Successful Outcome of Mother and Baby in a Woman With Severe COVID-19 Pneumonia in the Third Trimester of Pregnancy Who Required Extracorporeal Membrane Oxygenation Therapy.

Some studies have reported increased severe coronavirus disease (COVID-19) infection in the third trimester of pregnancy. Therefore, prenatal care in the third trimester requires careful judgment. It has been reported that extracorporeal membrane oxygenation (ECMO) therapy is useful for severe coronavirus disease 2019 (COVID-19) pneumonia; however, the optimal timing for the initiation of ECMO is controversial because the risks and benefits to the mother and fetus require careful consideration. We report a good outcome for mother and baby in a pregnant woman with severe COVID-19 pneumonia at 29 weeks gestation, who underwent urgent delivery and required ECMO therapy. A 34-year-old woman tested positive for COVID-19 at 27 weeks gestation. Despite treatment with remdesivir and prednisolone, her respiratory condition worsened. Consequently, she underwent emergent endotracheal intubation at 28 weeks and 2 days. Although the PaO2/FiO2 (P/F ratio) improved temporarily after endotracheal intubation, her respiratory condition progressively worsened. At 29 weeks gestation, an emergency cesarean section was performed and ECMO was initiated the next day. Although hematoma was observed after ECMO initiation, her respiratory condition improved. She was discharged home 54 days after the cesarean delivery without any complications. The neonate was intubated and transferred to the neonatal intensive care unit and was ultimately discharged home without any complications. Considering the risks and benefits of ECMO for the mother and fetus in the third trimester, ECMO should be initiated after delivery for better outcomes. The P/F ratio may be useful for an appropriate decision regarding delivery and the initiation of ECMO.

Association between PaO2/FiO2 ratio and thrombotic events in COVID-19 patients.

PaO2/FiO2 (P/F ratio) is considered a marker of hypoxia/hypoxemia and mortality. Several prothrombotic changes are associated with the decrease of P/F ratio. The role of P/F ratio in patients with arterial and venous thrombosis remains unclear. The aim of this study was to assess in patients with coronavirus disease 2019 (COVID-19), the association between P/F ratio and arterial/venous thrombosis. One thousand and four hundred and six COVID-19 patients were recruited; 289 (21%) patients had P/F ratio < 200 and 1117 (79%) ≥ 200. Compared to the patients with P/F ratio ≥ 200, those with P/F ratio < 200 were older and with higher levels of glycemia, D-dimer and lower levels of albumin. Multiple linear regression analysis showed that albumin (standardized coefficient ß:  0.156; SE: 0.001; p = 0.0001) and D-dimer (standardized coefficient ß: -0.135; SE: 0.0001; p = 0.0001) were associated with P/F ratio. During the hospitalization 159 patients were transferred in intensive care unit (ICU), 253 patients died, 156 patients had arterial or venous thrombotic events. A bivariate logistic analysis was performed to analyze the predictors of thrombosis in COVID-19 patients; P/F ratio < 200 (Odds Ratio: [OR] 1.718, 95% Confidence Interval [CI] 1.085-2.718, p = 0.021), albumin (OR 1.693, 95% CI 1.055-2.716, p = 0.029), D-dimer (OR 3.469, 95% CI 2.110-5.703, p < 0.0001), coronary artery disease (CAD) (OR 1.800, 95% CI 1.086-2.984, p = 0.023) and heart failure (OR 2.410 95% CI 1.385-4.193, p = 0.002) independently predicted thrombotic events in this population. This study suggests that the P/F ratio is associated with thrombotic events by promoting a hypercoagulation state in patients hospitalized for COVID-19.

Vaccination Status and Number of Vaccine Doses Are Independently Associated with the PaO2/FiO2 Ratio on Admission in Hospitalized COVID-19 Patients.

