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Emerging viral pathogens include newly discovered viruses as well as previously known viruses that are either increasing, or threatening to increase in incidence. While often first identified in the general population, they may affect transplant recipients, in whom their manifestations may be atypical or more severe. Enhanced molecular methods have increased the rate of viral discovery but have not overcome the problem of demonstrating pathogenicity. At the same time, improved clinical diagnostic methods have increased the detection of reemerging viruses in immunocompromised patients. In this review, we first discuss viral diagnostics and the developing field of viral discovery and then focus on rare and emerging viruses in the transplant population: human T-cell leukemia virus type 1; hepatitis E virus; bocavirus; KI and WU polyomaviruses; coronaviruses HKU1 and NL63; influenza, H1N1; measles; dengue; rabies; and lymphocytic choriomeningitis virus. Detection and reporting of such rare pathogens in transplant recipients is critical to patient care and improving our understanding of posttransplant infections. |
Severe acute respiratory syndrome (SARS) is a highly infectious, rapidly progressive, emerging disease. Early diagnosis and preventive measures are key for treatment and minimization of secondary spread. In the context of the armed forces, aggressive containment measures are essential to prevent an outbreak. In this study, we present the first reported case, to our knowledge, of SARS in a naval diver. The special physical requirements for divers and the potential complications associated with deep sea diving necessitate extensive investigation before certification of fitness for diving after SARS. In the early recovery period, potential problems during diving are caused by inadequate lung ventilation in relation to exercise level and increased breathing resistance attributable to weak respiratory muscles, with corresponding risk of hypoxia and hypercapnia, as well as decreased ability to respond to nonrespiratory problems during diving. Problems in the late recovery period include increased risk of diving complications (such as pulmonary barotrauma) resulting from fibrosis and scarring within the lung parenchyma, which are known complications of SARS. From our experience, we suggest that computed tomographic scans of the thorax, lung function tests, and careful follow-up monitoring should play a vital role in the assessment of patients during the convalescent period, before certification of fitness to dive. |
AIM: In addition to respiratory symptoms, COVID‐19 can present with gastrointestinal complaints suggesting possible faeco‐oral transmission. The primary aim of this review was to establish the incidence and timing of positive faecal samples for SARS‐CoV‐2 in patients with COVID‐19. METHODS: A systematic literature review identified studies describing COVID‐19 patients tested for faecal virus. Search terms for MEDLINE included ‘clinical’, ‘faeces’, ‘gastrointestinal secretions’, ‘stool’, ‘COVID‐19’, ‘SARS‐CoV‐2’ and ‘2019‐nCoV’. Additional searches were done in the American Journal of Gastroenterology, Gastroenterology, Gut, Lancet Gastroenterology and Hepatology, the World Health Organization Database, the Centre for Evidence‐Based Medicine, New England Journal of Medicine, social media and the National Institute for Health and Care Excellence, bioRxiv and medRxiv preprints. Data were extracted concerning the type of test, number and timing of positive samples, incidence of positive faecal tests after negative nasopharyngeal swabs and evidence of viable faecal virus or faeco‐oral transmission of the virus. RESULTS: Twenty‐six relevant articles were identified. Combining study results demonstrated that 53.9% of those tested for faecal RNA were positive. The duration of faecal viral shedding ranged from 1 to 33 days after a negative nasopharyngeal swab with one result remaining positive 47 days after onset of symptoms. There is insufficient evidence to suggest that COVID‐19 is transmitted via faecally shed virus. CONCLUSION: There is a high rate of positive polymerase chain reaction tests with persistence of SARS‐CoV‐2 in faecal samples of patients with COVID‐19. Further research is needed to confirm if this virus is viable and the degree of transmission through the faeco‐oral route. This may have important implications on isolation, recommended precautions and protective equipment for interventional procedures involving the gastrointestinal tract. |
BACKGROUND: 3,181,642 cases and 224,301 deaths in 212 regions of the world—this is the status of COVID-19 (Coronavirus Disease 2019) pandemic as of May 1, 2020. This pandemic has managed to overwhelm the health care system of the most advanced countries in the world. As the whole of the medical fraternity stands robed as health care professionals to fight against COVID-19, specialty emergencies like trauma continue to pester the already overburdened health care community. This situation calls for the need for a pandemic response protocol (PREP) in each specialty that helps the doctors to manage specialty emergencies without chaos and at the same time allowing them to play their part in pandemic management. CONCLUSION: PREP as an integrated pragmatic approach is essential in containing pandemics as they need international cooperation at various levels starting from knowledge sharing to monetary support. PREP which is in line with the WHO action plan, will be an essential minimum response of a non-frontline pandemic response specialty like orthopedics to combat and curtail the effects of a pandemic in a multispecialty tertiary health care centre. |
