ABSTRACT
mRNA vaccines open promising avenues for overcoming a variety of diseases due to their high therapeutic utilities, rapid growth capacities, and safe administration potentials. With the emergence of COVID-19, the use of mRNA vaccines has become even more widespread and far-reaching. However, for mRNA to be delivered to target cells and tissues, several obstacles must be overcome. For instance, naked mRNAs get easily and hastily degraded by ribonucleases in tissues and the bloodstream, and since mRNAs are large and polyanionic molecules, they cannot passively diffuse across cell membranes. Even though mRNAs are internalized by APCs, they must be able to reach the cytoplasm and escape endo-lysosomal traffic. Therefore, distinctive transport systems for efficient encapsulation of mRNAs using nanocarrier systems are required to ensure their delivery to cells’ cytoplasm. At this point, non-viral gene delivery systems such as polymers and lipids come to the fore, in which they can overcome the biological barriers and provide efficient delivery of mRNAs. Recently, mRNA vaccines have been used as a powerful weapon against COVID-19 pandemic which has affected the whole world since December 2019. This was clear by the emergence of Pfizer-BioNTech and Moderna vaccines, which offered mRNA vaccines with auspicious treatment abilities. A variety of carrying candidates have been utilized in such vaccines as polymers, metal nanoparticles, as well as LNPs, which each comes with its cons and pros in delivering mRNA. All of these mentioned points will be clarified and discussed in detail in this review paper.
ABSTRACT
Background: The coronavirus disease 2019 (COVID-19) pandemic has brought life to a standstill all over the world. Especially in Istanbul, the most populated city in Turkey, many hospitals served as pandemic hospitals and suspended the examination of patients who were not infected with COVID-19. On the other hand, in this period, lockdown was applied frequently to control the pandemic and to reduce the transmission. It is known that the delay in the diagnosis and treatment of cancer can sometimes be fatal. Initial treatment choice in classical Hodgkin lymphoma (cHL) patients is determined by various factors including the stage of the disease. Therefore, detection of the disease at an early stage has prognostic importance. Our aim was to compare the time from symptom onset to diagnosis and period between diagnosis and treatment initiation, as well as the distribution of stages and treatment responses in cHL patients diagnosed and treated during the COVID-19 pandemic and in the pre-pandemic period. Methods: Patients who were diagnosed within the 2 years before the pandemic (between March 2018 and March 2020) and in a 12-month period during the pandemic (between March 2020 and March 2021) were compared in terms of demographic data, disease related factors, time interval between symptom to diagnosis, and interim treatment response. Clinical data were obtained from manual and electronic medical records retrospectively. PET scans were performed at baseline, after two cycles of chemotherapy, and end of treatment (EOT). The Deauville five-point scale (5-PS) was used in the initial staging and assessment of treatment response. The 5-PS;a score of 1, 2, or 3 was considered negative. The 5-PS score 4 or 5 was positive. Results: This single-center study included 90 newly diagnosed cHL patients, with a median age of 33.5 years (range, 17 - 70 years) and a male predominance (53.3%). The most common presenting symptom was a lump in the neck (41.1%), and also, 61.1% (n=55) of the cases had at least one B symptom. Patient characteristics were summarized in Table 1. Age and sex distributions were similar in both groups. Also, the number of patients >60 years was comparable (p=0.868). The most common histopathological subtype in both groups was nodular sclerosis (47.7% vs. 48%). In the pre-pandemic period and during the pandemic, the percentages of patients with early unfavorable disease were 66.7% and 77.8%, respectively (p=0.526). Although the percentage of patients with advanced-stage disease was higher during the pandemic than that observed in the pre-pandemic period (64% vs. 53.8%), this difference did not reach statistical significance (p=0.384). The median interval between symptom onset to diagnosis was significantly longer during the pandemic than was observed within the pre-pandemic era (16 weeks vs. 8 weeks, p=0.042). The median durations between diagnosis and treatment initiation were similar in both groups (13 days vs. 15 days, p=0.253). The majority of patients in both groups received ABVD as first-line therapy, and IFRT was performed in some patients with early-stage cHL (Figure 1). Among all patients (n=90), 85% of the cases had negative interim PET scan results, and this percentage was similar for both patient groups (84.6% vs. 88%, p=0.999). In the pre-pandemic period, 80% of the patients had complete response at EOT, on the other hand, no comparison was performed between two groups regarding response level at EOT, since nearly half of patients (48%) treated during the pandemic were not evaluated for the EOT response at the time of the analysis. Discussion & Conclusion: In our cohort, the time interval between symptom onset to diagnosis was significantly prolonged during the pandemic. Most probably the patients were afraid of admitting to the hospital due to the fear of contagion, or patients might have experienced difficulties in applying to a health facility, and lastly maybe they had tolerable symptoms, which might all have roles in the diagnostic delay during the pandemic. Higher percentage of patients with advan ed-stage disease during the pandemic might also be associated with this delay, however, fortunately, this difference did not translate into a significant difference regarding interim treatment response in both groups. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
ABSTRACT
Objectives: We aim to investigate the involvement of the choroid and retinal nerve fiber layer (RNFL) in COVID-19 patients using spectral domain optical coherence tomography. Methods: This cross-sectional study was conducted between April and June 2020. 40 patients (23 female and 17 male) with COVID-19 and 42 healthy individuals (26 female and 16 male) were included in the study. The OCT scans were performed 4 weeks after the COVID-19 diagnosis. Results: In the COVID-19 group, in the right eyes, the mean nasal choroidal thickness was 295.70 +/- 7,046 mu m (p = 0.017), mean subfoveal choroidal thickness was 333.25 +/- 6,353 mu m (p = 0.003), mean temporal choroidal thickness was 296.63 +/- 6,324 mu m (p = 0.039), and mean RNFL was 89.23 +/- 1.30 mu m (p = 0.227). In the left eyes, mean nasal choroidal thickness was 287.88 +/- 9,033 mu m (p = 0.267), mean subfoveal choroidal thickness was 333.80 +/- 9,457 mu m (p = 0.013), mean temporal choroidal thickness was 298.50 +/- 9,158 mu m (p = 0.079), and mean RNFL was 89.48 +/- 1,289 mu m (p = 0.092). Compared with the control group, the patient group had significant thickening of the choroidal thickness in all quadrants of the right eyes, and significant thickening of the subfoveal choroidal thickness in the left eyes. There was no significant difference in the RNFL thickness between groups (p > 0.05). Conclusion: COVID-19 may cause a subclinical involvement in the choroidal layer.
ABSTRACT
Beyond pulmonary presentation, COVID-19 infection can manifest with a variety of both acute and chronic neurologic and neuropsychiatric (concomitant) symptoms and diseases. Nonspecific symptoms such as headache, fatigue, olfactory and gustatory disturbance have been reported more frequently, and severe disease such as encephalopathy, encephalitis, and cerebrovascular events have been reported relatively rarely. The heterogeneity of neurologic and neuropsychiatric presentations is large, as well as the range of recorded prevalences. Older patients, pre-existing neurologic and non neurologic comorbidities and severe COVID-19 disease were associated with increased risk of severe neurologic complications and higher in-hospital mortality. Probable neurotropic pathomechanisms of SARS-CoV2 have been discussed, but a multifactorial genesis of neurologic/neuropsychiatric symptoms and disease beyond these is likely.