INTRODUCTION: Coronavirus Disease-19 (COVID-19) vaccines reduce the risk of severe disease and mortality. However, the association between vaccination status and number of doses and the PaO2/FiO2 ratio, a clinical measure of hypoxemia associated with an increased risk of intensive care treatment and mortality, has not been investigated. METHODS: We retrospectively assessed a consecutive series of 116 patients admitted to hospital with a primary diagnosis of COVID-19 between January and April 2022. Demographic, clinical, and laboratory data were collected within 24 h from admission. RESULTS: There was a significant positive relationship between the number of vaccine doses and the PaO2/FiO2 ratio (r = 0.223, p = 0.012). This association remained significant after adjusting for confounders. Vaccinated patients had significantly higher PaO2/FiO2 ratios than the unvaccinated (median: 250; IQR: 195-309 vs. 200; IQR: 156-257, p = 0.013). CONCLUSION: These results highlight the importance of the number of vaccine doses received in reducing the degree of hypoxia on admission in hospitalized COVID-19 patients.

Efficacy of proning in acute respiratory distress syndrome on extracorporeal membrane oxygenation.

Objectives: Proning patients with acute respiratory distress syndrome (ARDS) has been associated with increased survival, although few data exist evaluating the safety and feasibility of proning patients with ARDS on extracorporeal membrane oxygenation (ECMO). Methods: A single-institution retrospective review of all patients with ARDS placed on ECMO between March 1 and May 31, 2020, was performed. All proning events were evaluated for complications, as well as change in compliance, sweep, oxygenation, and flow. The primary outcome of this study was the rate major morbidity associated with proning while on ECMO. Results: In total, 30 patients were placed on ECMO for ARDS, with 12 patients (40%) proned while on ECMO. A total of 83 proning episodes occurred, with a median of 7 per patient (interquartile range, 3-9). No ECMO cannula-associated bleeding, cannula displacement, or endotracheal tune dislodgements occurred (0%). Oropharyngeal bleeding occurred twice (50%). Four patients were proned with chest tubes in place, and none had complications (0%). Lung compliance improved after proning in 70 events (84%), from a mean of 15.4 mL/mm Hg preproning to 20.6 mL/mm Hg postproning (P < .0001). Sweep requirement decreased in 36 events (43%). Oxygenation improved in 63 events (76%), from a mean partial pressure of oxygen of 86 preproning to 103 postproning (P < .0001). Mean ECMO flow was unchanged. Conclusions: Proning in patients with ARDS on ECMO is safe with an associated improvement in lung mechanics. With careful planning and coordination, these data support the practice of appropriately proning patients with severe ARDS, even if they are on ECMO.

A Simple Non-Invasive Score Based on Baseline Parameters Can Predict Outcome in Patients with COVID-19.

We evaluated the role of CRP and other laboratory parameters in predicting the worsening of clinical conditions during hospitalization, ICU admission, and fatal outcome among patients with COVID-19. Consecutive adult inpatients with SARS-CoV-2 infection and respiratory symptoms treated in three different COVID centres were enrolled, and they were tested for laboratory parameters within 48 h from admission. Three-hundred ninety patients were enrolled. Age, baseline CRP, and LDH were associated with a P/F ratio < 200 during hospitalization. Male gender and CRP > 60 mg/L were shown to be independently associated with ICU admission. Lymphocytes < 1000 cell/µL were associated with the worst P/F ratio. CRP > 60 mg/L predicted exitus. We subsequently devised an 11-points numeric ordinary scoring system based on age, sex, CRP, and LDH at admission (ASCL score). Patients with an ASCL score of 0 or 2 were shown to be protected against a P/F ratio < 200, while patients with an ASCL score of 6 to 8 were shown to be at risk for P/F ratio < 200. Patients with an ASCL score ≥ 7 had a significantly increased probability of death during hospitalization. In conclusion, patients with elevated CRP and LDH and an ASCL score > 6 at admission should be prioritized for careful respiratory function monitoring and early treatment to prevent a progression of the disease.

