Nirmatrelvir/ritonavir or Molnupiravir for treatment of non-hospitalized patients with COVID-19 at risk of disease progression.

BACKGROUND: In randomized controlled trials, Nirmatrelvir/ritonavir (NMV/r) and Molnupiravir (MPV) reduced the risk of severe/fatal COVID-19 disease. Real-world data are limited, particularly studies directly comparing the two agents. METHODS: Using the VA National COVID-19 database, we identified previously uninfected, non-hospitalized individuals with COVID-19 with ≥1 risk factor for disease progression who were prescribed either NMV/r or MPV within 3 days of a positive test. We used inverse probability of treatment weights (IPTW) to account for providers' preferences for a specific treatment. Absolute risk difference (ARD) with 95% confidence intervals were determined for those treated with NMV/r vs. MPV. The primary outcome was hospitalization or death within 30 days of treatment prescription using the IPTW approach. Analyses were repeated using propensity-score matched groups. RESULTS: Between January 1 and November 30, 2022, 9,180 individuals were eligible for inclusion (6,592 prescribed NMV/r; 2,454 prescribed MPV). The ARD for hospitalization/death for NMV/r vs MPV was -0.25 (95% CI -0.79 to 0.28). There was no statistically significant difference in ARD among strata by age, race, comorbidities, or symptoms at baseline. Kaplan-Meier curves did not demonstrate a difference between the two groups (p-value = 0.6). Analysis of the propensity-score matched cohort yielded similar results (ARD for NMV/r vs. MPV -0.9, 95% CI -2.02 to 0.23). Additional analyses showed no difference for development of severe/critical/fatal disease by treatment group. CONCLUSION: We found no significant difference in short term risk of hospitalization or death among at-risk individuals with COVID-19 treated with either NMV/r or MPV.

Risk factors for breakthrough SARS-CoV-2 infection in vaccinated healthcare workers.

BACKGROUND AND OBJECTIVE: The risk factors for breakthrough infections among healthcare workers (HCW) after completion of a full course of vaccination are poorly understood. Our objective was to determine the risk factors for breakthrough SARS-CoV-2 infection among HCWs at a national healthcare system in Qatar. METHODS: We identified all HCWs at Hamad Medical Corporation in Qatar between December 20, 2020 and May 18, 2021 with confirmed SARS-CoV-2 RT-PCR infection >14 days after the second vaccine dose. For each case thus identified, we identified one control with a negative test after December 20, 2020, matched on age, sex, nationality, job family and date of SARS-CoV-2 testing. We excluded those with a prior positive test and temporary workers. We used Cox regression analysis to determine factors associated with breakthrough infection. RESULTS: Among 22,247 fully vaccinated HCW, we identified 164 HCW who had breakthrough infection and matched them to 164 controls to determine the factors associated with SARS-CoV-2 breakthrough infection. In the breakthrough infection group the nursing and midwifery job family constituted the largest group, spouse was identified as the most common positive contact followed by a patient. Exposure to a confirmed case, presence of symptoms and all other job families except Allied Health Professionals when compared with nursing and Midwifery staff independently predicted infection. CONCLUSION: Presence of symptoms and contact with a confirmed case are major risk factors for breakthrough SARS-CoV-2 infection after vaccination, and these groups should be prioritized for screening even after full vaccination.

Prevalence and risk factors for SARS-CoV-2 infection and seroprevalence among clinical and non-clinical staff in a national healthcare system.

