Hypoxemic Pneumonia Research Articles

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs.

Life-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.

Pulse oximetry and oxygen services for the care of children with pneumonia attending frontline health facilities in Lagos, Nigeria (INSPIRING-Lagos): study protocol for a mixed-methods evaluation

IntroductionThe aim of this evaluation is to understand whether introducing stabilisation rooms equipped with pulse oximetry and oxygen systems to frontline health facilities in Ikorodu, Lagos State, alongside healthcare worker...

Implementation of solar powered oxygen delivery in a conflict zone: preliminary findings from Somalia on feasibility and usefulness

ABSTRACT Access to therapeutic oxygen in low-resource settings remains a significant global problem. Solar powered oxygen (SPO2) delivery is a reliable and cost-effective solution. We followed implementation research methodology to gather data on engineering parameters (remote monitoring), nurse training (before and after knowledge questionnaire), patients treated with SPO2 (descriptive case series), and qualitative user feedback (focus group discussions). In January 2021, SPO2 was installed at Hanano General Hospital in Dusamareb, Galmudug State, Somalia, in a conflict-affected region. Daily photovoltaic cell output (median 8.0 kWh, interquartile range (IQR) 2.6–14) exceeded the electrical load from up to three oxygen concentrators (median 5.0 kWh, IQR 0.90–12). Over the first six months after implementation, 114 patients (age 1 day to 89 years, 54% female) were treated for hypoxaemic illnesses, including COVID-19, pneumonia, neonatal asphyxia, asthma, and trauma. Qualitative end user feedback highlighted SPO2 acceptability. Violent conflict was identified as a contextual factor affecting local oxygen needs. We provide the preliminary findings of this implementation research study and describe the feasibility, fidelity, rapid adoption, usefulness, and acceptability of SPO2 in a low-resource setting characterized by violent conflict during the COVID-19 pandemic. Our findings demonstrated the lifesaving feasibility of SPO2 in volatile settings.

Long-term cognitive impairments following COVID-19: a possible impact of hypoxia.

BackgroundCognitive and emotional disorders frequently persist after recovery from the acute symptoms of COVID-19; possible explanations include pneumonia-induced hypoxia, infection of the central nervous system, and microstrokes. The objective of the present study was to characterize the impact of hypoxia on the cognitive and psychological profile following COVID-19.MethodsSixty-two patients with COVID-19 were enrolled in a cross-sectional study and divided into two groups based on disease severity: outpatients with no pulmonary complications vs. inpatients with hypoxemic pneumonia having received oxygen therapy. All the participants underwent a comprehensive neuropsychological evaluation that included depression, anxiety, fatigue, sleepiness, attentional, memory and executive processes, and social cognition. For the inpatients, we also collected laboratory data (blood gas, blood glucose, fibrin, fibrinogen, D-dimer, and C-reactive protein).ResultsCognitive disorders was found in patients with COVID-19: at least 18% had an impairment of memory and 11% had attentional dysfunctions. A high level of fatigue (90% of the patients), anxiety (52%), and depression (50%) was also observed. The impairments in attentional (p < 0.001 for omission and commission in CPT 3) and memory (p < 0.003 for Index Cue Efficiency from free and cue selected reminding test) functions were greater in COVID-19 inpatients that in COVID-19 outpatients. In contrast, levels of fatigue, depression, and anxiety were similarly high in both groups.ConclusionsThese findings might help to improve the management of COVID-19 patients as a function of the disease severity in particular for patients with hypoxia.

Prevalence of hypoxaemia in children with pneumonia in low-income and middle-income countries: a systematic review and meta-analysis