Interleukin 18 and IL-18 BP response to Sars-CoV-2 virus infection.

The immune response to the SARS-CoV-2 infection is crucial to the patient outcome. IL-18 is involved in the lymphocyte response to the disease and it is well established its important role in the complex developing of the host response to viral infection. This study aims at the analysis of the concentrations of IL-18, IL-18BP, INF-γ at the onset of the SARS-CoV-2 infection. The serum levels of measured interleukins were obtained through enzyme-linked immunosorbent assay. Furthermore, the free fraction of IL-18 was numerically evaluated. The enrolled patients were divided in two severity groups according to a threshold value of 300 for the ratio of arterial partial pressure of oxygen and fraction of inspired oxygen fraction and according to the parenchymal involvement as evaluated by computerized tomography at the admittance. In the group of patients with a more severe disease, a significant increase of the IL-18, INF-γ and IL-18BP levels have been observed, whereas the free IL-18 component values were almost constant. The results confirm that, at the onset of the disease, the host response keep the inflammatory cytokines in an equilibrium and support the hypothesis to adopt the IL-18BP modulation as a possible and effective therapeutic approach.

The Characteristics of Patients with Severe COVID-19 Pneumonia Treated with Direct Hemoperfusion Using Polymyxin B-Immobilized Fiber Column (PMX-DHP).

Purpose: The characteristics of patients with severe COVID-19 pneumonia who underwent direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP), in addition to steroids and immunomodulators, remain unclear. Patients and Methods: We conducted a retrospective observational study on 31 patients with severe COVID-19 pneumonia treated with PMX-DHP in an intensive care unit (ICU) from December 2020 to September 2021. Results: Outcomes 28 days after admission to the ICU were 20 in the survival group and 11 in the death group. Parameters significantly different between the survival and death group before PMX-DHP were percentage of invasive mechanical ventilation (25% vs 72.7%, P = 0.0209), PaO2/FIO2 (P/F) ratio (104.5 vs 75, P = 0.0317), and sequential organ failure assessment (SOFA) score (2 vs 3, P = 0.0356). Invasive mechanical ventilation avoidance rate was significantly different between the survival (100%) and death group (0%) (P = 0.0012). P/F ratio, respiratory ratio (RR), and lymphocyte counts improved significantly after PMX-DHP for all patients. The lymphocyte counts changed significantly in the survival (P < 0.0001), but not the death group (P = 0.7927). Conclusion: PMX-DHP, in addition to steroids and immunomodulators, may improve oxygenation and alleviate tachypnea by modulating the lymphocyte numbers and levels of various mediator against severe COVID-19 pneumonia. It may be better to perform PMX-DHP before multi organ dysfunction and lung injury has progressed. Furthermore, the early increase in lymphocyte counts after PMX-DHP might be an indicate a positive outcome.

Role of fecal calprotectin as a hypoxic intestinal damage biomarker in COVID-19 patients.

BACKGROUND: Gastrointestinal manifestations of coronavirus disease 2019 (COVID-19) appear to be substantial. Fecal calprotectin is a promising biomarker in COVID-19 associated gastrointestinal inflammation; however, its role in the severity of COVID-19 remains limited. We conducted a study to analyze the relationship between the severity of COVID-19 and hypoxic intestinal damage. METHODS: We assessed the severity of 44 hospitalized COVID-19 pneumonia patients based on the PaO2/FiO2 (P/F) ratio. Inflammatory markers were measured from blood samples, and fecal calprotectin was obtained from stool samples. RESULTS: Median levels of fecal calprotectin in COVID-19 patients involved in this study (n = 44) were found to be markedly elevated along with the severity of hypoxemia, as seen in the non-acute respiratory distress syndrome (ARDS) group 21.4 µg/g (5.2-120.9), mild ARDS 54.30 µg/g (5.2-1393.7), moderate ARDS 169.6 µg/g (43.4-640.5), and severe ARDS 451.6 µg/g (364.5-538.6). We also found significant differences in fecal calprotectin levels based on the severity of ARDS (P < 0.001), and although the patients were divided into ARDS and non-ARDS groups (P < 0.001). Furthermore, we found a strong negative correlation between the P/F ratio and fecal calprotectin levels (r = - 0.697, P < 0.001). CONCLUSION: Our findings support the potential role of fecal calprotectin as a biomarker of intestinal inflammation in COVID-19 as a consequence of hypoxic intestinal damage and as suggested by the reduced P/F ratio.

