mteb/CovidQA huggingface dataset:
diagnostic setting. New closed-system technologies which involve only minimal hands-on time (a few minutes) and that conduct both automated nucleic acid extraction and PCR for multiple pathogens are now available, but are currently limited for clinical diagnostic purposes due to low-throughput capabilities. 83 Next-generation sequencing technologies and PCR-based analyses with increasing sensitivity both offer considerable scope in diagnosis, although our current understanding of the clinical impact of pathogens at low levels or the presence of variants as minor virus populations is limited. Providing low-cost, sensitive assays for diagnosing respiratory virus infections in low/middle-income countries is challenging, but has the potential to improve treatment and avoid unnecessary antibiotic use in these regions.
Repurposed drugs for respiratory viral infections Nitazoxanide (NTX) is an antiparasitic agent approved for Giardia and Cryptosporidium infections that also inhibits replication in vitro of influenza and other respiratory viruses. 84 Treatment with NTX 600 mg twice daily for 5 days was associated with a reduction in the duration of symptoms in participants with acute uncomplicated influenza. 85 In a subset analysis of 238 patients with no confirmed virus infection, treatment with NTX 600 mg also led to a shorter time to alleviation of symptoms in comparison to placebo (88Á4 versus 105Á7 hours, P = 0Á02). 86 Systemic corticosteroids for respiratory virus infections A review of prospective observational studies has shown that SC increased the risks of mortality and morbidity (e.g. secondary infections, hospital-acquired pneumonia) in severe infection due to influenza A(H1N1)pdm09 especially with delayed antiviral therapy. 87 During SARS infections, a higher risk of avascular necrosis
and prolonged virus shedding were observed in patients who had received highdose SC therapy. 88 It is therefore important to avoid the use of high-dose SC in severe respiratory viral infections outside the context of clinical trials. Larger trials are needed to resolve the uncertainty regarding the effect of early SC therapy in ARDS. Low-dose SC is indicated for management of refractory septic shock, 89 and a short course of SC is indicated for acute exacerbations of obstructive airway diseases (asthma, COPD) 90 Current evidence does not support a clinically relevant effect of systemic or inhaled glucocorticoids on admission or length of hospitalisation for acute viral bronchiolitis in infants and young children. 91
Respiratory syncytial virus, influenza viruses, parainfluenza (PIV) viruses and adenoviruses (AdVs) cause the most serious disease in immunocompromised hosts, but other respiratory viruses are becoming increasingly appreciated as a cause of both upper and lower respiratory tract disease. The potential for these viruses to cause lower respiratory tract infections (LRTI) after transplantation varies. Human metapneumovirus infections have similar outcomes to RSV infection in hematopoietic stem cell transplant (HSCT) recipients, including potentially severe and fatal pneumonia. HRV and coronavirus infections are very frequent in transplant recipients, but severe lower respiratory tract disease is uncommon.
In a prospective study of 112 lung transplant recipients, the virus infection rates upon screening, routine and emergency visits were 14%, 15% and 34%, respectively. Picornaviruses were identified most frequently in nasopharyngeal (85/140; 61%) and BAL specimens (20/34; 59%). Asymptomatic virus carriage, mainly of picornaviruses, was found at 10% of screening visits. Infections were associated with transient lung function loss and high calcineurin inhibitor blood levels. The hospitalisation rate was 50% for influenza and PIV and 16Á9% for other viruses. Acute rejection was not associated with virus infection. 92 The risk factors for severe LRTI among transplant recipients include early onset post-transplant (<3 m), steroid boluses, young children (<1 year), chronic GVHD, lymphopenia/lymphodepletion and allogeneic HSCT patients. 92 Influenza Immunocompromised patients with influenza exhibit more complications, longer virus shedding and more antiviral resistance, while often
