Case series report: radiation-induced oropharyngeal carcinoma.

The incidence of radiation-induced secondary primary tumors (SPTs) is estimated to be between 1 and 20%. The oropharynx is not a common site for postradiotherapy head and neck SPTs. We describe the cases of eight patients, each with an SPT of the oropharynx. These developed after a long median latency of 17.7 years with each receiving two-dimensional radiation therapy and delivery of at least 5000 cGy per pharynx, except for one who was treated with IMRT. Tumor histological commonalities revealed squamous cell carcinoma p16 negative staining, local invasion, and limited lymphatic spread, with posterior wall of the oropharynx and the base of the tongue being the most common locations. Limited and challenging treatment options have been reported such as surgery, reirradiation, or clinical trials. Radiation-induced SP oropharyngeal carcinoma has unique clinical and pathological features. Patients with this disease have limited treatment options, which should be discussed in a multidisciplinary tumor board meeting. For this population, lifelong follow-up may help in early diagnosis and improve outcomes.

Combined nasal- and oropharyngeal self-swab provides equivalent performance compared to professionally collected oropharyngeal swabs in detecting SARS-CoV-2 in a real-life setting.

PURPOSE: To investigate the performance of a combined nasal midturbinate- and oropharyngeal (NAOP) self-swab compared to a deep oropharyngeal (OP) swab by health care workers (HCW) in detecting SARS-CoV-2 in a real-life setting. METHODS: Paired swabs from 1119 participants were included. RT-PCR were used to detect SARS-CoV-2 in both swab samples. RESULTS: 330 participants tested positive. The sensitivity of the combined self-swab and OP swab was 96.9 % and 95.4 % respectively, whereas the Ct-values for self-swabs were significantly lower compared to OP swabs. CONCLUSION: The combined NAOP self-swab outperformed the OP swab and thus, the NAOP self-swab may be an alternative sampling method under the given circumstances.

Performance & clinical utility of oropharyngeal versus nasopharyngeal swabs in COVID-19.

Background & objectives: The oropharyngeal (OP) and nasopharyngeal (NP) swab samples are the most recommended clinical specimens for detecting SARS-CoV-2 in an individual through the quantitative real-time reverse-transcriptase-polymerase chain reaction (rRT-PCR) method. The primary objective of this study was to compare the performance of NP and OP swabs for the diagnosis of COVID-19 among 2250 concomitant samples (1125 NP + 1125 OP) using rRT-PCR test. Methods: This study was conducted at a tertiary care hospital in southern India. The study compared the specificity and efficacy of the two samples (NP & OP swabs) in 1125 individuals suspected having COVID-19 infection. The rRT-PCR values from all the samples were compared based on gender, age group and viral load. The differences between unmatched proportion and matched proportion were analysed. Agreement between the two methods was assessed using Kappa statistic. Absolute sensitivity, specificity, positive and negative predictive values (PPV and NPV) for OP and NP swabs were analysed. Results: The study identified a fair degree of agreement between OP and NP swabs in diagnosis of COVID-19 (kappa = 0.275, P <0.001). There was also a fair degree of agreement between NP and OP swabs irrespective of gender, age or duration of symptoms. NP swabs had better sensitivity and NPV as compared to OP swabs, however, specificity and PPV were 100 per cent for both. Interpretation & conclusions: The present study showed that both OP and NP swabs had similar sensitivity and specificity for predicting the presence of SARS-CoV-2.

Hypopharynx, oropharynx morphology and histology in severe Coronavirus 2 patients treated by noninvasive ventilation: comparison between full-face mask and helmet strategies.

