Novel application of large bore aspiration in the treatment of COVID-19 associated acute limb ischemia using the penumbra CAT 12 lightning aspiration system

COVID-19 associated cardiovascular complications have been well documented throughout the pandemic and are associated with higher rates of morbidity and mortality. Hypercoagulable states resulting from systemic inflammation have been associated with increasing incidences of acute myocardial infarctions (AMI) and acute limb ischemia (ALI). Herein, we present a case of AMI complicated by ALI in a patient with COVID-19 in which aspiration thrombectomy using the Penumbra CAT 12 thrombectomy catheter was used in the management of acute popliteal artery occlusion.

Novel application of large bore aspiration in the treatment of COVID-19 associated acute limb ischemia using the penumbra CAT 12 lightning aspiration system.

COVID-19 associated cardiovascular complications have been well documented throughout the pandemic and are associated with higher rates of morbidity and mortality. Hypercoagulable states resulting from systemic inflammation have been associated with increasing incidences of acute myocardial infarctions (AMI) and acute limb ischemia (ALI). Herein, we present a case of AMI complicated by ALI in a patient with COVID-19 in which aspiration thrombectomy using the Penumbra CAT 12 thrombectomy catheter was used in the management of acute popliteal artery occlusion.

Evaluating the efficacy and safety of SpikoGen®, an Advax-CpG55.2-adjuvanted severe acute respiratory syndrome coronavirus 2 spike protein vaccine: a phase 3 randomized placebo-controlled trial.

OBJECTIVES: We sought to investigate the efficacy and safety of SpikoGen®, a subunit coronavirus disease 2019 (COVID-19) vaccine composed of a recombinant severe acute respiratory syndrome coronavirus 2 spike protein with Advax-CpG55.2™ adjuvant. METHODS: This randomized, placebo-controlled, double-blind, phase 3 trial was conducted on 16 876 participants randomized (3:1) to receive two intramuscular doses of SpikoGen® or a saline placebo 21 days apart. The primary outcome was to assess the efficacy of SpikoGen® in preventing symptomatic COVID-19. Secondary outcomes included safety assessments and evaluation of SpikoGen® vaccine's efficacy in preventing severe COVID-19. The study aimed for 147 COVID-19 symptomatic cases. RESULTS: Overall, 12 657 and 4219 participants were randomized to the SpikoGen® and placebo group and followed for a median of 55 days (interquartile range, 48-60 days) and 51 days (interquartile range, 46-58 days) after 14 days of the second dose, respectively. In the final per-protocol analysis, the number of COVID-19 cases was 247 of 9998 (2.4%) in the SpikoGen® group and 119 of 3069 (3.8%) in the placebo group. This equated to a vaccine efficacy of 43.99% (95% CI, 30.3-55.0%). The efficacy was calculated to be 44.22% (95% CI, 31.13-54.82%) among all participants who received both doses. From 2 weeks after the second dose, 5 of 9998 (0.05%) participants in the SpikoGen® group and 6 of 3069 (0.19%) participants in the placebo group developed severe COVID-19, equating to a vaccine efficacy against severe disease of 77.51% (95% CI, 26.3-93.1%). The SpikoGen® vaccine was well tolerated. DISCUSSION: A 2-dose regimen of SpikoGen® reduced the rate of COVID-19 and severe disease in the wave of the Delta variant.

Analysis of medicinal and therapeutic potential of Withania somnifera derivatives against COVID-19.

