Risk factors for clinically significant diffuse parenchymal lung abnormalities persisting after severe COVID-19 pneumonia

Background & objectives: The risk factors for clinically significant diffuse parenchymal lung abnormalities (CS-DPLA) persisting after severe coronavirus disease 2019 (COVID-19) pneumonia remain unclear. The present study was conducted to assess whether COVID-19 severity and other parameters are associated with CS-DPLA. Methods: The study participants included patients who recovered after acute severe COVID-19 and presented with CS-DPLA at two or six month follow up and control group (without CS-DPLA). Adults volunteers without any acute illness, chronic respiratory illness and without a history of severe COVID-19 were included as healthy controls for the biomarker study. The CS-DPLA was identified as a multidimensional entity involving clinical, radiological and physiological pulmonary abnormalities. The primary exposure was the neutrophil-lymphocyte ratio (NLR). Recorded confounders included age, sex, peak lactate dehydrogenase (LDH), advanced respiratory support (ARS), length of hospital stay (LOS) and others; associations were analyzed using logistic regression. The baseline serum levels of surfactant protein D, cancer antigen 15-3 and transforming growth factor-? (TGF-?) were also compared among cases, controls and healthy volunteers. Results: We identified 91/160 (56.9%) and 42/144 (29.2%) participants with CS-DPLA at two and six months, respectively. Univariate analyses revealed associations of NLR, peak LDH, ARS and LOS with CS-DPLA at two months and of NLR and LOS at six months. The NLR was not independently associated with CS-DPLA at either visit. Only LOS independently predicted CS-DPLA at two months [adjusted odds ratios (aOR) (95% confidence interval [CI]), 1.16 (1.07-1.25); P<0.001] and six months [aOR (95% CI) and 1.07 (1.01-1.12); P=0.01]. Participants with CS-DPLA at six months had higher baseline serum TGF-? levels than healthy volunteers. Interpretation and conclusions: Longer hospital stay was observed to be the only independent predictor of CS-DPLA six months after severe COVID-19. Serum TGF-? should be evaluated further as a biomarker.

Presence of diarrhea associated with better outcomes in patients with COVID-19 – A prospective evaluation

Purpose: Gastrointestinal (GI) manifestations have been well documented in patients with coronavirus disease 2019 (COVID-19), but its clinical impact on the course of the disease is debatable. Majority of the available data is retrospective, and hence this prospective study was planned to study the impact of GI symptoms on COVID-19 outcome. Methods: All COVID-19 patients admitted in a tertiary care centre from August–October 2020 were screened and patients without pre-existing GI diseases were included. A detailed history of the various symptoms including duration was documented. Various baseline laboratory investigations and inflammatory markers were conducted as per the protocol. Patients with and without diarrhea were compared for the various disease outcome parameters. Results: Of the 244 patients screened, 203 patients (128 males; 63.1%) were included. Respiratory symptoms alone were present in 49 (24.1%), GI symptoms alone in 20 (9.9%) and 117 (57.6%) had both. Overall GI symptoms was noted in 137 (67.5%) cases with the commonest being diarrhea (61; 30.0%). Patients with both respiratory and any GI symptoms showed a lower trend towards need for mechanical ventilation (12.2% vs 7.7%; p ¼ 0.35) and mortality (10.2% vs 4.3%; p ¼ 0.14) compared to respiratory symptoms alone, although not statistically significant. Patients with diarrhea (n ¼ 61) had no mortality (0% vs 7.7%; p ¼ 0.036) or need for mechanical ventilation and shorter hospital stay compared to those who did not have diarrhea. Conclusion: GI symptoms are frequent in patients with SARS-CoV-2 infection and the commonest is diarrhea. Diarrhea is a harbinger of better outcome with lower mortality among COVID-19 positive patients.