demonstrating milder clinical symptoms and signs on initial clinical assessment. 93 Influenza A (H1N1)pdm09 viruses have the potential for rapid emergence of oseltamivir resistance and causing severe morbidity, particularly in immunocompromised patients with lymphopenia and delayed antiviral therapy. 94 Influenza viraemia may serve as a marker for overall poor outcome with increased risk of progression to LRTI, hypoxaemia, respiratory failure and death. Influenza RNA in blood (viraemia) was detected in nine of 79 (11Á4%) HSCT recipients with influenza. Among patients with LRTI, viraemia was associated with increased hazards of overall as well as influenzaassociated death (hazard ratio 3Á5, 1Á1-12). 95 In 143 HSCT recipients with documented seasonal influenza infection, treatment with high-dose corticosteroids was associated with a trend towards prolonged virus shedding [(OR), 3Á3; 95% CI 1Á0-11; P = 0Á05], whereas antiviral therapy initiated to treat upper respiratory tract infection
(URTI) was associated with fewer cases of LRTI (OR, 0Á04; 95% CI, 0-0Á2; P < 0Á01) and fewer hypoxaemia episodes (OR, 0Á3; 95% CI, 0Á1-0Á9; P = 0Á03). 96 In view of the risks of prolonged replication and drug resistance emergence, 97 a longer duration and a higher NAI dose may be beneficial. Early therapy was consistently demonstrated to have improved outcomes. [98] [99] [100] [101] Other treatment options under study are the use of triple combination therapy with amantadine, oseltamivir and ribavirin, 102 or intravenous peramivir 103 or zanamivir. 104 Therapy of influenza in lung transplant recipients is associated with a reduced risk of developing bronchiolitis obliterans syndrome. 105 Parainfluenza DAS181 is inhibitory for PIV and influenza viruses, including those resistant to the amantadine and NAIs 106 and may be effective in treating immunocompromised patients with severe PIV lung disease. 107 In a study of four severely immunocompromised children with PIV disease treatment
with DAS181 for 5-10 days, by dry powder inhalation or nebulisation, was well tolerated. Transient increase in serum alkaline phosphatase, liver function and coagulation tests were observed, but nasal wash virus loads were reduced in all patients within 1 week with improved clinical features. 108
In a RCT of lung transplant recipients with RSV infection, the incidence of new or progressive bronchiolitis obliterans syndrome at day 90 was significantly reduced in 16 patients who received a small interfering RNA against the RSV Ngene (ALN-RSV01) compared with placebo (n = 8) (6Á3% versus 50%, P = 0Á027). 109 In a larger follow-up multicentre phase IIb study, treatment with ALN-RSV01 showed a greater than eightfold reduced risk in developing bronchiolitis obliterans syndrome at day 180. 110
Adenovirus is a serious, often fatal infection in immunocompromised patients, especially in HSCT recipients. The control of AdV is mostly T-cell mediated, and therefore, patients who have received T-cell suppressive regimens are at an increased risk for AdV infection. The annual incidence of AdV infections in HSCT recipients ranges from 5% to 50%, and is increasing, likely due to increased use of T-celldepleted allografts and cord blood as source. The mortality rate is up to 80%. 111 Brincidofovir (BCV; formerly CMX-001) is an orally bioavailable lipid-conjugate of cidofovir (CDV) that provides high intracellular concentrations of CDV diphosphate with a long intracellular half-life (up to 4-6Á5 days). BCV is 65-fold more potent against AdV than CDV in vitro with a low risk of myeloidor nephrotoxicity, but gastrointestinal side effects are more common. 112 In a retrospective study of 13 immunocompromised patients given BCV for AdV disease after failing or intolerance to i.v. cidofovire
nine patients (69Á2%) demonstrated a virological response (VR), which was defined as a 99% drop from baseline or undetectable AdV DNA in serum by week 8. Patients with VR had longer survival than those without VR (median 196 days versus 54Á5 days; P = 0Á04). 113
Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054964/

SHA: 77b0c98d1a2ca46b219ad090074814c387c80d8f

Authors: Chen, Weilie; Lan, Yun; Yuan, Xiaozhen; Deng, Xilong; Li, Yueping; Cai, Xiaoli; Li, Liya; He, Ruiying; Tan, Yizhou; Deng, Xizi; Gao, Ming; Tang, Guofang; Zhao, Lingzhai; Wang, Jinlin; Fan, Qinghong; Wen, Chunyan; Tong, Yuwei; Tang, Yangbo; Hu, Fengyu; Li, Feng; Tang, Xiaoping
Date: 2020-02-26
DOI: 10.1080/22221751.2020.1732837
License: cc-by
Abstract: The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.