Molecular analysis of respiratory viruses and the host response to both infection and vaccination have transformed our understanding of these ubiquitous pathogens. Polymerase chain reaction for the rapid and accurate diagnosis of viral infections has led to a better understanding of the epidemiology and impact of many common respiratory viruses and resulted in better patient care. Over the past decade a number of new respiratory viruses including human metapneumovirus and new coronaviruses have been discovered using molecular techniques such as random primer amplification, pan-viral array and next generation sequencing. Analysis of the host transcriptional response during respiratory viral infection using in-vitro, animal models and natural and experimental human challenge have furthered the understanding of the mechanisms and predictors of severe disease and may identify potential therapeutic targets to prevent and ameliorate illness. |
One of the main challenges of the measures against the COVID-19 epidemic is to reduce the amplitude of the epidemic peak without increasing without control its timescale. We investigate this problem using the SIR model for the epidemic dynamics, for which reduction of the epidemic peak I(P) can be achieved only at the price of increasing the time t(P) of its occurrence and its entire time-span t(E). By means of a time reparametrization we linearize the equations for the SIR dynamics. This allows us to solve exactly the dynamics in the time domain and to derive the scaling behaviour of the size, the timescale and the speed of the epidemics, by reducing the infection rate α and by increasing the removal rate β by a factor of λ. We show that for a given value of the size (I(P), the total, I(E) and average [Formula: see text] number of infected), its occurrence time t(P) and entire time-span t(E) can be reduced by a factor 1/λ if the reduction of I is achieved by increasing the removal rate instead of reducing the infection rate. Thus, epidemic containment measures based on tracing, early detection followed by prompt isolation of infected individuals are more efficient than those based on social distancing. We apply our results to the COVID-19 epidemic in Northern Italy. We show that the peak time t(P) and the entire time span t(E) could have been reduced by a factor 0.9 ≤ 1/λ ≤ 0.34 with containment measures focused on increasing β instead of reducing α. |
BACKGROUND: There is limited information on SARS‐CoV‐2 infection clustering within families with children. We aimed to study the transmission dynamics of SARS‐CoV‐2 within families with children in Greece. METHODS: We studied 23 family clusters of COVID‐19. Infection was diagnosed by RT‐PCR in respiratory specimens. The level of viral load was categorized as high, moderate, or low based on the cycle threshold values. RESULTS: There were 109 household members (66 adults and 43 children). The median attack rate per cluster was 60% (range: 33.4%‐100%). An adult member with COVID‐19 was the first case in 21 (91.3%) clusters. Transmission of infection occurred from an adult to a child in 19 clusters and/or from an adult to another adult in 12 clusters. There was no evidence of child‐to‐adult or child‐to‐child transmission. In total 68 household members (62.4%) tested positive. Children were more likely to have an asymptomatic SARS‐CoV‐2 infection compared to adults (40% versus 10.5%, p‐value=0.021). In contrast, adults were more likely to develop a severe clinical course compared to children (8.8% versus 0%, p‐value=0.021). In addition, infected children were significantly more likely to have a low viral load while adults were more likely to have a moderate viral load (40.7% and 18.5% versus 13.8% and 51.7%, respectively; p‐value=0.016). CONCLUSIONS: While children become infected by SARS‐CoV‐2, they do not appear to transmit infection to others. Furthermore, children more frequently have an asymptomatic or mild course compared to adults. Further studies are needed to elucidate the role of viral load on these findings. This article is protected by copyright. All rights reserved. |
Morbidity and mortality from bovine respiratory disease (BRD) and associated losses in performance and carcass merit continue to plague the beef cattle industry. Several viral/bacterial agents are responsible for BRD, and interactions occur among the agents. Viral agents often predispose animals to bacterial infections, and Mannheimia haemolytica is the most frequently isolated organism in cattle with BRD. Laboratory tests are available to characterize organisms causing BRD using easily obtained nasal swab samples. Testing for persistent infection with bovine viral diarrhea virus can be done by a 2-stage technique using PCR and immunohistochemistry. Preconditioning programs that include preweaning viral vaccination programs along with castration could have a significant influence on decreasing BRD in the cattle feeding industry. Metaphylactic antibiotic programs continue to be effective; however, antibiotic resistance is a public concern, and additional management options (e.g., direct-fed microbials or other compounds with