINVASIVE VENTILATION IN PATIENTS WITH COPD EXACERBATIONS

USING THE RATIO OF OXYGEN SATURATION (ROX) INDEX TO PREDICT TREATMENT OUTCOME FOR HIGH-FLOW NASAL CANNULA AND/OR NONINVASIVE VENTILATION IN PATIENTS WITH COPD EXACERBATIONS

Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19

BackgroundMost severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are asymptomatic or only exhibit mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children.ObjectiveWe evaluated 31 young patients aged 0.5 to 19 years who had preexisting inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with coronavirus disease 2019 (COVID-19) complications.MethodsGenetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2–specific antibodies, autoantibodies against type I IFN (IFN-I), and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients.ResultsA potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T- and B-cell function, the inflammasome, and the complement system. From tested patients 65.5% had detectable virus-specific antibodies, and 6.8% had autoantibodies neutralizing IFN-I. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children. Eleven patients (35.4%) died of COVID-19 complications. All together, at least 381 IEI children with COVID-19 have been reported in the literature to date. Although many patients with asymptomatic or mild disease may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases, and the mortality rate was 8.7%.ConclusionsYoung patients with preexisting IEI may have higher mortality than children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.

Lower disease activity but higher risk of severe COVID-19 and herpes zoster in patients with systemic lupus erythematosus with pre-existing autoantibodies neutralising IFN-α

ObjectivesType-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-β and/or IFN-ω subtypes are strong determinants of...

Characteristics of our hypoxemic COVID-19 pneumonia patients receiving corticosteroids and mortality-associated factors

ABSTRACT Background COVID-19 is a disease associated with diffuse lung injury that has no proven effective treatment yet. It is thought that glucocorticoids may reduce inflammation-mediated lung injury, disease progression, and mortality. We aimed to evaluate our patient’s characteristics and treatment outcomes who received corticosteroids for COVID-19 pneumonia. Methods We conducted a multicenter retrospective study and reviewed 517 patients admitted due to COVID-19 pneumonia who were hypoxemic and administered steroids regarding demographic, laboratory, and radiological characteristics, treatment response, and mortality-associated factors. Results Of our 517 patients with COVID-19 pneumonia who were hypoxemic and received corticosteroids, the mortality rate was 24.4% (n = 126). The evaluation of mortality-associated factors revealed that age, comorbidities, a CURB-65 score of ≥ 2, higher SOFA scores, presence of MAS, high doses of steroids, type of steroids, COVID-19 treatment, stay in the intensive care unit, high levels of d-dimer, CRP, ferritin, and troponin, and renal dysfunction were associated with mortality. Conclusion Due to high starting and average steroid doses are more associated with mortality, high-dose steroid administration should be avoided. We believe that knowing the factors associated with mortality in these cases is essential for close follow-up. The use of CURB-65 and SOFA scores can predict prognosis in COVID-19 pneumonia.

Introducing pulse oximetry for outpatient management of childhood pneumonia: An implementation research adopting a district implementation model in selected rural facilities in Bangladesh.

SummaryBackgroundPulse oximetry has potential for identifying hypoxaemic pneumonia and substantially reducing under-five deaths in low- and middle-income countries (LMICs) setting. However, there are few examples of introducing pulse oximetry in resource-constrained paediatric outpatient settings, such as Integrated Management of Childhood Illness (IMCI) services.MethodsThe National IMCI-programme of Bangladesh designed and developed a district implementation model for introducing pulse oximetry in routine IMCI services through stakeholder engagement and demonstrated the model in Kushtia district adopting a health system strengthening approach. Between December 2020 and June 2021, two rounds of assessment were conducted based on WHO's implementation research framework and outcome variables, involving 22 IMCI service-providers and 1680 children presenting with cough/difficulty-in-breathing in 12 health facilities. The data collection procedures included structured-observations, re-assessments, interviews, and data-extraction by trained study personnel.FindingsWe observed that IMCI service-providers conducted pulse oximetry assessments on all eligible children in routine outpatient settings, of which 99% of assessments were successful; 85% (95% CI 83,87) in one attempt, and 69% (95% CI 67,71) within one minute. The adherence to standard operating procedure related to pulse oximetry was 92% (95% CI 91,93), and agreement regarding identifying hypoxaemia was 97% (95% CI 96,98). The median performance-time was 36 seconds (IQR 20,75), which was longer among younger children (2-11 months: 44s, IQR 22,78; 12-59 months: 30s, IQR 18,53, p < 0.01) and among those classified as pneumonia/severe-pneumonia than as no-pneumonia (41s, IQR 22,70; 32s, IQR 20,62, p < 0.01). We observed improvements in almost all indicators in round-2. IMCI service-providers and caregivers showed positive attitudes towards using this novel technology for assessing their children.InterpretationThis implementation research study suggested the adoption, feasibility, fidelity, appropriateness, acceptability, and sustainability of pulse oximetry introduction in routine IMCI services in resource-poor settings. The learning may inform the evidence-based scale-up of pulse oximetry linked with an oxygen delivery system in Bangladesh and other LMICs.FundingThis research was funded by the UK National Institute for Health Research (NIHR) (Global Health Research Unit on Respiratory Health (RESPIRE); 16/136/109) using UK aid from the UK Government to support global health research.