Late surfactant replacement therapy and its efficacy on severe bronchopulmonary dysplasia in National Children Hospital

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that is most commonly seen in premature infants who require prolonged mechanical ventilation and oxygen therapy. 75% of intubated infants have episodes of dysfunctional surfactants associated with lower levels of surfactant proteins. This study aims to evaluate the effectiveness of late surfactant therapy in treating BPD in premature infants. Nineteen preterm infants diagnosed with severe BPD requiring mechanic ventilation, according to Jobe and Bancalari, were treated with surfactant (Poractant alpha 100mg/kg intra-tracheal). Patients were observed for change in oxygen requirement before and at 1-h, 6-h, 12-h, 24-h, and 48-h after treatment. There were 13 boys and 6 girls; boy to girl ratio was 2.16/1. The mean gestation age was 28.3 ± 2 weeks; the mean birth weight was 1134.7 ± 314 gram. There was an increase in SpO2 (saturation of peripheral oxygen), PaO2 (the partial pressure of oxygen in arterial blood) and reduction in FiO2 (fraction of inspired oxygen), PaCO2 (the partial pressure of carbon dioxide in arterial blood), OI (oxygen index), MAP (mean airway pressure) and AaDO2 (Alveolar-to-arterial oxygen gradient) after surfactant (p < 0.05). Conclusion: In patients with severe BPD, late surfactant therapy has shown initial benefits in lung functions and reducing oxygen requirement.

Assessment of Safety of Remdesivir in Covid −19 Patients with Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min per 1.73 m^2

Purpose Safety of remdesivir in patients with renal impairment is unknown. Incidence of liver injury secondary to remdesivir is also unknown. The objective of this study is to assess the incidence of acute kidney injury (AKI) and to trend the liver enzymes during remdesivir treatment and change in eGFR from baseline to end of treatment as well as 48 h post completion of remdesivir therapy. Methods This is a retrospective chart review study including adult patients admitted with COVID-19 receiving remdesivir with a baseline eGFR < 30 ml/min per 1.73 m^2 from December 2020 to May 2021. The primary outcome was to assess the incidence of AKI and hepatic injury. The secondary outcome was to assess the efficacy of remdesivir defined by change in oxygen requirement. Results Seventy-one patients were included in the study. Patients experienced an improvement in eGFR from baseline (T0) to end of remdesivir treatment (T1), as well as 48 h after the end of the treatment (T2) ( + 30.3% and + 30.6% respectively, P < .0001). Creatinine reduced from baseline (T0) to T1 and T2 (-20.9% and −20.5% respectively, P < .0001). Creatinine clearance improved from baseline to T1 and T2 ( + 26.6% and + 26.2% respectively, p < .0001). Elevation of aminotransferase (AST) was observed at T1 ( + 2.5%, P = .727), however, AST reduction was seen at T2 (-15.8%, P = .021). Elevation in alanine transaminase (ALT) was observed at T1 and T2 ( + 25% and + 12%, P = .004 and P = .137 respectively). Both direct and total bilirubin remained stable and were not significantly changed from baseline. Conclusion Our study showed that remdesivir use in renally-impaired patients with eGFR < 30 ml/min is safe. Remdesivir may be considered as a therapeutic option in this population with COVID-19 infection.

A case report of COVID-19 positive Becker Muscular Dystrophy

Background: Becker and Duchenne muscular dystrophies constitute the most common inherited dystrophinopathies. The chronic steroid treatment predisposes them to any infection, hence, we sought to determine the current COVID-19 infection in them. We conducted an analysis on a real-world database to identify the effect of COVID-19 infection and identified a case of Becker muscular dystrophy who tested positive for COVID-19. For our analysis, we utilized Cerner Real-World DataTM that was provided through Cerner's HealtheDataLab research tool. Case report: A 63-year-old Caucasian male with Becker muscular dystrophy, hyperlipidemia, and atrial fibrillation, was hospitalized with COVID-19 infection. Our search revealed June 22, 2020, as the patient's COVID-19 service date when tested positive. The patient received antibiotics and supportive therapy during hospitalization. Intricate details like oxygen requirement, blood gas analysis, and mechanical ventilation could not be retrieved if used. The patient developed complications like sepsis, pneumonia, acute respiratory failure that resulted in prolonged hospitalization. Our data reported that the patient was alive during discharge. Conclusion: Although patient developed complications during hospitalization, no death from the COVID-19 infection was observed in our analysis.

Comparison between two natural surfactant poractant alfa and bovine lipid extract in respiratory distress syndrome amongst preterm neonates-a quasi-experimental study

Background: A comparison study of two natural surfactants in preterm babies admitted in neonatal intensive care unit (NICU) and sick newborn care unit (SNCU) of a tertiary care hospital to find out efficacy and consequences.Methods: A Quasi-experimental study. InSurE technique applied for administering Poractant alfa (CUROSURF) and bovine surfactant (NEOSURF) in two comparison group of preterm neonates with respiratory distress syndrome (RDS) during May 2018 to April 2019. The need of mechanical ventilation, oxygen requirement (FiO2), duration of oxygen requirement and the consequences were assessed.Results: The CUROSURF is 6.67% more efficacious than NEOSURF in respect to less requirement of mechanical ventilation. The differences were found between two groups in terms of FiO2adjusted (33.49% vs 37.17%) and common side effects respectively but the difference of mean duration of oxygenation (69.8 hrs vs 111.9 hrs) was less and statistically significant in CUROSURF group. Mean duration of hospitalization (9.55 day’s vs 14.9 days) also were found to be less and statistically significant.Conclusions: Treatment with CUROSURF was associated with faster improving oxygenation, less additional doses, and decreased need of mechanical ventilation.