antimicrobial properties) deserve attention. Diets with an increased energy concentration achieved by decreasing the dietary roughage concentration may slightly increase the rate of BRD morbidity; however, these diets also increase ADG, DMI, and G:F compared with lower-energy, greater-roughage diets. The extent to which performance and BRD morbidity are affected by dietary protein concentration needs further study, but low and high protein concentrations should probably be avoided. Several trace minerals (e.g., Cu, Se, and Zn) affect immune function, but the effects of supplementation on performance and immune function in model challenge systems and in field studies are equivocal. Adding vitamin E to receiving diets at pharmacological levels (e.g., >1,000 IU·animal(−1)·day(−1)) seems beneficial for decreasing BRD morbidity, but it has little effect on performance. Given the limited ability to consistently modify immune function and BRD morbidity through dietary manipulations, we recommend that the diets for newly received cattle be formulated to adjust nutrient concentrations for low feed intake and to provide optimal performance during the receiving period. |
The infection of a novel coronavirus found in Wuhan of China (2019-nCoV) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for 2019-nCoV, various strategies are being tested in China, including drug repurposing. In this study, we used our pretrained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of 2019-nCoV. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing a inhibitory potency with Kd of 94.94 nM against the 2019-nCoV 3C-like proteinase, followed by efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of 2019-nCoV with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra, could be used for the treatment of 2019-nCoV, although there is no real-world evidence supporting the prediction. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for 2019-nCoV. |
Bronchiolitis is the first lower respiratory tract viral infection manifesting in infants younger than 12 months of age. Our aim was to evaluate clinical and serological differences in infants with bronchiolitis from a single or from multiple viruses. Our secondary aim was to investigate differences in recurrent wheezing episodes after 12‐24‐36 months of follow‐up. We reviewed the clinical records for 486 full‐term infants hospitalized for bronchiolitis with at least one virus detected in the nasopharyngeal aspirate. In 431 (88.7%) patients one virus was detected and in 55 (11.3%) infants more than one virus was found. No differences were observed in the length of hospitalization, clinical severity score, O(2) supplementation or admission to the intensive care unit. Single virus was associated with higher serum C‐reactive protein (C‐RP) than infants with multiple viruses and higher blood neutrophil counts. Respiratory syncytial virus (RSV) was the most frequently detected virus. RSV alone was associated with higher C‐RP (P = 0.007), compared to RSV coinfection. Infants with human rhinovirus (hRV) alone had higher white blood cell counts, higher blood neutrophils, and higher serum C‐RP levels than hRV co‐infection (P = 0.029, P = 0.008, P = 0.008). RSV + hRV, the most frequent co‐infection, was associated with lower neutrophil count and lower C‐RP levels (P = 0.008, P = 0.016) and less fever (P = 0.012), when comparing RSV versus hRV versus RSV + hRV. No differences were found in the frequency of recurrent wheezing between single versus multiple viruses after bronchiolitis. Our findings suggest that in infants with bronchiolitis multiple viral co‐infections can occur, without influence in the clinical severity of the disease. Infants with co‐infection seems to mount a lower inflammatory response. |
Abstract Recombinase polymerase amplification (RPA) is a highly sensitive and selective isothermal amplification technique, operating at 37–42°C, with minimal sample preparation and capable of amplifying as low as 1–10 DNA target copies in less than 20 min. It has been used to amplify diverse targets, including RNA, miRNA, ssDNA and dsDNA from a wide variety of organisms and samples. An ever increasing number of publications detailing the use of RPA are appearing and amplification has been carried out in solution phase, solid phase as well as in a bridge amplification format. Furthermore, RPA has been successfully integrated with different detection strategies, from end-point lateral flow strips to real-time fluorescent detection amongst others. This review focuses on the different methodologies and advances related to RPA technology, as well as highlighting some of the advantages and drawbacks of the technique. |
Ion channels of viruses (viroporins) represent a common type of protein targets for drugs. The relative simplicity of channel architecture allows convenient computational modeling and enables virtual search for new inhibitors. In this review, we analyze the data published over the last 10 years on known ion channels of viruses that cause socially significant diseases. The effectiveness of inhibition by various types of heterocyclic compounds of the viroporins of influenza virus, hepatitis С virus, human immunodeficiency virus, human papillomaviruses, coronaviruses, and respiratory syncytial virus is discussed. The presented material highlights the promise held by the search for heterocyclic antiviral compounds that act by inhibition of viroporins. |