Clinical characteristics & outcome of SARS-CoV-2 infected neonates presenting to paediatric emergency

Background & objectives: Data on neonatal COVID-19 are limited to the immediate postnatal period, with a primary focus on vertical transmission in inborn infants. This study was aimed to assess the characteristics and outcome of COVID-19 in outborn neonates. Methods: All neonates admitted to the paediatric emergency from August 1 to December 31, 2020, were included in the study. SARS-CoV-2 reverse transcription- (RT)-PCR test was done on oro/nasopharyngeal specimens obtained at admission. The clinical characteristics and outcomes of SARS-CoV-2 positive and negative neonates were compared and the diagnostic accuracy of a selective testing policy was assessed. Results: A total of 1225 neonates were admitted during the study period, of whom SARS-CoV-2 RT-PCR was performed in 969. The RT-PCR test was positive in 17 (1.8%). Mean (standard deviation) gestation and birth weight of SARS-CoV-2-infected neonates were 35.5 (3.2) wk and 2274 (695) g, respectively. Most neonates (11/17) with confirmed COVID-19 reported in the first two weeks of life. Respiratory distress (14/17) was the predominant manifestation. Five (5/17, 29.4%) SARS-CoV-2 infected neonates died. Neonates with COVID-19 were at a higher risk for all-cause mortality [odds ratio (OR): 3.1; 95% confidence interval (CI): 1.1-8.9, P=0.03]; however, mortality did not differ after adjusting for lethal malformation (OR: 2.4; 95% CI: 0.7-8.7). Sensitivity, specificity, accuracy, positive and negative likelihood ratios (95% CI) of selective testing policy for SARS-CoV-2 infection at admission was 52.9 (28.5-76.1), 83.3 (80.7-85.6), 82.8 (80.3-85.1), 3.17 (1.98-5.07), and 0.56 (0.34-0.93) per cent, respectively. Interpretation & conclusions: SARS-CoV-2 positivity rate among the outborn neonates reporting to the paediatric emergency and tested for COVID-19 was observed to be low. The selective testing policy had poor diagnostic accuracy in distinguishing COVID-19 from non-COVID illness.

Development of a cost-effective ex vivo lung perfusion system for lung transplantation in India

Background & objectives: Standard donor lung preservation with cold flush and storage allows up to six hours between retrieval of lungs from the donor and transplantation in the recipient. Ex vivo lung perfusion (EVLP) systems mimic physiological ventilation and perfusion in the donor lungs with potential for prolonged lung preservation and donor lung reconditioning. In this study, it was aimed to perform EVLP on discarded donor lungs using a locally developed EVLP system. Methods: Equipment that are routinely used for cardiac surgeries were collected and a functional EVLP system was assembled. This system was used on five pairs of lungs retrieved from brain-dead organ donors. The lungs were ventilated and pulmonary circulation was continuously perfused with a solution containing oxygen and nutrients for four hours. The system was tested without red blood cells (RBCs) added to the solution (acellular group; n=3; A1, A2 and A3) and also with RBCs added to the solution (cellular group; n=2; C1 and C2). Results: The EVLP system was successfully used in four (A1, A2, A3 and C2) of the five lung pairs. Mechanical and gas exchange functions of the lungs were preserved in these lung pairs. One lung pair (C1) worsened and developed pulmonary oedema. Histopathological examination of all five lung pairs was satisfactory at the end of the procedure. Major challenges faced were leakage of solution from the system and obstruction to drainage of RBCs containing solution from the lungs. Interpretation & conclusions: The results of the present study suggest that, it is possible to maintain the lungs retrieved for transplantation in a physiological condition using a locally prepared EVLP system and a solution without RBCs.

Hydroxychloroquine in Treatment of Asymptomatic and Mildly Symptomatic COVID-19: A Multi-Centre Cohort Study

