Preferences of health care workers using tongue swabs for tuberculosis diagnosis during COVID-19 (preprint)

Healthcare workers (HCW) who come into contact with tuberculosis (TB) patients are at elevated risk of TB infection and disease. The collection and handling of sputum samples for TB diagnosis poses exposure risks to HCW, particularly in settings where aerosol containment is limited. An alternative sample collection method, tongue swabbing, was designed to help mitigate this risk, and is under evaluation in multiple settings. This study assessed risk perceptions among South African HCW who used tongue swabbing in TB diagnostic research during the COVID-19 pandemic. We characterized their context-specific preferences as well as the facilitators and barriers of tongue swab use in clinical and community settings. Participants (n=18) were HCW with experience using experimental tongue swabbing methods at the South African Tuberculosis Vaccine Initiative (SATVI). We used key informant semi-structured interviews to assess attitudes toward two tongue swab strategies: Provider-collected swabbing (PS) and supervised self-swabbing (SSS). Responses from these interviews were analyzed by rapid qualitative analysis and thematic analysis methods. Facilitators included aversion to sputum (PS and SSS), perceived safety of the method (SSS), and educational resources to train patients (SSS). Barriers included cultural stigmas, as well as personal security and control of their work environment when collecting swabs in community settings. COVID-19 risk perception was a significant barrier to the PS method. Motivators for HCW use of tongue swabbing differed substantially by use case, and whether the HCW has the authority and agency to implement safety precautions in specific settings. These findings point to a need for contextually specific educational resources to enhance safety of and adherence to the SSS collection method.

Association Between Maintenance Immunosuppressive Regimens and COVID-19 Mortality in Kidney Transplant Recipients

Purpose: Kidney transplant recipients (KTR) are at increased risk of mortality from COVID-19. We conducted a cohort study among KTR from the French Solid Organ Transplant COVID-19 (SOT COVID) registry to investigate the association between maintenance immunosuppressive drugs and 60-day mortality in KTR with COVID-19. Method(s): Data from all KTR with COVID-19 included in SOT COVID 02/28/2020 and 12/30/2020 were retrieved. Among them, 116 were excluded because of missing data on immunosuppressive therapy. We evaluated associations between immunosuppressive drugs and death <=60 days of 1st symptoms using logistic regression, with all baseline characteristics considered to influence outcome or immunosuppressive regimen. Benjamini-Hochberg correction was used for controlling false positive rate;40 multiple imputations were performed. Adjusted p-value <0.05 was considered statistically significant. Result(s): There were 1,451 KTR included. Median age was 58 years, 963 (66.4%) were men. Most frequent comorbidities were hypertension (n=1188, 81.9%), diabetes (501, 34.5%), cardiovascular disease (428, 29.5%). Median time since transplant was 71 months. Maintenance immunosuppression regimen included calcineurin inhibitors (1295, 89.2%), antimetabolites (1205, 83%), corticosteroids (1094, 75.4%), Mammalian Target of Rapamycin inhibitors (144, 9.9%) and belatacept (58, 4.0%). Among 1,451 KTR, 201 (13.9%) died <=60 days. Older age and baseline creatininemia were associated with mortality (OR: 1.09 [1.07-1.11];1.01 [1.005- 1.009], p<0.001). Corticosteroid-free regimens were associated with a significantly lower risk of death (OR: 0.48 [0.31;0.76], p=0.011). All other variables yielded non-significant adjusted p-values. Conclusion(s): Corticosteroid-free regimens were associated with a lower risk of death in KTR with COVID-19. While a short course of high-dose corticosteroids is beneficial in severely ill COVID-19 patients, prolonged maintenance corticosteroids expose to chronic immune disorders that may predispose KTR to severe forms of COVID-19.

The Lived Experiences of Bereaved Filipino Families of the Deceased Due to the COVID-19 Pandemic.

