Assessment of QuantuMDx Q-POC Assay for Rapid Detection of SARS-CoV-2 Using Middle Turbinate Swabs.

Currently, a rapid detection of SARS-CoV-2 in clinical settings such as patients from emergency surgery is needed. The QuantuMDx Q-POC assay is a real-time-PCR test that was created for the rapid detection of SARS-CoV-2 in only 30 min. This study aimed to compare QuantuMDx Q-POC with our standard algorithm with Cobas 6800 for SARS-CoV-2 detection. The samples were run in parallel in both platforms. First, a comparison analysis was carried out. Second, the limit of detection was determinate in both platforms using a serial dilution of SARS-CoV-2 inactivated virus. A total of 234 samples were analyzed. For a Ct <30, the sensitivity and specificity was 100.0% and 92.5%, respectively. Positive predictive value was 86.2% and negative predictive value was 100.0%. Both COBAS 6800 and QuantuMDx Q-POC could detect up to 100 copies/mL. The QuantuMDx Q-POC system it is a reliable option when a rapid detection of SARS-CoV-2 is necessary. IMPORTANCE In different health care settings, such as patients from emergency surgery, rapid detection of SARS-CoV-2 is needed. The QuantuMDx Q-POC is an automatized fast workflow platform based on detection of three genes: two genes encoding structural proteins that can be used to differentiate SARS-CoV-2 from other coronavirus and a third target gene encoding a nonstructural region that is unique for SARS-CoV-2 such as the open reading frame (ORF1). This assay enables a rapid detection of SARS-CoV-2 with a high sensitivity in a short time frame (30 min). Therefore, QuantuMDx is a simple, rapid and easy SARS-CoV-2 detection test from direct middle nasal swabs.

Diagnostic Performance of Six Rapid Antigen Tests for SARS-CoV-2.

Microbiological diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a challenge. Although real-time reverse transcription PCR (RT-PCR) represents the gold standard method, strategies that allow rapid and simple diagnosis are necessary for the early identification of cases. In this study, we evaluated the diagnostic performance of six different commercial rapid antigen tests (Coronavirus antigen [Ag] rapid test cassette [Healgen Scientific, Houston, TX, USA], COVID-19 Ag FIA [Vircell, SD Biosensor Inc., Gyeonggi-do, Republic of Korea], Clinitest rapid COVID-19 antigen test [Siemens, Healthineers, Erlangen, Germany], SARS-CoV-2 rapid antigen test [SD Biosensor; Roche Diagnostics, Basel, Switzerland], Panbio COVID-19 Ag rapid test device [Abbott, Chicago, IL, USA], and SARS-CoV-2 test [MonLab, Barcelona, Spain]) in 130 nasopharyngeal swab samples tested previously by RT-PCR. The overall sensitivity of the rapid tests ranged from 65% to 79%, and the specificity was 100% for all of them. The sensitivity was higher for those samples with RT-PCR cycle threshold (CT) values below 25 and those from patients presenting within the first week of symptoms. The Siemens test showed the highest sensitivity for patients with high viral loads while the Vircell test performed better than the rest for CT values of ≥25. IMPORTANCE The rapid detection of people infected with SARS-CoV-2 is essential for a correct and effective control of the disease it causes. This process must be sensitive, fast, and simple, and it must be possible to carry out in any type of health center. Rapid antigen tests are the answer to this need. Knowing its ability to detect the virus in different stages of the disease is essential for a correct diagnosis, which is why this study has been carried out to evaluate the sensitivity and specificity of 6 different antigens tests in nasopharyngeal smear samples.

Genetic Study of SARS-CoV-2 Non Structural Protein 12 in COVID-19 Patients Non Responders to Remdesivir.

