Rapamycin golden jubilee and still the miraculous drug: a potent immunosuppressant, antitumor, rejuvenative agent, and potential contributor in COVID-19 treatment

Although celebrating its golden jubilee, rapamycin’s importance keeps increasing by the day. Starting as a promising antifungal agent, then as a potent immunosuppressant, strong anticancer drug, and now rapamycin is attracting serious attention as a rejuvenative agent and a possible contributor in treating this era pandemic, COVID-19. Due to its diverse biological activities and promising medical applications, we aimed in this review to put rapamycin under the spot and highlight its discovery, famous microbial producers, reported biological activities, chemical structure, famous analogues, and biosynthesis. Moreover, discuss some rapamycin production approaches including solid-state fermentation, and stressing out producing strain. On the other hand, describe its action mechanism and trials to use it in treatment of COVID-19. Additionally, we highlighted some of the side effects accompanying its use, and describe some approaches reported to minimize these undesired effects. Finally, we report the current status of rapamycin and its analogues in global market, and discuss future prospects of this potent drug.

Multi-Classification of Chest X-rays for COVID-19 Diagnosis Using Deep Learning Algorithms

Accurate detection of COVID-19 is of immense importance to help physicians intervene with appropriate treatments. Although RT-PCR is routinely used for COVID-19 detection, it is expensive, takes a long time, and is prone to inaccurate results. Currently, medical imaging-based detection systems have been explored as an alternative for more accurate diagnosis. In this work, we propose a multi-level diagnostic framework for the accurate detection of COVID-19 using X-ray scans based on transfer learning. The developed framework consists of three stages, beginning with a pre-processing step to remove noise effects and image resizing followed by a deep learning architecture utilizing an Xception pre-trained model for feature extraction from the pre-processed image. Our design utilizes a global average pooling (GAP) layer for avoiding over-fitting, and an activation layer is added in order to reduce the losses. Final classification is achieved using a softmax layer. The system is evaluated using different activation functions and thresholds with different optimizers. We used a benchmark dataset from the kaggle website. The proposed model has been evaluated on 7395 images that consist of 3 classes (COVID-19, normal and pneumonia). Additionally, we compared our framework with the traditional pre-trained deep learning models and with other literature studies. Our evaluation using various metrics showed that our framework achieved a high test accuracy of 99.3% with a minimum loss of 0.02 using the LeakyReLU activation function at a threshold equal to 0.1 with the RMSprop optimizer. Additionally, we achieved a sensitivity and specificity of 99 and F1-Score of 99.3% with only 10 epochs and a 10−4 learning rate.

Out of Hospital Cardiac Arrest: Saudi Red Crescent Experience Throughout COVID-19 Era.

PURPOSE: The quality of resuscitation for out hospital cardiac arrest (OHCA) during the COVID-19 era could be affected. We aim to describe prehospital healthcare providers' resuscitative efforts for OHCA cases and their definitive outcomes. PATIENTS AND METHODS: This retrospective cross-sectional study included all OHCA cases between April and June 2021 across all regions in the Kingdom of Saudi Arabia (KSA). Demographic variables, response times, CPR providers, initial rhythm, use of AED/Defibrillator, medical interventions, ROSC data, and dispatch codes were extracted from a central electronic platform. RESULTS: A total of 1307 OHCA cases were included in this study, males constituted 65% and 42% were ≥65 years. Although the median response time to initiate CPR was 13 min, 11% of OHCA cases had a response time between 0 and 6 min. About 75% of CPR was provided on scene by BLS units, 78% of OHCA cases had asystole as their initial rhythm, an AED/Defibrillator was used more than 90% of the time for pulseless VT/VF rhythm, and ROSC was achieved in 8% of OHCA patients. CONCLUSION: During the COVID-19 pandemic, maintaining resuscitative efforts for OHCA continues in KSA. Closing knowledge gaps in the community and a better description of OHCA for the dispatcher could guide dispatch-assisted CPR and minimize OHCA response times.

A Colorimetric Test to Differentiate Patients Infected with Influenza from COVID-19.

Patients infected with SARS-CoV-2 and influenza display similar symptoms, but treatment requirements are different. Clinicians need to accurately distinguish SARS-CoV-2 from influenza to provide appropriate treatment. Here, the authors develope a color-based technique to differentiate between patients infected with SARS-CoV-2 and influenza A using a nucleic acid enzyme-gold nanoparticle (GNP) molecular test requiring minimal equipment. The MNAzyme and GNP probes are designed to be robust to viral mutations. Conserved regions of the viral genomes are targeted, and two MNAzymes are created for each virus. The ability of the system to distinguish between SARS-CoV-2 and influenza A using 79 patient samples is tested. When detecting SARS-CoV-2 positive patients, the clinical sensitivity is 90%, and the specificity is 100%. When detecting influenza A, the clinical sensitivity and specificity are 93% and 100%, respectively. The high clinical performance of the MNAzyme-GNP assay shows that it can be used to help clinicians choose effective treatments.

So much nuance: A qualitative analysis of parental perspectives on child passenger safety.

