Evaluation of the Abbott Alinity m STI assay for diagnosis of the primary causes of sexually transmitted infections in the United States.

Objectives: The sexually transmitted infections, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), and Mycoplasma genitalium (MG), have similar risk factors and symptoms, supporting use of a quadruplex test as an efficient diagnostic modality.We assessed the clinical and analytical performance of the Abbott Alinity m STI assay to detect these pathogens. Design and methods: Urine and genital swabs from 142 patient samples were tested from an adult outpatient population in the Northeast United States. The positive and negative percent agreement for CT, NG, and TV were determined by comparison with the Hologic Panther Aptima assay. The analytical sensitivity was determined through serial dilution of standards for CT, NG, TV, and MG in negative urine and swab matrix. Results: The positive and negative percent agreement of the Alinity m assay in comparison with the Hologic Panther Aptima assay were, respectively: CT [100.0% (90.6-100.0%) and 99.1% (94.8-100.0%)], NG [100.0% (89.6-100.0%) and 99.1% (94.9-100.0%)]; and TV [96.3% (81.7-99.8%) and 99.1% (95.2-100.0%)]. The limits of detection in urine and swab matrix were, respectively: CT ≤ 5, ≤1; NG ≤ 5, ≤5; TV ≤ 0.5, ≤0.5; and MG ≤ 500, ≤250 genome copies/mL. Conclusions: The Alinity m assay demonstrated excellent performance characteristics and identifies CT, NG, and TV accurately compared with a well-established comparator.

Association between bisphosphonate use and COVID-19 related outcomes.

Background: Although there are several efficacious vaccines against COVID-19, vaccination rates in many regions around the world remain insufficient to prevent continued high disease burden and emergence of viral variants. Repurposing of existing therapeutics that prevent or mitigate severe COVID-19 could help to address these challenges. The objective of this study was to determine whether prior use of bisphosphonates is associated with reduced incidence and/or severity of COVID-19. Methods: A retrospective cohort study utilizing payer-complete health insurance claims data from 8,239,790 patients with continuous medical and prescription insurance January 1, 2019 to June 30, 2020 was performed. The primary exposure of interest was use of any bisphosphonate from January 1, 2019 to February 29, 2020. Bisphosphonate users were identified as patients having at least one bisphosphonate claim during this period, who were then 1:1 propensity score-matched to bisphosphonate non-users by age, gender, insurance type, primary-care-provider visit in 2019, and comorbidity burden. Main outcomes of interest included: (a) any testing for SARS-CoV-2 infection; (b) COVID-19 diagnosis; and (c) hospitalization with a COVID-19 diagnosis between March 1, 2020 and June 30, 2020. Multiple sensitivity analyses were also performed to assess core study outcomes amongst more restrictive matches between BP users/non-users, as well as assessing the relationship between BP-use and other respiratory infections (pneumonia, acute bronchitis) both during the same study period as well as before the COVID outbreak. Results: A total of 7,906,603 patients for whom continuous medical and prescription insurance information was available were selected. A total of 450,366 bisphosphonate users were identified and 1:1 propensity score-matched to bisphosphonate non-users. Bisphosphonate users had lower odds ratios (OR) of testing for SARS-CoV-2 infection (OR = 0.22; 95%CI:0.21-0.23; p<0.001), COVID-19 diagnosis (OR = 0.23; 95%CI:0.22-0.24; p<0.001), and COVID-19-related hospitalization (OR = 0.26; 95%CI:0.24-0.29; p<0.001). Sensitivity analyses yielded results consistent with the primary analysis. Bisphosphonate-use was also associated with decreased odds of acute bronchitis (OR = 0.23; 95%CI:0.22-0.23; p<0.001) or pneumonia (OR = 0.32; 95%CI:0.31-0.34; p<0.001) in 2019, suggesting that bisphosphonates may protect against respiratory infections by a variety of pathogens, including but not limited to SARS-CoV-2. Conclusions: Prior bisphosphonate-use was associated with dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations. Prospective clinical trials will be required to establish a causal role for bisphosphonate-use in COVID-19-related outcomes. Funding: This study was supported by NIH grants, AR068383 and AI155865, a grant from MassCPR (to UHvA) and a CRI Irvington postdoctoral fellowship, CRI2453 (to PH).