Apart from chemical and allopathic drugs, several medicinal plants contain phytochemicals that are potentially useful to counter the COVID-19 pandemic. Withania somnifera (Ashwagandha), which has a good effect on some viral infections, can be considered as a candidate against the virus. In the present study, thirty-nine natural compounds of Ashwagandha were investigated in terms of their binding to the important drug targets to treat the COVID-19. Although the molecular docking calculations reveal the binding affinities of the compounds to Mpro, TMPRSS2, NSP15, PLpro, Spike RBD + ACE2, RdRp and NSP12 as targets in controlling the coronavirus enzymes, Withanoside II is expected to be the most effective compound due to the high affinity in binding with many of considered targets. Furthermore, the Withanoside III, IV, V, X, and XI have favorable binding affinities as ligands with respect to the MM/GBSA calculations. The molecular dynamics simulations MD explore a stable hydrogen bond network between ligands and the active sites residues. Also, the dynamic fluctuations of the binding site residues verify their tight binding to ligands. Moreover, the stability of ligand-protein complexes is approved by the RMSD ranges lower than 0.5 Å in equilibration zone for all mentioned complexes. The TMPRSS2-Withanolide Q and Mpro-Withanoside IV complexes are the most stable pairs using the MM/GBSA calculations and MD simulation.

Developing Cytokine Storm-Sensitive Therapeutic Strategy in COVID-19 Using 8P9R Chimeric Peptide and Soluble ACE2.

Currently, the COVID-19 pandemic is an international challenge, largely due to lack of effective therapies. Pharmacotherapy has not yet been able to find a definitive treatment for COVID-19. Since SARS-CoV-2 affects several organs, treatment strategies that target the virus in a wider range are expected to be ultimately more successful. To this end, a two-step treatment strategy has been presented. In the first phase of the disease, when the patient is newly infected with the virus and the cytokine storm has not yet been developed, a chimeric peptide is used to inhibit virus entry into the host cell cytosol (by inhibiting endosomal pH acidification) and viral replication. After the virus entry and decrease of angiotensin converting enzyme 2 (ACE2) level, some people are unable to properly compensate for the ACE2 pathway and progress toward the cytokine storm. In the beginning of the cytokine storm, sACE2 protein is very effective in regulating the immune system toward the anti-inflammatory pathway, including M2 macrophages. Hence, the genes of 8P9R chimeric peptide and sACE2 would be inserted in an episomal vector with a separate promoter for each gene: the chimeric peptide gene promoter is a CMV promoter, while the sACE2 gene promoter is a NF-κB-sensitive promoter. The NF-κB-sensitive promoter induces the expression of sACE2 gene soon after elevation of NF-κB which is the main transcription factor of inflammatory genes. Thus, as the expression of inflammatory cytokines increases, the expression of sACE2 increases simultaneously. In this condition, sACE2 can prevent the cytokine storm by inhibiting the pro-inflammatory pathways. To deliver the designed vector to the target cells, mesenchymal stem cell-derived (MSC-derived) exosome-liposome hybrids are used. Herein, the strategy can be considered as a personalized clinical therapy for COVID-19, that can prevent morbidity and mortality in the future.

COVID-19 and psoriasis: biologic treatment and challenges.

BACKGROUND: There is concern about susceptibility of psoriatic patients on biologics to coronavirus disease 2019 (COVID-19) and its clinical course. PURPOSE: The aims of present review were to determine whether the biologic treatment of psoriasis increases the risk of SARS-CoV-2 infection and if biologics affect the clinical course of COVID-19 in these patients. METHODS: We searched database of MEDLINE (PubMed) for key term of psoriasis biologic and COVID-19 until June 9, 2020 and all published 14 papers and an experience from Iran (10509 cases) related to the psoriatic patients on biologics and COVID-19 along with relevant papers were summarized. In spite of limitation in some reports, due to some of strengths that will be discussed, all papers were included in this review. RESULTS: According to 8769 medical reports around 0.3% of psoriatic patients had COVID-19 and the rate of hospitalization was 0.1%. No death due to COVID-19 was reported among 10509 patients. Reports indicated psoriatic patients on biologics were not more susceptible to COVID-19 and the severe clinical course of disease. CONCLUSION: While there is not definitive controlled trial data, the available evidence suggests that patients with psoriasis without COVID-19 can continue the biologic therapy for psoriasis.