Characterization of the SARS-CoV-2 B.1.621 (Mu) variant.

The SARS-CoV-2 B.1.621 (Mu) variant emerged in January 2021 and was categorized as a variant of interest by the World Health Organization in August 2021. This designation prompted us to study the sensitivity of this variant to antibody neutralization. In a live virus neutralization assay with serum samples from individuals vaccinated with the Pfizer/BioNTech or Moderna mRNA vaccines, we measured neutralization antibody titers against B.1.621, an early isolate (spike 614D), and a variant of concern (B.1.351, Beta variant). We observed reduced neutralizing antibody titers against the B.1.621 variant (3.4- to 7-fold reduction, depending on the serum sample and time after the second vaccination) compared to the early isolate and a similar reduction when compared to B.1.351. Likewise, convalescent serum from hamsters previously infected with an early isolate neutralized B.1.621 to a lower degree. Despite this antibody titer reduction, hamsters could not be efficiently rechallenged with the B.1.621 variant, suggesting that the immune response to the first infection is adequate to provide protection against a subsequent infection with the B.1.621 variant.

Loop-Mediated Isothermal Amplification Detection of SARS-CoV-2 and Myriad Other Applications.

As the second year of the COVID-19 pandemic begins, it remains clear that a massive increase in the ability to test for SARS-CoV-2 infections in a myriad of settings is critical to controlling the pandemic and to preparing for future outbreaks. The current gold standard for molecular diagnostics is the polymerase chain reaction (PCR), but the extraordinary and unmet demand for testing in a variety of environments means that both complementary and supplementary testing solutions are still needed. This review highlights the role that loop-mediated isothermal amplification (LAMP) has had in filling this global testing need, providing a faster and easier means of testing, and what it can do for future applications, pathogens, and the preparation for future outbreaks. This review describes the current state of the art for research of LAMP-based SARS-CoV-2 testing, as well as its implications for other pathogens and testing. The authors represent the global LAMP (gLAMP) Consortium, an international research collective, which has regularly met to share their experiences on LAMP deployment and best practices; sections are devoted to all aspects of LAMP testing, including preanalytic sample processing, target amplification, and amplicon detection, then the hardware and software required for deployment are discussed, and finally, a summary of the current regulatory landscape is provided. Included as well are a series of first-person accounts of LAMP method development and deployment. The final discussion section provides the reader with a distillation of the most validated testing methods and their paths to implementation. This review also aims to provide practical information and insight for a range of audiences: for a research audience, to help accelerate research through sharing of best practices; for an implementation audience, to help get testing up and running quickly; and for a public health, clinical, and policy audience, to help convey the breadth of the effect that LAMP methods have to offer.

Accessing Patient Electronic Health Record Portals Safely Using Social Credentials: Demonstration Pilot Study.

BACKGROUND: Patient portals allow communication with clinicians, access to test results, appointments, etc, and generally requires another set of log-ins and passwords, which can become cumbersome, as patients often have records at multiple institutions. Social credentials (eg, Google and Facebook) are increasingly used as a federated identity to allow access and reduce the password burden. Single Federated Identity Log-in for Electronic health records (Single-FILE) is a real-world test of the feasibility and acceptability of federated social credentials for patients to access their electronic health records (EHRs) at multiple organizations with a single sign-on (SSO). OBJECTIVE: This study aims to deploy a federated identity system for health care in a real-world environment so patients can safely use a social identity to access their EHR data at multiple organizations. This will help identify barriers and inform guidance for the deployment of such systems. METHODS: Single-FILE allowed patients to pick a social identity (such as Google or Facebook) as a federated identity for multisite EHR patient portal access with an SSO. Binding the identity to the patient's EHR records was performed by confirming that the patient had a valid portal log-in and sending a one-time passcode to a telephone (SMS text message or voice) number retrieved from the EHR. This reduced the risk of stolen EHR portal credentials. For a real-world test, we recruited 8 patients and (or) their caregivers who had EHR data at 2 independent health care facilities, enrolled them into Single-FILE, and allowed them to use their social identity credentials to access their patient records. We used a short qualitative interview to assess their interest and use of a federated identity for SSO. Single-FILE was implemented as a web-based patient portal, although the concept can be readily implemented on a variety of mobile platforms. RESULTS: We interviewed the patients and their caregivers to assess their comfort levels with using a social identity for access. Patients noted that they appreciated only having to remember 1 log-in as part of Single-FILE and being able to sign up through Facebook. CONCLUSIONS: Our results indicate that from a technical perspective, a social identity can be used as a federated identity that is bound to a patient's EHR data. The one-time passcode sent to the patient's EHR phone number provided assurance that the binding is valid. The patients indicated that they were comfortable with using their social credentials instead of having to remember the log-in credentials for their EHR portal. Our experience will help inform the implementation of federated identity systems in health care in the United States.

Initial Evaluation of a Mobile SARS-CoV-2 RT-LAMP Testing Strategy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) control in the United States remains hampered, in part, by testing limitations. We evaluated a simple, outdoor, mobile, colorimetric reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay workflow where self-collected saliva is tested for SARS-CoV-2 RNA. From July 16, 2020, to November 19, 2020, surveillance samples (n = 4704) were collected from volunteers and tested for SARS-CoV-2 at 5 sites. Twenty-one samples tested positive for SARS-CoV-2 by RT-LAMP; 12 were confirmed positive by subsequent quantitative reverse-transcription polymerase chain reaction (qRT-PCR) testing, whereas 8 tested negative for SARS-CoV-2 RNA, and 1 could not be confirmed because the donor did not consent to further molecular testing. We estimated the false-negative rate of the RT-LAMP assay only from July 16, 2020, to September 17, 2020 by pooling residual heat-inactivated saliva that was unambiguously negative by RT-LAMP into groups of 6 or fewer and testing for SARS-CoV-2 RNA by qRT-PCR. We observed a 98.8% concordance between the RT-LAMP and qRT-PCR assays, with only 5 of 421 RT-LAMP-negative pools (2493 total samples) testing positive in the more-sensitive qRT-PCR assay. Overall, we demonstrate a rapid testing method that can be implemented outside the traditional laboratory setting by individuals with basic molecular biology skills and that can effectively identify asymptomatic individuals who would not typically meet the criteria for symptom-based testing modalities.