SummaryBackgroundPneumonia accounts for around 15% of all deaths of children younger than 5 years globally. Most happen in resource-constrained settings and are potentially preventable. Hypoxaemia is one of the strongest predictors of these deaths. We present an updated estimate of hypoxaemia prevalence among children with pneumonia in low-income and middle-income countries.MethodsWe conducted a systematic review using the following key concepts “children under five years of age” AND “pneumonia” AND “hypoxaemia” AND “low- and middle-income countries” by searching in 11 bibliographic databases and citation indices. We included all articles published between Nov 1, 2008, and Oct 8, 2021, based on observational studies and control arms of randomised and non-randomised controlled trials. We excluded protocol papers, articles reporting hypoxaemia prevalence based on less than 100 pneumonia cases, and articles published before 2008 from the review. Quality appraisal was done with the Joanna Briggs Institute tools. We reported pooled prevalence of hypoxaemia (SpO2 <90%) by classification of clinical severity and by clinical settings by use of the random-effects meta-analysis models. We combined our estimate of the pooled prevalence of pneumonia with a previously published estimate of the number of children admitted to hospital due to pneumonia annually to calculate the total annual number of children admitted to hospital with hypoxaemic pneumonia.FindingsWe identified 2825 unique records from the databases, of which 57 studies met the eligibility criteria: 26 from Africa, 23 from Asia, five from South America, and four from multiple continents. The prevalence of hypoxaemia was 31% (95% CI 26–36; 101 775 children) among all children with WHO-classified pneumonia, 41% (33–49; 30 483 children) among those with very severe or severe pneumonia, and 8% (3–16; 2395 children) among those with non-severe pneumonia. The prevalence was much higher in studies conducted in emergency and inpatient settings than in studies conducted in outpatient settings. In 2019, we estimated that over 7 million children (95% CI 5–8 million) were admitted to hospital with hypoxaemic pneumonia. The studies included in this systematic review had high τ2 (ie, 0·17), indicating a high level of heterogeneity between studies, and a high I2 value (ie, 99·6%), indicating that the heterogeneity was not due to chance. This study is registered with PROSPERO, CRD42019126207.InterpretationThe high prevalence of hypoxaemia among children with severe pneumonia, particularly among children who have been admitted to hospital, emphasises the importance of overall oxygen security within the health systems of low-income and middle-income countries, particularly in the context of the COVID-19 pandemic. Even among children with non-severe pneumonia that is managed in outpatient and community settings, the high prevalence emphasises the importance of rapid identification of hypoxaemia at the first point of contact and referral for appropriate oxygen therapy.FundingUK National Institute for Health Research (Global Health Research Unit on Respiratory Health [RESPIRE]; 16/136/109).

Interleukin-18 binding protein in infants and children hospitalized with pneumonia in low-resource settings.

Pneumonia is the leading infectious cause of death in children, with especially high mortality in low- and middle-income countries. Interleukin-18 binding protein (IL-18BP) is a natural antagonist of the pro-inflammatory cytokine interleukin-18 and is elevated in numerous autoimmune conditions and infectious diseases. We conducted a prospective cohort study to determine the association between admission IL-18BP levels and clinical severity among children admitted to two hospitals in Uganda for hypoxemic pneumonia. A total of 42 children (median age of 1.2years) were included. IL-18BP levels were higher in patients with respiratory distress, including chest indrawing (median 15ng/mL (IQR 9.8-18) versus 4.5ng/mL (IQR 3.8-11) without chest indrawing, P=0.0064) and nasal flaring (median 15ng/mL (IQR 9.7-19) versus 11ng/mL (IQR 5.4-14) without nasal flaring, P=0.034). IL-18BP levels were positively correlated with the composite clinical severity score, Pediatric Early Death Index for Africa (PEDIA-e, ρ=0.46, P=0.0020). Patients with IL-18BP>14ng/mL also had slower recovery times, including time to sit (median 0.69days (IQR 0.25-1) versus 0.15days (IQR 0.076-0.36) with IL-18BP<14ng/mL, P=0.036) and time to fever resolution (median 0.63days (IQR 0.16-2) versus 0.13days (IQR 0-0.42), P=0.016). In summary, higher IL-18BP levels were associated with increased disease severity and prolonged recovery times in Ugandan children with pneumonia.

Human genetic and immunological determinants of critical COVID-19 pneumonia.

SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1%across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons(IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1-5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFNα, IFNβ and/or IFNω, which are more common in men than in women, are found in approximately 15-20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation.