BACKGROUND: While many studies have reported the rate and risk of SARS-CoV-2 infection among healthcare workers (HCWs), there are scant data regarding the impact of employment type and job grades upon such risk. METHODS: We determined the rate of SARS-CoV-2 infection based on a positive nasopharyngeal swab (NPS) PCR among employees of a large national healthcare system. Antibody testing was performed on those who agreed to provide a blood sample. Using logistic regression analysis, we determined the risk of infection (PCR+) associated with demographic characteristics, job family and job grade. RESULTS: We identified 35,075 staff (30,849 full-time, 4,226 outsourced) between March 1-October 31, 2020. Among full-time employees, 78.0% had a NPS (11.8% positive). Among outsourced staff, 94.4% had a NPS (31.1% positive). Antibody testing was performed on 33.9% full-time employees (13.0% reactive), and on 39.1% of the outsourced staff (47.0% reactive). PCR-positivity was higher among outsourced staff (31.0% vs. 18.3% in non-clinical and 9.0% in clinical full-time employees) and those in the low-grade vs. mid-grade and high-grade job categories. Male sex (OR 1.88), non-clinical job family (OR 1.21), low-grade job category (OR 3.71) and being an outsourced staff (OR 2.09) were associated with a higher risk of infection. CONCLUSION: HCWs are a diverse population with varying risk of infection. Clinical staff are at a lower risk likely due to increased awareness and infection prevention measures. Risk is higher for those in the lower socioeconomic strata. Infection is more likely to occur in non-healthcare setting than within the healthcare facilities.

Digestive system involvement and clinical outcomes among COVID-19 patients: A retrospective cohort study from Qatar.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 virus most commonly presents with respiratory symptoms. While gastrointestinal (GI) manifestations either at presentation or during hospitalization are also common, their impact on clinical outcomes is controversial. Some studies have described worse outcomes in COVID-19 patients with GI symptoms, while others have shown either no association or a protective effect. There is a need for consistent standards to describe GI symptoms in COVID-19 patients and to assess their effect on clinical outcomes, including mortality and disease severity. AIM: To investigate the prevalence of GI symptoms in hospitalized COVID-19 patients and their correlation with disease severity and clinical outcomes. METHODS: We retrospectively reviewed 601 consecutive adult COVID-19 patients requiring hospitalization between May 1-15, 2020. GI symptoms were recorded at admission and during hospitalization. Demographic, clinical, laboratory, and treatment data were retrieved. Clinical outcomes included all-cause mortality, disease severity at presentation, need for intensive care unit (ICU) admission, development of acute respiratory distress syndrome, and need for mechanical ventilation. Multivariate logistic regression model was used to identify independent predictors of the adverse outcomes. RESULTS: The prevalence of any GI symptom at admission was 27.1% and during hospitalization was 19.8%. The most common symptoms were nausea (98 patients), diarrhea (76 patients), vomiting (73 patients), and epigastric pain or discomfort (69 patients). There was no difference in the mortality between the two groups (6.21% vs 5.5%, P = 0.7). Patients with GI symptoms were more likely to have severe disease at presentation (33.13% vs 22.5%, P < 0.001) and prolonged hospital stay (15 d vs 14 d, P = 0.04). There was no difference in other clinical outcomes, including ICU admission, development of acute respiratory distress syndrome, or need for mechanical ventilation. Drugs associated with the development of GI symptoms during hospitalization were ribavirin (diarrhea 26.37% P < 0.001, anorexia 17.58%, P = 0.02), hydroxychloroquine (vomiting 28.52%, P = 0.009) and lopinavir/ritonavir (nausea 32.65% P = 0.049, vomiting 31.47% P = 0.004, and epigastric pain 12.65% P = 0.048). In the multivariate regression analysis, age > 65 years was associated with increased mortality risk [odds ratio (OR) 7.53, confidence interval (CI): 3.09-18.29, P < 0.001], ICU admission (OR: 1.79, CI: 1.13-2.83, P = 0.012), and need for mechanical ventilation (OR: 1.89, CI:1.94-2.99, P = 0.007). Hypertension was an independent risk factor for ICU admission (OR: 1.82, CI:1.17-2.84, P = 0.008) and need for mechanical ventilation (OR: 1.66, CI: 1.05-2.62, P = 0.028). CONCLUSION: Patients with GI symptoms are more likely to have severe disease at presentation; however, mortality and disease progression is not different between the two groups.

Epidemiological investigation of the first 5685 cases of SARS-CoV-2 infection in Qatar, 28 February-18 April 2020.