BACKGROUND: Non-invasive ventilation may alter the morphology and histology of the upper airway mucosa. This study aimed to investigate the alterations of hypopharynx and oropharynx mucosa, identified during oro-tracheal intubation procedure via video-assisted laryngoscopy, in severe acute respiratory syndrome Coronavirus 2 related, treated by non-invasive ventilation via full-face mask or helmet. METHODS: Data of patients affected by Coronavirus 2 admitted to COVID Hospital of L'Aquila (Italy), presenting hypopharynx and oropharynx morphology alterations, requiring oro-tracheal intubation for invasive ventilation and initially treated with non-invasive ventilation were included in the study. The study aimed to investigate the upper airway mucosa alterations using oropharyngeal and hypopharyngeal images and biopsies taken during video-assisted-laryngoscopy. Data from the hypopharynx and oropharynx morphology and histology alterations between non-invasive ventilation via a full-face mask or helmet used during hospitalization were compared. RESULTS: From 220 data recorded, 60 patients were included in the study and classified into non-invasive ventilation full-face mask group (30/60) and via helmet group. Comparing data between groups, significant differences were found with respect to hyperemia (77% vs. 20%), laryngeal bleeding ulcerations (87% vs. 13%), and vocal cord edema with >50% narrowing of the tracheal lumen (73% vs. 7%), respectively. The histology examination revealed fibrin-necrotic exudate with extensive necrotic degenerative changes in the sample tissue of the groups. There were not any differences in the duration time of non-invasive ventilation, time from hospitalization and the start of ventilation between groups. CONCLUSIONS: The data from this research suggested that there were differences in airway mucosa damages among patients treated with a full-face mask or helmet. Further studies should be planned to understand which non-invasive ventilation support may mitigate upper airway mucosa damages when oro-tracheal intubation is requested for invasive respiratory support.

[Composition of oropharyngeal microbiota in patients with COVID-19 of different pneumonia severity].

AIM: To identify features of the taxonomic composition of the oropharyngeal microbiota of COVID-19 patients with different disease severity. MATERIALS AND METHODS: The study group included 156 patients hospitalized with confirmed diagnosis of COVID-19 in the clinical medical center of Yevdokimov Moscow State University of Medicine and Dentistry between April and June 2021. There were 77 patients with mild pneumonia according to CT (CT1) and 79 patients with moderate to severe pneumonia (CT2 and CT3). Oropharyngeal swabs were taken when the patient was admitted to the hospital. Total DNA was isolated from the samples, then V3V4 regions of the 16s rRNA gene were amplified, followed by sequencing using Illumina HiSeq 2500 platform. DADA2 algorithm was used to obtain amplicon sequence variants (ASV). RESULTS: When comparing the microbial composition of the oropharynx of the patients with different forms of pneumonia, we have identified ASVs associated with the development of both mild and severe pneumonia outside hospital treatment. Based on the results obtained, ASVs associated with a lower degree of lung damage belong predominantly to the class of Gram-negative Firmicutes (Negativicutes), to various classes of Proteobacteria, as well as to the order Fusobacteria. In turn, ASVs associated with a greater degree of lung damage belong predominantly to Gram-positive classes of Firmicutes Bacilli and Clostridia. While being hospitalized, patients with severe pneumonia demonstrated negative disease dynamics during treatment significantly more often. CONCLUSION: We have observed differences in the taxonomic composition of the oropharyngeal microbiota in patients with different forms of pneumonia developed outside hospital treatment against COVID-19. Such differences might be due to the presumed barrier function of the oropharyngeal microbiota, which reduces the risk of virus titer increase.

