Epigenetic Targets and Pathways Linked to SARS-CoV-2 Infection and Pathology.

The scale at which the SARS-CoV-2/COVID-19 pandemic has spread remains enormous. Provided the genetic makeup of the virus and humans is readily available, the quest for knowing the mechanism and epidemiology continues to prevail across the entire scientific community. Several aspects, including immunology, molecular biology, and host-pathogen interaction, are continuously being dug into for preparing the human race for future pandemics. The exact reasons for vast differences in symptoms, pathophysiological implications of COVID-infections, and mortality differences remain elusive. Hence, researchers are also looking beyond traditional genomics, proteomics, and transcriptomics approach, especially entrusting the environmental regulation of the genetic landscape of COVID-human interactions. In line with these questions lies a critical process called epigenetics. The epigenetic perturbations in both host and parasites are a matter of great interest to unravel the disparities in COVID-19 mortalities and pathology. This review provides a deeper insight into current research on the epigenetic landscape of SARS-CoV-2 infection in humans and potential targets for augmenting the ongoing investigation. It also explores the potential targets, pathways, and networks associated with the epigenetic regulation of processes involved in SARS-CoV-2 pathology.

Tools to Alleviate the Drug Resistance in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen's favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb, the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.

The Saudi Critical Care Society practice guidelines on the management of COVID-19 in the ICU: Therapy section.

BACKGROUND: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). METHODS: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. RESULTS: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. CONCLUSION: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.

Quarantine COVID-19 compliance in families with an allergic and immunological diseased child and its psychological impact in KSA

Background: With the onset of the spread of the Coronavirus around the world, the Saudi Ministry of Health has taken protective measures early to prevent the spread of the disease in the region, and the most effective of these measures is Quarantine and home isolation, which can have an impact on the individual's mental health. The purpose of this study is to assess the compliance of Quarantine in a family with an allergic and immunologically diseased child and its psychological impact on them. Methods: A cross-sectional study conducted between June-August 2020 was conducted via a selfreported online questionnaire that includes fear of COVID-19 scale for parents, Revised children's anxiety and depression scale to assess Quarantine's psychological effect, fear of getting the infection and also to know the family's attitude towards COVID-19 and public health measures. Results: This study included 4,436 participants, and the findings revealed that (13.3%) of participants had a child with allergies or immune diseases, (30.2%) had children between 6-10 years of age, the mean fear score was 18.74 ± 6.48 (7-35) which is nearly moderate;the mean values of the Child Anxiety and Depression Sub-Scale for Parents (RCADS) were 4.81 5.61 and 18.74 ± 6.48, respectively. This study showed a highly statistically significant positive relationship between the mean values for fear of COVID-19 Score scale and mean scores for child anxiety and depression (P = <0.001), and also showed that 73.8% of the families thought that quarantine is a necessary action that should continue until the end of the Pandemic. Conclusion: The Quarantine impacted psychologically and financially on some parents. Children are also more vulnerable to psychological effects resulting from the commitment of families to Quarantine, so we see that special attention and care is needed to prevent these effects on them, especially children with allergic or immune diseases. [ABSTRACT FROM AUTHOR] Copyright of Middle East Journal of Family Medicine is the property of Medi+WORLD International Pty. Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Alterations in the Plasma Proteome Induced by SARS-CoV-2 and MERS-CoV Reveal Biomarkers for Disease Outcomes for COVID-19 Patients.

PURPOSE: This study aimed to understand the pathophysiology of host responses to infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/(COVID-19) and Middle East respiratory syndrome coronavirus (MERS-CoV) and to identify proteins for patient stratification with different grades of illness severity. PATIENTS AND METHODS: Peripheral blood samples from 43 patients with different grades of COVID-19, 7 MERS-CoV patients admitted to the ICU, and 10 healthy subjects were analyzed using label-free quantitative liquid chromatography-mass spectrometry (LC-MS). RESULTS: We identified 193 and 91 proteins that differed significantly between COVID-19 and MERS-CoV sample groups, respectively, and 49 overlapped between datasets. Only 10 proteins are diagnostic of asymptomatic cases, 12 are prognostic of recovery from severe illness, and 28 are prognostic of a fatal outcome of COVID-19. These proteins are implicated in virus-specific/related signaling networks. Notable among the top canonical pathways are humoral immunity, inflammation, acute-phase response signaling, liver X receptor/retinoid X receptor (LXR/RXR) activation, coagulation, and the complement system. Furthermore, we confirmed positive viral shedding in 11.76% of 51 additional peripheral blood samples, indicating that caution should be taken to avoid the possible risk of transfusion of infected blood products. CONCLUSION: We identified COVID-19 and MERS-CoV protein panels that have potential as biomarkers and might assist in the prognosis of SARS-CoV-2 infection. The identified markers further our understanding of COVID-19 disease pathophysiology and may have prognostic or therapeutic potential in predicting or managing host cell responses to human COVID-19 and MERS-CoV infections.