The typical highlight of Filipino mourning of conducting funerals and burials has ceased due to recent health guidelines which required the deceased, who tested positive for the virus, to be cremated and buried right away to avoid further spread of the disease - making bereavement more complicated. This paper investigates the experiences of bereaved Filipino families who lost their loved ones to COVID-19 through a qualitative research design. Researchers explored the experiences of at least three (3) COVID-19 bereaved families through a descriptive phenomenological approach and analyzed the data using thematic analysis to extract the bereavement process experienced by the participants. The findings of the study highlight the changes to the Filipino funeral practice caused by the pandemic and the major roles of connectedness, and cultural and religious beliefs in the Filipino bereavement experience.

Sudden hearing loss and COVID-19 vaccine: A potential signal?

Introduction: Vaccination against COVID-19 appears to be a promising approach to mitigate this pandemic. The French agency of medicinal products (ANSM) issued a signal concerning cases of sudden hearing loss (SHL) following vaccination with elasomeran (Spikevax® Moderna) [1] and AZD1222 (Vaxzevria® AstraZeneca) [2]. SHL is defined as a sensorineural hearing loss ≥30 dB within 72 hours [3]. We aimed to investigate the potential signal of SHL associated with COVID-19 vaccines. Material and methods: We queried VigiBase® (World Health Organization pharmacovigilance database), for all reports of "Sudden Hearing Loss" (MedDRA Preferred Term) related to "COVID-19 vaccine" (Active Ingredient), from 1967 to December 30, 2021 [4]. Disproportionality analysis was based on the Reporting Odds Ratio (ROR) with its 95% Confidence Interval (CI) and the Information Component (IC). A positive IC025 is statistically needed to confirm the detection of a signal [5]. Results: In VigiBase®, 1,602 cases of COVID-19 vaccine-associated SHL were collected. Tozinameran (Pfizer-BioNTech) was mostly notified with 1,053 (65.7%) reports, followed by elasomeran (Moderna, 281, 17.5%), AZD1222 (AstraZeneca, 217, 13.5%), and JNJ 78436735 (Janssen, 43, 2.7%). Most cases concerned women (885, 55.2%), with a median age of 51 years, and 827 (51.6%) were considered serious. The association of COVID-19 vaccines and SHL showed significant disproportionality, with a ROR of 7.4 (95% CI 6.9-7.9) and an IC025>0. Tozinameran reached the strongest ROR (8.2;95% CI 7.6-8.8), followed by elasomeran (4.6;95% CI 4.0-5.2), JNJ-78436735 (3.0;95% CI 2.2-4.0), and AZD1222 (2.7;95% CI 2.3-3.1), all with IC025>0. Discussion/Conclusion: Significant disproportionality was identified for COVID-19 vaccines and SHL. Even though this adverse drug event may rely on an inflammatory mechanism, causality cannot be established by this pharmacovigilance study. However, this finding may strengthen the signals issued by ANSM, concerning elasomeran and AZD1222. SHL following COVID-19 vaccination might be evoked and treated as soon as possible.

COVID-19 vaccine-associated trigeminal neuralgia: Analysis of the WHO safety database

