Introduction Coronavirus disease 2019 (COVID-19) can progress to severe respiratory compromise and lead to mortality due to induction of cytokine storm. Tocilizumab (TCZ) is approved by the FDA for the treatment of cytokine release syndrome (CRS). This study aims to analyze the outcomes among patients who received TCZ in the United Arab Emirates. Methods A retrospective cohort study was conducted among COVID-19 patients who received TCZ in a tertiary care hospital from May 2020 to August 2021. For analysis, patients were divided into two groups based on survival and clinical improvement. Results Overall, 80% of patients receiving TCZ were discharged by day 28. There was a gradual improvement in oxygen requirements in our patients with a majority of them on room air by day 28. Age more than 50 years (P=0.034) and comorbidities such as cardiovascular disease (CVD) (P=0.002) and renal insufficiency (P=0.013) were significantly associated with mortality. Discussion. In our analysis, patients who were mechanically ventilated at the time of administration of TCZ had a significantly higher risk of death by day 28. In both survived and improved groups, younger patients had better outcomes than older patients. Patients who received TCZ earlier during therapy from the onset of symptoms had better survival outcomes. There was only one death among 14 patients who received vaccination. There was no significant difference in mortality among patients with comorbidities such as diabetes, hypertension, dyslipidemia, obesity, and pulmonary diseases, hypothesizing that administration of TCZ improves the outcomes in COVID-19 patients with these comorbidities.

/pdf/real-life-use-of-tocilizumab-in-the-treatment-of-severe-3f73yecz.pdf

Real-Life Use of Tocilizumab in the Treatment of Severe COVID-19 Pneumonia

The invasion and integrin-dependent adhesion of neutrophils to lung tissues and their secretion lead to the development of pneumonia in various pulmonary pathologies, including acute respiratory distress syndrome in coronavirus disease. We studied the effect of ivermectin, a possible therapeutic agent for inflammation and cancer, on integrin-dependent neutrophil adhesion to fibronectin and the concomitant secretion. Ivermectin did not affect the attachment of neutrophils to the substrate and the reactive oxygen species production but sharply inhibited the adhesion-induced release of hydroxylysine and stimulated the release of phenylalanine and cathepsin G. Hydroxylysine is a product of lysyl hydroxylase, which is overexpressed in tumor cells with an increased ability to invade and metastasize. The inhibition of hydroxylysine release by ivermectin, by analogy, may indicate the suppression of neutrophil invasion into tissue. The increase in the release of phenylalanine in our experiments coincided with the secretion of cathepsin G, which indicates the possible role of this enzyme in the cleavage of phenylalanine. What is the substrate in such a reaction is unknown. We demonstrated that exogenously added angiotensin II (1–8) can serve as a substrate for phenylalanine cleavage. Mass spectrometry revealed the formation of angiotensin II (1–7) in the secretion of neutrophils, which attached to fibronectin in the presence of ivermectin and exogenous angiotensin II (1–8), indicating a possible involvement of ivermectin in the inactivation of angiotensin II.

https://www.mdpi.com/2227-9059/10/12/3284/pdf?version=1671676955

Ivermectin Affects Neutrophil-Induced Inflammation through Inhibition of Hydroxylysine but Stimulation of Cathepsin G and Phenylalanine Secretion

Objective The present study aimed to assess the psychological and clinical determinants of coronavirus disease 2019 (COVID-19) and their association with the disease severity and outcomes. Methods This prospective study was conducted at Hayatabad Medical Complex, Peshawar-Pakistan. Admitted patients were screened for COVID-19 with reverse transcription-polymerase chain reaction (RT-PCR) and subsequently, 250 COVID positive patients were included in the final analysis. Data were obtained from the patient's medical chart;demographic and clinical characteristics were recorded using a structured questionnaire. Psychological determinants, including anxiety and depression, were measured using the Hospital Anxiety and Depression Scale (HADS). The predictors of disease severity and outcomes (recovery vs. mortality) were also studied. Results A total of 250 patients were included in this study;out of which, 193 patients recovered from this deadly virus and 57 died. Based on psychological assessment, 58.4% of the enrolled COVID-19 patients had poor HADS scores. Most of the patients who died (70.2%) had severe symptoms (poor HADS scores). Similarly, 49.6% of the total cases were observed with poor HADS, and 50.9% of those who died had severe depression. Conclusion It is concluded from the study results that psychological distress is frequent in COVID-19 patients. Age, hypertension, fatigue, abnormal respiratory rate, oxygen saturation, ferritin, and poor HADS sore were determined as the significant predictors of COVID-19 severity and outcomes.

Psychological and Clinical Predictors of COVID-19 Severity and Outcomes

Ivermectin is an anti-parasitic agent that has gained attention as a potential COVID-19 therapeutic. It is a compound of the type Avermectin, which is a fermented by-product of Streptomyces avermitilis. Bifidobacterium is a member of the same phylum as Streptomyces spp., suggesting it may have a symbiotic relation with Streptomyces. Decreased Bifidobacterium levels are observed in COVID-19 susceptibility states, including old age, autoimmune disorder, and obesity. We hypothesize that Ivermectin, as a by-product of Streptomyces fermentation, is capable of feeding Bifidobacterium, thereby possibly preventing against COVID-19 susceptibilities. Moreover, Bifidobacterium may be capable of boosting natural immunity, offering more direct COVID-19 protection. These data concord with our study, as well as others, that show Ivermectin protects against COVID-19.