A retrospective observational study of utility of nonrebreathing mask in moderate to severe hypoxemic COVID-19 pneumonia

A retrospective observational study of utility of nonrebreathing mask in moderate to severe hypoxemic COVID-19 pneumonia

Automated left atrial strain analysis for predicting atrial fibrillation in severe COVID-19 pneumonia: a prospective study

BackgroundAtrial fibrillation (AF) is the most documented arrhythmia in COVID-19 pneumonia. Left atrial (LA) strain (LAS) analysis, a marker of LA contractility, have been associated with the development of AF in several clinical situations. We aimed to assess the diagnostic ability of LA strain parameters to predict AF in patients with severe hypoxemic COVID-19 pneumonia. We conducted a prospective single center study in Amiens University Hospital intensive care unit (ICU) (France). Adult patients with severe or critical COVID-19 pneumonia according to the World Health Organization definition and in sinus rhythm were included. Transthoracic echocardiography was performed within 48 h of ICU admission. LA strain analysis was performed by an automated software. The following LA strain parameters were recorded: LA strain during reservoir phase (LASr), LA strain during conduit phase (LAScd) and LA strain during contraction phase (LASct). The primary endpoint was the occurrence of AF during ICU stay.ResultsFrom March 2020 to February of 2021, 79 patients were included. Sixteen patients (20%) developed AF in ICU. Patients of the AF group were significantly older with a higher SAPS II score than those without AF. LAScd and LASr were significantly more impaired in the AF group compared to the other group (− 8.1 [− 6.3; − 10.9] vs. − 17.2 [− 5.0; − 10.2] %; P < 0.001 and 20.2 [12.3;27.3] % vs. 30.5 [23.8;36.2] %; P = 0.002, respectively), while LASct did not significantly differ between groups (p = 0.31). In a multivariate model, LAScd and SOFA cv were significantly associated with the occurrence of AF. A LAScd cutoff value of − 11% had a sensitivity of 76% and a specificity of 75% to identify patients with AF. The 30-day cumulative risk of AF was 42 ± 9% with LAScd > − 11% and 8 ± 4% with LAScd ≤ − 11% (log rank test P value < 0.0001).ConclusionFor patients with severe COVID-19 pneumonia, development of AF during ICU stay is common (20%). LAS parameters seem useful in predicting AF within the first 48 h of ICU admission.Trial registration: NCT04354558.

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial

BackgroundThe antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support.MethodsDisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948.FindingsBetween March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77–1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome).InterpretationNo clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support.FundingEuropean Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation.TranslationFor the French translation of the abstract see Supplementary Materials section.

Covid-19 severe hypoxemic pneumonia: A clinical experience using high-flow nasal oxygen therapy as first-line management

PurposeTo report a French experience in patients admitted to Intensive Care Unit (ICU) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring high fractional concentration of inspired oxygen supported by high flow nasal cannula (HFNC) as first-line therapy. MethodsRetrospective cohort study conducted in two ICUs of a French university hospital. All consecutive patients admitted during 28-days after the first admission for SARS-CoV-2 pneumonia were screened. Demographic, clinical, respiratory support, specific therapeutics, ICU length-of-stay and survival data were collected. ResultsData of 43 patients were analyzed: mainly men (72%), median age 61 (51–69) years, median body mass index of 28 (25–31) kg/m2, median simplified acute physiology score (SAPS II) of 29 (22–37) and median PaO2/fraction of inspired oxygen (FiO2) (P/F) ratio of 146 (100–189) mmHg. HFNC was initiated at ICU admission in 76% of patients. Median flow was 50 (45–50) L/min and median FiO2 was 0.6 (0.5–0.8). 79% of patients presented at least one comorbidity, mainly hypertension (58%). At day (D) 28, 32% of patients required invasive mechanical ventilation, 3 patients died in ICU. Risk factors for intubation were diabetes (10% vs. 43%, P=0.04) and extensive lesions on chest computed tomography (CT) (P=0.023). Patients with more than 25% of lesions on chest CT were more frequently intubated during ICU stay (P=0.012). At ICU admission (D1), patients with higher SAPS II and Sequential Organ Failure Assessment (SOFA) scores (respectively 39 (28–50) vs. 27 (22–31), P=0.0031 and 5 (2–8) vs. 2 (2–2.2), P=0.0019), and a lower P/F ratio (98 (63–109) vs. 178 (126–206), P=0.0005) were more frequently intubated. Among non-intubated patients, the median lowest P/F was 131 (85–180) mmHg. Four caregivers had to stop working following coronavirus 2 contamination, but did not require hospitalization. ConclusionOur clinical experience supports the use of HFNC as first line-therapy in patients with SARS-COV-2 pneumonia for whom face mask oxygen does not provide adequate respiratory support.

