Mathematical model of replication-mutation dynamics in coronaviruses (preprint)

RNA viruses are known for their fascinating evolutionary dynamics, characterised by high mutation rates, fast replication, and ability to form quasispecies - clouds of genetically related mutants. Fast replication in RNA viruses is achieved by a very fast but error-prone RNA-dependent RNA polymerase (RdRP). High mutation rates are a double-edged sword: they provide RNA viruses with a mechanism of fast adaptation to a changing environment or host immune system, but at the same time they pose risk to virus survivability in terms of virus mutating beyond its error threshold. Coronaviruses, being a subset of RNA viruses, are unique in having a special enzyme, exoribonuclease (ExoN), responsible for proofreading and correcting errors induced by the RdRP. In this paper we consider replication dynamics of coronaviruses with account for mutations that can be neutral, deleterious or lethal, as well as ExoN. Special attention is paid to different virus replication modes that are known to be crucial for controlling the dynamics of virus populations. We analyse extinction, mutant-only and quasispecies steady states, and study their stability in terms of different parameters, identifying regimes of error catastrophe and lethal mutagenesis. With coronaviruses being responsible for some of the largest pandemics in the last twenty years, we also model the effects of antiviral treatment with various replication inhibitors and mutagenic drugs.

Informal employment and catastrophic health expenditures: Evidence from Pakistan.

Workers in informal employment suffered significant out-of-pocket healthcare expenditures (OOPHEs) due to their low earnings and a lack of a social safety net or health insurance. There is little or no evidence of impoverishment caused by OOPHEs in the context of labor market categorization. Therefore, this study examines the economic burden of OOPHEs and its associated consequences on households, whose members are in informal employment. This study estimates the incidence of catastrophic health expenditures (CHEs) and impoverishment across the households in formal and informal employment and their key determinants in Pakistan by employing the data from the two rounds of the Household Integrated Economic Survey (2015-16, 2018-19). For measuring CHEs and impoverishment, the budget share and capacity-to-pay approaches are applied. Various thresholds are used to demonstrate the sensitivity of catastrophic measures. We found a higher incidence of catastrophic healthcare payments among the informal workers, that is, 4.03% and 7.11% for 2015-16 and 2018-19, respectively, at a 10% threshold, while at a 40% threshold, the incidence of CHEs is found to be 0.40% and 2.34% for 2015-16 and 2018-19, respectively. These OOPHEs caused 1.53% and 3.66% of households who are in informal employment to become impoverished, compared with their formal counterparts. The study demonstrates that the probability of incurring CHEs and becoming impoverished is high among informal workers, compared with their formal counterparts. This result has clear policy implications, in which to protect the informal workers, it is necessary to expand the insurance coverage, particularly during the COVID-19 response and recovery efforts.

The Study of Catastrophic Health Expenditure (CHE) for Hospitalization in Urban Kerala (preprint)

Health financing in the post-Covid period is considered the primary policy tool for the government to fortify and reinforce public healthcare infrastructure, mitigating emergency susceptibilities and meeting societal health disparities. Kerala, the southernmost urbanised province of India, despite having the best human development index (HDI) in the country, now faces rising cases of healthcare breakdown. The rising household healthcare costs and expenses incurred during hospitalisation are now making demand-side financing models such as publicly-funded health insurance (PFHI) schemes crucial for accessing healthcare services. The presence of supply-side moral hazards in the roll-out of PFHI leads to unnecessary care, exacerbating the already existing inequities in the incidence of out-of-pocket expenses (OOPE). In this context, the study, through descriptive statistics, logistic regression, and the concentration index by looking at the unit-level data from the 75th round of the National Sample Survey, attempts to determine the determinants of and inequalities in the incidence of Catastrophic Health Expenditure (CHE). The study finds considerable deficiencies in financial risk protection and equity in hospitalisation expenditure. The paper looks at pre-existing inequalities and finds that multi-sectoral collaboration is imperative to attain Universal health coverage.