Microbiome-Based Hypothesis on Ivermectin’s Mechanism in COVID-19: Ivermectin Feeds Bifidobacteria to Boost Immunity

Objectives: Patient risk stratification is the cornerstone of COVID-19 disease management; that has impacted health systems globally. We evaluated the performance of the Brescia-COVID Respiratory Severity Scale (BCRSS), CALL (Co-morbid, age, Lymphocyte and Lactate dehydrogenase) Score, and World Health Organization (WHO) guidelines in Emergency department (ED) on arrival, as predictors of outcomes; Intensive care unit (ICU) admission and in-hospital mortality. Methods: A two-month retrospective chart review of 88 adult patients with confirmed COVID-19 pneumonia; requiring emergency management was conducted at ED, Indus Hospital and Health Network (IHHN), Karachi, Pakistan, (April 1 to May 31, 2020). The sensitivity, specificity, receiver operator characteristic curve (ROC) and area under the curve (AUC) for the scores were obtained to assess their predictive capability for outcomes. Results: The in-hospital mortality rate was 48.9 % with 59.1 % ICU admissions and with a mean age at presentation of 56 ± 13 years. Receiver operator curve for BCRSS depicted good predicting capability for in hospital mortality [AUC 0.81(95% CI 0.71-0.91)] and ICU admission [AUC 0.73(95%CI 0.62-0.83)] amongst all models of risk assessment. Conclusion: BCRSS depicted better prediction of in-hospital mortality and ICU admission. Prospective studies using this tool are needed to assess its utility in predicting high-risk patients and guide treatment escalation in LMIC’s.

/pdf/underneath-the-visible-covid-19-risk-prediction-tools-in-a-3vrms9ih.pdf

“Underneath the visible” - COVID-19 Risk prediction tools in a high-volume, low-resource Emergency Department

Introduction Coronavirus disease 2019 (COVID-19) has become a global threat to public health. The current study investigates alterations in the biological estimates concerning the severity, recovery, mortality, and assessment of treatment-based outcomes. Methods A case series of 165 COVID-19 patients admitted to OMI Institute (a tertiary care hospital) was conducted between May and August 2020. The data regarding demographic characteristics, comorbid conditions, radiographic abnormalities, biological estimations, symptoms, treatment, disease progression, complications, and outcomes were recorded using a structured questionnaire. Laboratory estimations included complete blood count (CBC), renal and electrolyte profile, liver function tests (LFTs), hematological indices, and inflammatory markers. Chest X-ray, electrocardiogram (ECG), and a high-resolution computed tomography (HRCT) scan were also performed, and data were extracted from the medical records. Analysis was done using the Statistical Package for the Social Sciences (SPSS) version 22.0. Results Out of the 165 COVID-19 patients, 79.4% recovered and were successfully discharged, while 20.6% of inpatient died. The patients' mean age was 56.03 ± 15.96 years, with a male majority (55.1%). The most common comorbid conditions were diabetes and hypertension; fever and dry cough were among the most frequently reported symptoms. The chest imaging findings among the severe/critical COVID-19 patients showed extensive bilateral patchy opacities. The median laboratory investigations, including neutrophil-to-lymphocyte ratio (NLR) (14.83), C-reactive protein (CRP) (7.4 mg/dl), lactate dehydrogenase (LDH) (786 IU/L), ferritin (1401.15 mcg/ml), and mean oxygen saturation (88.25%), were significantly altered among cases with increased disease severity and those who expired (p<0.05). The proportion of acute respiratory distress syndrome (ARDS) and sepsis development was significantly high among severe/critical COVID-19 patients (p<0.05). Treatment with tocilizumab, remdesivir, doxycycline, ivermectin, enoxaparin sodium, and steroids was deemed to be potentially effective treatment options in terms of reducing COVID-19 severity and chances of recovery. Furthermore, age (OR 1.05; p=0.047), presence of comorbidity (OR 8.471; p=0.004), high NLR, LDH (final outcome) (OR 1.361 and 1.018; p<0.05), and CRP levels (midpoint) (OR 1.631; p=0.05) were identified as the strong predictors of death among COVID-19 patients. Conclusion The study identified several alterations in the clinical profile of the COVID-19 patients concerning severity during the hospital stay, affecting prognosis. Clinically, tocilizumab, remdesivir, doxycycline, ivermectin, enoxaparin sodium, and steroids were identified as potential therapeutic options for COVID-19 due to their ability to alter disease-associated severity and recovery rate.

/pdf/clinical-variants-characteristics-and-outcomes-among-covid-2sjasc6b7t.pdf

Clinical Variants, Characteristics, and Outcomes Among COVID-19 Patients: A Case Series Analysis at a Tertiary Care Hospital in Karachi, Pakistan

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Clinical Variants, Characteristics, and Outcomes Among COVID-19 Patients: A Case Series Analysis at a Tertiary Care Hospital in Karachi, Pakistan