Background: Although hydroxychloroquine (HCQ) lacks benefit in patients with moderate-to-severe COVID-19, its role in asymptomatic and mildly symptomatic disease needs better elucidation. Methods: This multi-centre cohort study included asymptomatic and mildly symptomatic, RT-PCR confirmed COVID-19 cases between 30 March and 20 May, 2020. Patients were categorized into two groups (HCQ-treated and untreated) based on exposure to HCQ. Dose of HCQ used was 400 mg twice daily (day one) followed by once daily for seven days. HCQ-untreated patients were managed supportively without any active antiviral or immunomodulatory therapy.h Nasopharyngeal SARS-CoV-2 clearance by RT-PCR (primary outcome) was compared between HCQ-treated and untreated patients using Kaplan-Meier analysis and Cox proportional-hazards regression. Clinical efficacy and safety profile of HCQ were assessed (secondary outcomes). Results:162 patients [84 (51·9%) males; mean age 38·2 (15·2) years] were included. Forty-four (27·2%) patients had mild disease, rest 118 (72·8%) were asymptomatic. Seventy-five (46·3%) patients received HCQ. Median time to virological negativity was lesser in HCQ-treated (13 days) versus untreated patients (15 days) (log- rank<0·001) in both asymptomatic and mildly symptomatic patients. Treatment with HCQ was the only independent predictor of virological negativity (hazard- ratio=2·24; adjusted p-value<0·001). Two (5·4%) mildly symptomatic patients progressed to severe disease within 24 hours (two doses) of HCQ initiation, compared to none in the HCQ-untreated group. Five HCQ-treated patients developed minor gastrointestinal side effects, not requiring drug discontinuation. Conclusion: HCQ reduced the time to virologic negativity (by 2 days) in asymptomatic and mildly symptomatic COVID-19, without any serious adverse events. However, no obvious clinical benefit was noted.

Short-term outcome of polytetrafluoroethylene membrane valve versus transannular pericardial patch reconstruction of right ventricular outflow tract in tetralogy of fallot: a randomized controlled trial

Abstract Introduction: Reconstruction of right ventricular outflow tract during primary repair of tetralogy of Fallot often requires the placement of a transannular patch which results in pulmonary regurgitation (PR). We compared the short-term outcomes of bicuspid polytetrafluoroethylene membrane valve versus transannular pericardial patch reconstruction of the right ventricular outflow tract. Methods: Thirty consecutive patients undergoing primary repair of tetralogy of Fallot were randomly allocated to two groups - polytetrafluoroethylene valve (PTFEV) group (n=15) and transannular pericardial patch (TAP) group (n=15). The two groups had similar preoperative demographic characteristics. We compared the short-term clinical and echocardiographic outcomes between these groups. The transthoracic echocardiographic follow-up was performed at one week, one month and six months after surgery. Results: The PTFEV group had significantly lower central venous pressure in the immediate postoperative period compared to the TAP group (7.60±2.06 vs. 10.13±1.73, P=0.002). Extubation time was significantly shorter in the PTFEV group compared to the TAP group (12.93±7.55 hrs vs. 22.23±15.11 hrs, P=0.04). PR in the PTFEV group was absent in five patients at 24 hours post-surgery. At the study endpoint, PR was absent in six, trivial in one and mild in eight patients in the PTFEV group compared to TAP group, where all 15 patients had severe PR. Conclusion: The bicuspid polytetrafluoroethylene membrane valves significantly decrease the central venous pressure in the immediate postoperative period, facilitate early extubation and, thus, prevent ventilator-related comorbidities. They achieve a high degree of pulmonary competence and do not increase the right ventricular outflow tract gradient in short-term follow-up.

Early thrombolysis is associated with decreased operative mortality in postinfarction ventricular septal rupture

Background Post myocardial infarction ventricular septal rupture (PMI-VSR) is a dreaded mechanical complication of acute coronary syndromes. Given that surgical mortality approaches 50%, it is pragmatic that the risk factors for mortality and outcomes after surgical correction of PMI- VSR are carefully scrutinized. Methods We performed a single-center, retrospective cohort study of 35 patients presenting for surgical closure of post myocardial infarction ventricular septal rupture over six years. We reviewed patient characteristics, clinical, echocardiographic, angiographic and perioperative risk factors which may affect mortality after surgical repair of PMIVSR and 30 day and one year mortality rates of these patients. Univariate and multivariate logistic and cox proportional hazard regression analysis was used to identify predictors of operative and overall mortality. Long term survival was presented with Kaplan-Meier Survival Curve. Results Sixteen patients (46%) were in cardiogenic shock. Concomitant coronary artery bypass grafting (CABG) was done in 22 patients (63%) but did not influence survival. Preoperative thrombolysis was done in 12 patients (34%) out of which 10 (53%) survived Operative mortality was 46% and one-year mortality was 49%. Multivariate analysis identified preoperative thrombolysis: Hazards ratio, 0.12; 95% CI, 0.02-0.61; p value of 0.01, as significant independent predictor of survival in PMIVSR cohort. Conclusions Preoperative thrombolysis is associated with decreased odds of operative and overall mortality after surgical repair in PMIVSR patients.