Estimating the best fraction of inspired oxygen for calculation of PaO2/FiO2 ratio in acute respiratory distress syndrome due to COVID-19 pneumonia.

Background: The ratio of partial pressure of oxygen in arterial blood (PaO2) to the fraction of inspiratory oxygen concentration (FiO2) is an indicator of pulmonary shunt fraction. PaO2/FiO2 (P/F) ratio is used to classify severity of acute respiratory distress syndrome (ARDS). With the same shunt fraction, P/F ratio decreases with increases in FiO2 which may lead to errors in classifying severity of ARDS. The effect of FiO2 on P/F ratio has not been investigated in COVID-19 pneumonia. In this study, we estimated the best FiO2 for the calculation of P/F ratio in a sample of patients with ARDS due to COVID-19 pneumonia. Materials and Methods: Blood gas and ventilatory data of 108 COVID-19 ARDS patients were analyzed in a cross-sectional observational study. Using Oxygen Status Algorithm the calculated shunt fraction served a basis for calculating P/F ratio for different FiO2. The severity of ARDS determined by P/F ratios at each FiO2s was compared with the shunt-based severity to find the optimum FiO2 for calculation of P/F ratio so the resulting classification has the best match with the reference classification. Results: A FiO2 of 1.0 for calculation of P/F ratio and ARDS classification showed the best match with shunt-based ARDS classification. A regression model was obtained with the PaO2, patient's original FiO2, Hemoglobin concentration, and SaO2 as the independent predictors of the P/F ratio for the FiO2 of 1.0. Conclusion: This study shows a FiO2 of 1.0 as the best value for correct calculation of P/F ratio and proper classification of ARDS.

Real-world use of inhaled nitric oxide therapy in patients with COVID-19 and mild-to-moderate acute respiratory distress syndrome.

Background: Inhaled nitric oxide (iNO) has been studied in patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 when it may be too late to impact disease course. This article aims to describe real-world iNO use and outcomes in patients with COVID-19 with mild-to-moderate ARDS in the United States. Methods: This was a retrospective medical chart review study that included patients who were ≥18 years old, hospitalized for COVID-19, met the Berlin ARDS definition, received iNO for ≥24 hours continuously during hospitalization, and had a partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (P/F ratio) of >100 to ≤300 mmHg at iNO initiation. Outcomes included oxygenation parameters, physician-rated Clinical Global Impression-Improvement (CGI-I) scale scores, and adverse events. Response to iNO was defined as >20% improvement in P/F ratio. Results: Thirty-seven patients at six sites were included. A P/F ratio of ≤100 was the most common reason for exclusion (n=146; 83% of excluded patients). The mean P/F ratio (SD) increased from 136.7 (34.4) at baseline to 140.3 (53.2) at 48 hours and 151.8 (50.0) at 72 hours after iNO initiation. The response rate was 62% (n=23). During hospitalization, no patient experienced adverse events, including methemoglobinaemia, airway injury, or worsening pulmonary oedema associated with iNO. At discharge, 54.0% (n=20) of patients improved or remained stable according to the CGI-I. Conclusion: In patients hospitalized with COVID-19 and mild-to-moderate ARDS, iNO was associated with improvement in the P/F ratio with no reported toxicity. This study provides additional evidence supporting a favourable benefit-risk profile for iNO in the treatment of mild-to-moderate ARDS in patients with COVID-19 infection.

