Higher coronavirus disease-19 mortality linked to comorbidities: A comparison between low-middle income and high-income countries.

BACKGROUND: Global burden of disease (GBD) provides the estimates of mortality and morbidity, while case fatality rate (CFR) helps in understanding the severity of the disease. People infected with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) with underlying medical conditions have shown higher levels of unfavorable outcomes including mortality. We assessed the association of SARS-CoV-2 CFR with disability-adjusted life years (DALY) of various comorbidities in the low-middle income countries (LMIC) and high-income countries (HIC) to study the relationship of coronavirus disease-19 (COVID-19) mortality with GBDs and to understand the linkage between COVID-19 mortality and comorbidities. MATERIALS AND METHODS: This was an ecological study with secondary data analysis comparing the DALY of various morbidities from GBD with CFR of COVID-19. Gross domestic product was the basis of stratifying 177 countries into low-middle income (LMIC) and high-income groups (HIC). The mortality was analyzed using Pearson correlation and linear regression. RESULTS: The median global CFR of SARS-CoV-2 was 2.15. The median CFR among LMIC (n = 60) and HIC (n = 117) was 2.01 (0.00-28.20) and 2.29 (0.00-17.26), respectively. The regression analysis found that, in both LMIC and HIC, maternal disorders were associated with higher SARS-CoV-2 CFR, while tuberculosis, mental health disorders, and were associated with lower CFR. Further, in LMIC, musculoskeletal disorders and nutritional deficiencies were associated with higher CFR, while respiratory disorders were associated with lower CFR. CONCLUSIONS: SARS-CoV-2 infection appears to be a systemic disease. Individuals with comorbidities, such as maternal disorders, neurological diseases, musculoskeletal disorders, and nutritional deficiencies, have poorer outcomes with COVID-19, leading to higher mortality.

Alzheimer disease immunotherapeutics: then and now.

Dementia is a public health priority and one of the major contributors to morbidity and global non-communicable disease burden, thus necessitating the need for significant health-care interventions. Alzheimer disease (AD) is the most common cause of dementia and may contribute to 60-70% of cases. The cause and progression of AD are not well understood but have been thought to be due at least in part to protein misfolding (proteopathy) manifest as plaque accumulation of abnormally folded ß-amyloid and tau proteins in brain. There are about 8 million new cases per year. The total number of people with dementia is projected to almost double every 20 years, to 66 million in 2030 and 115 million in 2050. Immunotherapy in AD aimed at ß-amyloid covers 2 types of vaccination: active vaccination against Aß42 in which patients receive injections of the antigen itself, or passive vaccination in which patients receive injections of monoclonal antibodies (mAb) against Aß42. Three of the peptide vaccines for active immunizations, CAD106, ACC001, and Affitope, are in phase 2 clinical trials. Three of the mAbs solanezumab, gantenerumab, and crenezumab, are or were in phase 2 and 3 clinical studies. While the phase 3 trials failed, one of these may have shown a benefit at least in mild forms of AD. There is a need for a greater initiative in the development of immunotherapeutics. Several avenues have been explored and still to come.

Vaccination for pregnant women: need to address.

Pregnancy is a critically important state for any women in her life time. Administration of a vaccine to a pregnant woman is not a routine event and it is generally preferred to administer vaccines either prior to conception or in the postpartum period. Currently vaccination with inactivated vaccines are recommended due to potential risk to mother and fetus with live vaccines. Multiple factors determine the administration of the vaccines for example age, life style, medical conditions (e.g., asthma, diabetes etc.), type and location of travel and status of previous vaccination. If pregnant woman is exposed to these vaccines or if pregnancy occurs soon after vaccination, the women should be counselled regarding the risks to the fetus and vaccination should not be a reason to consider termination of pregnancy. Further research in vaccination among pregnancy is warranted for the safety of the pregnant women and their newborn for a healthy living and better life.

Dengue vaccine: a valuable asset for the future.

Dengue has emerged as one of the major global public health problems. The disease has broken out of its shell and has spread due to increased international travel and climatic changes. Globally, over 2.5 billion people accounting for >40% of the world's population are at risk from dengue. Since the 1940s, dengue vaccines have been under investigation. A live-attenuated tetravalent vaccine based on chimeric yellow fever-dengue virus (CYD-TDV) has progressed to phase III efficacy studies. Dengue vaccine has been found to be a cost-effective intervention to reduce morbidity and mortality. Current dengue vaccine candidates aim to protect against the 4 dengue serotypes, but the recent discovery of a fifth serotype could complicate vaccine development. In recent years, an urgent need has been felt for a vaccine to prevent the morbidity and mortality from this disease in a cost-effective way.

Malaria vaccine: a step toward elimination.