Temporal dynamics of oropharyngeal microbiome among SARS-CoV-2 patients reveals continued dysbiosis even after Viral Clearance.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has posed multiple challenges to global public health. Clinical features and sequela of SARS-CoV-2 infection include long-term and short-term complications often clinically indistinguishable from bacterial sepsis and acute lung infection. Post-hoc studies of previous SARS outbreaks postulate secondary bacterial infections with microbial dysbiosis. Oral microbial dysbiosis, particularly the altered proportion of Firmicutes and Proteobacteria, observed in other respiratory virus infection, like influenza, has shown to be associated with increased morbidity and mortality. Oropharynx and lung share similar kinds of bacterial species. We hypothesized that alteration in the Human Oropharyngeal Microbiome in SARS-CoV-2 patients can be a clinical indicator of bacterial infection related complications. We made a longitudinal comparison of oropharyngeal microbiome of 20 SARS-CoV-2 patients over a period of 30 days; at three time points, with a 15 days interval; contrasting them with a matched group of 10 healthy controls. Present observation indicates that posterior segment of the oropharyngeal microbiome is a key reservoir for bacteria causing pneumonia and chronic lung infection on SARS-CoV-2 infection. Oropharyngeal microbiome is indeed altered and its α-diversity decreases, indicating reduced stability, in all SARS-CoV-2 positive individuals right at Day-1; i.e. within ~24 h of post clinical diagnosis. The dysbiosis persists long-term (30 days) irrespective of viral clearance and/or administration of antibiotics. There is a severe depletion of commensal bacteria phyla like Firmicutes among the patients and that depletion is compensated by higher proportion of bacteria associated with sepsis and severe lung infection from phyla Proteobacteria. We also found elevated proportions of certain genus that have previously been shown to be causal for lung pneumonia in studies of model organisms and human autopsies' including Stenotrophomonas, Acenetobactor, Enterobactor, Klebsiella and Chryseobacterium that were to be elevated among the cases. We also show that responses to the antibiotics (Azithromycin and Doxycycline) are not uniform for all individuals.

Self-collected gargle specimen as a patient-friendly sample collection method for COVID-19 diagnosis in a population context.

Scaling up SARS-CoV-2 testing and tracing continues to be plagued with the limitation of the sample collection method, which requires trained healthcare workers to perform and causes discomfort to the patients. In response, we assessed the performance and user preference of gargle specimens for qRT-PCR-based detection of SARS-CoV-2 in Indonesia. Inpatients who had recently been diagnosed with COVID-19 and outpatients who were about to perform qRT-PCR testing were asked to provide nasopharyngeal and oropharyngeal (NPOP) swabs and self-collected gargle specimens. We demonstrated that self-collected gargle specimens can be an alternative specimen to detect SARS-CoV-2 and the viral RNA remained stable for 31 days at room temperature storage. The developed method was validated for use on multiple RNA extraction kits and commercially available COVID-19 RT-PCR kits. Our developed method achieved a sensitivity of 91.38% when compared to paired NPOP swab specimens (Ct < 35), with 97.10% of patients preferring the self-collected gargle method.

Efficacy and hazards of 425 nm oral cavity light dosing to inactivate SARS-CoV-2.

OBJECTIVE: Using a battery of preclinical tests to support development of a light-based treatment for COVID-19, establish a range of 425 nm light doses that are non-hazardous to the tissues of the oral cavity and assess whether a 425 nm light dose in this non-hazardous range can inactivate SARS-CoV-2 in artificial saliva. METHODS: The potential hazards to oral tissues associated with a range of acute 425 nm light doses were assessed using a battery of four preclinical tests: (1) cytotoxicity, using well-differentiated human large airway and buccal epithelial models; (2) toxicity to commensal oral bacteria, using a panel of model organisms; (3) light-induced histopathological changes, using ex vivo porcine esophageal tissue, and (4) thermal damage, by dosing the oropharynx of intact porcine head specimens. Then, 425 nm light doses established as non-hazardous using these tests were evaluated for their potential to inactivate SARS-CoV-2 in artificial saliva. RESULTS: A dose range was established at which 425 nm light is not cytotoxic in well-differentiated human large airway or buccal epithelial models, is not cytotoxic to a panel of commensal oral bacteria, does not induce histopathological damage in ex vivo porcine esophageal tissue, and does not induce thermal damage to the oropharynx of intact porcine head specimens. Using these tests, no hazards were observed for 425 nm light doses less than 63 J/cm2 delivered at irradiance less than 200 mW/cm2. A non-hazardous 425 nm light dose in this range (30 J/cm2 at 50 mW/cm2) was shown to inactivate SARS-CoV-2 in vitro in artificial saliva. CONCLUSION: Preclinical hazard assessments and SARS-CoV-2 inactivation efficacy testing were combined to guide the development of a 425 nm light-based treatment for COVID-19. CLINICAL SIGNIFICANCE: The process used here to evaluate the potential hazards associated with 425 nm acute light dosing of the oral cavity to treat COVID-19 can be extended to other wavelengths, anatomical targets, and therapeutic applications to accelerate the development of novel photomedicine treatments.

