Development of SARS-CoV-2 infection in patients with rheumatic conditions on hydroxychloroquine monotherapy vs. patients without rheumatic conditions: A retrospective, propensity-matched cohort study.

BACKGROUND: The primary purpose of the current study was to examine whether patients with rheumatologic conditions receiving only chronic hydroxychloroquine therapy for their disease are at less risk of developing SARS-CoV-2 infection than a comparative group of patients without rheumatologic conditions. METHODS: A retrospective, observational, nationwide stratified propensity analysis was conducted comparing patients only on chronic treatment with hydroxychloroquine for their rheumatologic condition to a random sample of patients without rheumatologic conditions and not receiving hydroxychloroquine, utilizing a Veterans Health Administration nationwide clinical administrative database. RESULTS: The 1-to-1 stratified propensity analysis was undertaken using a random sample of patients without rheumatoid conditions and not receiving hydroxychloroquine (n  33,081) and patients with rheumatoid conditions receiving hydroxychloroquine as the lone medication for their condition (n  6047). A total of 5,474 patients in each group were successfully matched. The incidence of documented SARS-CoV-2 infections during the study period did not differ between patients receiving hydroxychloroquine and patients not receiving hydroxychloroquine (41/5,474 [0.749%] vs. 36/5,474 [0.658%], respectively, p = 0.57; Odds ratio [OR] 1.14, 95% confidence interval [CI] 0.73-1.79). There were no statistically-significant differences in secondary outcomes between the two groups in patients who developed active SARS-CoV-2 infection. Multivariate logistic regression to determine independent variables associated with the development of active SARS-CoV-2 infection failed to include receipt of hydroxychloroquine (OR 0.99, 95% CI 0.62-1.56). CONCLUSIONS: Hydroxychloroquine failed to demonstrate a preventative effect against SARS-CoV-2 infection in a large group of patients with rheumatologic conditions compared to patients without rheumatologic conditions.

Characteristics and outcomes of US Veterans at least 65 years of age at high risk of severe SARS-CoV-2 infection with or without receipt of oral antiviral agents.

OBJECTIVES: Molnupiravir and nirmatrelvir/ritonavir each became available in the United States (US) through the Food and Drug Administration (FDA) emergency use authorization (EUA) in December 2021 after their respective initial prospective randomized controlled trials demonstrated efficacy for patients with mild-to-moderate SARS-CoV-2 active infection considered to be at high risk for progression of disease and hospitalization. Although sufficiently powered for this wide group, the mean age for patients in these studies was only 43 and 46 years of age, respectively. We sought to compare outcomes of US Veterans 65 years and older who received either of these oral antivirals to those who did not receive oral antivirals for mild-to-moderate SARS-CoV-2 active infection. METHODS: The current project was a retrospective, observational, nationwide propensity-matched analysis comparing outcomes of US Veterans 65 years and older who received either of these oral antivirals to US Veterans 65 years and older who did not receive oral antivirals for mild-to-moderate SARS-CoV-2 active infection. RESULTS: The composite primary outcome of admission or death within 30 days of diagnosis was reached less often in those receiving either molnupiravir or nirmatrelvir/ritonavir versus those that received no antiviral (65/1370 [4.75%] vs. 139/1370 [10.2%]; odds ratio 0.44, 95% confidence interval 0.32-0.60, p<0.0001). Baseline differences between Veterans selected for molnupiravir vs. nirmatrelvir/ritonavir therapy were noted, particularly in the number of concomitant medications with cautions or contraindications with nirmatrelvir/ritonavir. CONCLUSIONS: Our findings support the use of molnupiravir or nirmatrelvir/ritonavir in patients 65 years of age and older. Patients with higher medication caution and contraindication burdens to nirmatrelvir/ritonavir are selected for molnupiravir therapy, which in the absence of a prospective head-to-head trial, may limit any efforts to compare the effectiveness of the two drugs.

