The impact of delayed access to COVID-19 vaccines in low- and lower-middle-income countries.

Introduction: A majority of low-income (LIC) and lower-middle-income countries (LMIC) were unable to achieve at least 10% population coverage during initial vaccine rollouts, despite the rapid development of the coronavirus disease 2019 (COVID-19) vaccines. Nearly three years into this pandemic, evaluating the impact of inequities in vaccine access, uptake, and availability is long overdue. We hypothesized that a delay in receiving COVID-19 vaccines was associated with an increased toll on cumulative cases and mortality. Furthermore, this relationship was modified by the size of a country's economy. Methods: We performed an ecological study assessing these relationships, in which a country's economic standing was assessed by world bank income classification, gross domestic product based on the purchasing power parity (GDP PPP) per capita category, and crude GDP PPP. Results: Countries with the smallest economies reported first vaccination much later than larger economies on all three rankings, as much as 100 days longer. Among low-income countries, a one-day increase until the first vaccination was associated with a 1.92% (95% CI: 0.100, 3.87) increase in cumulative cases when compared to high-income countries (p = 0.0395) when adjusting for population size, median age, and testing data availability. Similarly, among the lowest GDP PPP countries a one-day increase until the first vaccination was associated with a 2.73% (95% CI: 0.100, 5.44) increase in cumulative cases when compared to the highest GDP PPP countries (p = 0.0415). When modeling cumulative mortality, effects in the same direction and magnitude were observed, albeit statistically non-significant. Conclusion: Economic standing modified the effects of delayed access to COVID-19 vaccination on cumulative cases and mortality, in which LMICs tended to fare worse in outcomes than high-income countries despite the eventual rollout of vaccines. These findings highlight the importance of prioritizing equitable and timely access to COVID-19 vaccines across all countries, irrespective of economic size. Future studies should examine the impacts that vaccine inequities had on local transmission dynamics.

The impact of delayed access to COVID-19 vaccines in low- and lower-middle-income countries

Introduction A majority of low-income (LIC) and lower-middle-income countries (LMIC) were unable to achieve at least 10% population coverage during initial vaccine rollouts, despite the rapid development of the coronavirus disease 2019 (COVID-19) vaccines. Nearly three years into this pandemic, evaluating the impact of inequities in vaccine access, uptake, and availability is long overdue. We hypothesized that a delay in receiving COVID-19 vaccines was associated with an increased toll on cumulative cases and mortality. Furthermore, this relationship was modified by the size of a country's economy. Methods We performed an ecological study assessing these relationships, in which a country's economic standing was assessed by world bank income classification, gross domestic product based on the purchasing power parity (GDP PPP) per capita category, and crude GDP PPP. Results Countries with the smallest economies reported first vaccination much later than larger economies on all three rankings, as much as 100 days longer. Among low-income countries, a one-day increase until the first vaccination was associated with a 1.92% (95% CI: 0.100, 3.87) increase in cumulative cases when compared to high-income countries (p = 0.0395) when adjusting for population size, median age, and testing data availability. Similarly, among the lowest GDP PPP countries a one-day increase until the first vaccination was associated with a 2.73% (95% CI: 0.100, 5.44) increase in cumulative cases when compared to the highest GDP PPP countries (p = 0.0415). When modeling cumulative mortality, effects in the same direction and magnitude were observed, albeit statistically non-significant. Conclusion Economic standing modified the effects of delayed access to COVID-19 vaccination on cumulative cases and mortality, in which LMICs tended to fare worse in outcomes than high-income countries despite the eventual rollout of vaccines. These findings highlight the importance of prioritizing equitable and timely access to COVID-19 vaccines across all countries, irrespective of economic size. Future studies should examine the impacts that vaccine inequities had on local transmission dynamics.

Human Placental Mesenchymal Stem Cells for the Treatment of ARDS in Rat.

The acute respiratory distress syndrome (ARDS) is one of the main causes of high mortality in patients with coronavirus (COVID-19). In recent years, due to the coronavirus pandemic, the number of patients with ARDS has increased significantly. Unfortunately, until now, there are no effective treatments for ARDS caused by COVID-19. Many drugs are either ineffective or have a low effect. Currently, there have been reports of efficient use of mesenchymal stem cells (MSCs) for the treatment of ARDS caused by COVID-19. We investigated the influence of freeze-dried human placenta-derived mesenchymal stem cells (HPMSCs) in ARDS rat model. All animals have received intratracheal injection of 6 mg/kg of lipopolysaccharide (LPS). The rats were randomly divided into five groups: I: LPS, II: LPS+dexamethasone, III: LPS+HPMSCs, IV: HPMSC, and V: saline. ARDS observation time was short-term and amounted to 168 hours. The study has shown that HPMSCs are able to migrate and attach to damaged lung tissue, contributing to the resolution of pathology, restoration of function, and tissue repair in the alveolar space. Studies have also shown that the administration of HPMSCs in animals with ARDS model significantly reduced the levels of key cytokines such as IL-1ß, IL-6, and TNF-α. Freeze-dried placental stem cell is a very promising biomaterial for the treatment of ARDS. The human placenta can be easily obtained because it is considered as a medical waste. At the same time, a huge number of MSCs can be obtained from the placental tissue, and there is no ethical controversy around their use. The freeze-dried MSCs from human placental tissue can be stored sterile at room temperature for a long time before use.

Targeted, Site-Specific, Delivery Vehicles of Therapeutics for COVID-19 Patients. Brief Review.

Definitive pharmacological therapies for COVID-19 have yet to be identified. Several hundred trials are ongoing globally in the hope of a solution. However, nearly all treatments rely on systemic delivery but COVID-19 damages the lungs preferentially. The use of a targeted delivery approach is reviewed where engineered products are able to reach damaged lung tissue directly, which includes catheter-based and aerosol-based approaches. In this review we have outlined various target directed approaches which include microbubbles, extracellular vesicles including exosomes, adenosine nanoparticles, novel bio-objects, direct aerosol targeted pulmonary delivery and catheter-based drug delivery with reference to their relative effectiveness for the specific lesions. Currently several trials are ongoing to determine the effectiveness of such delivery systems alone and in conjunction with systemic therapies. Such approaches may prove to be very effective in the controlled and localized COVID-19 viral lesions in the lungs and potential sites. Moreover, localized delivery offered a safer delivery mode for such drugs which may have systemic adverse effects.

Viral Coagulopathy in Patients With COVID-19: Treatment and Care.

COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation-like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.