Respiratory mechanics and mortality in coronavirus disease 2019 acute respiratory distress syndrome: A retrospective cohort study.

BACKGROUND: The association between commonly monitored respiratory parameters, including compliance and oxygenation and clinical outcomes in acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19) remains unclear, limiting prognostication and the delivery of targeted treatments. Our project aim was to identify if any such associations exist between clinical outcomes and respiratory parameters. METHODS: We performed a retrospective observational cohort study of confirmed COVID-19 positive patients admitted to a single dedicated intensive care unit at a university hospital from March 27 to April 26, 2020. We collected information on baseline clinical and demographic characteristics and initial respiratory parameters. Our primary outcome was in-hospital mortality. RESULTS: A total of 22 patients met criteria for ARDS and were included in our study. Nine of the 22 (40.9%) patients with ARDS died during hospitalization. The initial static respiratory system compliance of survivors was 39 (interquartile range [IQR] 34, 55) and nonsurvivors was 27 (IQR 24, 33, P < 0.01). A lower respiratory system compliance was associated with an increased adjusted odd of in-hospital mortality (odds ratio 1.2, 95% confidence interval 1.01, 1.45 P = 0.04). CONCLUSION: In our cohort of 22 patients mechanically ventilated with ARDS from COVID-19, having lower respiratory system compliance after intubation was associated with an increased risk of in-hospital mortality, consistent with ARDS from non-COVID etiologies.

PMX-DHP Therapy for Dyspnea and Deoxygenation in Severe COVID-19 Pneumonia: A Case Series.

Hypercytokinemia induced by coronavirus disease-19 (COVID-19) is associated with severe pulmonary involvement, which may lead to respiratory failure. These conditions play an important role in the worsening of clinical symptoms in patients with severe COVID-19. There is no established treatment for hypercytokinemia. We report on two patients whose clinical symptoms improved after direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP), following the administration of the anti-inflammatory agent tocilizumab. Case A was a 70-year-old man diagnosed with COVID-19 pneumonia. Despite treatment with ciclesonide and favipiravir, supplemental oxygen was administered due to the worsening of dyspnea with tachypnea. Although tocilizumab was started on day 6, the patient deteriorated into deoxygenation, presenting with the PaO2/FIO2 (P/F) ratio of 92. On days 8 and 10, the patient received PMX-DHP therapy. On day 11, his dyspnea improved. On day 13, his P/F ratio began to improve, and oxygen therapy was discontinued on day 18. The patient recovered without requiring mechanical ventilation. Case B was a 70-year-old man diagnosed with COVID-19 pneumonia and treated with favipiravir, starting on day 0. Despite starting ciclesonide inhalation and tocilizumab on day 2, his P/F ratio was 53. On day 5, he received PMX-DHP therapy. On day 6, his dyspnea improved, as did his P/F ratio, reaching 81 on day 8. Finally, his clinical symptoms resolved, and he was discharged from the intensive care unit without requiring mechanical ventilation. These cases indicate that PMX-DHP therapy might be a suitable treatment option for dyspnea and deoxygenation in COVID-19 pneumonia, especially in cases where an anti-inflammatory agent, such as tocilizumab, has failed to achieve the desired effect.

Lung Ultrasound in Severe COVID-19 Pneumonia in the Sub-Intensive Care Unit: Beyond the Diagnostic Purpose.

Lung Ultra-Sound (LUS) can be very helpful at the diagnostic stage of COVID-19 pneumonia. We describe four clinical cases that summarize other helpful employment of LUS during the management of severe COVID-19 pneumonia with lung failure. LUS, together with clinical signs and arterial blood gases values, assists in guiding prompt clinical management of potential worsening of conditions. The monitoring of size and signs of aeration of consolidations is an important adjuvant in evaluating clinical evolution. The monitoring of LUS patterns can guide the management of non-invasive ventilation as well as the timing of CPAP weaning.