Routine universal testing versus selective or incidental testing for oropharyngeal Chlamydia trachomatis in women in the Netherlands: a retrospective cohort study.

BACKGROUND: Pharyngeal Chlamydia trachomatis in women might contribute to autoinoculation and transmission to sexual partners. Data for effectiveness of different testing practices for pharyngeal C trachomatis are scarce. We therefore aimed to assess the prevalence of pharyngeal C trachomatis, determinants, and effectiveness of different testing practices in women. METHODS: We did a retrospective cohort study, in which surveillance data for all women visiting sexually transmitted infection clinics in all regions in the Netherlands between Jan 1, 2008, and Dec 31, 2017, were used. We collected consultation-level data and individual-level data from 2016 onwards for sociodemographic characteristics, sexual behaviour in the past 6 months, self-reported symptoms, and STI diagnoses. The primary outcome was the positivity rate of pharyngeal C trachomatis infection compared between routine universal testing (>85% tested pharyngeally per clinic year), selective testing (5-85% tested pharyngeally per clinic year), and incidental testing (<5% pharyngeally tested per clinic year). We calculated the number of missed infections by extrapolating the positivity rate assessed by routine universal testing to all selectively tested women. We used multivariable generalised estimating equations logistic regression analyses to assess independent risk factors for pharyngeal C trachomatis and used the assessed risk factors as testing indicators for comparing alternative testing scenarios. FINDINGS: Between Jan 1, 2008, and Dec 31, 2017, a total of 550 615 consultations with at least one C trachomatis test was recorded, of which 541 945 (98·4%) consultations (including repeat visits) were included in this analysis. Pharyngeal C trachomatis positivity was lower in the routine universal testing group than in the selective testing group (1081 [2·4%; 95% CI 2·2-2·5] of 45 774 vs 3473 [2·9%; 2·8-3·0] of 121 262; p<0·0001). The positivity rate was also higher among consultations done in the incidental testing group (44 [4·1%; 95% CI 3·1-5·5] of 1073; p<0·0001) than in the routine universal testing group. Based on extrapolation, selective testing would have hypothetically missed 64·4% (95% CI 63·5-65·3; 6363 of 9879) of the estimated total of C trachomatis infections. The proportion of pharyngeal-only C trachomatis was comparable between routinely universally tested women (22·9%) and selectively tested women (20·4%), resulting in a difference of 2·5% (95% CI -0·3 to 5·3; p=0·07). When using risk factors for pharyngeal C trachomatis as testing indicators, 15 484 (79·6%) of 19 459 women would be tested to detect 398 (80·6%) of 494 infections. INTERPRETATION: No optimal testing scenario was available for pharyngeal C trachomatis, in which only a selection of high-risk women needs to be tested to find most pharyngeal C trachomatis infections. The relative low prevalence of pharyngeal-only C trachomatis (0·5%) and probably limited clinical and public health effect do not provide support for routine universal testing. FUNDING: Public Health Service South Limburg.

Characterization of Altered Oropharyngeal Microbiota in Hospitalized Patients With Mild SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by full-length 16S rRNA gene sequencing through the NANOPORE platform of oropharynx swab specimens from 10 mild COVID-19 patients and 10 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in mild COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Peptostreptococcus anaerobius and Pseudomonas stutzeri and depletion of Sphingomonas yabuuchiae, Agrobacterium sullae, and Pseudomonas veronii. Based on the relative abundance of the oropharyngeal microbiota at the species level, we built a microbial classifier to distinguish COVID-19 patients from healthy controls, in which P. veronii, Pseudomonas fragi, and S. yabuuchiae were identified as the most prominent signatures for their depletion in the COVID-19 group. Several members of the genus Campylobacter, especially Campylobacter fetus and Campylobacter rectus, which were highly enriched in COVID-19 patients with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and showed a significant correlation with disease status and several routine clinical blood indicators, indicate that several bacteria may transform into opportunistic pathogen in COVID-19 patients when facing the challenges of viral infection. We also found the diver taxa Streptococcus anginosus and Streptococcus alactolyticus in the network of disease patients, suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the microbial association patterns. In conclusion, the low sample size of SARS-CoV-2 infection patients (n = 10) here makes these results tentative; however, we have provided the overall characterization that oropharyngeal microbiota alterations and microbial correlation patterns were associated with COVID-19 severity in Anhui Province.

