Impact of SARS-CoV-2 vaccination and booster on COVID-19 symptom severity over time in the COVID-OUT trial.

BACKGROUND: SARS-CoV-2 vaccination has decreasing protection from acquiring any infection with emergence of new variants; however, vaccination continues to protect against progression to severe COVID-19. The impact of vaccination status on symptoms over time is less clear. METHODS: Within a randomized trial on early outpatient COVID-19 therapy testing metformin, ivermectin, and/or fluvoxamine, participants recorded symptoms daily for 14 days. Participants were given a paper symptom diary allowing them to circle the severity of 14 symptoms as none (0), mild (1), moderate (2), or severe (3). This is a secondary analysis of clinical trial data on symptom severity over time using generalized estimating equations comparing those unvaccinated, SARS-CoV-2 vaccinated with primary vaccine series only, or vaccine-boosted. RESULTS: The parent clinical trial prospectively enrolled 1323 participants, of whom 1062 (80%) prospectively recorded some daily symptom data. Of these, 480 (45%) were unvaccinated, 530 (50%) were vaccinated with primary series only, and 52 (5%) vaccine-boosted. Overall symptom severity was least for the vaccine-boosted group and most severe for unvaccinated at baseline and over the 14 days (P < 0.001). Individual symptoms were least severe in the vaccine-boosted group including: cough, chills, fever, nausea, fatigue, myalgia, headache, and diarrhea, as well as smell and taste abnormalities. Results were consistent over delta and omicron variant time periods. CONCLUSIONS: SARS-CoV-2 vaccine-boosted participants had the least severe symptoms during COVID-19 which abated the quickest over time.

Female Gender Is Associated with Lower Satisfaction with Postoperative Telemedicine Visits in Sports Medicine.

Introduction: Telemedicine is a relatively new adjunct in orthopedic care but it has emerged from the periphery, driven in part by the COVID-19 pandemic. Although it has drastically increased in use, little is known of the factors that drive satisfaction with telemedicine. The purpose of the current study was to evaluate the patient's satisfaction with postoperative telemedicine visits in those undergoing knee or shoulder arthroscopy, and to analyze the factors associated with satisfaction with telemedicine. Methods: A prospective study was performed to evaluate satisfaction comparing postoperative telemedicine and in-office visits, in those undergoing shoulder and knee arthroscopy. Multiple factors were analyzed for correlation with satisfaction via multi-linear regression, including demographics such as gender, education, age, and race. Patients were also evaluated for preference for future visits with reference to the group in which they were placed. Results: Overall, 215 patients were included with a subgroup analysis of 93 patients receiving telemedicine visits. Patients reported overall similar satisfaction with telemedicine visits after shoulder and knee arthroscopy, with a high level of satisfaction seen in both. Female sex was found to be associated with decreasing satisfaction with telemedicine visits (p = 0.036). In addition, as a whole, the cohort was found to prefer future visits to be the same as the group they were placed in, but females statistically did not have this preference for their familiar group and were skewed toward the preference of in-person visits (p = 0.377). Conclusions: Our study found that female patients were less likely to be satisfied with postoperative telemedicine visits after knee or shoulder arthroscopy. Further, females were also less likely to indicate preference for future telemedicine visits. In contrast, education, history of prior surgery, age, and race were not associated with postoperative satisfaction.

Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19.

BACKGROUND: Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHODS: In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARS-CoV-2 vaccination and receipt of other trial medications. RESULTS: A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P = 0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P = 0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P = 0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine. CONCLUSIONS: None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19. (Funded by the Parsemus Foundation and others; COVID-OUT ClinicalTrials.gov number, NCT04510194.).

Management of Outpatient Elective Surgery for Arthroplasty and Sports Medicine During the COVID-19 Pandemic: A Scoping Review.

BACKGROUND: The onset of the coronavirus disease 2019 (COVID-19) pandemic has presented unforeseeable challenges to the orthopaedic community, especially arthroplasty and sports medicine subspecialities, as many surgeries were deemed nonessential and delayed. Although there is a glimpse of hope with the approval and distribution of vaccines, daily case numbers and death tolls continue to rise at the time of this review. PURPOSE: To summarize the available literature on the management of elective sports medicine and arthroplasty procedures in the outpatient setting to gather a consolidated source of information. STUDY DESIGN: Scoping review; Level of evidence, 5. METHODS: A scoping review of 3 databases (PubMed, Embase, and OVID Medline) was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. All retrospective and prospective analyses, systematic reviews and meta-analyses, expert opinions, and societal guidelines were included for review, with 29 articles meeting the inclusion criteria. RESULTS: Guidance for resumption of elective arthroplasty and sports medicine surgery and patient selection during the COVID-19 pandemic focuses on resource availability, patient fitness, and time sensitivity of the procedure, with patient and surgical team safety as the highest priority. Telemedicine and other innovative technology can be used to continue patient care during periods of delayed surgery through monitoring disease progression and offering nonoperative management options. CONCLUSION: While the current societal recommendations provide guidance on safety protocols and patient prioritization, each orthopaedic practice must consider its unique situation and use evidence-based medicine when determining surgical timing and patient selection.

Limited variation between SARS-CoV-2-infected individuals in domain specificity and relative potency of the antibody response against the spike glycoprotein (preprint)

The spike protein of SARS-CoV-2 is arranged as a trimer on the virus surface, composed of three S1 and three S2 subunits. Infected and vaccinated individuals generate antibodies against spike, which can neutralize the virus. Most antibodies target the receptor-binding domain (RBD) and N-terminal domain (NTD) of S1; however, antibodies against other regions of spike have also been isolated. The variation between infected individuals in domain specificity of the antibodies and in their relative neutralization efficacy is still poorly characterized. To this end, we tested serum and plasma samples from 85 COVID-19 convalescent subjects using 7 immunoassays that employ different domains, subunits and oligomeric forms of spike to capture the antibodies. Samples were also tested for their neutralization of pseudovirus containing SARS-CoV-2 spike and of replication-competent SARS-CoV-2. We observed strong correlations between the levels of NTD- and RBD-specific antibodies, with a fixed ratio of each type to all anti-spike antibodies. The relative potency of the response (defined as the measured neutralization efficacy relative to the total level of spike-targeting antibodies) also exhibited limited variation between subjects, and was not associated with the overall amount of anti-spike antibodies produced. Accordingly, the ability of immunoassays that use RBD, NTD and different forms of S1 or S1/S2 as capture antigens to estimate the neutralizing efficacy of convalescent samples was largely similar. These studies suggest that host-to-host variation in the polyclonal response elicited against SARS-CoV-2 spike is primarily limited to the quantity of antibodies generated rather than their domain specificity or relative neutralization potency. IMPORTANCEInfection by SARS-CoV-2 elicits antibodies against various domains of the spike protein, including the RBD, NTD and S2. Different infected individuals generate vastly different amounts of anti-spike antibodies. By contrast, as we show here, there is a remarkable similarity in the properties of the antibodies produced. Different individuals generate the same proportions of antibodies against each domain of the spike protein. Furthermore, the relationship between the amount of anti-spike antibodies produced and their neutralization efficacy of SARS-CoV-2 is highly conserved. Therefore, the observed variation in the neutralizing activity of the antibody response in COVID-19 convalescent subjects is caused by differences in the amounts of antibodies rather than their recognition properties or relative antiviral activity. These findings suggest that COVID-19 vaccine strategies that focus on enhancing the overall level of the antibodies will likely elicit a more uniformly efficacious protective response.