Automated left atrial strain analysis for predicting new-onset atrial fibrillation in severe hypoxemic COVID-19 pneumonia: A prospective study

IntroductionAtrial fibrillation (AF) is the most documented arrhythmia in COVID-19 pneumonia. Left atrial (LA) strain analysis, assessing LA contractility have been associated with the development of new-onset atrial fibrillation (NOAF) in several clinical situations. We aimed to assess the diagnostic ability of LA strain parameters to predict NOAF in patients with severe hypoxemic COVID-19 pneumonia.MethodWe conducted a prospective single center study at Amiens Hospital University (NCT04354558). The population study was composed of adult patients with a severe or critical Covid-19 pneumonia in sinus rhythm at inclusion. Transthoracic echocardiography was performed within 48 hours of admission. LA strain analysis was performed by an automated software. The following LA strain parameters were recorded: LA strain during reservoir phase (LASr), LA strain during conduit phase (LAScd) and LA strain during contraction phase (LASct). The primary endpoint was the occurrence of NOAF during the intensive care unit (ICU) stay.ResultsFrom March 2020 to February 2021, 79 patients were included. Sixteen patients (18%) developed NOAF in ICU. LAScd and LASr were significantly reduced in the NOAF group compared to the other group (8.1[6.3-10.9] vs. 17.2[5.0-10.2]%; P < 0.001 and 20.2 [12.3-27.3] % vs. 30.5 [23.8-36.2] %; P = 0.002 respectively). After adjustment, only LAScd remained independently predictive of NOAF (OR:2.43; 95%CI:1.18-3.37). A LAScd cut-off value of 11.1% had a sensitivity of 76% and a specificity of 75% to identify patients with NOAF. The 30-day cumulative risk of NOAF was 42 ± 9% with LAScd < 11% and 8 ± 4% with LAScd > 11% (log rank test P value < 0.0001) (Fig. 1).ConclusionIn patients with severe hypoxemic COVID-19 pneumonia, LAScd ≤ 11% at admission is a strong risk factor of NOAF development during critical care.

Hyperthyroidism diagnosed in a patient hospitalized for COVID-19 hypoxaemic pneumonia : Diagnostic and therapeutic challenges

Hyperthyroidism diagnosed in a patient hospitalized for COVID-19 hypoxaemic pneumonia : Diagnostic and therapeutic challenges

In-hospital mortality of pulmonary tuberculosis with acute respiratory failure and related clinical risk factors

Background/objectiveData on acute respiratory failure (ARF) in pulmonary tuberculosis (PTB) patients is limited. This study aims to investigate in-hospital mortality, its clinical risk factors and the accuracy of the existing scoring system in predicting in-hospital mortality. MethodsAn observational prospective cohort study involving PTB patients with ARF in tertiary hospital, between January 2017 and December 2018, was conducted. The in-hospital mortality was predicted using the National Early Warning Score 2 (NEWS2), quick Sequential Organ Failure Assessment (qSOFA) and CRB-65. Regression models were run to analyze the clinical risk factors for in-hospital Mortality. Sensitivity and specificity of scoring systems were calculated using a Wilson score interval. ResultsA total of 111 subjects were included. Most of subjects were hypoxemic type respiratory failure (68.5%), advanced lesions (62.2%), new cases (70.3%) and pneumonia co-infection (72.1%) patients. Invasive mechanical ventilation was utilized for 29.73% of cases. There were 53 (47.75%) in-hospital mortality cases and its risk factors were intensive phase treatment (3.34 OR; CI95% 1.27–8.78), P/F ratio < 100 (OR 4.30; CI 95% 1.75–10.59) and renal insufficiency (4.09 OR; CI95% 1.46–11.49). The sensitivity and specificity of NEWS2 ≥ 6, qSOFA ≥ 2 and CRB-65 ≥ 2 were 62.26% and 67.24%; 60.38% and 72.41%; 41.51% and 84.48% respectively. ConclusionsMost of PTB with ARF were new cases, advanced lesion and hypoxemic type respiratory failure. Intensive phase treatment, severe hypoxemia and renal insufficiency are independent predictors of in-hospital mortality in PTB patients with ARF. NEWS2, qSOFA and CRB-65 scores were poor to predict the in-hospital mortality.

