Modulation of host epigenome by coronavirus infections and developing treatment modalities for COVID-19 beyond genetics.

The recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) outbreak has resulted in coronavirus disease 2019 (COVID-19) pandemic worldwide, affecting millions of lives. Although vaccines are presently made available, and vaccination drive is in progress to immunize a larger population; still the risk of SARS-CoV-2 infection and related mortality is persistent amid threats of the third wave of the ongoing pandemic. In the scenario of unavailability of robust and efficient treatment modalities, it becomes essential to understand the mechanism of action of the virus and deeply study the molecular mechanisms (both at the virus level and the host level) underlying the infection processes. Recent studies have shown that coronaviruses (CoVs) cause-specific epigenetic changes in the host cells to create a conducive microenvironment for replicating, assembling, and spreading. Epigenetic mechanisms can contribute to various aspects of the SARS-CoV-2 multiplication cycle, like expressing cytokine genes, viral receptor ACE2, and implicating different histone modifications. For SARS-CoV-2 infection, viral proteins are physically associated with various host proteins resulting in numerous interactions between epigenetic enzymes (i.e., histone deacetylases, bromodomain-containing proteins). The involvement of epigenetic mechanisms in the virus life cycle and the host immune responses to control infection result in epigenetic factors recognized as emerging prognostic COVID-19 biomarkers and epigenetic modulators as robust therapeutic targets to curb COVID-19. Therefore, this narrative review aimed to summarize and discuss the various epigenetic mechanisms that control gene expression and how these mechanisms are altered in the host cells during coronavirus infection. We also discuss the opportunities to exploit these epigenetic changes as therapeutic targets for SARS-CoV-2 infection. Epigenetic alterations and regulation play a pivotal role at various levels of coronavirus infection: entry, replication/transcription, and the process of maturation of viral proteins. Coronaviruses modulate the host epigenome to escape the host immune mechanisms. Therefore, host epigenetic alterations induced by CoVs can be considered to develop targeted therapies for COVID-19.

Healthcare-associated infections: the hallmark of Middle East respiratory syndrome coronavirus with review of the literature.

Middle East respiratory syndrome coronavirus (MERS-CoV) is capable of causing acute respiratory illness. Laboratory-confirmed MERS-CoV cases may be asymptomatic, have mild disease, or have a life-threatening infection with a high case fatality rate. There are three patterns of transmission: sporadic community cases from presumed non-human exposure, family clusters arising from contact with an infected family index case, and healthcare-acquired infections among patients and from patients to healthcare workers. Healthcare-acquired MERS infection has become a well-known characteristic of the disease and a leading means of spread. The main factors contributing to healthcare-associated outbreaks include delayed recognition, inadequate infection control measures, inadequate triaging and isolation of suspected MERS or other respiratory illness patients, crowding, and patients remaining in the emergency department for many days. A review of the literature suggests that effective control of hospital outbreaks was accomplished in most instances by the application of proper infection control procedures. Prompt recognition, isolation and management of suspected cases are key factors for prevention of the spread of MERS. Repeated assessments of infection control and monitoring of corrective measures contribute to changing the course of an outbreak. Limiting the number of contacts and hospital visits are also important factors to decrease the spread of infection.

Contraindicated drug-drug interactions associated with oral antimicrobial agents prescribed in the ambulatory care setting in the United States.

OBJECTIVES: Antimicrobial agents are commonly used in ambulatory care settings. Our objective was to examine national-level patterns of contraindications between oral antibacterial or antifungal agents and patients' other oral medications in the US ambulatory care setting. METHODS: This cross-sectional study included multiple year pooled data (2003-2011) from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey (NHAMCS Outpatient Department). Visits by adults (age ≥18 years) in ambulatory settings in the United States who were prescribed oral antibacterial or antifungal agents were evaluated for potential drug-drug interaction (DDI) contraindications. Findings with relative standard error >30% or unweighted sample size <30 were not reported because these were deemed unreliable estimates. RESULTS: From 2003 to 2011, there were 1 235 000 outpatient visits (proportion = 0.52%; 95% confidence interval (CI), 0.29-0.74) in which a patient was prescribed an antimicrobial agent associated with a contraindicated DDI. The most prevalent antimicrobials with contraindicated combination among outpatients were simultaneous use of macrolide-containing products (erythromycin or clarithromycin) with statin medication-containing products (simvastatin or lovastatin) (841 864 visits, proportion = 1.91%; 95% CI, 0.96-2.86). The next most common combination was use of fluoroquinolones with antiarrhythmic agents (amiodarone, sotalol, quinidine or procainamide) (365 622 visits, proportion = 0.19%; 95% CI, 0.06-0.32). CONCLUSIONS: Providers should be aware of potential contraindicated DDIs when prescribing antibiotics, especially macrolides and fluoroquinolones.

