Microneedle technology for potential SARS-CoV-2 vaccine delivery.

INTRODUCTION: Microneedle fabrication was conceptualized in the 1970s as devices for painless transdermal drug delivery. The last two decades have seen considerable research and financial investment in this area with SARS-CoV-2 and other vaccines catalyzing their application to in vivo intradermal vaccine delivery. Microneedle arrays have been fabricated in different shapes, geometries, formats, and out of different materials. AREAS COVERED: The recent pandemic has offered microneedle platforms the opportunity to be employed as a vehicle for SARS-CoV-2 vaccine administration. Various modes of vaccination delivery and the potential of microneedle array-based vaccines will be presented, with a specific focus placed on recent SARS-CoV-2 research. The advantages of microneedle-based vaccine administration, in addition to the major hurdles to their en masse implementation, will be examined. EXPERT OPINION: Considering the widely acknowledged disadvantages of current vaccine delivery, such as anxiety, pain, and the requirement for professional administration, a large shift in this research sphere is imminent. The SARS-CoV-2 pandemic has catalyzed the development of alternate vaccination platforms, working to avoid the requirement for mass vaccination centers. As microneedle vaccine patches are transitioning through clinical study phases, research will be required to prepare this technology for a more mass production environment.

Molecular Imprinted Polymers on Microneedle Arrays for Point of Care Transdermal Sampling and Sensing of Inflammatory Biomarkers.

The skin interstitial fluid (ISF) contains biomarkers that complement other biofluids such as blood, sweat, saliva, and urine. It can be sampled in a minimally invasive manner and used either for point of care testing or real time, continuous monitoring of analytes, the latter using microneedle arrays. The analytes present in the skin ISF are indicative of both systemic and local (i.e., skin) physiology. In this paper, we describe combining microneedle technology with molecularly imprinted polymers to demonstrate the potential of transdermal electrochemical sensing. The molecularly imprinted polymer employed here is easy to produce; it can be thought of as plastic antibody. Its synthesis is scalable, and the resulting sensor has a short measurement time (6 min), with high accuracy and a low limit of detection. It provides the requisite specificity to detect the proinflammatory cytokine IL-6. IL-6 is present in the skin ISF with other cytokines and is implicated in many clinical states including neurodegenerative diseases and fatal pneumonia from SARSCoV 2. The ability to mass produce microneedle arrays and plastic antibodies will allow for low-cost transdermal sensing devices. The transdermal sensors were able to detect IL-6 at concentrations as low as 1 pg/mL in artificial skin ISF, indicating its utility for routine point of care, bloodless measurements in simpler settings, worldwide.

Large Vessel Occlusions By Free Floating Thrombi in Strokes During the COVID-19 pandemic- A Single Center Observational Study.

Background: An increased incidence of systemic macrothrombotic phenomena such as strokes has been observed in moderate and severe COVID. However, strokes have also been increasingly observed in mild COVID, post COVID, or without obvious COVID illness. Objective: To share our experience with a specific stroke type noted during the COVID pandemic period. Materials and Methods: A single-center observational study was conducted in Western India from January to December 2020, and data regarding stroke patients admitted under Neurology services were noted. Clinical, laboratory, and radiological characteristics of strokes and subtypes were documented. Results: A total of 238 stroke patients were admitted in 2020, 76.5% during the COVID pandemic period. Among 153 ischemic strokes, 16.3% and 56.2% had large vessel occlusion (LVO) in pre-COVID and COVID pandemic period, respectively. Of all ischemic strokes, 20.9% (18 patients) and 12% (3 patients) had free floating thrombus (FFT) in the COVID versus pre-COVID period, respectively. Only 44.4% of all FFT patients could be proven SARS-CoV-2 RT-PCR positive while 50% were COVID suspect with surrogate markers of heightened inflammation at time of stroke. All patients were given anticoagulation and average mRS at discharge was 3.1 (range: 1-6) and 1.84 (range: 0-4) at 3-month follow-up in survivors. Conclusions: This study highlights the presence of FFT causing LVO as a new stroke subtype during the COVID-19 pandemic. With renewed and steeper spike in COVID-19 cases, especially new variants, the resurgence of this stroke subtype needs to be actively explored early in the course of illness to reduce morbidity and mortality.

Basilar Artery Thrombosis in the Postpartum Period During COVID - 19 Pandemic: A Lethal But Avoidable Complication.

PURPOSE: To highlight the factors leading to the delayed diagnosis of basilar artery occlusion and poor outcome in the postpartum period during the prevailing Corona Virus Disease-2019 (COVID-19) pandemic. CASE REPORT: We here report a case of a 34-year female who presented with a headache localized to the occipital region after cesarean section under spinal anesthesia. Her headache severity increased over time, and she developed a generalized seizure episode and became unconscious. Subsequently, basilar artery thrombosis was diagnosed. Despite all efforts, she succumbed to death. We believe that we might have saved the patient's life if we could have made the diagnosis beforehand. CONCLUSION: We recommend that unless shown otherwise, postpartum headache and neck discomfort, even in individuals with no known risk factors, should have a low index of suspicion, early diagnosis using non-invasive radiological study such MRI to rule out this uncommon but deadly illness quickly.

Conducting and critically appraising a high-quality systematic review and Meta-analysis pertaining to COVID-19.