Malaria has long been recognized as a public health problem. At the community level, vector control, and antimalarial medicines are the main means for reducing incidence, morbidity, and mortality of malaria. A vaccine not only would bring streamlining in the prevention of morbidity and mortality from malaria but also would be more accessible if integrated with Expanded Programme of Immunization (EPI). Globally, an estimated 3.4 billion people are at risk of malaria. Most cases (80%) and deaths (90%) occurred in Africa, and most deaths (77%) are in children under 5 years of age. An effective vaccine has long been envisaged as a valuable addition to the available tools for malaria control. Although research toward the development of malaria vaccines has been pursued since the 1960s, there are no licensed malaria vaccines. The RTS,S/AS01 vaccine, which targets P. falciparum, has reached phase 3 clinical trials and results are promising. Malaria Vaccine Technology Road Map 2013 has envisaged the world aiming for a licensed vaccine by 2030 that would reduce malaria cases by 75% and be capable of eliminating malaria. It will not only fill the gaps of today's interventions but also be a cost-effective method of decreasing morbidity and mortality from malaria.

Vaccination in HIV positive adults: need to address.

Human Immunodeficiency Virus (HIV) continues to be a major public health program. Without treatment, average survival time without treatment after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype. Vaccination recommendations are determined by weighing the benefits of vaccination against the risks. It is preferable to have patients on antiretroviral therapy (ART) prior to receipt of vaccination, as that may help blunt or eliminate vaccine-associated viremia and potentially improve immune response to vaccination. : Although data are limited, in general, HIV-infected individuals who are on ART with well-controlled HIV RNA levels and CD4 counts of >200 cells/µL (or = 15%) may receive indicated live-virus vaccines. Vaccination can play a vital role in enhancing the immunity against opportunistic infections. Further research, is the need for a better and healthy living of the people with HIV.

Hepatitis C: is a vaccine the solution?

Hepatitis C Virus (HCV) infection is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Following acute infection, 20% of people eliminate the virus over weeks or months and are often asymptomatic. The remaining 80% of people will develop chronic disease, of which approximately 20% will eventually develop liver cirrhosis and 1-5% will develop liver cancer. About 150 million people are chronically infected with HCV, and more than 350,000 people die every year from hepatitis C related liver diseases. The economic cost of hepatitis C is significant both to the individual and to the society. In the United States the average lifetime cost of the disease was estimated at $33,407 USD with the cost of a liver transplant approximately $200,000 USD. PEG-IFN and ribavirin treatment is also expensive and, at an average cost of approximately GB £7000 in the UK for a treatment course, is unaffordable in developing countries. Hepatitis C, not only brings down the quality of the life of individuals but also affect progress of the nation by adding financial burden. If we prevent the disease from occurring or find a perfect cure of the disease, in form of a prophylactic or therapeutic vaccine, it will be a boon to not only to the individual but to the nation as a whole.

Vaccination for safe travel to India.

Worldwide more than 900 million international journeys are undertaken every year. India is one of the favorite tourist destinations around the world. International travel exposes travelers to a range of health risks. Traveling to India possess a threat to travelers with waterborne diseases like bacterial diarrhea, hepatitis A and E, and typhoid fever; vector borne diseases like dengue fever, Japanese encephalitis, and malaria; animal contact disease like rabies. Furthermore diseases spreading through behavior aspects cannot be ruled out hence posing a risk for hepatitis B, HIV/AIDS, hepatitis C as well. Hence, before travel the travelers are advised about the risk of disease in the country or countries they plan to visit and the steps to be taken to prevent illness. Vaccination offers the possibility of avoiding a number of infectious diseases that may be countered abroad. There is no single vaccination schedule that fits all travelers. Each schedule must be individualized according to the traveler's previous immunizations, countries to be visited, type and duration of travel, and the amount of time available before departure.

Adult immunization: the need to address.

Vaccination is recommended throughout life to prevent vaccine-preventable diseases and their sequel. The primary focus of vaccination programs has historically been directed to childhood immunizations. For adults, chronic diseases have been the primary focus of preventive and medical health care, though there has been increased emphasis on preventing infectious diseases. Adult vaccination coverage, however, remains low for most of the routinely recommended vaccines. Though adults are less susceptible to fall prey to traditional infectious agents, the probability of exposure to infectious agents has increased manifold owing to globalization and increasing travel opportunities both within and across the countries. Thus, there is an urgent need to address the problem of adult immunization. The adult immunization enterprise is more complex, encompassing a wide variety of vaccines and a very diverse target population. There is no coordinated public health infrastructure to support an adult immunization program as there is for children. Moreover, there is little coordination among adult healthcare providers in terms of vaccine provision. Substantial improvement in adult vaccination is needed to reduce the health consequences of vaccine-preventable diseases among adults. Routine assessment of adult patient vaccination needs, recommendation, and offer of needed vaccines for adults should be incorporated into routine clinical care of adults.

M-Track: detecting short-lived protein-protein interactions in vivo.

We developed a protein-proximity assay in yeast based on fusing a histone lysine methyltransferase onto a bait and its substrate onto a prey. Upon binding, the prey is stably methylated and detected by methylation-specific antibodies. We applied this approach to detect varying interaction affinities among proteins in a mitogen-activated protein kinase pathway and to detect short-lived interactions between protein phosphatase 2A and its substrates that have so far escaped direct detection.