OBJECTIVE: To explore barriers and facilitators to optimal child restraint system (CRS) use for diverse parents of newborn infants and to obtain input from parents on the use of technology-assisted remote car seat checks as tools for promoting optimal CRS use. METHODS: Parents were recruited using purposive sampling. Interviews were conducted with English- or Spanish-speaking parents with a full term newborn and regular access to a car. Interviews were conducted by phone, and recorded and transcribed verbatim. Interviews were conducted until thematic saturation was reached. Data were organized for analysis using Atlas.ti, and codes grouped by theme using constant comparison. RESULTS: 30 parents were enrolled. Barriers and facilitators to optimal CRS use were classified into three themes, as were thoughts on the pros and cons regarding remote car seat checks. Themes on barriers and facilitators included motor vehicle and CRS features (such as age and size of the motor vehicle and presence of the Lower Anchors and Tethers for Children LATCH system), resources (availability, accessibility, and accuracy of resources), and parental factors (parental emotions and characteristics). Themes related to pros and cons of remote car seat checks included the ability (and challenge) of remote car seat checks to identify and correct errors, the potential use of remote car seat checks in certain situations (such as CRS transitions and periods of growth), and convenience of remote car seat checks (including increased availability and ease of access). Subthemes with further detail were arranged within each theme identified. CONCLUSION: From a parent perspective, there are several identified barriers and facilitators of optimal CRS use. Although car seat checks were identified as a resource, in-person accessibility was an issue, and there were mixed opinions on technology-assisted remote car seat checks. These results provide a foundation for additional study on targeted interventions, including remote interventions for which there is an increased need due to the COVID-19 pandemic.

Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease.

ABSTRACT: There are conflicting data regarding the use of hydroxychloroquine (HCQ) in COVID-19 hospitalized patients. The objective of this study was to assess the efficacy of HCQ in increasing SARS-CoV-2 viral clearance.Hospitalized adult patients with confirmed SARS-CoV-2 infection were retrospectively included in the study. The primary outcome was the time from a confirmed positive nasopharyngeal swab to turn negative. A negative nasopharyngeal swab conversion was defined as a confirmed SARS-CoV-2 case followed by 2 negative results using RT-PCR assay with samples obtained 24 hours apart. Multiple linear regression analysis was used to adjust for potential confounders.Thirty-four confirmed COVID-19 patients completed the study. Nineteen (55.9%) patients presented with symptoms, and 14 (41.2%) had pneumonia. Only 21 (61.8%) patients received HCQ. The time to SARS-CoV-2 negativity nasopharyngeal test was significantly longer in patients who received HCQ than those who did not receive HCQ [17 (13-21) vs 10 (4-13) days, P = .023]. HCQ was independently associated with time to negativity test after adjustment for potential confounders (symptoms, comorbidities, antiviral drugs, pneumonia, or oxygen therapy) in multivariable Cox proportional hazards regression analysis (hazard ratio = 0.33, 95% confidence interval: 0.13-0.9, P = .024). On day 14, 47.8% (14/23) patients tested negative in the HCQ group compared with 90.9% (10/11) patients who did not receive HCQ (P = .016).HCQ was associated with a slower viral clearance in COVID-19 patients with mild to moderate disease. Data from ongoing randomized clinical trials with HCQ should provide a definitive answer regarding the efficacy and safety of this treatment.

Renal Transplant Recipient with Concurrent COVID-19 and Stenotrophomonas maltophilia Pneumonia Treated with Trimethoprim/Sulfamethoxazole Leading to Acute Kidney Injury: A Therapeutic Dilemma.

BACKGROUND Although coronavirus disease 2019 (COVID-19) manifests primarily as a lung infection, its involvement in acute kidney injury (AKI) is gaining recognition and is associated with increased morbidity and mortality. Concurrent infection, which may require administration of a potentially nephrotoxic agent, can worsen AKI and lead to poor outcomes. Stenotrophomonas maltophilia is a multidrug-resistant gram-negative bacillus associated with nosocomial infections, especially in severely immunocompromised and debilitated patients. Trimethoprim/sulfamethoxazole combination (TMP/SMX) is considered the treatment of choice but can itself lead to AKI, posing a significant challenge in the management of patients with concomitant COVID-19 and S. maltophilia pneumonia. CASE REPORT A 64-year-old male with end-stage renal disease and post renal transplant presented with severe respiratory symptoms of COVID-19 and was intubated upon admission. His renal functions were normal at the time of admission. The patient subsequently developed superimposed bacterial pneumonia with S. maltophilia requiring administration of TMP/SMX. However, TMP/SMX led to the development of AKI, which continued to worsen despite appropriate management including hemodialysis. This coincided with and most likely resulted in the patient's clinical deterioration and ultimate death. CONCLUSIONS The etiology of kidney disease involvement in patients with COVID-19 is still evolving and appears to be multifactorial. The condition can significantly worsen especially when nephrotoxic agents are given, probably due to a cumulative or synergistic effect. Great caution should be taken when administering nephrotoxic agents in the setting of COVID-19 as it can lead to adverse patient outcomes.