Remdesivir (RDV) was the first antiviral drug approved by the FDA to treat severe coronavirus disease-2019 (COVID-19) patients. RDV inhibits SARS-CoV-2 replication by stalling the non structural protein 12 (nsp12) subunit of the RNA-dependent RNA polymerase (RdRp). No evidence of global widespread RDV-resistance mutations has been reported, however, defining genetic pathways to RDV resistance and determining emergent mutations prior and subsequent antiviral therapy in clinical settings is necessary. This study identified 57/149 (38.3%) patients who did not respond to one course (5-days) (n = 36/111, 32.4%) or prolonged (5 to 20 days) (n = 21/38, 55.3%) RDV therapy by subgenomic RNA detection. Genetic variants in the nsp12 gene were detected in 29/49 (59.2%) non responder patients by Illumina sequencing, including the de novo E83D mutation that emerged in an immunosuppressed patient after receiving 10 + 8 days of RDV, and the L838I detected at baseline and/or after prolonged RDV treatment in 9/49 (18.4%) non responder subjects. Although 3D protein modeling predicted no interference with RDV, the amino acid substitutions detected in the nsp12 involved changes on the electrostatic outer surface and in secondary structures that may alter antiviral response. It is important for health surveillance to study potential mutations associated with drug resistance as well as the benefit of RDV retreatment, especially in immunosuppressed patients and in those with persistent replication. IMPORTANCE This study provides clinical and microbiologic data of an extended population of hospitalized patients for COVID-19 pneumonia who experienced treatment failure, detected by the presence of subgenomic RNA (sgRNA). The genetic variants found in the nsp12 pharmacological target of RDV bring into focus the importance of monitoring emergent mutations, one of the objectives of the World Health Organization (WHO) for health surveillance. These mutations become even more crucial as RDV keeps being prescribed and new molecules are being repurposed for the treatment of COVID-19. The present article offers new perspectives for the clinical management of non responder patients treated and retreated with RDV and emphasizes the need of further research of the benefit of combinatorial therapies and RDV retreatment, especially in immunosuppressed patients with persistent replication after therapy.

Respiratory viruses: their importance and lessons learned from COVID-19.

Respiratory virus infection can cause severe illnesses capable of inducing acute respiratory failure that can progress rapidly to acute respiratory distress syndrome (ARDS). ARDS is related to poor outcomes, especially in individuals with a higher risk of infection, such as the elderly and those with comorbidities, i.e. obesity, asthma, diabetes mellitus and chronic respiratory or cardiovascular disease. Despite this, effective antiviral treatments available for severe viral lung infections are scarce. The coronavirus disease 2019 (COVID-19) pandemic demonstrated that there is also a need to understand the role of airborne transmission of respiratory viruses. Robust evidence supporting this exists, but better comprehension could help implement adequate measures to mitigate respiratory viral infections. In severe viral lung infections, early diagnosis, risk stratification and prognosis are essential in managing patients. Biomarkers can provide reliable, timely and accessible information possibly helpful for clinicians in managing severe lung viral infections. Although respiratory viruses highly impact global health, more research is needed to improve care and prognosis of severe lung viral infections. In this review, we discuss the epidemiology, diagnosis, clinical characteristics, management and prognosis of patients with severe infections due to respiratory viruses.

Correction: Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients.

[This corrects the article DOI: 10.1371/journal.pone.0242184.].

Greening of the syllabus in faculties of education sciences through sustainable development goals: the case of public Andalusian universities (Spain)

Purpose>The purpose of this paper is to analyse the presence of the sustainable development goals (SDGs) proposed by the UN (2015) in university degrees within the fields of education, humanities and environmental sciences (ES) at Andalusian public institutions (Spain).Design/methodology/approach>This paper shows an empirical analysis from a mixed methodological model on a total of 99 syllabi and training programs from nine different universities. The collection of information has been carried out through a rubric specifically designed within the framework of this body of research.Findings>The results show that the syllabus of the subjects in the faculties of education includes the SDGs related to the social aspect of sustainability, with special focus on SDG4, SDG5, SDG10, SDG16 and SDG17, whereas others like SDG6 and SDG7 are less represented. SDGs are present in the majority of syllabus of the subjects analysed. It is certainly a positive finding which shows predisposition and a high interest on by the teachers involved. However, this is not enough as there is still a long way to go until achieving a thorough and complete incorporation of the principles of sustainability.Originality/value>This research sheds light on the changes and transformations that the discourse linked to sustainability is generating in the university syllabi. Taking the SDG as a framework this paper highlights the most original aspects: a replicable methodology that allows diagnosing the level of curricular greening of the university syllabi is provided to other contexts the innovative value of connecting teaching with local and global environmental problems in their physical-chemical social and economic dimensions is shown and it has been possible to compare the difficulties of some universities in addressing compliance with the SDGs and curricular sustainability from a systemic and integrative perspective that will lead to methodological transformation and pedagogical renewal.

Impact of coronavirus disease 2019 epidemics on prevention and care for HIV and other sexually transmitted infections.