Feasibility study: Proposed alternative to N95 respirator during the personal protective equipment shortage from COVID-19 pandemic.

INTRODUCTION: Having an adequate supply of personal protective equipment during the COVID-19 pandemic has been a constant challenge for hospitals across the United States. In the event of shortages, our assembled mask might offer noninferior protection compared to an N95 respirator. OBJECTIVE: To study the ability of an assembled mask to pass a quantitative fit testing. METHODS: We conducted a feasibility study at the Oklahoma City Veteran Affairs Health Care System. Volunteers were fitted with an assembled mask made of either a Hans Rudolph half-face mask or a Respironics Performax full-face mask, attached to an Iso-Gard HEPA light Filter 28022 through a Performax SE elbow hinge. Quantitative fit testing was conducted using the Occupation Safety and Health Administration fit testing protocol. The primary outcome was the percentage of participants who pass the quantitative fit test. Secondary outcomes included the overall fit factor (FF), average FF for different exercises, changes in pulse oximetry and end-tidal CO2 at 0 and 15 minutes, willingness to use the mask, and visibility assessment. RESULTS: Twenty participants completed the study, and all (100 percent) passed the quantitative fit testing. The overall FF had a geometric mean of 2,317 (range: 208-16,613) and a geometric standard deviation of 3.8. The lowest FF was recorded while the subjects were talking. Between time 0 and 15 minutes, there was no clinically significant change in pulse oximetry and end-tidal CO2 levels. Most participants reported "very good" visibility and were "highly likely" to use the Hans Rudolph half-face mask in the case of shortage. CONCLUSION: Our assembled respirator offers noninferior protection to N95 respirators in the setting of hypothetical protective equipment shortage.

Increased procoagulant platelet levels are predictive of death in COVID-19.

Prior research has identified abnormal platelet procoagulant responses in COVID-19. Coated-platelets, a form of procoagulant platelets, support thrombin formation and are elevated in ischemic stroke patients with increased risk for recurrent infarction. Our goal was to examine changes in coated-platelet levels over the course of COVID-19 infection and determine their association with disease severity, thrombosis, and death. Coated-platelet levels were assayed after admission and repeated weekly in COVID-19 patients, and in COVID-19 negative controls. Receiver operator characteristic (ROC) analysis was used to calculate area under the curve (AUC) values for a model including baseline coated-platelets to predict death. Kaplan-Meier and Cox proportional hazards analysis was used to predict risk for death at 90 days. We enrolled 33 patients (22 with moderate and 11 with severe infection) and 20 controls. Baseline coated-platelet levels were lower among moderate (mean ± SD; 21.3 ± 9.8%) and severe COVID-19 patients (28.5 ± 11.9%) compared to controls (38.1 ± 10.4%, p < 0.0001). Coated-platelet levels increased during follow-up in COVID-19 patients by 7% (relative) per day from symptom onset (95% CI 2-12%, p = 0.007). A cut-off of 33.9% for coated-platelet levels yielded 80% sensitivity and 96% specificity for death at 90 days, with resulting AUC of 0.880 (95% CI 0.680-1.0, p = 0.0002). The adjusted hazard ratio for death in patients with coated-platelet levels > 33.9% was 40.99 when compared to those with levels ≤ 33.9% (p < 0.0001). Platelet procoagulant potential is transiently decreased in most patients during COVID-19; however, increased baseline platelet procoagulant levels predict death. Defining the mechanisms involved and potential links with aging may yield novel treatment targets.

Mycobacterium neoaurum Bloodstream Infection Associated with a Totally Implanted Subclavian Port in an Adult with Diabetes and History of Colon Cancer.