Text: The 2019 novel coronavirus (2019-nCoV), originally outbreaking from Wuhan China, has transmitted in an extremely short period to 25 countries and infected over 31 000 individuals as of Feb 06, 2020, causing an international alarm. Basic scientific research has achieved significantly in the investigation of viral origination [1, 2] , transmission and evolution [3] , and unprecedented public health control actions in China have been activated and effectively prevented the otherwise dramatic spread. The 2019-nCoV virus seems more infectious in its public transmission capacity compared to the well-known 2003 SARS virus in spite of the unavailability of convincingly scientific evidence. The mechanism of viral transmission is still worthy of further exploration.
Currently, one urgent and critical challenge is to treat infected patients and save their lives. Several studies have roughly described the overall clinical features of 2019-nCoV patients [4, 5] . However, the more specific and classified clinical characteristics of the infected patients still require further investigation, particularly for those with severe symptoms, which is roughly estimated to be approximately 15-20 percent of totally confirmed cases based on the local data in our hospital. Clinically, for those severe patients, the main symptoms of 2019-nCoV pneumonia are fever, decreased white blood cell and lymphocyte count, increased C reaction protein and abnormally expressed cytokines [6] .
One remaining question to be resolved is whether the 2019-nCoV virus can replicate in extra-pulmonary sites, which might account for the deteriorated clinical manifestation. In this study, we investigated whether the patients with severe clinical symptoms exhibited special profiles of virus replication or/and distribution compared to those only with mild symptoms.
Patients, who were confirmed to be infected by the 2019-nCoV virus, were firstly enrolled in or transferred to Guangzhou Eighth People's Hospital for treatment purposes. This study followed the guideline of the Ethics Committee of Guangzhou Eighth People's Hospital. All blood, pharyngeal swab, and anal swab samples were collected for diagnostic purposes in the laboratory and our study added no extra burden to patients. Viral RNA was extracted with Nucleic Acid Isolation Kit (Da'an Gene Corporation, Cat: DA0630) on an automatic workstation Smart 32 (Da'an Gene Corporation) following the guidelines. Real-time reverse transcriptional polymerase chain reaction (RT-PCR) reagent (Da'an Gene cooperation, Cat DA0930) was employed for viral detection per the protocol. In brief, two PCR primer and probe sets, which target orf1ab (FAM reporter) and N (VIC reporter) genes separately, were added in the same reaction tube. Positive and negative controls were included for each batch of detection.
Samples were considered to be viral positive when either or both set(s) gave a reliable signal(s).
All patients had pneumonia-based diseases but with diversified clinical manifestation. To simplify data analysis, the patients were only classified as either mild or severe clinical symptom groups based on the guideline newly released by Chinese government. Patients who were with at least one of the following symptom should be diagnosed to be severe case, 1) distress of respiratory with respiratory rate > = 30/min; 2) Oxygen saturation < = 93% in the rest state, and 3) arterial oxygen tension (PaO₂) over inspiratory oxygen fraction (FIO₂) of less than 300 mm Hg. In the blood detection cohort (Figure 1 (A)), patients who had at less one serum sample measurement with the PCR method were included. In the 57, 6 cases were detected to be blood positive, all of them (100%) were severe in symptom requiring special care attention, and the blood of the rest 51 cases was without detectable virus in the blood, only 12 of them (23.5%) were severe cases. The ratio of severe symptoms between these
two groups was significantly different (p value = 0.0001). In the anal swab cohort (Figure 1 (B)), 11 of 28 cases were detected to be anal swab positive, 8 of them (72.7%) were with severe symptoms, which was significantly higher than that 4 (23.5%) of the rest 17 cases without detectable virus in anal were severe cases.