Survival and outcomes of tocilizumab use in severe and critically ill Covid-19 patients not responding to steroids

BackgroundMortality and morbidity are highest in severe and critically ill patients with COVID -19 pneumonia. Recently corticosteroids have shown a definite mortality benefit in these patients. In this study we used interleukin -6 inhibitor, tocilizumab in patients who failed to show any clinical improvement after initial treatment with steroids.Patients and methodsThis is a retrospective observational study conducted at a tertiary care referral hospital in India. Severe and critical COVID 19 patients, who got admitted to intensive care unit and subsequently received tocilizumab were included. Patients who worsened clinically or had no change in oxygen requirement even after 24hrs of receiving Intravenous methylprednisolone at a dose of 1-2mg/kg/day received a maximum total dose of 800mg of intravenous tocilizumab. The day 28 all cause mortality and progression to mechanical ventilation were the primary outcome measures. Clinical improvement and oxygen requirements after tocilizumab administration along with trends in inflammatory markers were secondary outcome. Secondary infections rates and other drug related side effects were also noted.ResultsA total of 51 patients who did not show clinical improvement even after 24 hours of intravenous steroids and received tocilizumab were included. In these patients, there was a significant decrease in oxygen requirement by day 3 and clinical improvement by day 7 of tocilizumab administration. Among the inflammatory markers, we observed elevated median baseline values of CRP (114.2 mg/L), IL-6 (55.4 pg/ml) and Neutrophil to Lymphocyte Ratio (12.4). Out of these only CRP showed a significant decrease after the drug administration. 13 (26.5%) of the 49 patients who were on non-invasive or conventional oxygen support progressed to mechanical ventilation. The day 28 all-cause mortality rate was 10/51(19.6%). 10(19.6%) of the 51 patients had life threatening infections, 5/51 had thrombocytopenia, 3/51 had pneumo-mediastenum/pneumothorax, 1 patient had colonic perforation and 1 patient had transaminitis following tocilizumab administration.ConclusionEarly and timely administration of tocilizumab only in selected severe and critical covid patients not responding to initial steroids appears to increase the survival. Further randomized controlled trials are required to confirm this finding.

Protection offered by COVID-19 vaccine against morbidity and mortality due to COVID-19 infection: a postvaccination cohort study

Background: Many vaccines have been developed, approved and administered against the COVID-19. Phase 2 and 3 trials have proved the safety and tolerability of these. This study was conducted to assess effect of the vaccines on morbidity and mortality due to postvaccination new COVID-19 infection.Methods: This was an observational, retrospective cohort study. The patients admitted with COVID-19 from 1st April 2021 till 30th April 2021 who were willing to participate were included. All the patients were telephonically contacted post discharge and enquired regarding history of vaccination, events during hospitalization and outcome. The data so collected was analysed to compare the morbidity (oxygen requirement, need of ICU admission and need of BiPAP or invasive ventilation) and mortality between vaccinated and nonvaccinated COVID-19 patients and relation of time elapsed post vaccination with morbidity and mortality.Results: Total 431 patients were included. There was significant difference between the two groups in terms of need for ICU admission (OR 0.503; CI 0.30-0.82, p=0.008) as well as requirement of BiPAP or invasive ventilation (OR 0.57; CI 0.33-0.98, p=0.05). Mortality was significantly less in the vaccinated group; OR 0.48 (0.24-0.95), p=0.04). Ten patients had received both doses. Only one required ICU while none of them required invasive ventilation and none expired.Conclusions: COVID-19 vaccine gives significant protection against COVID-19 infection related ICU admission, need of mechanical ventilation and mortality even after single dose. Two doses of vaccine may afford better protection against the disease.

The Effects of Different Types of Steroids on Clinical Outcomes in Neonates with Meconium Aspiration Syndrome: A Systematic Review, Meta-Analysis, and GRADE Assessment