Background. Mycobacterium neoaurum is a rapidly growing nontuberculosis mycobacterium (NTM) that was first isolated from soil in 1972 and is ubiquitous in soil, water, and dust. The first reported case of human infection by M. neoaurum was published in 1988, presenting as a Hickman catheter-related bacteremia in a patient with ovarian cancer. M. neoaurum has since been recognized as a source of predominantly opportunistic bloodstream infections in immunocompromised hosts. We report the case of an adult diabetic male with M. neoaurum bloodstream infection secondary to an infected venous-access port that had been implanted nearly six years prior for temporary chemotherapy. Case Presentation. A 66-year-old male with schizophrenia, type 2 diabetes mellitus, and a history of excision and chemotherapy to treat adenocarcinoma of the colon 6 years prior, presented with fever and behavioral changes. He was found to have a M. neoaurum bloodstream infection secondary to his implanted subclavian port. Multiple preoperative blood cultures, as well as the removed catheter tip culture, were positive for M. neoaurum. The patient's condition improved to near premorbid levels after port removal and 6 weeks of targeted antimicrobial therapy. Discussion and Conclusions. Bloodstream infections due to rapidly growing NTM, such as M. neoaurum, have been infrequently reported; however, improved isolation and identification techniques based on genomic testing are resulting in a more in-depth recognition of these widely scattered environmental microbes in human infections. Nonetheless, lengthy identification and susceptibility processes remain a diagnostic and treatment barrier. Patients such as ours who have a history of malignancy and an indwelling foreign body have most often been reported as acquiring M. neoaurum bacteremia. Fortunately, device removal and appropriate antimicrobial therapy guided by susceptibility data is often enough to manage these atypical mycobacterial infections.

Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study.

BACKGROUND: Hydroxychloroquine is one of several agents being evaluated in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to examine whether patients with rheumatological conditions receiving chronic hydroxychloroquine therapy are at less risk of developing SARS-CoV-2 infection than those not receiving hydroxychloroquine. METHODS: This retrospective cohort study included de-identified information of all veterans in the US Veterans Health Administration clinical administrative database aged 18 years or older with rheumatoid arthritis, systemic lupus erythematosus, or associated rheumatological conditions (based on International Classification of Diseases, 10th edition, diagnostic codes) who were alive on March 1, 2020. A propensity score was calculated for each patient, and each patient who was receiving hydroxychloroquine was matched to two patients who were not receiving hydroxychloroquine (controls). The primary endpoint was the proportion of patients with PCR-confirmed SARS-CoV-2 infection among those receiving chronic hydroxychloroquine versus the propensity-matched patients not receiving chronic hydroxychloroquine between March 1 and June 30, 2020. Secondary outcomes were hospital admission associated with SARS-CoV-2 infection; intensive care requirement associated with SARS-CoV-2 infection; mortality associated with SARS-CoV-2 infection; and overall rates of any hospital admission and mortality (ie, all cause). Multivariate logistic regression analysis was done to determine independent variables for the development of active SARS-CoV-2 infection. FINDINGS: Between March 1 and June 30, 2020, 10 703 patients receiving hydroxychloroquine and 21 406 patients not receiving hydroxychloroquine were included in the primary analysis. The incidence of active SARS-CoV-2 infections during the study period did not differ between patients receiving hydroxychloroquine and patients not receiving hydroxychloroquine (31 [0·3%] of 10 703 vs 78 [0·4%] of 21 406; odds ratio 0·79, 95% CI 0·52-1·20, p=0·27). There were no significant differences in secondary outcomes between the two groups in patients who developed active SARS-CoV-2 infection. For all patients in the study, overall mortality was lower in the hydroxychloroquine group than in the group of patients who did not receive hydroxychloroquine (odds ratio 0·70, 95% CI 0·55-0·89, p=0·0031). In multivariate logistic regression analysis, receipt of hydroxychloroquine was not associated with the development of active SARS-CoV-2 infection (odds ratio 0·79, 95% CI 0·51-1·42). INTERPRETATION: Hydroxychloroquine was not associated with a preventive effect against SARS-CoV-2 infection in a large group of patients with rheumatological conditions. FUNDING: None.