#29: Clinical Evaluation of Pediatric Patients with Respiratory Symptoms with Confirmed and Negative Influenza in a Third-level Pediatric Center in Mexico City

Abstract Background Influenza virus is responsible for 3 to 5 million cases every year with an estimated mortality in children around 0.15 deaths per 100,000 population. Mexico reported in the 2018–2019 Influenza season 7,210 confirmed cases with 811 deaths (11%) with AH1N1 the most frequent type with 67% of the cases and 88% of the deaths. Clinical assessment of children with influenza is difficult because of the overlap of symptoms between other viral diseases so we evaluated the severity of respiratory symptoms in influenza-positive and -negative children to attain better clinical assessment of influenza cases. Methods We evaluated 846 children less than 18 years old who were screened for influenza in the emergency department at our hospital by using the WHO Influenza Like Disease (ILD) definition between epidemiological week 40 up to week 20 of the 2018–2019 influenza season. Clinical characteristics, evolution and comorbidities were assessed between positive and negative influenza test. Influenza was confirmed by RT–PCR of a nasal swab. Both χ 2 test and t-test were used for statistical analysis of both groups. Results Of the 846 children evaluated for ILD, 177 were positive and 669 were negative for influenza virus. 53.6% of the positive group and 52.2% of the negative group were male, mean ages were 5.25 years and 3.73 years, respectively (P &amp;lt; 0.0001) with 55% and 73.9% less than 5 years old, respectively. 75.7% of the positive group had severe disease defined as hypoxemic pneumonia and 78.6% of the negative group. Statistically significant differences in clinical evaluation were observed regarding frequency of fever, cough, sore throat, chills, myalgias, arthralgias, malaise, conjunctivitis and sudden onset of symptoms. Also, in the positive group there was higher probability of having a positive close contact (6.8%) case than in the negative group (2.5%) (P = 0.005). Cardiopathy, immunosuppression and cancer were the most frequent comorbidities in the influenza group. Four percent of the influenza-positive group and 5% of the negative group were vaccinated. Influenza types were 55.4% AH1N1pdm09, 35% B (29% Yamagata, 22.6% Victoria, 48.4% undetermined) and 9% of AH3. Two deaths were reported in the influenza-positive group. Conclusions Influenza can produce a severe disease in children, especially with those with co-morbidity; therefore, careful evaluation of respiratory symptoms, contact history to ILD, and highly sensitive diagnostics will accurately diagnose influenza. Patients with severe influenza should be promptly treated with antivirals and isolated to decrease intrahospital transmission.

Use of Fibroquel® (Polymerized type I collagen) in patients with hypoxemic inflammatory pneumonia secondary to COVID-19 in Veracruz, Mexico

Since the beginning of the pandemic, there is currently no specific treatment, however some drugs, after systematic reviews and meta-analysis have been positioned as potential treatments (dexamethasone, tocilizumab, baricitinib), however, other drugs with therapeutic potential are being investigated, such as Polymerized type I collagen (Fibroquel). Material and methods: Adult patients are admitted to the study from December 2020 to January 2021, with prior informed consent, carriers of viral pneumonia confirmed by axial tomography, secondary to infection by Sars Cov2 virus identified by RT-PCR or antigen test, who also present severity data (dyspnea, desaturation -saturation at room air of 92% or less-, persistent fever), as well as inflammation markers (D-dimer 1000ng/ml±100; ferritin&gt; 300mg) and that allow treatment with Polymerized type I collagen (Fibroquel®) at home or in a hospital area. Results: We include data from 35 patients, 19 (54.3%) women and 16 (45.7%) men, with a median age of 51.0 (38.0-76.0) years. The number of patients with a history of previous comorbidities was 34 (97.1%) and 20 (57.1%) had multiple comorbidities (3 or more synchronous comorbidities). The most frequent comorbidities among these patients were obesity in 94.3%, DM2 62.9%, Arterial hypertension 60.0%, COPD 14.3%, heart disease 8.6%, nephropathy 5.7%, in addition to SLE and trisomy 21, both in 2.9% of patients. In the baseline evaluation laboratory, we found that 33 (94.3%) patients had lymphocytopenia and 3 (8.6%) had thrombocytopenia. Median D-Dimer and Ferritin serum levels were 1,200.0 (990.0- 1,800.0) ng/mL and 394.5 (320.0-492.5) ug/L, respectively. The neutrophil-lymphocyte index was calculated, which on average was 10.8 (8.0 - 14.7) and an ABC-GOALSclx index of 14.0 (11.0 - 16.0) was calculated, which translate severe disease and an indication of stay in an intensive care unit. Relation to the pulse oximetry at ambient air in the baseline evaluation, we found that the median O2 saturation was 88.0% (86.0% - 89.0%). The median number of days of evolution from the onset of symptoms to the moment in which treatment with Fibroquel was started was 8.0 (7.0-9.0) days. The pulse oximetry quantified 7 days after the start of treatment had a median of 94.0% (93.0-95.0%); Regarding the measurement of prognostic biomarkers, the median d-dimer and ferritin in serum measured at 7 days of follow-up were 656.0 (497.0 - 697.5) ng/mL and 394.5 (320.0-492.5) ug/L, respectively. Conclusion: Polymerized type I collagen (Fibroquel) is an effective drug in patients with inflammatory and hypoxemic pneumonia secondary to Sars COV 2 infection, favoring clinical improvement and favoring extubation, oxygenation, and inflammation indices, as well as a biosafety profile that ensures its use without restrictions in these patients.