Background and Objectives: Meconium aspiration syndrome (MAS) is a condition caused by the aspiration of meconium-stainted amniotic fluid into the lungs, resulting in pulmonary inflammation, neonatal morbidity, and mortality. It is important that these MAS infants receive appropriate care to avoid further complications. Steroids have an anti-inflammatory effect and may be effective in the management of MAS. The objective of the this study was to evaluate the effect of different steroids on clinical outcomes in infants with MAS. Materials and Methods: We systematically searched of PubMed/Medline, Scopus, Embase, Clinical Trials.gov, and Cochrane Library databases from inception to 24 January 2021 without language restriction. Only randomized controlled trials (RCTs) evaluating the effects of steroids in neonates with MAS were included. We calculated relative risks and weighted mean differences (MDs) with 95% confidence intervals (CIs) using a random-effects model to determine the associations between MAS and steroids and GRADE approach was employed for quality of evidence. The main outcomes measures were duration of respiratory distress, oxygen requirement, hospitalization, need for mechanical ventilation, death, and adverse drug reactions. Results: Seven RCTs involving 397 patients were analyzed. Nebulized budesonide and intravenous (IV) methylprednisolone shortened the duration of respiratory distress (MD, −2.46 days; 95% CI, −3.09 to −1.83 and MD, −3.30 days; 95% CI, −4.07 to −2.52, respectively) (moderate certainty). There was a reduction in duration of oxygen requirement in nebulized budesonide use (MD, −2.40 days; 95% CI, −3.40 to −1.40) (low certainty) and IV methylprednisolone use (MD, −3.30 days; 95% CI, −4.07 to −2.52) (moderate certainty). Nebulized budesonide shortened hospitalization stay (MD, −4.47 days; 95% CI, −8.64 to −0.30 days) (low certainty) as IV methylprednisolone use (MD, −7.23 days; 95% CI, −8.19 to −6.07 days) (moderate certainty). None of steroids benefits in death (low certainty). Conclusions: Certain types of steroids may benefit the respiratory aspect, but there was no decrease in mortality in MAS infants.

Early and rapid identification of COVID-19 patients with neutralizing type I-interferon auto-antibodies by an easily implementable algorithm

Purpose Six-19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable strategy for early identification of IFN-AAB-positive patients for potential subsequent clinical interventions. Methods We analysed sera of 430 COVID-19 patients with severe and critical disease from four hospitals for presence of IFN-AABs by ELISA. Binding specificity and neutralizing activity were evaluated via competition assay and virus-infection-based neutralization assay. We defined clinical parameters associated with IFN-AAB positivity. In a subgroup of critically ill patients, we analyzed effects of therapeutic plasma exchange (TPE) on the levels of IFN-AABs, SARS-CoV-2 antibodies and clinical outcome. Results The prevalence of neutralizing AABs to IFN-α and IFN-ω in COVID-19 patients was 4.2% (18/430), while being undetectable in an uninfected control cohort. Neutralizing IFN-AABs were detectable exclusively in critically affected, predominantly male (83%) patients (7.6% IFN-α and 4.6% IFN-ω in 207 patients with critical COVID-19). IFN-AABs were present early post-symptom onset and at the peak of disease. Fever and oxygen requirement at hospital admission co-presented with neutralizing IFN-AAB positivity. IFN-AABs were associated with higher mortality (92.3% versus 19.1 % in patients without IFN-AABs). TPE reduced levels of IFN-AABs in three of five patients and may increase survival of IFN-AAB-positive patients compared to those not undergoing TPE. Conclusion IFN-AABs may serve as early biomarker for development of severe COVID-19. We propose to implement routine screening of hospitalized COVID-19 patients according to our algorithm for rapid identification of patients with IFN-AABs who most likely benefit from specific therapies.

Pre-morbidity and COVID-19 disease outcomes in Pakistani population: A cross-sectional study

Objectives: To identify association of underlying pre-morbidities with disease severity and mortality in hospitalized patients with Corona virus disease 2019. Methods: Total 884 COVID RT-PCR positive patients admitted to KRL Hospital Islamabad from April 2020 to August 2020 were included in this cross-sectional study. Pre-morbidities recorded were hypertension, diabetes mellitus, ischemic heart disease, chronic respiratory disease, chronic kidney disease, chronic liver disease, chronic neuro-psychiatric conditions (stroke and depression) and malignancy. Oxygen requirement, requirement of invasive ventilation, and outcome (recovered versus died) was documented. WHO categories for disease severity were used. Demographic profile and symptoms were also noted. SPSS 22 was used for data analysis. Pearson’s Chi square test was used to see association between pre-morbidities and disease severity categories, oxygen requirement, invasive ventilation and outcome. Pearson’s correlation was applied to analyze the correlation between individual pre-morbidities and disease severity categories. P-value < 0.05 was considered statistically significant. Results: The mean age was 40 ± 12.21 years with 98.5% being males. Majority patients (74.8%) were asymptomatic. Fever was the most common symptom. Diabetes mellitus and hypertension were the most commonly recorded co-morbidity. Significant correlation (p-value < 0.05) was found between the presence of underlying pre-morbidities and disease severity as well as oxygen requirement, requirement of invasive ventilation and mortality. Conclusion: Results are compatible with worldwide studies and underlying pre-morbidities are convincing risk factors for disease severity and mortality. doi: https://doi.org/10.12669/pjms.38.1.4235 How to cite this:Toori KU, Qureshi MA, Chaudhry A. Pre-morbidity and COVID-19 disease outcomes in Pakistani population: A cross-sectional study. Pak J Med Sci. 2022;38(1):---------. doi: https://doi.org/10.12669/pjms.38.1.4235 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.