OBJECTIVE: To define the epidemiological curve of COVID-19 in Qatar and determine factors associated with severe or critical illness. DESIGN: Case series of first 5685 COVID-19 cases in Qatar. SETTING AND PARTICIPANTS: All confirmed COVID-19 cases in the State of Qatar between 28 February and 18 April 2020. MAIN OUTCOME MEASURES: Number of total and daily new COVID-19 infections; demographic characteristics and comorbidity burden and severity of infection; factors associated with severe or critical illness. RESULTS: Between 28 February and 18 April 2020, 5685 cases of COVID-19 were identified. Median age was 34 (IQR 28-43) years, 88.9% were male and 8.7% were Qatari nationals. Overall, 83.6% had no concomitant comorbidity, and 3.0% had three or more comorbidities. The overwhelming majority (90.9%) were asymptomatic or with minimal symptoms, with 2.0% having severe or critical illness. Seven deaths were observed during the time interval studied. Presence of hypertension or diabetes was associated with a higher risk of severe or critical illness, but age was not. The epidemiological curve indicated two distinct patterns of infection, a larger cluster among expatriate craft and manual workers and a smaller one among Qatari nationals returning from abroad during the epidemic. CONCLUSION: COVID-19 infections in Qatar started in two distinct clusters, but then became more widespread in the population through community transmission. Infections were mostly asymptomatic or with minimal symptoms and associated with very low mortality. Severe/critical illness was associated with presence of hypertension or diabetes but not with increasing age.

COVID-19 infection among healthcare workers in a national healthcare system: The Qatar experience.

BACKGROUND: Our aim was to determine the prevalence of COVID-19 infection in healthcare workers (HCWs) in a national healthcare system and to understand the risk factors for infection. METHODS: The study was conducted at Hamad Medical Corporation (HMC) in Qatar, a national healthcare system with 14 hospitals and >28,000 employees, between March 10 and June 24, 2020. Data on COVID-19+ HCWs were retrieved from the electronic health records and employment records, followed by an email survey and a focused telephone interview. RESULTS: Among 16,912 HCWs tested, 10.6% tested positive. Hospitalization rate was 11.6%, 1.3% required supplemental oxygen, 0.6% needed intensive care unit admission, and 0.3% required mechanical ventilation. There were no deaths. In a follow-up survey of 393 HCWs, 5% reported acquiring infection at a COVID-19-designated facility and 95% at a non-COVID-19 facility having acquired the infection through accidental exposure to a colleague (45%) or a patient (29%). Full personal protective equipment (PPE) adherence was 82% at COVID-19-designated facilities but only 68% at non-COVID-19 facilities. CONCLUSIONS: COVID- 19 infection among HCWs often occurs among those not directly working with COVID-19 patients. PPE use is less stringent in such settings. Risk of exposure and need for strict PPE must be stressed upon all HCWs in all settings.

Treatment of HCV reduces viral hepatitis-associated liver-related mortality in patients: An ERCHIVES study.

BACKGROUND & AIMS: Treating HCV infection reduces overall mortality and reduces the risk of multiple extrahepatic complications. Whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications is unknown. METHODS: We identified HCV-positive individuals treated for HCV, and propensity score-matched them to HCV-positive/untreated and HCV-uninfected individuals in ERCHIVES between 2002-2016. We extracted cause of death data from the National Center for Health Statistics' National Death Index. Viral hepatitis-associated liver-related mortality rates among treated and untreated HCV-infected persons were calculated by treatment and attainment of sustained virologic response (SVR). RESULTS: Among 50,674 HCV-positive/treated (Group A), 31,749 HCV-positive/untreated (Group B) and 73,526 HCV-uninfected persons (Group C), 8.6% in Group A, 35.0% in Group B, and 14.3% in Group C died. Among those who died, viral hepatitis-associated liver-related mortality rates per 100 patient-years (95% CI) were: 0.28 (0.27-0.30) for Group A; 1.44 (1.38-1.49) for Group B; and 0.06 (0.05-0.06) for Group C; (p <0.0001 for both comparisons). Among HCV-positive/treated persons, rates were 0.06 (0.05-0.06) for those with SVR vs. 0.78 (0.74-0.83) for those without SVR. In competing risks Cox proportional hazards analysis, treatment with all-oral DAA regimens (adjusted hazard ratio 0.11; 95% CI 0.09-0.14) and SVR (adjusted hazard ratio 0.10; 95% CI 0.08-0.11) were associated with reduced hazards of liver-related mortality. CONCLUSIONS: Treatment for HCV is associated with a significant reduction in viral hepatitis-associated liver-related mortality, which is particularly pronounced in those treated with DAA regimens and those who attain SVR. This may account for a significant proportion of the reduction in all-cause mortality reported in previous studies. LAY SUMMARY: Treating hepatitis C virus (HCV) infection is known to reduce overall mortality. However, whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications was previously unknown. Herein, we show that while treating HCV with direct-acting antiviral regimens has numerous extrahepatic benefits, a significant benefit can be attributed specifically to the reduction in liver-related mortality.