Evaluation of visual triage for screening of Middle East respiratory syndrome coronavirus patients.

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in September 2012 in Saudi Arabia had attracted the attention of the global health community. In 2017 the Saudi Ministry of Health released a visual triage system with scoring to alert healthcare workers in emergency departments (EDs) and haemodialysis units for the possibility of occurrence of MERS-CoV infection. We performed a retrospective analysis of this visual score to determine its sensitivity and specificity. The study included all cases from 2014 to 2017 in a MERS-CoV referral centre in Riyadh, Saudi Arabia. During the study period there were a total of 2435 suspected MERS cases. Of these, 1823 (75%) tested negative and the remaining 25% tested positive for MERS-CoV by PCR assay. The application of the visual triage score found a similar percentage of MERS-CoV and non-MERS-CoV patients, with each score from 0 to 11. The percentage of patients with a cutoff score of ≥4 was 75% in patients with MERS-CoV infection and 85% in patients without MERS-CoV infection (p 0.0001). The sensitivity and specificity of this cutoff score for MERS-CoV infection were 74.1% and 18.6%, respectively. The sensitivity and specificity of the scoring system were low, and further refinement of the score is needed for better prediction of MERS-CoV infection.

Using targeted solution tools as an initiative to improve hand hygiene: challenges and lessons learned.

The Joint Commission Centre for Transforming Healthcare's Web-based Targeted Solutions Tool (TST) for improving hand hygiene was implemented to elucidate contributing factors to low compliance rates of hand hygiene. Monitoring of compliance was done by trained unknown and known observers and rates of hospital-acquired infections were tracked and correlated against the changes in hand hygiene compliance. In total, 5669 of hand hygiene observations were recorded by the secret observers. The compliance rate increased from 75·4% at baseline (May-August 2014) to 88·6% during the intervention (13 months) and the control periods (P < 0·0001). Reductions in healthcare-associated infection rates were recorded for Clostridium difficle infections from 7·95 (CI 0·8937-28·72) to 1·84 (CI 0·02411-10·26) infections per 10 000 patient-days (P = 0·23), central line-associated blood-stream infections from 5·9 (CI 1·194-17·36) to 2·9 (0·7856-7·475) per 1000 device days (P = 0·37) and catheter-associated urinary tract infections from 5·941 (CI 1·194-17·36) to 0 per 1000 device days (P = 0·42). The top contributing factors for non-compliance were: improper use of gloves, hands full of supplies or medications and frequent entry or exit in isolation areas. We conclude that the application of TST allows healthcare organisations to improve hand hygiene compliance and to identify the factors contributing to non-compliance.

Hematologic, hepatic, and renal function changes in hospitalized patients with Middle East respiratory syndrome coronavirus.

BACKGROUND: There are no longitudinal data on the changes in hematologic, hepatic, and renal function findings in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. METHODS: This is a retrospective cohort study of 16 MERS-CoV patients, to describe the hematological, hepatic, and renal findings of patients with MERS-CoV. RESULTS: During the 21 days of observation, there was no significant change in the hepatic panel or creatinine tests. There was a significant increase in the mean ± SD of the white blood cell count from 8.3 ± 4.6 to 14.53 ± 7 (P value = 0.001) and an increase in mean ± SD of the absolute neutrophil count from 6.33 ± 4.2 to 12 ± 5.5 (P value = 0.015). Leukocytosis was observed in 31% (5/16) of the patients on day 1 and in 80% (4/5) on day 21. Transient leukopenia developed in 6% (1/16) of the patients on day 1 and in 13% (1/8) on day 8. None of the patients had neutropenia. Lymphopenia was a prominent feature with a rate of 44% (7/16) of the patients on day 1 and 60% (3/5) on day 21. Lymphocytosis was not a feature of MERS-CoV infection. Thrombocytopenia developed in 31% (5/16) of the patients on day 1 and 40% (2/5) on day 21. Thrombocytosis was not a prominent feature and was observed in 6% (1/16) of the patients on day 1 and 17% (1/6) on day 9. CONCLUSIONS: Patients with MERS-CoV infection showed variable hematologic parameters over time. Lymphocytosis and neutropenia were not features of MERS-CoV infection.

