Coronaviruses - drug discovery and therapeutic options Zumla, Alimuddin; Chan, Jasper F W; Azhar, Esam I ...
Nature reviews. Drug discover/Nature reviews. Drug discovery,
05/2016, Letnik:
15, Številka:
5
Journal Article
Recenzirano
Odprti dostop
In humans, infections with the human coronavirus (HCoV) strains HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as the ...common cold. By contrast, the CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which were discovered in Hong Kong, China, in 2003, and in Saudi Arabia in 2012, respectively, have received global attention over the past 12 years owing to their ability to cause community and health-care-associated outbreaks of severe infections in human populations. These two viruses pose major challenges to clinical management because there are no specific antiviral drugs available. In this Review, we summarize the epidemiology, virology, clinical features and current treatment strategies of SARS and MERS, and discuss the discovery and development of new virus-based and host-based therapeutic options for CoV infections.
Severe acute respiratory syndrome coronavirus (SARS-CoV), emerged from China and rapidly spread worldwide. Over 8098 people fell ill and 774 died before the epidemic ended in July 2003. Bats are ...likely an important reservoir for SARS-CoV. SARS-like CoVs have been detected in horseshoe bats and civet cats. The main mode of transmission of SARS-CoV is through inhalation of respiratory droplets. Faeco-oral transmission has been recorded. Strict infection control procedures with respiratory and contact precautions are essential. Fever and respiratory symptoms predominate, and diarrhea is common. Treatment involves supportive care. There are no specific antiviral treatments or vaccines available.
The epidemic of severe acute respiratory syndrome (SARS) had a significant effect on global society in the early 2000s and the potential of its resurgence exists. Studies on the modes of transmission ...of SARS are limited though a number of outbreak studies have revealed the possible airborne route. To develop more specific and effective control strategies, we conducted a detailed mechanism-based investigation that explored the role of fomite transmission in the well-known Ward 8A outbreak. We considered three hypothetical transmission routes, i.e., the long-range airborne, fomite and combined routes, in 1,744 scenarios with combinations of some important parameters. A multi-agent model was used to predict the infection risk distributions of the three hypothetical routes. Model selection was carried out for different scenarios to compare the distributions of infection risk with that of the reported attack rates and select the hypotheses with the best fitness. Our results reveal that under the assumed conditions, the SARS coronavirus was most possible to have spread via the combined long-range airborne and fomite routes, and that the fomite route played a non-negligible role in the transmission.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a novel single-stranded, positive-sense RNA betacoronavirus (MERS-CoV). Dromedary camels, hosts for ...MERS-CoV, are implicated in direct or indirect transmission to human beings, although the exact mode of transmission is unknown. The virus was first isolated from a patient who died from a severe respiratory illness in June, 2012, in Jeddah, Saudi Arabia. As of May 31, 2015, 1180 laboratory-confirmed cases (483 deaths; 40% mortality) have been reported to WHO. Both community-acquired and hospital-acquired cases have been reported with little human-to-human transmission reported in the community. Although most cases of MERS have occurred in Saudi Arabia and the United Arab Emirates, cases have been reported in Europe, the USA, and Asia in people who travelled from the Middle East or their contacts. Clinical features of MERS range from asymptomatic or mild disease to acute respiratory distress syndrome and multiorgan failure resulting in death, especially in individuals with underlying comorbidities. No specific drug treatment exists for MERS and infection prevention and control measures are crucial to prevent spread in health-care facilities. MERS-CoV continues to be an endemic, low-level public health threat. However, the virus could mutate to have increased interhuman transmissibility, increasing its pandemic potential.
Abstract Context Routine symptom assessment represents the cornerstone of symptom management. Edmonton Symptom Assessment System (ESAS) is one of the first quantitative symptom assessment batteries ...that allows for simple and rapid documentation of multiple patient-reported symptoms at the same time. Objective To discuss the historical development of ESAS, its current uses in different settings, and future developments. Methods Narrative review. Results Since its development in 1991, ESAS has been psychometrically validated and translated into over 20 languages. We will discuss the variations, advantages, and limitations with ESAS. From the clinical perspective, ESAS is now commonly used for symptom screening and longitudinal monitoring in patients seen by palliative care, oncology, nephrology, and other disciplines in both inpatient and outpatient settings. From the research perspective, ESAS has offered important insights into the nature of symptom trajectory, symptom clusters, and symptom modulators. Furthermore, multiple clinical studies have incorporated ESAS as a study outcome and documented the impact of various interventions on symptom burden. On the horizon, multiple groups are actively investigating further refinements to ESAS, such as incorporating it in electronic health records, using ESAS as a trigger for palliative care referral, and coupling ESAS with personalized symptom goals to optimize symptom response assessment. Conclusion ESAS has evolved over the past 25 years to become an important symptom assessment instrument in both clinical practice and research. Future efforts are needed to standardize this tool and explore its full potential to support symptom management.