OBJECTIVE: To assess the impact of coronavirus disease 2019 (COVID-19) epidemics on the prevention and care for HIV and other sexually transmitted infections at a major reference centre providing preventive and clinical services in Catalonia, Spain. DESIGN: We retrospectively compared anonymized clinical and laboratory data from March to December 2020 vs. 2019. METHODS: Monthly clinical data on HIV preexposure and postexposure prophylaxis users and on adults with HIV infection were retrieved from the administrative hospital database. Monthly tests for HIV, hepatitis B and C, Treponema pallidum, Neisseria gonorrhoeae,and Chlamydia trachomatis, and plasma lipids and glucose were recovered from the laboratory database. RESULTS: There were less (↓28%, P  = 0.003) but more advanced (mean CD4+ cells/µl 305 vs. 370, P  < 0.001) HIV infections and more gonorrhoea (↑39%, P  < 0.001) and chlamydia (↑37%, P  < 0.001) infections in 2020 vs. 2019. In people with HIV, rates of HIV RNA less than 50 copies/ml remained stable (11 vs. 11%, P  = 0.147) despite less scheduled visits (↓25%, P  < 0.001). However, they had less antiretroviral prescription changes (↓10%, P  = 0.018), worse plasma lipids [mean total cholesterol 190 vs. 185 mg/dl, P  < 0.001;mean low-density lipoprotein (LDL) cholesterol 114 vs. 110 mg/dl, P  < 0.001; mean triglycerides 136 vs. 125 mg/dl, P  < 0.001; mean high-density lipoprotein (HDL) cholesterol 47 vs. 48 mg/dl, P  = 006], and an excess of mortality (↑264%, P  = 0.006) due in great part not only to COVID-19 but also to other causes. CONCLUSION: In our setting, COVID-19 epidemics was associated with an increase in some prevalent sexually transmitted infections, with less but more advanced HIV infections, and with worse nonvirologic healthcare outcomes and higher mortality in people living with HIV.

Lack of Prognostic Value of SARS-CoV2 RT-PCR Cycle Threshold in the Community.

The immense impact of the COVID-19 pandemic on health systems has motivated the scientific community to search for clinical prognostic factors for SARS-CoV-2 infection. Low cycle threshold values (Ct) of diagnostic real-time RT-PCR assays in hospitalized patients have been associated with a poor prognosis in several studies, whereas other studies did not find this association. We explored whether SARS-CoV-2 Ct values at diagnosis were associated with a poor outcome (admission to hospital and death) in 604 community patients diagnosed at primary health centers. Although lower Ct values were found in patients who died of COVID-19, the Ct value was not significantly associated with a worse outcome in a multivariate analysis, while age remained an independent prognostic factor. We did not find evidence to support the role of Ct values as a prognostic factor of COVID-19 in community cases.

Minimally Invasive Tissue Sampling Findings in 12 Patients With Coronavirus Disease 2019.

BACKGROUND: Minimally invasive tissue sampling (MITS), a postmortem procedure that uses core needle biopsy samples and does not require opening the body, may be a valid alternative to complete autopsy (CA) in highly infectious diseases such as coronavirus disease-19 (COVID-19). This study aimed to (1) compare the performance of MITS and CA in a series of COVID-19 deaths and (2) evaluate the safety of the procedure. METHODS: From October 2020 to February 2021, MITS was conducted in 12 adults who tested positive before death for COVID-19, in a standard, well-ventilated autopsy room, where personnel used reinforced personal protective equipment. In 9 cases, a CA was performed after MITS. A thorough histological evaluation was conducted, and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The diagnoses provided by MITS and CA matched almost perfectly. In 9 patients, COVID-19 was in the chain of events leading to death, being responsible for diffuse alveolar damage and mononuclear T-cell inflammatory response in the lungs. No specific COVID-19 features were identified. Three deaths were not related to COVID-19. All personnel involved in MITS repeatedly tested negative for COVID-19. SARS-CoV-2 was identified by RT-PCR and immunohistochemistry in the MITS samples, particularly in the lungs. CONCLUSIONS: MITS is useful for evaluating COVID-19-related deaths in settings where a CA is not feasible. The results of this simplified and safer technique are comparable to those of CA.