SARS-CoV-2 Viral Load Is Correlated With the Disease Severity and Mortality in Patients With Cancer.

The correlation between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and risk of disease severity in cancer patients is poorly understood. Given the fact that cancer patients are at increased risk of severe coronavirus disease 2019 (COVID-19), analysis of viral load and disease outcome in COVID-19-infected cancer patients is needed. Here, we measured the SARS-CoV-2 viral load using qPCR cycle threshold (Ct) values collected from 120 noncancer and 64 cancer patients' nasopharyngeal swab samples who are admitted to hospitals. Our results showed that the in-hospital mortality for high viral load cancer patients was 41.38%, 23.81% for medium viral load and 14.29% for low viral load patients (p < -0.01). On the other hand, the mortality rate for noncancer patients was lower: 22.22% among patients with high viral load, 5.13% among patients with medium viral load, and 1.85% among patients with low viral load (p < 0.05). In addition, patients with lung and hematologic cancer showed higher possibilities of severe events in proportion to high viral load. Higher attributable mortality and severity were directly proportional to high viral load particularly in patients who are receiving anticancer treatment. Importantly, we found that the incubation period and serial interval time is shorter in cancer patients compared with noncancer cases. Our report suggests that high SARS-CoV-2 viral loads may play a significant role in the overall mortality and severity of COVID-19-positive cancer patients, and this warrants further study to explore the disease pathogenesis and their use as prognostic tools.

Safety and Efficacy of Convalescent Plasma for Severe COVID-19: Interim Report of a Multicenter Phase II Study from Saudi Arabia.

OBJECTIVE: To present the interim findings from a national study investigating the safety and efficacy of convalescent plasma (CP) containing detectable IgG antibodies as a treatment strategy for severe coronavirus disease 2019 (COVID-19). TRIAL DESIGN AND PARTICIPANTS: An open label, two-arm, phase-II clinical trial conducted across 22 hospitals from Saudi Arabia. The intervention group included 40 adults (aged ≥18 years) with confirmed severe COVID-19 and the control group included 124 patients matched using propensity score for age, gender, intubation status, and history of diabetes and/or hypertension. Intervention group included those (a) with severe symptoms (dyspnea; respiratory rate, ≥30/min; SpO2, ≤93%, PaO2/FiO2 ratio, <300; and/or lung infiltrates >50% within 24-48 h), (b) requiring intensive care unit (ICU) care or (c) experiencing life-threatening conditions. The control group included confirmed severe COVID-19 patients of similar characteristics who did not consent for CP infusion or were not able to receive CP due to its nonavailability. INTERVENTIONS: The intervention group participants were infused 300 ml (200-400 ml/treatment dose) CP at least once, and if required, daily for up to 5 sessions, along with receiving the best standard of care. The control group only received the best standard of care. OUTCOMES: The primary endpoints were safety and ICU length of stay (LOS). The secondary endpoints included 30-day mortality, days on mechanical ventilation and days to clinical recovery. RESULTS: CP transfusion did not result in any adverse effects. There was no difference in the ICU LOS (median 8 days in both groups). The mortality risk was lower in the CP group: 13% absolute risk reduction (P = 0.147), hazard ratio (95% confidence interval): 0.554 (0.299-1.027; P = 0.061) by log-rank test. There was no significant difference in the days on mechanical ventilation and days to clinical recovery. CONCLUSION: CP containing detectable antibodies is a safe strategy and may result in a decrease in mortality in patients with severe COVID-19. The results of the completed trial with a larger study sample would provide more clarity if this difference in mortality is significant. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04347681; Saudi Clinical Trials Registry No.: 20041102.