Co-infection in patients with hypoxemic pneumonia due to COVID-19 in Reunion Island.

This study aimed to evaluate the incidence of co-infection with different types of pathogens in patients with hypoxemic pneumonia due to coronavirus disease 2019 (COVID-19) in Reunion Island.This observational study using a prospectively collected database of hypoxemic pneumonia due to COVID-19 cases was conducted at Félix Guyon University Hospital in Reunion Island, France.Between 18 March 2020 and 15 April 2020, 156 patients were admitted to our hospital for COVID-19. A total of 36 patients had hypoxemic pneumonia (23.1%) due to COVID-19. Thirty of these cases (83.3%) were imported by travelers returning mainly from metropolitan France and Spain. Patients were screened for co-infection with other pathogens at admission: 31 (86.1%) by multiplex polymerase chain reaction (PCR) and 16 (44.4%) by cytobacteriological examination of sputum culture. Five patients (13.9%) were found to have co-infection: 1 with influenza virus A H1N1 (pdm09) associated with Branhamella catarrhalis, 1 with Streptococcus pneumoniae associated with Haemophilus influenzae, 1 with Human Coronavirus 229E, 1 with Rhinovirus, and 1 with methicillin-susceptible Staphylococcus aureus. Patients with co-infection had higher D-dimer levels than those without co-infection (1.36 [1.34–2.36] μg/mL vs 0.63 [0.51–1.12] μg/mL, P = .05).The incidence of co-infection in our cohort was higher than expected (13.9%). Three co-infections (with influenza virus A(H1N1) pdm09, Streptococcus pneumoniae, and Staphylococcus aureus) required specific treatment. Patients with hypoxemic pneumonia due to COVID-19 should be screened for co-infection using respiratory cultures or multiplex PCR. Whilst our study has a number of limitations, the results from our study suggest that in the absence of screening, patients should be commenced on treatment for co-infection in the presence of an elevated D-dimer.

The Liver in COVID-19-Related Death: Protagonist or Innocent Bystander?

Introduction: The coronavirus disease 2019 (COVID-19) infection, caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), involves several organs through participation of angiotensin-conversion enzyme 2 (ACE2) receptors. The presence of ACE2 receptors in the liver renders this organ a potential target for the novel coronavirus. Methods: We performed 14 complete autopsies of patients infected with SARS-CoV-2. In each case we stained liver tissue sections with haematoxylin/eosin, Masson blue trichrome stain, periodic acid-Schiff (PAS), Perls, and performed cytokeratin-7 (CK7) immunochemistry. Results: Macroscopically, livers were pale and yellowish in 8 of 14 (57%) patients, and had a nutmeg appearance in the other 6 cases (42%). Histologically, centrolobular necrosis was observed in 12 cases (86%), and was associated with discreet to moderate lobular or portal inflammation. Steatosis was seen in 8 cases (57%), but fibrosis was rare. Cholestasis and discrete bile duct proliferation was observed in 5 cases (36%). Discussion/Conclusion: The main histological changes can be explained by the hypoxic status as a result of severe hypoxemic pneumonia leading to death. Drug toxicity may also play a role in certain cases. Other histological changes may be explained by previous hepatic conditions or underlying hepatic diseases. We concluded that COVID-19 infection was not associated with a specific histopathological pattern of the liver.

