Success rate of Remdesivir, Convalescent Plasma, and Tocilizumab in moderate to severe Covid-19 pneumonia: our experience in a tertiary care center.

INTRODUCTION: After the first case of Covid-19 was identified in Wuhan City, China, the numbers increased rapidly all over the world putting a huge burden on the entire healthcare system. Managing these cases posed a great challenge to the treating clinicians in the absence of targeted therapy. At this juncture, few modalities got approved as EUA (Emergency use under authorization) drugs namely Remdesivir, Convalescent Plasma (CP), and Tocilizumab (TCZ) to treat this deadly disease. AIM: To analyze the success rates of EUA therapies for Covid-19 pneumonia in our hospital. MATERIALS AND METHODS: This was a prospective observational study conducted from April 2020 to October 2020 in the department of Medicine at Tata Main Hospital, Jamshedpur, Jharkhand. All adults with moderate to severe Covid-19 as per the WHO criteria were enrolled in the study with their informed consent. Patients with estimated glomerular filtration rate <30 mL/min, deranged liver function tests, electrocardiographic abnormalities, and deranged hematological parameters were excluded from the study. Thorough clinical evaluation was done in all cases. Routine investigations together with CRP, LDH, serum Ferritin, D Dimer and IL6, Chest X-Ray, and HRCT thorax were done in all cases. ECG was done in all cases and 2D-ECHO in selected ones. Depending on their clinical and radiological criteria, patients were treated with various modalities approved under EUA with close monitoring of clinical, biochemical, and radiological parameters. Presenting symptoms, clinical findings, co-morbidities, laboratory parameters, and radiological assessment were analyzed, and statistical analysis was done. The survival rate and in-hospital mortality was analyzed. OBSERVATIONS AND RESULTS: We had a total of 448 patients who were included in our study, out of which 326 were males and 122 were females with a male to female ratio of 2.7:1. Their age varied between 16 and 91 years with an average age of 51.4 years with a standard deviation (SD) of +/- 6.4 years. About 255 patients (57%) received only Remdesivir (176 males, 79 females), 139 (105 males, 35 females) patients (31%) received Remdesivir along with two units of CP, and 38 (32 males, 6 females) patients received a combination of Remdesivir, CP, and TCZ. All patients in our study tolerated the drugs well. About 5% of cases who received CP had minor transfusion reactions. One patient had TRALI and three patients had TACO, which was managed aggressively. Asymptomatic transaminitis was seen in 36% patients. The survival rate in patients treated with Remdesivir was 78%, those with Remdesivir and CP was 44%, and those with all three was 13%. The mean length of stay was 14.23 days with a SD of 9.06 days in patients treated with TCZ in comparison to other two modalities, which was 13.88 days with a standard variation of +/- 8.71 days in Remdesivir and 13.88 days with a SD of 8.73 days in patients treated with CP that was stastically significant. CONCLUSIONS: Though the success rate of various drugs under EUA varies in different studies from all over the world, the data to support their use are encouraging. We also observed satisfying results in our study specially with the use of Remdesivir. Therefore, EUA agents should be used early to fight against COVID-19 along with the other measures as per the protocol laid by ICMR and MoHFW.

Potential detrimental role of soluble ACE2 in severe COVID-19 comorbid patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2) receptor. Other important proteins involved in this process include disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) also known as tumour necrosis factor-α-converting enzyme and transmembrane serine protease 2. ACE2 converts angiotensin II (Ang II) to angiotensin (1-7), to balance the renin angiotensin system. Membrane-bound ACE2 ectodomain shedding is mediated by ADAM17 upon viral spike binding, Ang II overproduction and in several diseases. The shed soluble ACE2 (sACE2) retains its catalytic activity, but its precise role in viral entry is still unclear. Therapeutic sACE2 is claimed to exert dual effects; reduction of excess Ang II and blocking viral entry by masking the spike protein. Nevertheless, the paradox is why SARS-CoV-2 comorbid patients struggle to attain such benefit in viral infection despite having a high amount of sACE2. In this review, we discuss the possible detrimental role of sACE2 and speculate on a series of events where protease primed or non-primed virus-sACE2 complex might enter the host cell. As extracellular virus can bind many sACE2 molecules, sACE2 level could be reduced drastically upon endocytosis by the host cell. A consequential rapid rise in Ang II level could potentially aggravate disease severity through Ang II-angiotensin II receptor type 1 (AT1R) axis in comorbid patients. Hence, monitoring sACE2 and Ang II level in coronavirus disease 2019 comorbid patients are crucial to ensure safe and efficient intervention using therapeutic sACE2 and vaccines.