Introduction: To contain the COVID-19 pandemic, vaccination is deemed as a promising approach. A French pharmacovigilance survey identified five cases of trigeminal neuralgia (TN) following vaccination with AZD1222 (Vaxzevria®, AstraZeneca) [1]. Furthermore, a case report mentioned such an adverse reaction with tozinameran (Comirnaty®, Pfizer-BioNTech) [2]. TN is characterized by recurrent, unilateral, and brief electric shock-like pain in one or more trigeminal divisions [3]. TN is triggered by innocuous stimuli. We aimed to investigate the potential signal of TN related to COVID-19 vaccines. Material and methods: We queried VigiBase® (World Health Organization pharmacovigilance database) for all reports of "Trigeminal Neuralgia" (MedDRA Preferred Term) associated with "COVID-19 vaccine" (Active Ingredient), from 1967 to December 29, 2021 [4]. Disproportionality analysis relied on the Reporting Odds Ratio (ROR) with its 95% Confidence Interval (CI), and the Information Component (IC). A positive IC025 is statistically needed to confirm the detection of a signal [5]. Results: In VigiBase®, we gathered 1,283 cases of COVID-19 vaccine-related TN. Most reports involved women (998, 77.8%), with a median age of 52 years, and 510 (39.8%) were deemed serious. Tozinameran was mostly reported with 782 (61.0%) cases, followed by AZD1222 (264, 20.6%), elasomeran (Spikevax® Moderna, 185, 14.4%), and JNJ-78436735 (Janssen® Johnson & Johnson, 37, 2.9%). The association of COVID-19 vaccines and TN revealed significant disproportionality, with an IC025>0 and a ROR of 3.1 (95% CI 2.9-3.3). Tozinameran showed the strongest ROR (3.6;95% CI 3.3-3.8), followed by AZD1222 (2.3;95% CI 2.0-2.6), elasomeran (2.0;95% CI 1.7-2.3), and JNJ-78436735 (1.8 95% CI 1.3-2.5), each with IC025>0. Discussion/Conclusion: COVID-19 vaccines and TN showed relevant disproportionality. Albeit this reaction may rely on an immune-mediated inflammation, causality can only remain hypothetical in this pharmacovigilance study. Nonetheless, this finding may suggest a signal, strengthening reports mentioned by literature and French pharmacovigilance. A TN occurring after COVID-19 vaccination should alert the clinician.

Is transient global amnesia an adverse event associated with COVID-19 vaccines?

Introduction: Vaccination against COVID-19 appears to be a promising approach to mitigate this pandemic. The French agency of medicinal products (ANSM) issued a signal concerning cases of transient global amnesia (TGA) following vaccination with elasomeran (Spikevax® Moderna) [1]. TGA is characterized by the sudden onset of anterograde amnesia with preservation of other cognitive functions and a spontaneous resolution within 24 h [2]. We aimed to investigate the potential link of TGA with COVID-19 vaccines. Material and methods: We queried the WHO VigiBase® for all reports of "Transient global amnesia" (MedDRA Preferred Term) related to "Covid-19 vaccine"(Active Ingredient), from 1967 to December 6, 2021 [3]. Disproportionality analysis was based on the Reporting Odds Ratio (ROR) with its 95% Confidence Interval [CI] and the Information Component (IC) [4]. A positive IC025 statistically detects a signal [5]. Results: The search yielded 289 COVID-19 vaccine-associated TGAs, 178 of which (61.6%) were deemed serious. Most cases concerned women (187, 64.7%), with a median age of 66 years. Tozinameran (T: Comirnarty® Pfizer-BioNTech) was the most represented with 147 reports (50.8%), followed by AZD1222 (A: Vaxzevria® AstraZeneca) with 69 reports (23,8%), elasomeran (E: Spikevax®, Moderna) with 60 reports (20.8%), and JNJ-78436735 (J: Janssen® Johnson & Johnson) with 12 reports (4.2%). With a IC025 > 0, COVID-19 vaccines proved a significant disproportionality (global ROR 5.1 [4.4-6.0]), with respective RORs at 4.6 [3.9-5.0] for T, E at 4.4 [3.4-6.0], A at 3.8 [3.0-5.0], and J at 3.7 [2.1-6.0]. Discussion/Conclusion: Our analysis of COVID-19 vaccines and TGA shows significant disproportionality. Various mechanisms, such as cerebrovascular, inflammatory, or migrainous, may underlie this association. Yet causality cannot be ascertained solely with this approach, although it strengthens the signal issued by the ANSM. Further studies may help to identify the causality of COVID-19 vaccines in triggering TGAs.