Pilot study of extended-release lorcaserin for cocaine use disorder among men who have sex with men: A double-blind, placebo-controlled randomized trial.

OBJECTIVE: To determine if men who have sex with men (MSM) with cocaine use disorder (CUD) and actively-using cocaine could be enrolled and retained in a pharmacologic intervention trial of lorcaserin-a novel 5-HT2cR agonist-and determine the degree to which participants would adhere to study procedures. METHODS: This was a phase II randomized, double-blind, placebo-controlled pilot study with 2:1 random parallel group assignment to daily extended-release oral lorcaserin 20 mg versus placebo (clinicaltrials.gov identifier-NCT03192995). Twenty-two of a planned 45 cisgender MSM with CUD were enrolled and had weekly follow-up visits during a 12-week treatment period, with substance use counseling, urine specimen collection, and completion of audio-computer assisted self-interview (ACASI) behavioral risk assessments. Adherence was measured by medication event monitoring systems (MEMS) caps and self-report. This study was terminated early because of an FDA safety alert for lorcaserin's long-term use. RESULTS: Eighty-six percent completed the trial, with 82% of weekly study follow-up visits completed. Adherence was 55.3% (lorcaserin 51.6% vs. placebo 66.2%) by MEMS cap and 56.9% (56.5% vs. placebo 57.9%) by self-report and did not differ significantly by treatment assignment. Intention-to-treat analyses (ITT) did not show differences in cocaine positivity by urine screen between the lorcaserin and placebo groups by 12 week follow-up (incidence risk ratio [IRR]: 0.96; 95%CI = 0.24-3.82, P = 0.95). However, self-reported cocaine use in timeline follow-back declined more significantly in the lorcaserin group compared to placebo (IRR: 0.66; 95%CI = 0.49-0.88; P = 0.004). CONCLUSION: We found that it is feasible, acceptable, and tolerable to conduct a placebo-controlled pharmacologic trial for MSM with CUD who are actively using cocaine. Lorcaserin was not associated with significant reductions in cocaine use by urine testing, but was associated with significant reductions in self-reported cocaine use. Future research may be needed to continue to explore the potential utility of 5-HT2cR agonists.

Safe and effective medication utilization in pediatric patients requiring rehabilitation services during the Coronavirus pandemic of 2019.

The role of pediatric rehabilitation providers during the Coronavirus Disease 2019 (COVID) pandemic of 2020 highlighted the need for improved knowledge about medications utilized in pediatric patients. Pediatric patients with cerebral palsy who were previously receiving botulinum toxin injections on a regular basis went prolonged periods of time between injections, and patients who have intrathecal baclofen pumps were called in to get refills with different intervals. The medically complex patients treated by rehabilitation providers were limited in the type and scope of care they received, and some may have developed adverse outcomes related to this delay in care. As a Pediatric Physiatrist who has advanced training and significant research experience within the realm of Clinical Pharmacology, I have seen this pandemic demonstrate the Sisyphean challenge of continuing appropriate tone management in patients with cerebral palsy while ensuring those patients with neuromuscular conditions maintain their highest level of function. Both of these clinical problems received significant attention within this issue, which I hope allows providers taking care of these populations a reference point to take to the bedside.

A risk-stratified approach toward safely resuming OnabotulinumtoxinA injections based on dosing and ambulatory status in pediatric patients with cerebral palsy during the Coronavirus pandemic of 2019 (COVID-19).

PURPOSE: After the onset of the Coronavirus pandemic of 2019-2020 (COVID-19), physicians who inject OnabotulinumtoxinA (BoNT-A) were left with determining risks and benefits in pediatric patients with cerebral palsy. Many of these patients have pre-existing conditions that make them more prone to COVID-19 symptoms, and this susceptibility potentially increases after BoNT-A injections. METHODS: A retrospective chart review of 500 patients identified 256 pediatric patients with cerebral palsy who received an intramuscular BoNT-A injection to determine relative doses used for each Gross Motor Functional Classification Score (GMFCS). Data regarding age, weight, GMFCS, BoNT-A total body dosage, and inpatient hospitalizations for 6 months post-injection were collected. Differences between GMFCS levels were analyzed using one-way analysis of variance testing. Inpatient hospitalizations were recorded and assessed using relative risk to determine the population risk of hospitalization in the setting of initiating injections during the COVID-19 pandemic. RESULTS: Based on GMFCS level, patients who were GMFCS I or II received fewer units of BoNT-A medication per kilogram of body weight compared to GMFCS III-V (p< 0.0005, F= 25.38). There was no statistically significant difference in frequency or time to hospitalization when comparing patients receiving BoNT-A compared to a control group. CONCLUSIONS: Resumption of BoNT-A injections during the time of COVID-19 requires a systematic approach based on risks and potential benefits. Data from this analysis does not show increased risk for patients who received injections historically; however, recommendations for resumption of injections has not previously been proposed in the setting of a pandemic. In this manuscript, a tiered approach to considerations for injections was proposed. Botulinum toxin type A injections have a history of improving spasticity in the pediatric patient with cerebral palsy. Ensuring appropriate selection of patients for injection with BoNT-A during this pandemic is increasingly important.