Household catastrophic health expenditure for COVID-19 during March-August 2021, in South India: a cross-sectional study.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic increased the utilisation of healthcare services. Such utilization could lead to higher out-of-pocket expenditure (OOPE) and catastrophic health expenditures (CHE). We estimated OOPE and the proportion of households that experienced CHE by conducting a cross-sectional survey of 1200 randomly selected confirmed COVID-19 cases. METHODS: A cross-sectional survey was conducted by telephonic interviews of 1200 randomly selected COVID-19 patients who tested positive between 1 March and 31 August 2021. We collected household-level information on demographics, income, expenditure, insurance coverage, direct medical and non-medical costs incurred toward COVID-19 management. We estimated the proportion of CHE with a 95% confidence interval. We examined the association of household characteristics; COVID-19 cases, severity, and hospitalisation status with CHE. A multivariable logistic regression analysis was conducted to ascertain the effects of variables of interest on the likelihood that households face CHE due to COVID-19. RESULTS: The mean (95%CI) OOPE per household was INR 122,221 (92,744-1,51,698) [US$1,643 (1,247-2,040)]. Among households, 61.7% faced OOPE, and 25.8% experienced CHE due to COVID-19. The odds of facing CHE were high among the households; with a family member over 65 years [OR = 2.89 (2.03-4.12)], with a comorbid individual [OR = 3.38 (2.41-4.75)], in the lowest income quintile [OR = 1.82 (1.12-2.95)], any member visited private hospital [OR = 11.85 (7.68-18.27)]. The odds of having CHE in a household who have received insurance claims [OR = 5.8 (2.81- 11.97)] were high. Households with one and more than one severe COVID-19 increased the risk of CHE by more than two-times and three-times respectively [AOR = 2.67 (1.27-5.58); AOR = 3.18 (1.49-6.81)]. CONCLUSION: COVID-19 severity increases household OOPE and CHE. Strengthening the public healthcare and health insurance with higher health financing is indispensable for financial risk protection of households with severe COVID-19 from CHE.

Disasters collide at the intersection of extreme weather and infectious diseases (preprint)

It is well understood that natural disasters interact to affect the resilience and prosperity of communities and disproportionately affect low income families and communities of color. However, given the lack of a common theoretical framework, it is rare for these interactions to be well understood or quantified. As an example, we consider the interaction of severe weather events (e.g., hurricanes and tornadoes) and epidemics (e.g., COVID-19). Observing events unfolding in southeastern U.S. communities has caused us to conjecture that the interactive effects of catastrophic disturbances and stressors might be much more considerable than previously recognized. For instance, hurricane evacuations increase human aggregation, a key factor that affects the transmission of acute respiratory infections like SARS-CoV-2. Similarly, weather damage to health infrastructure could significantly reduce a community’s ability to provide services to people sick with COVID-19 and other diseases. As globalization and human population and movement continue to increase and weather events due to climate change are becoming more intense and severe, such complex interactions are expected to magnify and significantly impact environmental and human health.

Role of Error Catastrophe in Transmission Ability of Virus (preprint)

The role played by "error catastrophe" is explicitly taken into account in the mathematical formulation to analyze the COVID-19 data. The idea is to combine the mathematical genetics formalism of the error catastrophe of mutations in the virus gene loci with the standard model of epidemics which lacks the explicit incorporation of the mutation effect on the spreading of the viruses. We apply the formalism to the case of SARS-CoV-2 virus. We assume the "universality" of the error catastrophe in the process of analyzing the data. This means that some basic parameter to describe the error catastrophe is independent of which group (country or city) we deal with. Concretely, we analyze the omicron data of South Africa and then analyze the cases of Japan using the same value of the basic parameter derived in the South Africa analysis. The result shows the validity of our universality assumption.

Impact of Catastrophic Health Expenditures on Chinese Household Consumption.