Efficacy and safety of oxygen-sparing nasal reservoir cannula for treatment of pediatric hypoxemic pneumonia in Uganda: a pilot randomized clinical trial

BackgroundOxygen is an essential therapy for hypoxemia but is scarce in low-income settings. Oxygen conserving devices optimize delivery, but to date have been designed for adults in high-income settings. Here we present the development and clinical pilot study of an oxygen-sparing nasal reservoir cannula (OSNRC) for pediatric use in low-income settings.Methods(1) Pre-clinical development of a novel OSNRC using a simulated respiratory circuit with metabolic simulator and anatomically accurate face-airway models. Simulated breathing waveforms were designed based on airway resistance, lung compliance, respiratory rate, and tidal volume of spontaneous breathing for three disease conditions. (2) Pilot, randomized, controlled, non-blinded, cross-over study of the OSNRC vs standard nasal cannula (SNC) among children hospitalized with hypoxemic pneumonia in Uganda. Eight children were randomized to OSNRC followed by SNC, and eight were randomized to SNC followed by OSNRC.ResultsThe laboratory simulation showed that the OSNRC provided the same or higher fraction of inspired oxygen at approximately 2.5-times lower flow rate compared to SNC. The flow savings ratio exhibited a linear relationship with the OSNRC volume to tidal volume ratio with a slope that varied with breathing waveforms. The range of performance from different breathing waveforms defined a performance envelope of the OSNRC. Two mask sizes (30 mL and 50 mL) provided sufficient coverage for patients between the 3rd and 97th percentile in our targeted age range. In the clinical pilot study, the rise in capillary blood pCO2 was similar in the OSNRC and SNC groups, suggesting that the OSNRC was not associated with CO2 retention. There were no significant differences between OSNRC and SNC with respect to clinical adverse events, lactate levels, pH, and SpO2. The OSNRC group had a higher mean SpO2 than the SNC group (adjusted mean difference, 1.4, 95% confidence interval 1.1 to 1.8), showing oxygen delivery enhancement.ConclusionThe OSNRC enhances oxygen delivery without causing CO2 retention and appears to be well-tolerated by pediatric patients. If safety, efficacy and tolerability are confirmed in larger trials, this device has the potential to optimize oxygen delivery in children in low-resource settings, reducing the global burden of pediatric pneumonia.Trial registrationThe trial was retrospectively registered (International Standard Registered Clinical/Social Study Number (ISRCTN): 15216845; Date of registration: 15 July 2020).

A comprehensive strategy for the early treatment of COVID-19 with azithromycin/hydroxychloroquine and/or corticosteroids: Results of a retrospective observational study in the French overseas department of Réunion Island

BackgroundThis study aimed to evaluate the prognosis of COVID-19 patients in Reunion Island, with a particular focus on the management of patients with hypoxemic pneumonia. MethodsThis retrospective observational study was conducted from 11 March to 17 April 2020 at the only hospital authorized to manage patients with COVID-19 in Reunion Island. ResultsOver the study period, 164 out of 398 patients (41.2%) infected with COVID-19 were admitted to Félix Guyon University Hospital. Of these, 36 (22%) developed hypoxemic pneumonia. Patients with hypoxemic pneumonia were aged 66 [56–77] years, 69% were male and 33% had hypertension. Ten patients (27.8%) were hospitalized in intensive care unit (ICU). Hydroxychloroquine/azithromycin treatment was associated with a lower ICU admission rate (P=0.008). None of the 6 patients treated with corticosteroids were hospitalized in ICU (P=0.16). There were no deaths at follow up (minimum 80 days). ConclusionsDespite the risk profile of COVID-19 patients with severe hypoxemic pneumonia, the mortality rate of the disease in Reunion Island was 0%. This may be due to the care bundle used in our hospital (early hospitalisation, treatment with hydroxychloroquine/azithromycin and/or corticosteroids, non-invasive respiratory support, etc).