Comparison of Efficacy of Dexamethasone and Methylprednisolone in Improving PaO2/FiO2 Ratio Among COVID-19 Patients.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the reason for the global pandemic that started from Wuhan, China, in December 2019, known as coronavirus diseases 2019 (COVID-19). Acute respiratory distress syndrome happened in COVID-19 not just because of uncontrolled viral replication but also because of an uncontrolled immune reaction from the host. That's why antiviral and anti-inflammatory treatments have become an increasing concern for clinicians. Methods A retrospective quasi-experimental study design was used to assess the effectiveness of methylprednisolone and dexamethasone in the improvement of PaO2/FiO2 (P/F) ratio in COVID-19 patients. We included 60 participants for this study by using a convenient sampling technique and divided them into two groups with 30 patients in each group. Group 1 was given dexamethasone 8 mg twice daily, and group 1 given methylprednisolone 40 mg twice daily for eight days. We recorded C-reactive protein (CRP), serum ferritin level, and P/F ratio before administration of both drugs and after administration of drugs for eight days. We used the paired t-test to assess the effect of both drugs on the P/F ratio of participants. Results The initial mean CRP in group 1 was 110.34, which reduced to 19.45 after administration of dexamethasone; similarly, the CRP in group 2 was 108.65, which reduced to 43.82 after administering methylprednisolone for eight days. In P/F ratio improvement, the calculated significance value for dexamethasone (p=0.000) was less than the table value at 0.05 in all sections, p-value for methylprednisolone (p=0.009) was also less than the table value at 0.05, which shows that both dexamethasone and methylprednisolone were effective in improving P/F ratio. Calculated p-value for dexamethasone (p=0.000) was lower than the calculated p-value for methylprednisolone (p=0.009), which shows that dexamethasone is more effective as compare to methylprednisolone. Conclusions Steroid therapy is effective in controlling inflammation markers, and especially dexamethasone is significantly effective in improving the P/F ratio in COVID-19 patients.

Lung ultrasound as diagnostic tool for SARS-CoV-2 infection.

The aim of this study was to explore the role of lung ultrasound (LUS) in the diagnosis of SARS-CoV-2 infection and to verify its utility in the prediction of lung disease's severity and outcome. Fifty-three consecutive patients presenting to the Emergency Department of Santa Maria delle Grazie Hospital with high suspicion of SARS-CoV-2 infection underwent diagnostic test for SARS-CoV-2 on samples obtained from nasopharyngeal swab as well as complete proper diagnostic work-up that included clinical evaluation, laboratory tests, blood gas analyses, chest CT and LUS. A semiquantitative analysis of B-lines distribution was performed to calculate the LUS score. Patients were divided into two groups according to the results of both SARS-CoV-2 diagnostic test and other exams (Group A = pneumonia due to SARS-CoV2 infection vs Group B = no SARS-CoV2 infection and another definite diagnosis). LUS showed an excellent accuracy in predicting the diagnosis of SARS-CoV-2 infection (area under the ROC curve of 0.92 with a sensibility of 73% and a specificity of 89% a the cut-off of 12.5). LUS score was more impaired in SARS-CoV-2 patients (18.1 ± 6.0 vs 7.6 ± 5.9, p < 0.00001) and it is significantly negatively correlated with PF ratio values (r = - 0.719, p < 0.0001). An intrahospital mortality rate of 46% was found; patients with adverse outcome had significant higher value of LUS, PF, LDH, and APACHE II score. None of these parameters was predictive of mortality. LUS is a useful tool for the early detection of SARS-CoV-2 infection and for the evaluation of the disease severity, but does not predict mortality. Further studies with repeated evaluations of LUS score are needed to further explore the role of LUS in the assessment of severity in SARS-CoV-2 disease and in the monitoring of the response to treatments.