Accuracy of Real-Time Polymerase Chain Reaction in COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is a mild to severe respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The diagnostic accuracy of the Centers for Disease Control and Prevention (CDC)- or World Health Organization (WHO)-recommended real-time PCR (RT-qPCR) primers in clinical practice remains unproven. We conducted a prospective study on the accuracy of RT-qPCR using an in-house-designed primer set (iNP) targeting the nucleocapsid protein as well as various recommended and commercial primers. The accuracy was assessed by culturing or seroconversion. We enrolled 12 confirmed COVID-19 patients with a total of 590 clinical samples. When a cutoff value of the cycle threshold (Ct) was set to 35, RT-qPCRs with WHO RdRp primers and CDC N1, N2, and N3 primers showed sensitivity of 42.1% to 63.2% and specificity of 90.5% to 100% in sputum, and sensitivity of 65.2% to 69.6% and specificity of 65.2% to 69.6% in nasopharyngeal samples. The sensitivity and specificity of iNP RT-qPCR in sputum and nasopharyngeal samples were 94.8%/100% and 69.6%/100%, respectively. Sputum testing had the highest sensitivity, followed by nasopharyngeal testing (P = 0.0193); self-collected saliva samples yielded better characteristics than oropharyngeal samples (P = 0.0032). Our results suggest that iNP RT-qPCR has better sensitivity and specificity than RT-PCR with WHO (P < 0.0001) or CDC (N1: P = 0.0012, N2: P = 0.0013, N3: P = 0.0012) primers. Sputum RT-qPCR analysis has the highest sensitivity, followed by nasopharyngeal, saliva, and oropharyngeal assays. Our study suggests that considerable improvement is needed for the RT-qPCR WHO and CDC primer sets for detecting SARS-CoV-2. IMPORTANCE Numerous research campaigns have addressed the vast majority of clinical and diagnostic specificity and sensitivity of various primer sets of SARS-CoV2 viral detection. Despite the impressive progress made to resolve the pandemic, there is still a need for continuous and active improvement of primers used for diagnosis in clinical practice. Our study significantly exceeds the scale of previously published research on the specificity and sensitivity of different primers comparing with different specimens and is the most comprehensive to date in terms of constant monitoring of primer sets of current usage. Henceforth, our results suggest that sputum samples sensitivity is the highest, followed by nasopharyngeal, saliva, and oropharyngeal samples. The CDC recommends the use of oropharyngeal specimens, leading to certain discrepancy between the guidelines set forth by the CDC and IDSA. We proved that the oropharyngeal samples demonstrated the lowest sensitivity for the detection of SARS-CoV-2.

Development and Evaluation of AccuPower COVID-19 Multiplex Real-Time RT-PCR Kit and AccuPower SARS-CoV-2 Multiplex Real-Time RT-PCR Kit for SARS-CoV-2 Detection in Sputum, NPS/OPS, Saliva and Pooled Samples.