China has built a social medical insurance system that covers the entire population so as to reduce the impact of diseases on individuals and families. Although the decline in the incidence of catastrophic health expenditures (CHEs) in China is encouraging, this issue remains important. On the basis of considering selectivity bias and heterogeneity, we applied propensity score matching (PSM) to analyze the 2018 data from the China Family Panel Studies. We assigned CHE households and non-CHE households to the treatment group and the control group, respectively, and used non-random data to simulate a randomized trial to investigate the impact of CHE on household consumption in China. The results of this study indicate that, when the threshold is set at 40%, the consumption of households experiencing CHEs (CHE household) is significantly lower than that of households not experiencing CHEs (non-CHE households) and that CHEs have a significant negative impact on other household consumption and a significant impact on the household property and debt. This effect still exists when the threshold is set lower, with household essential consumption most affected. The occurrence of CHEs leads to a reduction in household consumption and a significantly worsening financial situation for the CHE households, impacting the basic quality of life of the families. Therefore, it is necessary to further reform the medical and health system to reduce the high medical expenses.

Cat Que Virus (CQV): A potential threat of the tropics? “One Health Approach” to avert catastrophe: a narrative review (preprint)

The world is now experiencing the catastrophe of global pandemic ‘COVID-19’, most serious public health crises in this century. Recently, another virus named “Cat Que Virus” (CQV) seems to be causing its terrible repercussions in the worlds’ largest populous country ‘China’, the origin of SARS-CoV during 2002-2003, and the current pandemic SARS-CoV-2 since December 2019. Recently, the presence of IgG antibody among two persons in the state of Karnataka for CQV was reported in India, the worlds’ second-largest populous country. This means the virus is in circulation in the sub-continent. The presence of the vector mosquitoes (Aedes species, Culex species) and the ambient climatic conditions suitable for vector breeding in the country needs to be taken into account while planning to implement holistic strategies appropriate for control and preventive measures. “One Health approach” is the topmost option covering humans, animals/vectors and the environment to curb the spread/transmission of infectious diseases in general. It is also necessary to study the transmission dynamics and pattern of this emerging virus, its life cycle, the natural reservoir of the virus, the intermediate host and the accidental host with respect South-East Asia, so that necessary remedial action can be planned well before an epidemic. At present, the outbreak of CQV is certainly a warning to the general population around the world. Considering the global imminent health threats posed by CQV, there is an urgent need for active surveillance, monitoring, effective vaccination, and a standard treatment modality of this disease. Given the epidemiological aspect of CQV, control and prevention measures are essential to stop the spread of the virus. At present, there is no information available on CQV; however, this current review article has covered the required data, which will be helpful to control the spread of the CQV.

Rare yet catastrophic presentation of undiagnosed antiphospholipid syndrome.

A previously well 31-year-old woman initially presented to the emergency department with pneumonia, however, was found to be hypertensive and have new-onset cardiomegaly. She was admitted for intravenous antibiotics and concurrently a series of investigations were conducted to investigate hypertension and cardiomegaly. During the course of admission, she developed acute kidney injury and was found to have acute chronic occlusion in the abdominal aorta. She was diagnosed with catastrophic antiphospholipid syndrome. This is a rare form of antiphospholipid syndrome with a high mortality rate. Thus, it is important that clinicians are aware of this syndrome to facilitate early diagnosis and initiation of treatment.