The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or ...vaccinated individuals to understand potential loss of protection against infection by Omicron. We previously established that a 50% plaque reduction neutralization antibody titer (PRNT
) ≥25.6 in our live virus assay corresponded to the threshold for 50% protection from infection against wild-type (WT) SARS-CoV-2. Here we show markedly reduced serum antibody titers against the Omicron variant (geometric mean titer (GMT) < 10) compared to WT virus 3-5 weeks after two doses of BNT162b2 (GMT = 218.8) or CoronaVac vaccine (GMT = 32.5). A BNT162b2 booster dose elicited Omicron PRNT
titers ≥25.6 in 88% of individuals (22 of 25) who previously received 2 doses of BNT162b2 and 80% of individuals (24 of 30) who previously received CoronaVac. However, few (3%) previously infected individuals (1 of 30) or those vaccinated with three doses of CoronaVac (1 of 30) met this threshold. Our findings suggest that countries primarily using CoronaVac vaccines should consider messenger RNA vaccine boosters in response to the spread of Omicron. Studies evaluating the effectiveness of different vaccines against the Omicron variant are urgently needed.
IMPORTANCE: Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains ...uncertain. OBJECTIVES: To determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. Postoperative monitoring included nocturnal pulse oximetry and measurement of cardiac troponin concentrations. EXPOSURES: Obstructive sleep apnea was classified as mild (respiratory event index REI 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Proportional-hazards analysis was used to determine the association between obstructive sleep apnea and postoperative cardiovascular complications. RESULTS: Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 SD, 9 years; 40.2% women) were included in the analyses. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio HR, 1.49 95% CI, 1.19-2.01; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 95% CI, 1.49-3.34; P = .001) and not among those with moderate OSA (adjusted HR, 1.47 95% CI, 0.98-2.09; P = .07) or mild OSA (adjusted HR, 1.36 95% CI, 0.97-1.91; P = .08) (P = .01 for interaction). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 95% CI, 15.5-27.7 minutes) was longer than in those without (10.2 95% CI, 7.8-10.9 minutes) (P < .001). No significant interaction effects on perioperative outcomes were observed with type of anesthesia, use of postoperative opioids, and supplemental oxygen therapy. CONCLUSIONS AND RELEVANCE: Among at-risk adults undergoing major noncardiac surgery, unrecognized severe obstructive sleep apnea was significantly associated with increased risk of 30-day postoperative cardiovascular complications. Further research would be needed to assess whether interventions can modify this risk.
During the major outbreak of SARS-CoV infection in 2003, a randomized controlled trial showed that early use of hydrocortisone was associated with a higher plasma SARS-CoV viral load with delayed ...viral clearance compared with a control group that received normal saline (6).In patients hospitalized with influenza A (H7N9) viral pneumonia in China, an observational study has shown that high-dose corticosteroid therapy (defined as .150 mg/d methylprednisolone equivalent) was associated with increased risks in 30-day mortality (38.5% vs. 7.7%, P = 0.021) and 60-day mortality (50% vs. 15.4%, P = 0.022) and longer viral shedding (15 vs. 13 d, P = 0.039), whereas there was no difference between low-dose (25-150 mg/d methylprednisolone) and control subjects (8)....in a subgroup analysis among patients with PaO2/FIO2, 300 mm Hg, low to moderate dose of corticosteroid treatment (equivalent to 25-150 mg/d of methylprednisolone) significantly decreased both 30-day mortality (adjusted hazard ratio aHR, 0.49; 95% CI, 0.32-0.77) and 60-day mortality (aHR, 0.51; 95% CI, 0.33-0.78), whereas high-dose (.150 mg/d) corticosteroid therapy yielded no difference (9).More clinical studies, preferably with a randomized controlled trial design with a standardized treatment and serial viral sampling protocol, are needed to evaluate more scientifically the role of interferon, lopinavir, passive immunotherapy such as monoclonal/polyclonal antibodies, and systemic corticosteroids in the clinical management of MERS-CoV infection. n Author disclosures are available with the text of this article at www.atsjournals.org.
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