Rapid and accurate detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for the successful control of the current global COVID-19 pandemic. The real-time reverse transcription polymerase chain reaction (Real-time RT-PCR) is the most widely used detection technique. This research describes the development of two novel multiplex real-time RT-PCR kits, AccuPower® COVID-19 Multiplex Real-Time RT-PCR Kit (NCVM) specifically designed for use with the ExiStation™48 system (comprised of ExiPrep™48 Dx and Exicycler™96 by BIONEER, Korea) for sample RNA extraction and PCR detection, and AccuPower® SARS-CoV-2 Multiplex Real-Time RT-PCR Kit (SCVM) designed to be compatible with manufacturers' on-market PCR instruments. The limit of detection (LoD) of NCVM was 120 copies/mL and the LoD of the SCVM was 2 copies/µL for both the Pan-sarbecovirus gene and the SARS-CoV-2 gene. The AccuPower® kits demonstrated high precision with no cross reactivity to other respiratory-related microorganisms. The clinical performance of AccuPower® kits was evaluated using the following clinical samples: sputum and nasopharyngeal/oropharyngeal swab (NPS/OPS) samples. Overall agreement of the AccuPower® kits with a Food and Drug Administration (FDA) approved emergency use authorized commercial kit (STANDARD™ M nCoV Real-Time Detection kit, SD BIOSENSOR, Korea) was above 95% (Cohen's kappa coefficient ≥ 0.95), with a sensitivity of over 95%. The NPS/OPS specimen pooling experiment was conducted to verify the usability of AccuPower® kits on pooled samples and the results showed greater than 90% agreement with individual NPS/OPS samples. The clinical performance of AccuPower® kits with saliva samples was also compared with NPS/OPS samples and demonstrated over 95% agreement (Cohen's kappa coefficient > 0.95). This study shows the BIONEER NCVM and SCVM assays are comparable with the current standard confirmation assay and are suitable for effective clinical management and control of SARS-CoV-2.

SARS-CoV-2 in domestic cats (Felis catus) in the northwest of Iran: Evidence for SARS-CoV-2 circulating between human and cats.

This study aimed to investigate the prevalence of COVID-19 in domestic cats, focusing on the disease in the northwest of Iran and then showing the natural transmission of SARS-COV-2 circulating between domestic cats and humans. After receiving ethic codes from Tehran University of Medical Sciences (IR.TUMS.VCR.REC.1399.303) and confirmed by the Center of Communicable Diseases Control (CDC) of Iran, 124 domestic cats were collected from the homes and only one hospital of Meshkin -Shahr district from northwestern Iran where SARS-CoV-2 patients were hospitalized and quarantined during 2020. Samples were prepared from fluid materials of oropharynx and nasopharynx. All samples were tested by real-time PCR (RT-PCR) using specific genes N and ORF1ab in Pasteur Institute of Iran, and then partial sequence analyses of S gene were performed. All collected cats were kept in separated cages until SARS-COV-2 infection was confirmed with the RT-PCR. RT- PCR Ct values of 123 collected cats were ≥40; thus, all of them showed negative results, but one of the collected cats with close contact with its owner, whom confirmed SARS-CoV-2 showed positive results with gene N(Ct=30) and gene ORF1ab (Ct=32). Furthermore, the positive pet cat showed respiratory and gastro-intestinal clinical manifestations, and its owner was infected with SARS-CoV-2 two weeks ago. Cats are susceptible animals to SARS-CoV-2 infection. Epidemiological evidence showed that SARS-COV-2 is able to transmit to healthy cats due to having close contact with its owner as a reverse zoonosis.

SmartAmp method can rapidly detect SARS-CoV-2 in dead bodies.

Rapid and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in dead bodies is essential to prevent infection among those working with dead bodies. This study focused on the Smart Amplification (SmartAmp) method, which has a short examination time (approximately an hour), is simple to perform, and demonstrates high specificity and sensitivity. This method has already been used for clinical specimens; however, its effectiveness in dead bodies has not been reported. This study examined the SmartAmp method using 11 autopsies or postmortem needle biopsies performed from January to May, 2021 (of these, five cases tested positive for SARS-CoV-2 by quantitative real-time polymerase chain reaction (qRT-PCR) and six cases tested negative). Swab samples were collected from the nasopharynx, oropharynx, or anus and the SmartAmp and qRT-PCR results were compared. For the nasopharynx and oropharynx samples, the same results were obtained for both methods in all cases; however, for the anal swabs, there was one case that was positive according to qRT-PCR but negative according to the SmartAmp method. The SmartAmp method may therefore be less sensitive than qRT-PCR and results may differ in specimens with a low viral load, such as anal swabs. However, in the nasopharynx and oropharynx specimens, which are normally used for testing, the results were the same using each method, suggesting that the SmartAmp method is useful in dead bodies. In the future, the SmartAmp method may be applied not only during autopsies, but also in various situations where dead bodies are handled.