With constantly emerging new information regarding the epidemiology, pathogenesis, diagnosis and management of Coronavirus Disease 2019 (COVID-19), reviewing literature related to it has become increasingly complicated and resource-intensive. In the setting of this global pandemic, clinical decisions are being guided by the results of multiple pertinent studies; however, it has been observed that these studies are often heterogenous in design and population characteristics and results of initial trials may not be replicated in subsequent studies. The resulting clinical conundrum can be resolved by high-quality systematic review and meta-analysis with a robust and reliable methodology, encapsulating and critically appraising all the available literature relevant to the clinical scenario under scrutiny. It can condense the large volume of scientific information available and can also identify the cause of differences in the degree of effect under consideration across different studies. It can identify optimal diagnostic algorithms, assess efficacy of treatment strategies, and analyze inherent factors influencing the efficacy of treatment for COVID-19. The current review aims to provide a basic guide to plan and conduct a high-quality systematic review and meta-analysis pertaining to COVID-19, describing the main steps and addressing the pitfalls commonly encountered at each step. Knowledge of the basic steps would also allow the reader to critically appraise published systematic review and meta-analysis and the quality of evidence provided therein.

Catastrophic Presentation of COVID-19 with Solitary Large Denovo Tumefactive Demyelination.

BACKGROUND: The ongoing Coronavirus disease-19 (COVID-19) pandemic has revealed a plethora of extrapulmonary manifestations including neurological presentations. To date, nervous system demyelination has been relatively infrequently reported in this setting. Also, while most data point toward immune activation as a causative process, few studies propound a direct effect. CASE DESCRIPTION: A 35-year-old man presented with severe new-onset headache, hemiparesis, and focal seizures culminating in deeply altered sensorium. Radiological evaluation showed a large expansile demyelinating lesion in the right cerebral hemisphere. Nasopharyngeal swab COVID reverse transcription-polymerase chain reaction (RT-PCR) was positive. After initial non-response to steroids, the patient responded well to plasma exchange leading to complete recovery. CONCLUSIONS: This report highlights a case of active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting with tumefactive demyelination and subsequent response to therapy. It is important to recognize atypical presentations at this juncture as it may be crucial for planning treatment strategies.

Cardiac Magnetic Resonance Imaging in Coronavirus Disease 2019 (COVID-19): A Systematic Review of Cardiac Magnetic Resonance Imaging Findings in 199 Patients.

OBJECTIVE: Cardiac magnetic resonance imaging (CMR) with its new quantitative mapping techniques has proved to be an essential diagnostic tool for detecting myocardial injury associated with coronavirus disease 2019 (COVID-19) infection. This systematic review sought to assess the important imaging features on CMR in patients diagnosed with COVID-19. MATERIALS AND METHODS: We performed a systematic literature review within the PubMed, Embase, Google Scholar, and WHO databases for articles describing the CMR findings in COVID-19 patients. RESULTS: A total of 34 studies comprising 199 patients were included in the final qualitative synthesis. Of the CMRs 21% were normal. Myocarditis (40.2%) was the most prevalent diagnosis. T1 (109/150; 73%) and T2 (91/144; 63%) mapping abnormalities, edema on T2/STIR (46/90; 51%), and late gadolinium enhancement (LGE) (85/199; 43%) were the most common imaging findings. Perfusion deficits (18/21; 85%) and extracellular volume mapping abnormalities (21/40; 52%), pericardial effusion (43/175; 24%), and pericardial LGE (22/100; 22%) were also seen. LGE was most commonly seen in the subepicardial location (81%) and in the basal-mid part of the left ventricle in inferior segments. In most of the patients, ventricular functions were normal. Kawasaki-like involvement with myocardial edema without necrosis/LGE (4/6; 67%) was seen in children. CONCLUSION: CMR is useful in assessing the prevalence, mechanism, and extent of myocardial injury in COVID-19 patients. Myocarditis is the most common imaging diagnosis, with the common imaging findings being mapping abnormalities and myocardial edema on T2, followed by LGE. As cardiovascular involvement is associated with poor prognosis, its detection warrants prompt attention and appropriate treatment.

CT in coronavirus disease 2019 (COVID-19): a systematic review of chest CT findings in 4410 adult patients.

OBJECTIVE: The objective of this systematic review was to evaluate the key imaging manifestations of COVID-19 on chest CT in adult patients by providing a comprehensive review of the published literature. METHODS: We performed a systematic literature search from the PubMed, Google Scholar, Embase, and WHO databases for studies mentioning the chest CT imaging findings of adult COVID-19 patients. RESULTS: A total of 45 studies comprising 4410 patients were included. Ground glass opacities (GGO), in isolation (50.2%) or coexisting with consolidations (44.2%), were the most common lesions. Distribution of GGOs was most commonly bilateral, peripheral/subpleural, and posterior with predilection for lower lobes. Common ancillary findings included pulmonary vascular enlargement (64%), intralobular septal thickening (60%), adjacent pleural thickening (41.7%), air bronchograms (41.2%), subpleural lines, crazy paving, bronchus distortion, bronchiectasis, and interlobular septal thickening. CT in early follow-up period generally showed an increase in size, number, and density of GGOs, with progression into mixed areas of GGOs plus consolidations and crazy paving, peaking at 10-11 days, before gradually resolving or persisting as patchy fibrosis. While younger adults more commonly had GGOs, extensive/multilobar involvement with consolidations was prevalent in the older population and those with severe disease. CONCLUSION: This review describes the imaging features for diagnosis, stratification, and follow-up of COVID-19 patients. The most common CT manifestations are bilateral, peripheral/subpleural, posterior GGOs with or without consolidations with a lower lobe predominance. It is pertinent to be familiar with the various imaging findings to positively impact the management of these patients. KEY POINTS: • Ground glass opacities (GGOs), whether isolated or coexisting with consolidations, in bilateral and subpleural distribution, are the most prevalent chest CT findings in adult COVID-19 patients. • Follow-up CT shows a progression of GGOs into a mixed pattern, reaching a peak at 10-11 days, before gradually resolving or persisting as patchy fibrosis. • Younger people tend to have more GGOs. Older or sicker people tend to have more extensive involvement with consolidations.