Editorial

Because of its geographical location and economic significance for the whole country, the central government initiated the GBA Development Strategy (Chen, 2018). The framework agreement on deepening Guangdong–Hong Kong–Macao Cooperation in the development of the GBA was promulgated in 2017 (NDRC, July 2017), and in 2019, the CCP Central Committee and State Council announced the outline of the GBA Development Plan to the year 2035 (State Council, 2019). China's nationwide regional development strategy framework centers on the aim of building a more innovation economy that will support a structural rebalancing from a labor intensive, low investment, export-oriented economy to a high-tech manufacturing and service-based economy that relies more on domestic consumption. “Higher education institution in GBA can become world leaders in addressing problems like COVID-19, future pandemics, climate change, global poverty, equity and social justice, and sustainable development in innovative ways.

Performance of anterior nares and tongue swabs for nucleic acid, Nucleocapsid, and Spike antigen testing for detecting SARS-CoV-2 against nasopharyngeal PCR and viral culture.

OBJECTIVES: This study assesses and compares the performance of different swab types and specimen collection sites for SARS-CoV-2 testing, to reference standard real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and viral culture. METHODS: Symptomatic adults with COVID-19 who visited routine COVID-19 testing sites used spun polyester and FLOQSwabs to self-collect specimens from the anterior nares and tongue. We evaluated the self-collected specimen from anterior nares and tongue swabs for the nucleocapsid (N) or spike (S) antigen of SARS-CoV-2 by RT-PCR and then compared these results with results from RT-PCR and viral cultures from nurse-collected nasopharyngeal swabs. RESULTS: Diagnostic sensitivity was highest for RT-PCR testing conducted using specimens from the anterior nares collected on FLOQSwabs (84%; 95% CI 68-94%) and spun polyester swabs (82%; 95% CI 66-92%), compared to RT-PCR tests conducted using specimens from nasopharyngeal swabs. Relative to viral culture from nasopharyngeal swabs, diagnostic sensitivities were higher for RT-PCR and antigen testing of anterior nares swabs (91-100%) than that of tongue swabs (18-81%). Antigen testing of anterior nares swabs had higher sensitivities against viral culture (91%) than against nasopharyngeal RT-PCR (38-70%). All investigational tests had high specificity compared with nasopharyngeal RT-PCR. Spun polyester swabs are equally effective as FLOQSwabs for anterior nasal RT-PCR testing. CONCLUSIONS: We found that anterior nares specimens were more sensitive than tongue swab specimens or antigen testing for detecting SARS-CoV-2 by RT-PCR. Thus, self-collected anterior nares specimens may represent an alternative method for diagnostic SARS-CoV-2 testing in some settings.

Defining comprehensive biomarker-related testing and treatment practices for advanced non-small-cell lung cancer: Results of a survey of U.S. oncologists.

BACKGROUND: An ASCO taskforce comprised of representatives of oncology clinicians, the American Cancer Society National Lung Cancer Roundtable (NLCRT), LUNGevity, the GO2 Foundation for Lung Cancer, and the ROS1ders sought to: characterize U.S. oncologists' biomarker ordering and treatment practices for advanced non-small-cell lung cancer (NSCLC); ascertain barriers to biomarker testing; and understand the impact of delays on treatment decisions. METHODS: We deployed a survey to 2374 ASCO members, targeting U.S. thoracic and general oncologists. RESULTS: We analyzed 170 eligible responses. For non-squamous NSCLC, 97% of respondents reported ordering tests for EGFR, ALK, ROS1, and BRAF. Testing for MET, RET, and NTRK was reported to be higher among academic versus community providers and higher among thoracic oncologists than generalists. Most respondents considered 1 (46%) or 2 weeks (52%) an acceptable turnaround time, yet 37% usually waited three or more weeks to receive results. Respondents who waited ≥3 weeks were more likely to defer treatment until results were reviewed (63%). Community and generalist respondents who waited ≥3 weeks were more likely to initiate non-targeted treatment while awaiting results. Respondents <5 years out of training were more likely to cite their concerns about waiting for results as a reason for not ordering biomarker testing (42%, vs. 19% with ≥6 years of experience). CONCLUSIONS: Respondents reported high biomarker testing rates in patients with NSCLC. Treatment decisions were impacted by test turnaround time and associated with practice setting and physician specialization and experience.