Fortunately, two cases with detectable virus both in blood and anal swab cohort were recorded. Patient 1 (Figure 2 (A)) was admitted to ICU after enrollment evaluation and was highly suspected infection with 2019-nCoV because of his recent travelling from Wuhan and of confirmed pneumonia by radiographic diagnosis with 5-day fever and 1-day continuous dry coughing. He was then confirmed to be infected by the 2019-nCoV virus on illness day 6 by CDC. High concentrations of the viral RNA were detected in the pharyngeal swabs on illness days 5 (Ct = 17 + 25), 7, 8 (Ct = 25 + 26), and 11 (Ct = 15 + 25). In the blood, no viral RNA was detected on day 5 but the sample on day 6 gave a weak positive signal (Ct = Neg+39), and then the signal was gone again on day 8. On day 9, a low level of viral RNA (Ct = 36 + 41) was detected again in the blood. On day 12, the blood lost signal again. A high concentration of virus RNA (Ct = 23 + 27) was detected in the anal sample on day 13, on the day the
2019-nCoV virus was not detected in the pharyngeal swab. Unfortunately, he was transferred out to another hospital after an emergency expert consultation.
Patient 2 (Figure 2 (B)), who had a clear infection history and started fever 5-day ago and dry coughing 2-day ago, was admitted with clinically highly suspect of 2019-nCoV infection, considering the radiographical diagnosis which indicated clear pneumonia in the bilateral lung lobes. The virus was detected in his blood on illness day 7 (Ct = 34 + 36) and 8 (Ct = 38 + 38). His infection was also informed by the CDC on day 8. Because his disease advanced very fast, he was transferred to the ICU ward for special medical care requirements on day 9, on which day high titers of virus (Ct = 25 + 36) were detected in the pharyngeal sample. Importantly, virus RNA was detected in all pharyngeal (Ct = 23 + 24), blood (Ct = 34 + 39) and anal (Ct = 24 + 29) samples on day 10. He was transferred out to another hospital after an emergency expert consultation.
Finally, we described here the four patients with detectable serum viral RNA. Patient 3 (Figure 3(A) ) was transferred to the ICU directly on illness day 11 because of his severe condition, the 2019-nCoV virus was laboratory detected both in pharyngeal (Ct = 30 + 30) and blood samples (Ct = 37 + 39) on day 12, And his infection was confirmed by CDC on day 13. Pharyngeal samples were PCR positive on days 14 and 17 and became negative on day 22. Patient 4 (Figure 3(B) ) was transferred to the ICU ward on the illness day 6 with a CDC confirmation. His disease advanced pretty fast and became severe on day 7 and he was transferred to ICU after his blood sample was detected to be virus-positive (Ct = 32 + 37). On day 9, he was transferred out. Patient 5 (Figure 3(C) ) was admitted on illness day 4 and his blood sample was virus-positive (Ct = 38 + Neg) on day 6. Her disease progressed rapidly to a severe stage within the next 3 days. Patient 6 ( Figure 3 (D)) with a clear history of virus
infection was confirmed to be infected on infection day 7. Viral RNA was detected in his blood sample on day 9, one day ahead of his transfer into ICU. As his condition worsens, he was transferred out on day 13.
In this retrospective study, we analyzed the PCR data of virus detection in different tissues in our laboratory. Firstly, our observation indicated that the presence of viral RNA outside of the respiratory tract might herald the severity of the disease and alarm the requirement of special care. In the blood test cohort, all the 6 infected patients were in (or later progressed to) severe disease stage when serum viral RNA became detectable, which showed a significant difference compared to the blood negative group (p = 0.0001). Patient 2 (Figure 2(B) ), 5 (Figure 3 (C)) and 6 ( Figure 3(D) ) all had detectable viral RNA in the serum before they progressed to the clinical severe symptom stage. Unfortunately, we missed the earlier time points of patient 1 (Figure 2(A) ) and 3 (Figure 3(A) ) who were directly admitted to ICU on transfer to our hospital because of severe condition, of patient 4 (Figure 3(B) ) who had serum sample collected one day post the diagnosis of severe illness. We,
fortunately, observed high serum viral load in serum within their severe illness stage. In the anal swab cohort, we found that the presence of virus RNA in the anal digestive tract was also positively correlated with disease severity (p = 0.0102). The 3 patients detected with anal virus RNA but in mild stage should be monitored whether they will progress to the severe stage. We have summarized the information of approximately 70 percent of the patients in Guangzhou city, and the study represented nearly the whole picture of this region. However, the virus outbroke in such an emergence, allowing no delay in waiting for more patients to further confirm the findings.