Potential risk for drug resistance globalization at the Hajj.

Antibiotics were once considered the miracle cure for infectious diseases. The tragedy would be the loss of these miracles as we witness increased antibiotic resistance throughout the world. One of the concerns during mass gatherings is the transmission of antibiotic resistance. Hajj is one of the most common recurring mass gatherings, attracting millions of people from around the world. The transmission of drug-resistant organisms during the Hajj is not well described. In the current review, we summarize the available literature on the transmission and acquisition of antibiotic resistance during the Hajj and present possible solutions.

Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study.

The Saudi Arabian Ministry of Health implemented a pro-active surveillance programme for Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV). We report MERS-CoV data from 5065 Kingdom of Saudi Arabia individuals who were screened for MERS-CoV over a 12-month period. From 1 October 2012 to 30 September 2013, demographic and clinical data were prospectively collected from all laboratory forms received at the Saudi Arabian Virology reference laboratory. Data were analysed by referral type, age, gender, and MERS-CoV real-time PCR test results. Five thousand and 65 individuals were screened for MER-CoV: hospitalized patients with suspected MERS-CoV infection (n = 2908, 57.4%), healthcare worker (HCW) contacts (n = 1695; 33.5%), and family contacts of laboratory-confirmed MERS cases (n = 462; 9.1%). Eleven per cent of persons tested were children (<17 years of age). There were 108 cases (99 adults and nine children) of MERS-CoV infection detected during the 12-month period (108/5065, 2% case detection rate). Of 108 cases, 45 were females (six children and 39 adults) and 63 were males (three children and 60 adults). Of the 99 adults with MERS-CoV infection, 70 were hospitalized patients, 19 were HCW contacts, and ten were family contacts. There were no significant increases in MERS-CoV detection rates over the 12-month period: 2.6% (19/731) in July 2013, 1.7% (19/1100) in August 2013, and 1.69% (21/1238) in September 2013. Male patients had a significantly higher MERS-CoV infection rate (63/2318, 2.7%) than females (45/2747, 1.6%) (p 0.013). MERS-CoV rates remain at low levels, with no significant increase over time. Pro-active surveillance for MERS-CoV in newly diagnosed patients and their contacts will continue.

Emerging respiratory and novel coronavirus 2012 infections and mass gatherings.

Mass gatherings are attended by an increasingly global audience and thus raise the concern of possible acute public health risks not normally encountered by the host population. The potential acute risks to individual and population health include communicable diseases. The communicable disease risks include emerging and re-emerging diseases in host and visiting populations. In this review, we provide an overview ofthe literature on respiratory infections at mass gatherings, then describe the impact of novel coronavirus 2012 (nCoV), an emerging respiratory disease virus, on the preparations for mass gathering. Although, nCoV emerged prior to the 2012 Hajj pilgrimage season, Muslims completed their religious duty without acquiring infections by nCoV. Clearly, the global nature of mass gatherings and their potential risks to international health make it imperative that research on such events and guidelines produced for their management are relevant to diverse contexts and are a collaborative effort between global experts.

New type F lineage-related Tn1546 and a vanA/vanB type vancomycin-resistant Enterococcus faecium isolated from patients in Dammam, Saudi Arabia during 2006-2007.

Knowledge regarding vancomycin-resistant enterococci (VRE) from Middle Eastern countries is scarce. We therefore investigated the antimicrobial resistance profiles and genetic relationships of VRE Enterococcus faecium isolates obtained from patients attending the King Fahad Specialist Hospital, Dammam, during 2006-2007. The predominant VRE comprised 20 vanB, five vanA and one vanA/vanB type isolates, which tended to fall into two genetic clusters that were identifiable phenotypically by their susceptibility to tetracycline. Multi-locus sequence typing of a random selection of isolates showed that they were part of clonal cluster 17, showing the importance of this genotype in nosocomial VRE infections in Saudi Arabia. Further analysis showed that four of the vanA genotype isolates possessed a new type F Tn1546 transposon, associated with IS1216V and IS1251. Finally, E. faecium vanA/B isolates are rarely reported in the clinical setting including in Saudi Arabia.