Minimally Invasive Tissue Sampling as an Alternative to Complete Diagnostic Autopsies in the Context of Epidemic Outbreaks and Pandemics: The Example of Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Infectious diseases' outbreak investigation requires, by definition, conducting a thorough epidemiological assessment while simultaneously obtaining biological samples for an adequate screening of potential responsible pathogens. Complete autopsies remain the gold-standard approach for cause-of-death evaluation and characterization of emerging diseases. However, for highly transmissible infections with a significant associated lethality, such as COVID-19, complete autopsies are seldom performed due to biosafety challenges, especially in low-resource settings. Minimally invasive tissue sampling (MITS) is a validated new approach based on obtaining postmortem samples from key organs and body fluids, a procedure that does not require advanced biosafety measures or a special autopsy room. METHODS: We aimed to review the use of MITS or similar procedures for outbreak investigation up to 27 March 2021 and their performance for evaluating COVID-19 deaths. RESULTS: After a literature review, we analyzed in detail the results of 20 studies conducted at international sites, whereby 216 COVID-19-related deaths were investigated. MITS provided a general and more granular understanding of the pathophysiological changes secondary to the infection and high-quality samples where the extent and degree of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related damage could be evaluated. CONCLUSIONS: MITS is a useful addition in the investigation and surveillance of infections occurring in outbreaks or epidemics. Its less invasive nature makes the tool more acceptable and feasible and reduces the risk of procedure-associated contagion, using basic biosafety measures. Standardized approaches protocolizing which samples should be collected-and under which exact biosafety measures-are necessary to facilitate and expand its use globally.

Severe Acute Respiratory Syndrome Coronavirus 2 Normalized Viral Loads and Subgenomic RNA Detection as Tools for Improving Clinical Decision Making and Work Reincorporation.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction (RT-PCR) provides a highly variable cycle threshold (Ct) value that cannot distinguish viral infectivity. Subgenomic ribonucleic acid (sgRNA) has been used to monitor active replication. Given the importance of long RT-PCR positivity and the need for work reincorporation and discontinuing isolation, we studied the functionality of normalized viral loads (NVLs) for patient monitoring and sgRNA for viral infectivity detection. METHODS: The NVLs measured through the Nucleocapsid and RNA-dependent-RNA-polymerase genes and sgRNA RT-PCRs were performed in 2 consecutive swabs from 84 healthcare workers. RESULTS: The NVLs provided similar and accurate quantities of both genes of SARS-CoV-2 at 2 different timepoints of infection, overcoming Ct-value and swab collection variability. Among SARS-CoV-2-positive samples, 51.19% were sgRNA-positive in the 1st RT-PCR and 5.95% in the 2nd RT-PCR. All sgRNA-positive samples had >4 log10 RNA copies/1000 cells, whereas samples with ≤1 log10 NVLs were sgRNA-negative. Although NVLs were positive until 29 days after symptom onset, 84.1% of sgRNA-positive samples were from the first 7 days, which correlated with viral culture viability. Multivariate analyses showed that sgRNA, NVLs, and days of symptoms were significantly associated (P < .001). CONCLUSIONS: The NVLs and sgRNA are 2 rapid accessible techniques that could be easily implemented in routine hospital practice providing a useful proxy for viral infectivity and coronavirus disease 2019 patient follow-up.

Minimally Invasive Autopsy Practice in COVID-19 Cases: Biosafety and Findings.

Postmortem studies are crucial for providing insight into emergent diseases. However, a complete autopsy is frequently not feasible in highly transmissible diseases due to biohazard challenges. Minimally invasive autopsy (MIA) is a needle-based approach aimed at collecting samples of key organs without opening the body, which may be a valid alternative in these cases. We aimed to: (a) provide biosafety guidelines for conducting MIAs in COVID-19 cases, (b) compare the performance of MIA versus complete autopsy, and (c) evaluate the safety of the procedure. Between October and December 2020, MIAs were conducted in six deceased patients with PCR-confirmed COVID-19, in a basic autopsy room, with reinforced personal protective equipment. Samples from the lungs and key organs were successfully obtained in all cases. A complete autopsy was performed on the same body immediately after the MIA. The diagnoses of the MIA matched those of the complete autopsy. In four patients, COVID-19 was the main cause of death, being responsible for the different stages of diffuse alveolar damage. No COVID-19 infection was detected in the personnel performing the MIAs or complete autopsies. In conclusion, MIA might be a feasible, adequate and safe alternative for cause of death investigation in COVID-19 cases.

Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients.

Ivermectin has recently shown efficacy against SARS-CoV-2 in-vitro. We retrospectively reviewed severe COVID-19 patients receiving standard doses of ivermectin and we compared clinical and microbiological outcomes with a similar group of patients not receiving ivermectin. No differences were found between groups. We recommend the evaluation of high-doses of ivermectin in randomized trials against SARS-CoV-2.