Case Report: Hypercoagulopathy as a Severe Long-term Complication of Post SARS-CoV-19 Infection, Autopsy Findings in Three Patients (preprint)

Background: It has been less than two years since the advent of the COVID-19 pandemic, and there are plenty of publications describing the clinical and pathological features of this severe infectious disease, damaging not only lung but also other vital organs. However, the pathologic findings of long-term complications post virus infection have rarely been described. Case presentation: We are reporting three autopsy cases from patients who had COVID-19 one to six months before death. The patients were all SARS-CoV-2 negative at admission but expired shortly. At autopsy, the first patient showed subacute diffuse myocardial ischemic injury with microthrombi in pericardial small vessels, whereas the second patient showed catastrophic acute and subacute pulmonary infarctions with hemothorax leading to respiratory failure. The third patient showed subacute severe cerebral infarcts in the left middle cerebral artery region. Conclusions: : Our findings suggest the hypercoagulopathy and subsequent vital organ damage may persist beyond the active phase of SARS-CoV-2 infection. It is essential to evaluate and continue monitoring the COVID-19 patients after recovery, so as to identify the ones with vital organ injury in a timely manner and to take the steps to prevent severe consequence of COVID-19 complications.

Global Resilience Strategies: A Comparative Study of the One-Hundred Resilient Cities using Computational Text Analysis (preprint)

As the world’s cities continue to grow in population and their systems become increasingly interconnected, urban resilience is becoming more of a pressing imperative. Natural and manmade disasters will put more people, places, and capital at risk of catastrophic loss from cascading failures across interconnected sectors of society. However, the existing literature has no consensus on defining resilience, let alone identifying a common policy approach for achieving resilience. This paper uses computational text analysis of the Rockefeller Foundation’s “100 Resilient Cities” strategy publications to reveal global trends in resilience strategies and variations across regions that face different challenges to resilience. Results show the diverse set of threats to future urban centers, how cities are adapting to our turbulent times, and where the participating cities are putting vital limited resources. Of continued importance is the emphasis on hard infrastructure, political leadership, and community leadership. However, throughout the Rockefeller Foundation 100 Resilient Cities corpus, there is a lack of discussion of and preparation for epidemics or pandemics, which is a monumental oversight given the unprecedented effects COVID-19 has had on the world’s population centers. A critical view of our current resilience strategies can inform future planning and inform global cooperation through a better understanding of effective resilience strategy.

Evaluating discharges and readmissions using a COVID Virtual Ward model: a retrospective data study assessing patient outcomes and the likely staffing commitment (preprint)

Background COVID-19 has placed a catastrophic burden on acute hospitals. In an attempt to reduce admissions and enable safe early discharge, a COVID virtual ward (CVW) care pathway has been supported by NHS England. This includes discharging people who meet objective criteria based on acuity scores and oxygen saturations, with pulse oximeters and daily phone calls for up to 14 days. Observational studies have reported the safety of this system, but without describing the outcomes from usual care. Methods A retrospective study using routinely collected health data from all adults with a confirmed positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) swab result between 1 st June 2020 and 31 st Jan 2021 who attended the Emergency Department or Acute Medical Unit at QEHB, which does not have a CVW service. Criteria for CVW were applied using data from the first 24 hours of presentation to hospital and subsequent health outcomes were included for 28 days, including re-presentation, re-admission, ITU escalation and death. Results were compared to reported studies based in secondary care. Results During the study period, 26,127 patients presented to QEHB hospital. 2301 had a positive SARS-CoV-2 swab. Of these, 1730 (75.2%) did not meet the criteria for the CVW and 571 (24.8%) did. Of the 571, 325 (56.9%) were discharged home within 24 hours and 246 (43.1%) were admitted for 24 hours or longer. Those admitted were older, with increased co-morbidities, 80.9% required hospital-supported acute therapies after the first 24 hours and 10.6% died. Of the 325 discharged, 44 were readmitted (13.5%), 30 (9.2%) with COVID-related symptoms, 5 (1.5%) required ITU and 1 patient (0.3%) died. These results were comparable to published studies with a CVW service. Discussion In the current study, discharging patients without a CVW did not confer a greater risk of re-presentation, re-admission, ITU escalation or death. The majority of patients who remained in hospital despite meeting the CVW criteria did so for the provision of treatments or acute assessments. It remains uncertain whether a CVW delivers improvements in hard outcomes, and further research is needed.

