COVID-19 Vaccination Prioritization Strategies in Malaysia: A Retrospective Analysis of Early Evidence.

The coronavirus disease 2019 (COVID-19) that can cause extreme acute respiratory syndrome has posed a catastrophic threat to public health. The vaccines had indeed restored optimism and, after more than two years of battling the pandemic, there is renewed hope for the transition to endemicity. At the start of vaccination efforts, when supply shortages of vaccines were inevitable, every nation determined the high-risk population groups to be given priority for the COVID-19 vaccines. In this paper, the characteristics of the initial COVID-19 vaccine recipients in Malaysia are described. In line with the policies of many other countries, Malaysia firstly inoculated frontline healthcare workers, and subsequently the list of front liners grew to include defense and security personnel and those involved in the provision of essential services. People with disabilities or those with special needs and several underlying medical conditions that increased their risk of developing severe COVID-related illnesses were included in the priority categories. These included patients with severe lung disease, chronic heart disease, chronic kidney disease, chronic liver disease, neurological disease, diabetes mellitus and obesity in adults, splenic dysfunction, and severe mental illness. With little information and under circumstances of great uncertainty, the Health Ministry of a middle-income country had developed a vaccination priority-list based on the disease's epidemiology and clinical data, vaccine type, operational considerations, and risk evaluation. Early evidence was presented and suggested that the full vaccination with any of the three predominant vaccines (AZD1222, BNT162b2, and CoronaVac) in the country had been highly effective in preventing COVID-19 infections, COVID-19-related ICU admissions, and death. As many SARS-CoV-2 variants of concern (VoC), such as the Omicron BA.2/4/5, are emerging, future vaccination strategies may necessitate the need to change the immunogen of the vaccine, as well as considerations for when to give high-risk groups booster injections. These considerations are valuable for future planning by policymakers and healthcare providers to make vaccination policy and decisions, especially for the inclusion of the COVID-19 vaccines into national immunization programs.

The Race for Global Equitable Access to COVID-19 Vaccines.

COVID-19 vaccines are possibly the most effective medical countermeasures to mitigate and ultimately bring to a halt the COVID-19 pandemic. As we transition to endemicity, inequitable access to vaccines, and particularly in low- and middle-income countries (LMICs), still poses risks of unprecedented disruptions and the emergence of viral mutations, which potentially lead to notorious vaccine-resistant variants. The missteps learned from the previous responses to the human immunodeficiency virus (HIV) and influenza outbreaks founded the hypothetical plan to ensure that vaccine accessibility to LMICs is not impeded. The SARS-CoV-2 vaccines' social promise was to lessen the underlying racial, ethnic, and geographic inequities that COVID-19 has both made apparent and intensified. Vaccine nationalism was evident throughout the COVID-19 crisis. Many high-income countries directly negotiated large advance orders for the vaccines, leaving resource-limited countries scrambling for access. This occurred despite international initiatives to structure the development and equitable distribution of vaccines, channeled through a vaccine pillar: COVID-19 Vaccines Global Access (COVAX). The serious supply shortages and national procurement methods of some countries that bypassed the vaccine pillar hindered the optimal function of COVAX in delivering timely and adequate doses to participating countries. COVAX strategized its approach by promoting fundraising, coordinating vaccine donations from countries with surplus doses, expediting reviews of vaccine candidates, and facilitating the expansion of the manufacturing capacity. While increasing capacity for production, technology transfer led to lesser siloes, enhanced manufacturing standardization, and less secrecy over production data. Ultracold storage requirements for leading vaccines were a considerable hurdle to the global immunization efforts, and particularly in LMICs with limited equipment and resources to support sophisticated cold-chain systems. Manufacturers strived to ease cold-chain restrictions on the basis of stability data submitted to national regulatory bodies. The development of single-dose vaccines offered promising solutions to simplify the administrative and logistic complexities that existed within the COVID-19 vaccination programs. As such, the requirements for both ultracold storage conditions were eased, and concerns over booster doses were addressed. To expand coverage, the dosing intervals of the Oxford/AstraZeneca vaccines were extended according to data from Phase III clinical trials on effectiveness. In addition, with the recent outbreak of monkeypox, the lessons from past experiences of curbing infectious diseases, including COVID-19, must be learned and acted upon. The review summarizes the global efforts with respect to vaccine development, production, allocation, and deployment to achieve equitable access.

The paradoxical effect of IL-6 and implications for the use of Tocilizumab in Covid-19 patients.

In the context of the current SARS-CoV-2 pandemic, patients affected by chronic obstructive pulmonary disease (COPD) should be more vulnerable to Covid-19, whereas they seem to be protected against severe Covid-19. That paradox has important practical implications for the use of the drug Tocilizumab in Covid-19. Interleukin-6 (IL-6) orchestrates the so-called cytokine storm leading to the Acute Respiratory Distress Syndrome (ARDS), the life-threatening condition that is responsible for Covid-19 deaths. However, IL-6 has a paradoxical effect in many viral infections. For pathogens such as HIV and Hepatitis B for example, high elevations show a toxic effect and are associated with higher mortality (e.g. they promote progression to AIDS in HIV patients), whereas mild elevations show a protective effect. IL-6 can be therefore considered as being both a pro-inflammatory and an anti-inflammatory cytokine. Several studies have shown that severe COPD is associated with extremely-high levels of IL-6, whereas mild COPD is associated with mild elevations of IL-6. It is plausible that the chronic, mildly-elevated concentrations of IL-6 found in mild COPD patients is protective against the deterioration of Covid-19, as it is the case for other viral diseases. That may explain why COPD is surprisingly an uncommon comorbidity in Covid-19 intensive care units. This may have an important practical implication for the treatment of Covid-19 patients: our hypothesis is that Tocilizumab must be used exclusively in patients with an ongoing cytokine storm. Otherwise, an early use of Tocilizumab can be harmful, especially in patients affected by COPD or other conditions with mildly-elevated IL-6.

Hydrogen peroxide and viral infections: A literature review with research hypothesis definition in relation to the current covid-19 pandemic.

We reviewed the literature concerning the innate response from nasal and oral epithelial cells and their reaction to hydrogen peroxide (H2O2). Hydrogen peroxide is produced physiologically by oral bacteria and plays a significant role in the balance of oral microecology since it is an important antimicrobial agent. In the epithelial cells, the enzyme superoxide dismutase catalyzes a reaction leading from hydrogen peroxide to the ion superoxide. The induced oxidative stress stimulates a local innate response via activation of the toll-like receptors and the NF-κB. Those kinds of reactions are also activated by viral infections. Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. Therefore, nose/mouth/throat washing with hydrogen peroxide may enhance those local innate responses to viral infections and help protect against the current coronavirus pandemic. We strongly encourage the rapid development of randomized controlled trials in both SARS-CoV-2 positive and negative subjects to test the preliminary findings from the in-vitro and in-vivo observational studies that we identified.