A Look Inside: Oral Sampling for Detection of Non-oral Infectious Diseases.

Efforts to control transmissible infectious diseases rely on the ability to screen large populations, ideally in community settings. These efforts can be limited by the requirement for invasive or logistically difficult collection of patient samples, such as blood, urine, stool, sputum, and nasopharyngeal swabs. Oral sampling is an appealing, noninvasive alternative that could greatly facilitate high-throughput sampling in community settings. Oral sampling has been described for the detection of dozens of human pathogens, including pathogens whose primary sites of infection are outside of the oral cavity, such as the respiratory pathogens Mycobacterium tuberculosis and SARS-CoV-2. Oral sampling can demonstrate active infections as well as resolving or previous infections, the latter through the detection of antibodies. Its potential applications are diverse, including improved diagnosis in special populations (e.g., children), population surveillance, and infectious disease screening. In this minireview, we address the use of oral samples for the detection of diseases that primarily manifest outside the oral cavity. Focusing on well-supported examples, we describe applications for such methods and highlight their potential advantages and limitations in medicine, public health, and research.

Pooling in a Pod: A Strategy for COVID-19 Testing to Facilitate a Safe Return to School.

The COVID-19 pandemic prompted widespread closures of primary and secondary schools. Routine testing of asymptomatic students and staff members, as part of a comprehensive mitigation program, can help schools open safely. "Pooling in a pod" is a public health surveillance strategy whereby testing cohorts (pods) are based on social relationships and physical proximity. Pooled testing provides a single laboratory test result for the entire pod, rather than a separate result for each person in the pod. During the 2020-2021 school year, an independent preschool-grade 12 school in Washington, DC, used pooling in a pod for weekly on-site point-of-care testing of all staff members and students. Staff members and older students self-collected anterior nares samples, and trained staff members collected samples from younger students. Overall, 12 885 samples were tested in 1737 pools for 863 students and 264 staff members from November 30, 2020, through April 30, 2021. The average pool size was 7.4 people. The average time from sample collection to pool test result was 40 minutes. The direct testing cost per person per week was $24.24, including swabs. During the study period, 4 surveillance test pools received positive test results for COVID-19. A post-launch survey found most parents (90.3%), students (93.4%), and staff members (98.8%) were willing to participate in pooled testing with confirmatory tests for pool members who received a positive test result. The proportion of students in remote learning decreased by 62.2% for students in grades 6-12 (P < .001) and by 92.4% for students in preschool to grade 5 after program initiation (P < .001). Pooling in a pod is a feasible, cost-effective surveillance strategy that may facilitate safe, sustainable, in-person schooling during a pandemic.

Management of mass casualties due to COVID-19: handling the dead.

A high number of fatalities can occur during major disasters or during events like the COVID-19 pandemic. In a natural disaster, the dead must be removed from disaster sites while rescue work is in progress; otherwise, the health and safety of the community are threatened. The COVID-19 pandemic is analogous to a natural disaster with mass casualties where the disaster sites are hospitals with morgues that are overwhelmed. As the number of the deceased rise rapidly and hospital morgues are at their full capacity, hospitals use what is called a Body Collection Point (BCP). BCP is defined as a temporary refrigeration unit used to store decedents until transport is arranged. Decedents should always be handled in a manner denoting respect, and provisions and management of resources should be properly mobilized to ensure this. Contingency plans must be created to prepare for worsening of the disaster that further overwhelms the capacity of the health care systems.

Systemic dendrimer nanotherapies for targeted suppression of choroidal inflammation and neovascularization in age-related macular degeneration.

