ABSTRACT
This article is a response to an editorial on the role of tocilizumab in COVID-19 by Dr. Gokhale. The authors express their disagreement by presenting several data that showed tocilizumab had absolutely no effect on mortality or caused only slight reduction (8.5%) in mortality. In addition, the authors make the case against the use of tocilizumab for COVID-19 by mentioning the risk of serious adverse events according to available literature, as well as it being expensive.
ABSTRACT
Vaccination against SARS-CoV-2 was launched in India in January 2021. Though vaccination reduced hospitalization and mortality due to COVID-19, vaccine breakthrough infections have become common. The present study was initiated in May 2021 to understand the proportion of predominant variants in post-vaccination infections during the Delta dominated second wave of COVID-19 in the Mumbai Metropolitan Region (MMR) in India and to understand any mutations selected in the post-vaccination infections or showing association with any patient demographics. We collected samples (n=166) from severe/moderate/mild COVID-19 patients who were either vaccinated (COVISHIELD/COVAXIN; partial/fully vaccinated) or unvaccinated, from a city hospital and from home isolation patients in MMR. A total of 150 viral genomes were sequenced by Oxford Nanopore sequencing (using MinION) and the data of 136 viral genomes were analyzed for clade/lineage and for identifying mutations in all the genomes. The sequences belonged to three clades (21A, 21I and 21J) and their lineage was identified as either Delta (B.1.617.2) or Delta+ (B.1.617.2 + K417N) or sub-lineages of Delta variant (AY.120/AY.38/AY.99). A total of 620 mutations were identified of which 10 mutations showed an increase in trend with time (May-Oct 2021). Associations of 6 mutations (2 in spike, 3 in orf1a and 1 in nucleocapsid) were shown with milder forms of the disease and one mutation (in orf1a) with partial vaccination status. The results indicate a trend towards reduction in disease severity as the wave progressed.
Subject(s)
COVID-19 , Breakthrough PainABSTRACT
Background The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods and Findings We develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions There is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.
Subject(s)
COVID-19ABSTRACT
Background: The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of current and proposed treatments, and consequently research and procurement priorities, have not been clear. Methods: First, we used a model of SARS-CoV-2 transmission, COVID-19 disease and clinical care pathways to explore the potential impact of dexamethasone - the main treatment currently for hospitalised COVID-19 patients - under scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) the efficacy of dexamethasone in the absence of supportive care. We then fit the model to the observed epidemic trajectory to-date in 165 countries and analysed the potential future impact of dexamethasone in different countries, regions, and country-income strata. Finally, we constructed hypothetical profiles of novel therapeutics based on current trials, and compared the potential impact of each under different circumstances. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. Findings: We find the potential benefit dexamethasone is severely limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). However, therapeutics for different patient populations (in particular, those not in hospital and early in the course of infection) and types of benefit (in particular, reducing disease severity or infectiousness) could have much greater benefits. Such therapeutics would have particular value in resource-poor settings facing large epidemics, even if the efficacy or achievable coverage of such therapeutics is lower in comparison to other types. Interpretation: People in low-income countries will benefit the least from advances in the treatment of COVID-19 to date, which have focussed on hospitalised-patients with adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have much greater impact. Such therapeutics may be feasible and research into their efficacy and means of delivery should be a priority. Funding: None to declare. Declaration of Interest: None to declare.