Formulation, Device, and Clinical Factors Influencing the Targeted Delivery of COVID-19 Vaccines to the Lungs.

The COVID-19 pandemic has proven to be an unprecedented health crisis in the human history with more than 5 million deaths worldwide caused to the SARS-CoV-2 and its variants ( https://www.who.int/emergencies/diseases/novel-coronavirus-2019 ). The currently authorized lipid nanoparticle (LNP)-encapsulated mRNA vaccines have been shown to have more than 90% vaccine efficacy at preventing COVID-19 illness (Baden et al. New England J Med 384(5):403-416, 2021; Thomas et al., 2021). In addition to vaccines, other small molecules belonging to the class of anti-viral and anti-inflammatory compounds have also been prescribed to reduce the viral proliferation and the associated cytokine storm. These anti-viral and anti-inflammatory compounds have also been shown to be effective in reducing COVID-19 exacerbations especially in reducing the host inflammatory response to SARS-CoV-2. However, all of the currently FDA-authorized vaccines for COVID-19 are meant for intramuscular injection directly into the systemic circulation. Also, most of the small molecules investigated for their anti-COVID-19 efficacy have also been explored using the intravenous route with a few of them explored for the inhalation route (Ramakrishnan et al. Lancet Respir Med 9:763-772, 2021; Horby et al. N Engl J Med 384(8):693-704, 2021). The fact that the SARS-CoV-2 enters the human body mainly via the nasal and airway route resulting in the lungs being the primary organs of infection as characterized by acute respiratory distress syndrome (ARDS)-mediated cytokine storm in the alveolar region has made the inhalation route gain significant attention for the purposes of targeting both vaccines and small molecules to the lungs (Mitchell et al., J Aerosol Med Pulm Drug Deliv 33(4):235-8, 2020). While there have been many studies reporting the safety and efficacy of targeting various therapeutics to the lungs to treat COVID-19, there is still a need to match the choice of inhalation formulation and the delivery device platform itself with the patient-related factors like breathing pattern and respiratory rate as seen in a clinical setting. In that perspective, this review aims to describe the various formulation and patient-related clinical factors that can play an important role in the judicious choice of the inhalation delivery platforms or devices for the development of inhaled COVID-19 vaccines.

COVID-19 Vaccine-Related Arthritis: A Descriptive Study of Case Reports on a Rare Complication.

Large-scale coronavirus disease 2019 (COVID-19) vaccination programs have been rolled out worldwide. Vaccines that are widely used globally include mRNA vaccines, adenoviral vector vaccines, and inactivated whole-virus vaccines. COVID-19 vaccines can lead to varying side effects. Among the most common of these adverse effects are pain at the injection site, fatigue, and headaches. Some side effects, however, are not very well documented, and these include joint-related adverse effects. In this review, we assess the epidemiology and clinical features of post-COVID-19 vaccination joint-related adverse effects based on the analysis of 16 patient case reports. Based on our analysis, we found that females formed the majority of the cases, accounting for 62.5% of patients, while 37.5% of the cases were males. The mean age of presentation among the patients was 54.8 years, with a standard deviation (SD) of 17.49 years. In 37.5% of the cases, patients received the Sinovac vaccine. The proportion of patients who received other vaccines was as follows: the Pfizer vaccine: 31.25%; Sputnik V: 12.5%; Moderna, AstraZeneca, and Covaxin: 6.25% each. The characteristics of joint-related adverse effects following COVID-19 vaccination were analyzed in this study. We identified several key findings related to factors such as age, gender, type of vaccine, clinical features, and diagnosis modality. Our analysis showed that more cases were reported among individuals who received the Sinovac vaccine, as compared to the others. Further research is required to examine the underlying cause of this association.

Statin Induced Autoimmune Necrotizing Myopathy (SIANM): An Alarming Adverse Event of a Familiar Medication.

Statins are a widely prescribed medication that lowers serum cholesterol by inhibiting the HMG-CoA reductase enzyme, a rate-limiting step in cholesterol synthesis. Myopathy is one of the well-known adverse effects of statins, mainly when prescribed with the fibrates. However, statin-induced autoimmune necrotizing myopathy (SIANM) is an infrequent and severe complication. Hence, all clinicians should be more vigilant regarding this complication and treat it early to prevent acute kidney injury (AKI).

Role of Invasive Mechanical Ventilation and ECMO in the Management of COVID-19: A Systematic Review.