Measurement and determinants of financial protection in health in Afghanistan.

BACKGROUND: Out of pocket (OOP) payments for health are significant health financing challenges in Afghanistan as it is a source of incurrence of catastrophic health expenditure (CHE) and impoverishment. Measuring and understanding the drivers and impacts of this financial health hardship is an economic and public health priority, particularly in the time of COVID-19. This is the first study that measures the financial hardship and determines associated factors in Afghanistan. METHODS: Afghanistan Living Conditions Survey data for 2016-2017 was used for this study. We calculated incidence and intensity of catastrophic health expenditure by using different thresholds ranging from 5 to 40% of total and nonfood consumption and subsequent impoverishment due to OOPs. Logistic regression was used to assess the degree to which Afghan households are protected from the catastrophic household expenditure. RESULTS: Results revealed that 32% of the population in Afghanistan incurred catastrophic health expenditure (as 10% of total consumption) and when healthcare payments are netted out of household consumption, the Afghan population live in extreme poverty ($1.9 in 2011 PPP), increased from 29 to 36%. Based on our findings from logistic regression in Afghanistan, having an educated head or being employed are protective factors from financial hardship while having a female head, an elderly member, a disabled, or a sick member are the risk factors of facing catastrophic health expenditure. Moreover, the people living in rural/nomadic areas or facing an economic shock are more likely to face catastrophic health expenditure and hence to be impoverished due to direct OOPs on health. CONCLUSIONS: The high rate of poverty and catastrophic health expenditure in Afghanistan emphasizes the need to strengthen the health financing system. Although Afghanistan has made great efforts to support households against health expenditure burden during the pandemic, households are at higher risk of poverty and financial hardship due to OOPs. Therefore, there is need for more financial and supportive response policies by providing a better and easier access to primary health services, extending to all entitlement to health services particularly in the public sector, eliminating user fees for COVID-19 health services and suspending fees for other essential health services, expanding coverage of income support, and strengthening the overall health financing system.

Epidemic Financing Facilities: Pandemic Bonds and Endemic Swaps (preprint)

While the COVID-19 pandemic has shattered the world with severe human toll and catastrophic economic losses and sufferings, it has also heightened the need for more effective solutions for managing epidemic-related risks. In this paper, we pro- pose two capital market-based epidemic financing facilities to address two extremes of epidemic risks. The proposed pandemic bond is meant to hedge the severe pandemic outbreak while the proposed endemic swap can be used to hedge a recurrent endemic. Using coronavirus as an example of a pandemic and dengue fever as an example of an endemic, we discuss the modeling and pricing of the proposed epidemic securities. We price the proposed securities based on epidemiological models as well as actuarial models. We show that the proposed hedging securities can provide additional capital relief for pandemic recovery plans, effectively stabilize hedgers’ cash flows, and create attractive returns to different investors.

When Hospitals Sue Patients (preprint)

Grimly demonstrated by the COVID-19 pandemic, hospitals serve as the central hub of American health care. Increasingly exercising market power, setting clinical standards, and fostering innovation, hospitals’ influence over health care delivery and access is unmatched. They are the behemoth in the delivery chain, exerting unrivaled control.As such, hospitals have naturally become the locus of the worst of the collision between consumerism and universality, between cost and access—a gloomy setting for citizens who simply cannot afford the health care they need to flourish, or to survive. Indeed, the price of American health care—a cost that is increasingly borne by American patients—is unsustainable. Those costs continue to rise thanks to a pernicious mix of increasingly brittle and ineffective insurance plans, a squeeze on public funding, and a lack of price sensitivity among the providers of American health care. Patients are suffering. And hospitals aren’t getting paid.In a predictable but catastrophic turn, hospitals are suing their former patients for unpaid medical bills. Litigation has replaced systematic financing. The operating room has been swapped for the courtroom. And adversarial proceedings now follow the Hippocratic Oath. Tracking the phenomenon of these lawsuits, this article lays out the harms that result to the American health care system. When hospitals sue patients, they harm public health and destroy patient trust. And they shatter widely-held beliefs, highlighting the inadequacy of policy goals and the inequity of health finance rules. Further, once and for all, they expose the failure of the consumer-based paradigm of American health care, spotlighting the inapplicability of moral hazard, and demonstrating the means by which individuals with private insurance and high deductibles—a rapidly growing population in the United States—are inadequately protected against the very actors that undertake to protect their health and wellbeing. This article makes the moral, legal, and policy-based argument that hospital lawsuits against former patients must be brought to an end. American patients simply cannot afford it.