Inflammation and neovascularization are key pathological events in human age-related macular degeneration (AMD). Activated microglia/macrophages (mi/ma) and retinal pigmented epithelium (RPE) play an active role in every stage of disease progression. Systemic therapies that can target these cells and address both inflammation and neovascularization will broaden the impact of existing therapies and potentially open new avenues for early AMD where there are no viable therapies. Utilizing a clinically relevant rat model of AMD that mirrors many aspects that of human AMD pathological events, we show that systemic hydroxyl-terminated polyamidoamine dendrimer-triamcinolone acetonide conjugate (D-TA) is selectively taken up by the injured mi/ma and RPE (without the need for targeting ligands). D-TA suppresses choroidal neovascularization significantly (by >80%, >50-fold better than free drug), attenuates inflammation in the choroid and retina, by limiting macrophage infiltration in the pathological area, significantly suppressing pro-inflammatory cytokines and pro-angiogenic factors, with minimal side effects to healthy ocular tissue and other organs. In ex vivo studies on human postmortem diabetic eyes, the dendrimer is also taken up into choroidal macrophages. These results suggest that the systemic hydroxyl dendrimer-drugs can offer new avenues for therapies in treating early/dry AMD and late/neovascular AMD alone, or in combination with current anti-VEGF therapies. This hydroxyl dendrimer platform but conjugated to a different drug is undergoing clinical trials for severe COVID-19, potentially paving the way for faster clinical translation of similar compounds for ocular and retinal disorders.

Management of Lung Nodules and Lung Cancer Screening During the COVID-19 Pandemic: CHEST Expert Panel Report.

Background: The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic. Materials and Methods: An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed. The panel was provided with an overview of current evidence, summarized by recent guidelines related to lung cancer screening and lung nodule evaluation. The panel was convened by video teleconference to discuss and then vote on statements related to 12 common clinical scenarios. A predefined threshold of 70% of panel members voting agree or strongly agree was used to determine if there was a consensus for each statement. Items that may influence decisions were listed as notes to be considered for each scenario. Results: Twelve statements related to baseline and annual lung cancer screening (n = 2), surveillance of a previously detected lung nodule (n = 5), evaluation of intermediate and high-risk lung nodules (n = 4), and management of clinical stage I non-small cell lung cancer (n = 1) were developed and modified. All 12 statements were confirmed as consensus statements according to the voting results. The consensus statements provide guidance about situations in which it was believed to be appropriate to delay screening, defer surveillance imaging of lung nodules, and minimize nonurgent interventions during the evaluation of lung nodules and stage I non-small cell lung cancer. Conclusion: There was consensus that during the COVID-19 pandemic, it is appropriate to defer enrollment in lung cancer screening and modify the evaluation of lung nodules due to the added risks from potential exposure and the need for resource reallocation. There are multiple local, regional, and patient-related factors that should be considered when applying these statements to individual patient care.© 2020 RSNA; The American College of Chest Physicians, published by Elsevier Inc; and The American College of Radiology, published by Elsevier Inc.

Seat Assignments With Physical Distancing in Single-Destination Public Transit Settings.

While the importance of physical (social) distancing in reducing the spread of COVID-19 has been well-documented, implementing similar controls in public transit remains an open question. For instance, in the United States, guidance for maximum seating capacity in single-destination public transit settings, such as school buses, is only dependent on the physical distance between passengers. In our estimation, the available models/guidance are suboptimal/inefficient since they do not account for the possibility of passengers being from the same household. This paper discusses and addresses the aforementioned limitation through two types of physical distancing models. First, a mixed-integer programming model is used to assign passengers to seats based on the reported configuration of the vehicle and desired physical distancing requirement. In the second model, we present a heuristic that allows for household grouping. Through several illustrative scenarios, we show that seating assignments can be generated in near real-time, and the household grouping heuristic increases the capacity of the transit vehicles (e.g., airplanes, school buses, and trains) without increasing the risk of infection. A running application and its source code are available to the public to facilitate adoption and to encourage enhancements.

Internship commencement during COVID-19: the impact of an extended induction model.