Emerging respiratory and novel coronavirus 2012 infections and mass gatherings

Mass gatherings are attended by an increasingly global audience and thus raise the concern of possible acute public health risks not normally encountered by the host population. The potential acute risks to individual and population health include communicable diseases. The communicable disease risks include emerging and re-emerging diseases in host and visiting populations. In this review, we provide an overview of the literature on respiratory infections at mass gatherings, then describe the impact of novel coronavirus 2012 [nCoV], an emerging respiratory disease virus, on the preparations for mass gathering. Although, nCoV emerged prior to the 2012 Hajj pilgrimage season, Muslims completed their religious duty without acquiring infections by nCoV. Clearly, the global nature of mass gatherings and their potential risks to international health make it imperative that research on such events and guidelines produced for their management are relevant to diverse contexts and are a collaborative effort between global experts

The Hajj: updated health hazards and current recommendations for 2012.

This year the Hajj will take place during 24-29 October. Recent outbreaks of Ebola haemorrhagic fever in Uganda and the Democratic Republic of the Congo, cholera in Sierra Leone, and infections associated with a novel coronavirus in Saudi Arabia and Qatar required review of the health recommendations of the 2012 Hajj. Current guidelines foresee mandatory vaccination with quadrivalent meningococcal vaccine for all pilgrims, and yellow fever and poliomyelitis vaccine for pilgrims from high-risk countries. Influenza vaccine is strongly recommended.

Radiographic manifestations of culture-positive pulmonary tuberculosis: cavitary or non-cavitary?

OBJECTIVE: To examine the radiographic pattern of patients with pulmonary tuberculosis (PTB) in Saudi Arabia and the relation of these findings to demographic and microbiological data. DESIGN: A retrospective hospital-based series of patients with culture-positive PTB. RESULTS: Among 168 cases of culture-positive PTB identified, 97 (57.7%) were males and 71 females (42.3%); 136 (81%) were Saudis and 19% were non-Saudis. The mean age was 52.3 +/- 19.2 years: nine (5.4%) were children aged 60 years. Overall, 121 (78%) had upper lobe infiltrates, 35 (19.7%) had cavitary lesions and 33 (19.6%) had both upper lobe infiltrate and cavitation. Lymphadenopathy and pleural effusion were each present in 11.3% of the patients. Patients aged >60 years were less likely to have upper lobe infiltrate (38/64, 59.4%) compared to children (7/9, 77.8%) and adults aged 19-60 years (76/95, 80%, P = 0.001). Diabetes mellitus was documented in 57/135 (42.2%) patients. There was no difference in the presence of upper lobe infiltrate and the presence of cavitation in patients with and without diabetes mellitus. CONCLUSION: Cavitary or upper lobe infiltrate remains a common presentation of PTB. As patients aged >60 years often present with no cavitation and without upper lobe infiltrate, it is important to keep in mind the possibility of tuberculosis in this group of patients.

Spontaneous remission of acute monocytic leukemia after infection with Clostridium septicum.

Spontaneous remissions of acute myeloid leukemia (AML) have been reported in association with infection. Here, we report a case of spontaneous remission of AML in a 47-year-old Saudi Arabian male patient who presented with a few weeks history of recurrent abdominal pain, vomiting and fever. He was diagnosed with acute monocytic leukemia (AML, FAB M5b) and a perforated bowel. He also had Clostridium septicum bacteremia and thus chemotherapy was deferred. He received supportive therapy and intravenous antibiotics. Six weeks later, he achieved spontaneous and complete remission lasting for about 4 months. The remission and relapse were documented by bone marrow examination. Similarly, previous reports of spontaneous remission of AML were short lived and were followed by relapse and progression.

Cryptococcus neoformans abscess and osteomyelitis in an immunocompetent patient with tuberculous lymphadenitis.

Infection with Cryptococcus neoformans usually occurs in immunocompromised hosts and may occur in immunocompetent patients. Of all cryptococcal infections, 10-40% of patients have no apparent immune deficiency. Disseminated disease may occur in up to 62% of HIV-seronegative patients with cryptococcosis; however, cryptococcal osteomyelitis is rare. Here, we report an immunocompetent patient with cryptococcal vertebral osteomyelitis and concomitant tuberculous lymphadenitis. The patient received 12 weeks of fluconazole and a 1-year course of anti-tuberculous agents, with complete recovery.