Performance of a rapid antigen test for SARS-CoV-2 in Kenya.

Testing for SARS-CoV-2 in resource-poor settings remains a considerable challenge. Gold standard nucleic acid tests are expensive and depend on availability of expensive equipment and highly trained laboratory staff. More affordable and easier rapid antigen tests are an attractive alternative. This study assessed field performance of such a test in western Kenya. We conducted a prospective multi-facility field evaluation study of NowCheck COVID-19 Ag-RDT compared to gold standard PCR. Two pairs of oropharyngeal and nasopharyngeal swabs were collected for comparative analysis. With 997 enrolled participants the Ag-RDT had a sensitivity 71.5% (63.2-78.6) and specificity of 97.5% (96.2-98.5) at cycle threshold value <40. Highest sensitivity of 87.7% (77.2-94.5) was observed in samples with cycle threshold values ≤30. NowCheck COVID-19 Ag-RDT performed well at multiple healthcare facilities in an African field setting. Operational specificity and sensitivity were close to WHO-recommended thresholds.

Utility of Antigen-Based Rapid Diagnostic Test for Detection of SARS-CoV-2 Virus in Routine Hospital Settings.

OBJECTIVE: This study aims to evaluate the performance of an antigen-based rapid diagnostic test (RDT) for the detection of the SARS-CoV-2 virus. METHODS: A cross-sectional study was conducted on 677 patients. Two nasopharyngeal swabs and 1 oropharyngeal swab were collected from patients. The RDT was performed onsite by a commercially available immune-chromatographic assay on the nasopharyngeal swab. The nasopharyngeal and oropharyngeal swabs were examined for SARS-CoV-2 RNA by real-time reverse-transcription quantitative polymerase chain reaction (RT-qPCR) assay. RESULTS: The overall sensitivity of the SARS-CoV-2 RDT was 34.5% and the specificity was 99.8%. The positive predictive value and negative predictive value of the test were 96.6% and 91.5%, respectively. The detection rate of RDT in RT-qPCR positive results was high (45%) for cycle threshold values <25. CONCLUSION: The utility of RDT is in diagnosing symptomatic patients and may not be particularly suited as a screening tool for patients with low viral load. The low sensitivity of RDT does not qualify its use as a single test in patients who test negative; RT-qPCR continues to be the gold standard test.

SARS-CoV-2 Clinical Characteristics and Viral Shedding in Kuwait.

OBJECTIVES: We aimed to describe the clinical characteristics of SARS-CoV-2 infection and estimate viral shedding duration in respiratory specimens. METHODS: A retrospective cohort study was performed from February 25 to March 25, 2020. In Kuwait, all suspected coronavirus disease 2019 (COVID-19) cases, contacts of cases, and returning travelers were systematically tested for SARS-CoV-2 by RT-PCR. All infected persons, regardless of symptoms, were hospitalized and serially tested until they had two negative results. Descriptive statistics and regression analyses were performed. RESULTS: Two hundred seven cases of SARS-CoV-2 infection were included in this study. About half of the cases were asymptomatic and 1.9% died. The median time to negative RT-PCR was 22 days. Increasing age, ARDS, and low peripheral white blood cell count were associated with prolonged PCR positivity. CONCLUSION: Predictors for prolonged RT-PCR positivity included increasing age, ARDS, and low white blood cell count. The findings of this study may aid in better understanding of the epidemiology of SARS-CoV-2 infection and molecular testing dynamics.

Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial.

BACKGROUND: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. OBJECTIVE: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. DESIGN: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). SETTING: 23 hospitals in Norway. PATIENTS: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. INTERVENTION: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). MEASUREMENTS: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. RESULTS: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. LIMITATION: The trial had no placebo group. CONCLUSION: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. PRIMARY FUNDING SOURCE: National Clinical Therapy Research in the Specialist Health Services, Norway.