BACKGROUND: The COVID-19 pandemic necessitated an enforced 8-week induction period (18 May to 12 July 2020) for all new interns in Ireland. These unprecedented circumstances presented a unique opportunity to assess this induction period. AIM: To assess the impact of a prolonged induction period on the technical abilities of interns embarking on their clinical careers. METHOD: We distributed a 12-item questionnaire to new interns at our institution during the COVID-19 pandemic. Section 1 of the questionnaire was designed to assess the rate of self-reported improvement in the successful and independent execution of practical 'intern' tasks. Section 2 of the questionnaire captured the subjective experience of interns during this time in relation to the effectiveness of an 8-week induction period with senior intern support available. Statistical analysis of categorical predictor and ordinal outcome variables was performed using the two-sample Wilcoxon rank-sum (Mann-Whitney) test. RESULTS: Our results demonstrated a statistically significant improvement in the proficiency at first attempt phlebotomy in week 8 compared with week 1 (p < 0.0001). There was a significant improvement in placing first-attempt peripheral IV lines in week 8 compared with week 1 (p < 0.001). Regarding the need for senior assistance, we demonstrated a statistically significant reduction in week 8 compared with week 1 (p = 0.046). There were 95.56% (n = 43) of interns that said they would recommend the induction period for future incoming interns. CONCLUSION: The COVID-19 pandemic has inadvertently identified a model of internship induction that benefits interns, their colleagues and their patients through the production of more technically capable interns.

Sample adequacy controls for infectious disease diagnosis by oral swabbing.

Oral swabs are emerging as a non-invasive sample type for diagnosing infectious diseases including Ebola, tuberculosis (TB), and COVID-19. To assure proper sample collection, sample adequacy controls (SACs) are needed that detect substances indicative of samples collected within the oral cavity. This study evaluated two candidate SACs for this purpose. One detected representative oral microbiota (Streptococcus species DNA) and the other, human cells (human mitochondrial DNA, mtDNA). Quantitative PCR (qPCR) assays for the two target cell types were applied to buccal swabs (representing samples collected within the oral cavity) and hand swabs (representing improperly collected samples) obtained from 51 healthy U.S. volunteers. Quantification cycle (Cq) cutoffs that maximized Youden's index were established for each assay. The streptococcal target at a Cq cutoff of ≤34.9 had 99.0% sensitivity and specificity for oral swab samples, whereas human mtDNA perfectly distinguished between hand and mouth swabs with a Cq cutoff of 31.3. The human mtDNA test was then applied to buccal, tongue, and gum swabs that had previously been collected from TB patients and controls in South Africa, along with "air swabs" collected as negative controls (total N = 292 swabs from 71 subjects). Of these swabs, 287/292 (98%) exhibited the expected Cq values. In a paired analysis the three oral sites yielded indistinguishable amounts of human mtDNA, however PurFlockTM swabs collected slightly more human mtDNA than did OmniSwabsTM (p = 0.012). The results indicate that quantification of human mtDNA cannot distinguish swabs collected from different sites within the mouth. However, it can reliably distinguish oral swabs from swabs that were not used orally, which makes it a useful SAC for oral swab-based diagnosis.

Antibiotics and antimicrobial resistance in the COVID-19 era: Perspective from resource-limited settings.

The dissemination of COVID-19 around the globe has been followed by an increased consumption of antibiotics. This is related to the concern for bacterial superinfection in COVID-19 patients. The identification of bacterial pathogens is challenging in low and middle income countries (LMIC), as there are no readily-available and cost-effective clinical or biological markers that can effectively discriminate between bacterial and viral infections. Fortunately, faced with the threat of COVID-19 spread, there has been a growing awareness of the importance of antimicrobial stewardship programs, as well as infection prevention and control measures that could help reduce the microbial load and hence circulation of pathogens, with a reduction in dissemination of antimicrobial resistance. These measures should be improved particularly in developing countries. Studies need to be conducted to evaluate the worldwide evolution of antimicrobial resistance during the COVID-19 pandemic, because pathogens do not respect borders. This issue takes on even greater importance in developing countries, where data on resistance patterns are scarce, conditions for infectious pathogen transmission are optimal, and treatment resources are suboptimal.