OBJECTIVES: This systematic review aims to provide insight into the outcome of extracorporeal membrane oxygenation (ECMO) and invasive mechanical ventilation use in critically ill COVID-19 patients. DATA SOURCES: Electronic databases PubMed Central and PubMed were searched from January 2020 to June 2020 for published studies about ECMO and/or invasive mechanical ventilation use in COVID-19 patients. Data Extraction and Study Selection: The search strategy retrieved 766 articles, of which 19 studies consisting of 204 patients fulfilled the inclusion criteria and were included in the analysis. DATA SYNTHESIS: Primary outcomes evaluated were discharge and/or clinical improvement and mortality rate. Secondary outcomes evaluated included reported complications and the mean number of days of hospitalization for survivors. Weighted averages of included studies were calculated, and data were pooled in forest plots. Nearly, 68.1% of the patients received invasive mechanical ventilation without ECMO support, and 31.9% were placed on ECMO. Also, 22.5% of the patients were discharged and/or clinically improved and 51.5% died. Twenty-six percent of the study population deteriorated but remained alive or experienced no improvement in clinical condition. And 75.2% of those who died belonged to the non-ECMO group and 24.8% to the ECMO group. The mortality rate in the non-ECMO group was 56.8% compared to 40% in the ECMO group. CONCLUSION: The utility of ECMO during a pandemic is uncertain as it is a resource-intensive modality, especially when the mortality rate in severely ill patients infected with COVID-19 virus is already known to be high. HOW TO CITE THIS ARTICLE: Nagraj S, Karia R, Hassanain S, Ghosh P, Shah VR, Thomas A. Role of Invasive Mechanical Ventilation and ECMO in the Management of COVID-19: A Systematic Review. Indian J Crit Care Med 2021;25(6):691-698.

Pediatric bilateral vocal cord granulomas presenting as airway foreign body following prolonged intubation due to COVID-19 related multisystem inflammatory syndrome.

BACKGROUND: This report is a case of bilateral vocal cord granulomas (VCG) in a 9-year-old child presenting as an airway foreign body and stridor following prolonged intubation due to COVID-19 pneumonia complicated by multisystem inflammatory syndrome in children (MIS-C). CASE PRESENTATION: This case reports a 9-year-old male who presented to the emergency department with acute stridor concerning for airway obstruction. X-ray findings suggested an airway foreign body; however, on rigid bronchoscopy, ball-valving bilateral VCG obstructing 90% of the glottic airway were identified. After excision of the VCGs, the patient's symptoms resolved with no postoperative complications. CONCLUSION: With suspected foreign body aspiration in a pediatric patient with a history of prolonged intubation, it is important to consider a broad differential diagnosis. VCGs are rare complications of prolonged intubation that could be in children with prior history of intubation following COVID-19 pneumonia.

Assessing the interplay between travel patterns and SARS-CoV-2 outbreak in realistic urban setting.

BACKGROUND: The dense social contact networks and high mobility in congested urban areas facilitate the rapid transmission of infectious diseases. Typical mechanistic epidemiological models are either based on uniform mixing with ad-hoc contact processes or need real-time or archived population mobility data to simulate the social networks. However, the rapid and global transmission of the novel coronavirus (SARS-CoV-2) has led to unprecedented lockdowns at global and regional scales, leaving the archived datasets to limited use. FINDINGS: While it is often hypothesized that population density is a significant driver in disease propagation, the disparate disease trajectories and infection rates exhibited by the different cities with comparable densities require a high-resolution description of the disease and its drivers. In this study, we explore the impact of creation of containment zones on travel patterns within the city. Further, we use a dynamical network-based infectious disease model to understand the key drivers of disease spread at sub-kilometer scales demonstrated in the city of Ahmedabad, India, which has been classified as a SARS-CoV-2 hotspot. We find that in addition to the contact network and population density, road connectivity patterns and ease of transit are strongly correlated with the rate of transmission of the disease. Given the limited access to real-time traffic data during lockdowns, we generate road connectivity networks using open-source imageries and travel patterns from open-source surveys and government reports. Within the proposed framework, we then analyze the relative merits of social distancing, enforced lockdowns, and enhanced testing and quarantining mitigating the disease spread. SCOPE: Our results suggest that the declaration of micro-containment zones within the city with high road network density combined with enhanced testing can help in containing the outbreaks until clinical interventions become available.