Severe parapharyngeal abscess that developed significant complications: management during the COVID-19 pandemic.

A 50-year-old Caucasian man presented to the emergency department during the early stages of the COVID-19 pandemic with a rapidly progressive facial swelling, fever, malaise and myalgia. The patient had recently travelled to a COVID-19-prevalent European country and was therefore treated as COVID-19 suspect. The day before, the patient sustained a burn to his left forearm after falling unconscious next to a radiator. A CT neck and thorax showed a parapharyngeal abscess, which was surgically drained, and the patient was discharged following an intensive care admission. He then developed mediastinitis 3 weeks post-discharge which required readmission and transfer to a cardiothoracic unit for surgical drainage. This report discusses the evolution of a deep neck space infection into a mediastinitis, a rare and life-threatening complication, despite early surgical drainage. This report also highlights the difficulties faced with managing patients during the COVID-19 pandemic.

Prevalence of domestic violence in a time of catastrophic disease outbreaks including COVID 19 pandemic: A systematic review protocol (preprint)

Background Domestic violence is a public health issue that has a long term and irreversible effect on the victims. There are vulnerable groups like children, women, and elders. The problem becomes worse for these populations in the time of catastrophic events including disease pandemic. However, few attempts have been made to systematically review the prevalence and pattern of domestic violence during these times all over the world.Methods An initial search of PubMed will be followed by CINAHL, Scopus, Google Scholar, Embase, and ProQuest Health. Titles and abstracts of studies will be reviewed, and full-text articles will be selected if the inclusion criteria are met. Studies that meet the eligibility criteria will then be assessed by two independent reviewers. Full-text articles will be selected if the inclusion criteria are met. A standardized critical appraisal checklist for studies reporting prevalence data will be used to assess methodological quality and a standardized data extraction tool will be used. The results from the included studies will be analyzed using JBI SUMARI software.Discussion This systematic review will provide a solid evidence on the magnitude of domestic violence of any forms during catastrophic disease outbreaks including the current pandemic, COVID-19.Systematic review registration number: The systematic review protocol registration number in PROSPERO is CRD42020192255.

On Modeling of COVID-19 for the Indian Subcontinent using Polynomial and Supervised Learning Regression (preprint)

COVID-19, a recently declared pandemic by WHO has taken the world by storm causing catastrophic damage to human life. The novel cornonavirus disease was first incepted in the Wuhan city of China on 31st December 2019. The symptoms include fever, cough, fatigue, shortness of breath or breathing difficulties, and loss of smell and taste. Since the devastating phenomenon is essentially a time-series representation, accurate modeling may benefit in identifying the root cause and accelerate the diagnosis. In the current analysis, COVID-19 modeling is done for the Indian subcontinent based on the data collected for the total cases confirmed, daily recovered, daily deaths, total recovered and total deaths. The data is treated with total confirmed cases as the target variable and rest as feature variables. It is observed that Support vector regressions yields accurate results followed by Polynomial regression. Random forest regression results in overfitting followed by poor Bayesian regression due to highly correlated feature variables. Further, in order to examine the effect of neighbouring countries, Pearson correlation matrix is computed to identify geographic cause and effect.