The COVID-19 pandemic challenged the world to rapidly develop strategies to combat the virus responsible for the disease. While several effective vaccines and new drugs have since become available, these therapies are not always easy to access and take time to generate and distribute. To address these challenges, researchers have tried to find ways to repurpose existing medications that are already commonly used and known to be safe. One potential candidate are bisphosphonates, a family of drugs used to reduce bone loss in patients with osteoporosis. Bisphosphonates have been shown to boost the immune response to viral infections, and it has been observed that patients prescribed these drugs are less likely to develop or die from pneumonia. But whether bisphosphonates are effective against COVID-19 had not been fully explored. To investigate, Thompson, Wang et al. analyzed insurance claims data from about 8 million patients between January 2019 and June 2020, including around 450,000 individuals that had filled a prescription for bisphosphonates. Patients prescribed bisphosphonates were then compared to non-users that were similar in terms of their gender, age, the type of health insurance they had, their access to healthcare, and other health comorbidities. The study revealed that bisphosphonate users were around three to five times less likely to be tested for, diagnosed with, or hospitalized for COVID-19 during the first four months of the pandemic. They were also less commonly diagnosed with other respiratory infections in 2019, like bronchitis or pneumonia. Although the results suggest that bisphosphonates provide some protection against COVID-19, they cannot directly prove it. Verifying that bisphosphonates can treat or prevent COVID-19 and/or other respiratory infections requires more studies that follow patients in real-time rather than studying previously collected data. If such studies confirm the link, bisphosphonates could be a helpful tool to protect against COVID-19 or other virus outbreaks. The drugs are widely available, safe, and affordable, and therefore may provide an alternative for patients who cannot access other medications or vaccines.

Spontaneous Glycan Reattachment Following N-Glycanase Treatment of Influenza and HIV Vaccine Antigens.

In cells, asparagine/N-linked glycans are added to glycoproteins cotranslationally, in an attachment process that supports proper folding of the nascent polypeptide. We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution. This reaction, which we term N-glycanation, was confirmed by site-specific analysis of HA glycoforms by mass spectrometry prior to PNGase F exposure, during exposure to PNGase F, and after amidase removal. Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV. Covalent N-glycan reattachment was nonenzymatic as it occurred in the presence of metal ions that inhibit PNGase F activity. Rather, N-glycanation relied on a noncovalent assembly between protein and glycan, formed in the presence of the amidase, where linearization of the glycoprotein prevented this retention and subsequent N-glycanation. This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.

Comprehensive molecular detection of tick-borne phleboviruses leads to the retrospective identification of taxonomically unassigned bunyaviruses and the discovery of a novel member of the genus phlebovirus.

UNLABELLED: Until the recent emergence of two human-pathogenic tick-borne phleboviruses (TBPVs) (severe fever with thrombocytopenia syndrome virus [SFTSV] and Heartland virus), TBPVs have been neglected as causative agents of human disease. In particular, no studies have addressed the global distribution of TBPVs, and consequently, our understanding of the mechanism(s) underlying their evolution and emergence remains poor. In order to provide a useful tool for the ecological and epidemiological study of TBPVs, we have established a simple system that can detect all known TBPVs, based on conventional reverse transcription-PCR (RT-PCR) with degenerate primer sets targeting conserved regions of the viral L genome segment. Using this system, we have determined that several viruses that had been isolated from ticks decades ago but had not been taxonomically identified are novel TBPVs. Full-genome sequencing of these viruses revealed a novel fourth TBPV cluster distinct from the three known TBPV clusters (i.e., the SFTS, Bhanja, and Uukuniemi groups) and from the mosquito/sandfly-borne phleboviruses. Furthermore, by using tick samples collected in Zambia, we confirmed that our system had enough sensitivity to detect a new TBPV in a single tick homogenate. This virus, tentatively designated Shibuyunji virus after the region of tick collection, grouped into a novel fourth TBPV cluster. These results indicate that our system can be used as a first-line screening approach for TBPVs and that this kind of work will undoubtedly lead to the discovery of additional novel tick viruses and will expand our knowledge of the evolution and epidemiology of TBPVs. IMPORTANCE: Tick-borne phleboviruses (TBPVs) have been largely neglected until the recent emergence of two virulent viruses, severe fever with thrombocytopenia syndrome virus and Heartland virus. Little is known about the global distribution of TBPVs or how these viruses evolved and emerged. A major hurdle to study the distribution of TBPVs is the lack of tools to detect these genetically divergent phleboviruses. In order to address this issue, we have developed a simple, rapid, and cheap RT-PCR system that can detect all known TBPVs and which led to the identification of several novel phleboviruses from previously uncharacterized tick-associated virus isolates. Our system can detect virus in a single tick sample and novel TBPVs that are genetically distinct from any of the known TBPVs. These results indicate that our system will be a useful tool for the surveillance of TBPVs and will facilitate understanding of the ecology of TBPVs.