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.

Does Bacillus Calmette-Guerin vaccination protects from COVID-19? A Uni-center Study

Bacillus Calmette-Guerin (BCG) is a vaccine for tuberculosis and is administered at birth in several countries, however there are many countries that have no BCG vaccination policy and coincidently they are worst hit by Covid-19 pandemic in terms of disease severity and mortality.The study was conducted to determine the association between BCG vaccine and COVID-19 severity. Study included total 150 participants visiting Department of Medicine, Mayo Hospital, Lahore, Pakistan. Data regarding BCG vaccination, comorbidity, demographics, disease severity were collected through self-structured questionnaire using non-probability convenient sampling. Prior written informed consents were taken from the participants. Male and female were in equal proportion. 68.6% were married, only 3.9% were smokers. Analysis revealed that only 10 (6.5%) were hypertensive and10 (6.5%) were diabetic. There was no BCG vaccine protection against Covid-19 in the current study. Severity of disease was similar in vaccinated and non-vaccinated patients. But it can not be applicable to whole population. Another fact is that most of Pakistani population is BCG vaccinated due to national policy and coincidently Pakistan suffered less as compared to high hit countries. There maybe some association between BCG vaccination and Covid-19 or some other environmental factor and genetics that need to be explored.

Giving Birth at Times of COVID-19

Ever since Coronavirus disease 2019 (COVID-19) has been declared a pandemic by World Health Organization (WHO) it has gradually become top cause of morbidity. Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) possesses the tendency to cause severe symptoms in patients with a weakened immune system. In the setting where a mother develops mild COVID-19 infection yet remains stable, responds to medical treatment and there is no fetal compromise;the pregnancy may be continued to term with close surveillance. What is important in the current scenario is that the patients of COVID-19 along with any other comorbidities or medical conditions are at more risk of having fatal disease then the ones with COVID-19 alone. The pregnancy is one physiological condition in which a patient can face drastic pathological complications with COVID-19 if not given the due care. © 2020, Biomedica. All Rights Reserved.

Who is at a Higher Risk? A brief review of Recent Evidence on comorbidities in children infected with COVID-19

Background: COVID-19 has affected both adults and children with variable presentations and disease severity. Children can present with mild symptoms of fever, cough and shortness of breath, and rapidly progress to severe pneumonia, requiring mechanical ventilation. This population includes children who are younger than one year and older adolescents who have an underlying comorbidity-specifically immunosuppression or prior cardio-respiratory infections. In this review, we discuss the determinants of severe disease among the paediatric patients- primarily asthma, immune-status, obesity and multisystem inflammatory syndrome in children (MIS-C). Asthma and underlying lung pathologies can be a strong predictor (~20% prevalence) for development of severe COVID-19 infection, irrespective of age. However, as compared to asthma, a higher mortality rate was reported in immune-compromised patients. With a weakened immune system, immunosuppressed individuals were 1.55 times and immunocompromised patients 3.29 times more vulnerable to developing severer COVID-19 disease. Similarly, evidence suggests that a BMI of greater than 35 kg/m2 renders individuals more susceptible to developing COVID-19-related complications. This observation is based on the negative impacts obesity has on pulmonary functions and in downplaying the immune system. Furthermore, a possible association of COVID-19 and MIS-C has been reported by multiple studies across the globe but it needs further studies to strengthen its stance due to the scarcity of data when compared with the other determinants discussed in this article. Authors recommend researchers directing attention on synthesizing the evolving evidence to fill the knowledge void in the paediatric population, which will better enable paediatricians to make informed decisions.

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.

SARS-CoV-2: Cytokine Storm and Therapy

SARS-CoV-2 can vary on a spectrum of an asymptomatic disease process, to a severe stage characterized by a "Cytokine Storm". This phenomenon is a pro-inflammatory state marked by an intricate interplay of a cocktail of chemokines and cytokines. An excessively raised serum levels of cytokines and chemokines can lead to the development of acute respiratory distress syndrome. This article highlights the pathophysiologic mechanisms responsible for creating this cytokine havoc and delves into potential therapeutic interventions