Corona Collateral Damage Syndrome: Perception of the Damage.

How to cite this article: Ahmed A. Corona Collateral Damage Syndrome: Perception of the Damage. Indian J Crit Care Med 2021;25(4):358-359.

The impact of COVID-19 on pregnancy and therapeutic drug development.

Emerging data show that pregnant women with COVID-19 are at significantly higher risk of severe outcomes compared with non-pregnant women of similar age. This review discusses the invaluable insight revealed from vaccine clinical trials in women who were vaccinated and inadvertently became pregnant during the trial period. It further explores a number of clinical avenues in their management and proposes a drug development strategy in line with clinical trials for vaccines and drug treatments for the drug development community. Little is known of the long-term effects of COVID-19 on the mother and the baby. Our hypothesis that COVID-19 predisposes pregnant women to pre-eclampsia or hypertensive disorders during pregnancy is supported by a clinical study, and this may also adversely impact a woman's cardiovascular disease risk later in life. It may also increase a woman's risk of pre-eclampsia in subsequent pregnancy. This is an ever-evolving landscape, and early knowledge for healthcare providers and drug innovators is offered to ensure benefits outweigh the risks. COVID-19 mRNA vaccines appear to generate robust humoral immunity in pregnant and lactating women. This novel approach to vaccination also offers new ways to therapeutically tackle disorders of many unmet medical needs. LINKED ARTICLES: This article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc.

Lifestyle Acquired Immunity, Decentralized Intelligent Infrastructures, and Revised Healthcare Expenditures May Limit Pandemic Catastrophe: A Lesson From COVID-19.

Throughout history, the human race has often faced pandemics with substantial numbers of fatalities. As the COVID-19 pandemic has now affected the whole planet, even countries with moderate to strong healthcare support and expenditure have struggled to contain disease transmission and casualties. Countries affected by COVID-19 have different demographics, socioeconomic, and lifestyle health indicators. In this context, it is important to find out to what extent these parametric variations are modulating disease outcomes. To answer this, this study selected demographic, socioeconomic, and health indicators e.g., population density, percentage of the urban population, median age, health expenditure per capita, obesity, diabetes prevalence, alcohol intake, tobacco use, case fatality of non-communicable diseases (NCDs) as independent variables. Countries were grouped according to these variables and influence on dependent variables e.g., COVID-19 positive tests, case fatality, and case recovery rates were statistically analyzed. The results suggested that countries with variable median age had a significantly different outcome on positive test rate (P < 0.01). Both the median age (P = 0.0397) and health expenditure per capita (P = 0.0041) showed a positive relation with case recovery. An increasing number of tests per 100 K of the population showed a positive and negative relationship with the number of positives per 100 K population (P = 0.0001) and the percentage of positive tests (P < 0.0001), respectively. Alcohol intake per capita in liter (P = 0.0046), diabetes prevalence (P = 0.0389), and NCDs mortalities (P = 0.0477) also showed a statistical relation to the case fatality rate. Further analysis revealed that countries with high healthcare expenditure along with high median age and increased urban population showed more case fatality but also had a better recovery rate. Investment in the health sector alone is insufficient in controlling the severity of the pandemic. Intelligent and sustainable healthcare both in urban and rural settings and healthy lifestyle acquired immunity may reduce disease transmission and comorbidity induced fatalities, respectively.