Secondly, a high concentration of viral RNA in anal swabs suggested the digestive tract might be one extrapulmonary site for virus replication. For patient 1, a high concentration of viral RNA (Ct = 23 + 27, on day 13) was detected in anal swab but not in pharyngeal (the same day) and blood (1 d ahead). For patient 2, higher concentrations of viral RNAs were detected in anal swab (Ct = 24 + 39) and pharyngeal swab (Ct = 23 + 24) than in the blood (Ct = 34 + 39) on the same day. Angiotensin-converting enzyme 2 (ACE2) still is one of the receptors for 2019-nCoV attachment and entry [2] . Intensive structural analysis of the S protein of 2019-nCoV with the SARS-Coronavirus suggested that several critical residues in the viral spike protein might confer favourable interaction with human ACE2 [7] . Of note, ACE2 is also abundantly present in humans in the epithelia of the small intestine besides the respiratory tract and is ubiquitously present in endothelial cells [8] , which might
provide possible routes of transmission, and might account for the high transmission capacity of the new virus. We propose that rampant coronavirus replication in pulmonary alveolus results in the breakdown of the alveolar vessel and the subsequent virus leakage into the blood flow, through which the virus is disseminated across the whole body. Then the virus succeeds in establishing reinfection in the digestive tract by using the highly expressed ACE2 receptor, which exacerbated the disease vice versa. Bat originated coronavirus was found to replicate in the swine digestive tract recently, also suggesting the potential replication possibility in the human digestive tract [9] . Nevertheless, confirmation of virus transmission through the digestive tract warrants further virus isolation from the anal swab in high safety level lab.
Unfortunately, in our study, we did not collect stool samples from patients and did not pursue viral RNA in the stool. But we believe the existence of virus RNA in the stool samples from these patients because that a large amount of viral RNA was detected in anal swabs and that viral RNA had also been detected in a case reported from the United States [10] . Also, we didn't collect sputum and bronchoalveolar lavage fluid for virus detection because that the dry coughing characteristic of patients infected with 2019-nCoV prevents producing enough amount of sputum and that bronchoalveolar lavage fluid collection requires a sophisticated operation which increases virus exposure possibility of care providers to high concentrations of virus-containing aerosol.
In summary, we find that the presence of viral RNA in the blood and anal swab is positively correlated with the severe disease stage and that early monitoring of virus RNA in blood and the digestive tract on top of the respiratory tract might benefit the disease prediction.
‘Tiny Iceland’ preparing for Ebola in a globalized world

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507955/

SHA: efd94d1135c5ee11c2af624b344881e079a5ce7a

Authors: Gunnlaugsson, Geir; Hauksdóttir, Íris Eva; Bygbjerg, Ib Christian; Pinkowski Tersbøl, Britt
Date: 2019-05-07
DOI: 10.1080/16549716.2019.1597451
License: cc-by
Abstract: Background: The Ebola epidemic in West Africa caused global fear and stirred up worldwide preparedness activities in countries sharing borders with those affected, and in geographically far-away countries such as Iceland. Objective: To describe and analyse Ebola preparedness activities within the Icelandic healthcare system, and to explore the perspectives and experiences of managers and frontline health workers. Methods: A qualitative case study, based on semi-structured interviews with 21 staff members in the national Ebola Treatment Team, Emergency Room at Landspitali University Hospital, and managers of the response team. Results: Contextual factors such as culture and demography influenced preparedness, and contributed to the positive state of mind of participants, and ingenuity in using available resources for preparedness. While participants believed they were ready to take on the task of Ebola, they also had doubts about the chances of Ebola ever reaching Iceland.
Yet, factors such as fear of Ebola and the perceived stigma associated with caring for a potentially infected Ebola patient, influenced the preparation process and resulted in plans for specific precautions by staff to secure the safety of their families. There were also concerns about the teamwork and lack of commitment by some during training. Being a ‘tiny’ nation was seen as both an asset and a weakness in the preparation process. Honest information sharing and scenario-based training contributed to increased confidence amongst participants in the response plans. Conclusions: Communication and training were important for preparedness of health staff in Iceland, in order to receive, admit, and treat a patient suspected of having Ebola, while doubts prevailed on staff capacity to properly do so. For optimal preparedness, likely scenarios for future global security health threats need to be repeatedly enacted, and areas plagued by poverty and fragile healthcare systems require global