Tocilizumab therapy for severely-ill COVID-19 pneumonia patients: a single-centre retrospective study.

Systemic hyperinflammation is a hallmark of severe coronavirus disease-2019 (COVID-19). Tocilizumab (TCZ) (an interleukin-6 receptor blocker) therapy is currently used as an anti-inflammatory intervention alongside corticosteroids to modulate the hyperinflammatory response (cytokine storm) in hospitalized patients with severe COVID-19 to prevent mortality. There is, however, a wide uncertainty about its pros and cons in patients with COVID-19, particularly, its possible immunosuppressive effect is of serious concern for the clinicians. The present study aimed to report response of a cohort of severely-ill hospitalized COVID-19 pneumonia patients who were treated with tocilizumab after the initial corticosteroids therapy failed to improve the patients' clinical condition. This was a single-arm retrospective study of 100 severely-ill COVID-19 pneumonia patients who were admitted to the specialized COVID-19 units of Mayo Hospital, Lahore, Pakistan from March 12, 2020, to May 25, 2021. These COVID-19 patients had progressed to cytokine storm with persistent hypoxia, associated with pneumonia, and markedly elevated serum levels of inflammatory biomarkers including C-reactive protein (CRP), D-dimer, and ferritin. All the patients had received two separate doses of intravenous 400 mg (4 mg/kg) tocilizumab with an 8-hour interval alongside standard COVID-19 care which includes corticosteroid, antibiotics, and anticoagulants. Following tocilizumab intervention, 75 (75.0%) patients showed clinical improvement, continued to recover, and were safely discharged from the hospital, while in 25 (25.0%) patients, TCZ failed to prevent clinical deterioration, and patients eventually died in the hospital. Amongst the 25 (25.0%) deaths, 8 (32.0%) patients had a single comorbidity, while 9 (36.0%) had two or more comorbidities. The median IQR age for survivors was 57.0 (50.0, 60.0) years, and non-survivors was 60.0 (55.0, 70.0) years; and the period of hospitalization was 25 (20, 40) days and 20 (14, 34) days, respectively. Tocilizumab treatment improved serum inflammatory biomarker levels including CRP, D-dimer, and ferritin, by almost a similar magnitude in both survivors and non-survivors. Development of secondary infections were reported in 25 (25.0%) patients, including 21% patients with bacterial (Pseudomonas, Klebsiella, Acinetobacter) and 4% with fungal (Aspergillus) infection. The emergence of secondary infection was higher in patients who died (72.0%) as compared to those who survived (28.0%). In conclusion: in low- and middle-income countries in the presence of limited therapeutic options, a timely intervention of TCZ alongside corticosteroids may be a suitable anti-inflammatory therapy for severely-ill hospitalized COVID-19 pneumonia patients to prevent mortality. However, patients must be closely monitored for secondary bacterial/fungal infections. Early diagnosis and management of secondary infection can reduce morbidity and mortality.

Hepatic and Gastrointestinal Manifestations of COVID-19

Background: Coronavirus disease (COVID-19) is a global challenge affecting more than 45 million people with a significant mortality. Objective: To determine the frequency of hepatic and gastrointestinal manifestations in patients of COVID-19. Methodology: This was a cross sectional study conducted at King Edward Medical University (KEMU), Mayo Hospital, Lahore for three months. After ethical approval of the study, 230 COVID-19 positive cases of ages 15 to 80 years were included in the study. Complete history & examination regarding hepatic & gastrointestinal symptoms were noted. Liver function tests & prothrombin time (PT) were sent to pathology laboratory at the time of presentation & results were noted. Data was analyzed using SPSS version 26. Descriptive continuous variables like age, bilirubin, Aminotransferases & PT were taken as mean + standard deviation. Categorical variables like gender, hepatic & GI symptoms were taken as frequency and percentages. Results: In 230 patients, the most common gastrointestinal symptom at presentation was diarrhea 34 (14.8%), anosmia 10 (4.3%), nausea & vomiting, abdominal pain 8 (3.5%) each, dysgeusia & right hypochondrial pain 4(1.7%) & Hiccup malaise, anorexia 2 (0.9%). No patient presented with jaundice. Among hepatic manifestations, 8.7% patients had elevated bilirubin levels while Aspartate aminotransferase (AST) was raised in 40% of cases, Alanine aminotransferase (ALT) in 11.3%, Alkaline phosphatase in 1.7%, Gamma-glutamyl transferase (GGT) in 54.8% of cases. 8 (3.5%) cases showed decrease albumin levels and 6.1% cases had prolonged Prothrombin Time (PT). Conclusion: Hepatic & gastrointestinal symptoms were present as the main presenting symptoms of COVID-19 in many patients. So, careful history must be taken for these extra-pulmonary symptoms to avoid any delay in treatment & progression of disease with complications.

51.10 PARENTAL STRESS AND PARENTING IN TIMES OF THE COVID-19 PANDEMIC IN PAKISTAN

Objectives: As COVID-19 spreads around the globe, parents are being presented with new challenges to meet their children’s needs. We investigated parental stress and its impact on their parenting practices alongside focusing on the impact on mothers of hospitalized children, during the COVID-19 outbreak in Lahore, Pakistan. Methods: Following IRB approval, using a web-based questionnaire and telephonic interviews, data were collected in April 2020. Symptoms of depression and anxiety were assessed by the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scale. Parents were also asked to report on their parenting practices as well as emotional and behavior changes noticed in their children in the last 1 month. In-depth semi-structured telephonic interviews were also conducted with 24 mothers of COVID-19–positive children admitted at Mayo Hospital Lahore. Results: A total of 355 parents participated, with a mean age of 35.3 years ± 8.2, and 64.3% were mothers. The majority (55%) of the mothers had at least 1 child between the ages of 1 and 5 years, and 9% had children with special needs. The overall prevalence of depressive symptoms and anxiety were 25.6% and 21.6%, respectively. Mothers of hospitalized COVID-19–positive children reported stress, anxiety, irritability, grief, and fear of death and infecting others. The most commonly identified sources of worry were problems experienced during the hospital stay, worry about the admitted child’s physical and emotional health, care provision for children left at home, rumors, and stigma. Parental stress was affecting parenting, with at least 50% of parents reporting more than the usual consequences (shouting at children, taking privileges away, and slapping child) in the past 1 month. However, positive impacts—that is, parents spending more time in activities with their children (93%)—were also observed. Unhealthy eating and sleeping patterns (24.5%), irritability (21.1%), anxiety (16.3%), aggression (14.6%), and sleep difficulties (12.7%) were the most common problems noticed by parents in their children since the COVID-19 outbreak. Conclusions: Significant parental stress observed during the COVID-19 outbreak can adversely impact a child’s physical and mental health outcomes. Provision of effective strategies to support parents to respond to and care for children are urgently needed. PAT, FAM, STRESS