Effect of Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ledipasvir/Sofosbuvir Regimens on Survival Compared With Untreated Hepatitis C Virus-Infected Persons: Results From ERCHIVES.

BACKGROUND: Interferon-based regimens are associated with a substantial survival benefit for persons infected with hepatitis C virus (HCV). Survival data with direct-acting antiviral agents are not available. We conducted this study to quantify the effect of paritaprevir/ritonavir, ombitasvir, dasabuvir (PrOD) and ledipasvir/sofosbuvir (LDV/SOF) regimens upon mortality. METHODS: In the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well-established national cohort of HCV-infected Veterans, we identified HCV-infected persons initiated on PrOD or LDV/SOF, excluding those with human immunodeficiency virus, hepatitis B surface antigen positivity, hepatocellular carcinoma, or missing HCV RNA or FIB-4 scores. For each case, we identified a propensity score-matched control never initiated on treatment. Primary outcome was survival. Outcomes were assessed using frequency of events, Kaplan-Meier curves, and Cox proportional hazards regression analyses. RESULTS: We identified 1473 persons on PrOD, 5497 on LDV/SOF, and 6970 propensity score-matched untreated persons. Treated persons were more likely to be obese and have cirrhosis, but less likely to have stage 3-5 chronic kidney disease (CKD), alcohol or drug abuse or dependence diagnosis, and anemia. The proportion of persons who died was higher in the untreated group compared with either treatment group (PrOD, 0.3%; LDV/SOF, 1.4%; untreated controls, 2.5%; P < .001). A significantly larger percentage of treated patients survived to 18 months of follow-up, compared with untreated controls (P < .001). In multivariable Cox regression analysis, treatment with either regimen (hazard ratio [HR], 0.43; 95% confidence interval [CI], .33-.57) and attainment of sustained virologic response (SVR) were associated with significantly lower mortality (HR, 0.57; 95% CI, .33-.99). CONCLUSIONS: Treatment with PrOD or LDV/SOF and SVR are associated with a significant mortality benefit, apparent within the first 18 months of treatment.

Antibiotic prescription patterns for upper respiratory tract infections in the outpatient Qatari population in the private sector.

BACKGROUND: Antibiotics are often inappropriately prescribed for upper respiratory tract infections (URTIs) in developed countries. Data on the proportion of inappropriate prescriptions are lacking from the Middle East and other developing countries. METHODS: Health insurance claims for all antibiotics prescribed for URTIs in the private sector in the State of Qatar between May 2014 and December 2015 were retrieved. During the study period, health insurance was limited to Qatari nationals. Topical antibiotics were excluded. Data on the prescriber's specialty, as listed with the licensing authority, were also retrieved. Diagnoses were classified as appropriate or inappropriate based on the likelihood of a bacterial etiology that may warrant antibiotic use. RESULTS: A total of 75 733 claims were made during the study period. Of these, 41 556 (55%) were for an appropriate indication, while 34 177 (45%) were for an inappropriate indication. The most common antibiotic classes prescribed were cephalosporins (43% of claims; 44% inappropriate), penicillins (28% of claims; 44% inappropriate), macrolides (19% of claims; 52% inappropriate), and fluoroquinolones (9% of claims; 40% inappropriate). Nearly 5% of antibiotics were prescribed in intravenous formulations. The most common prescribers were General/Family Practice physicians (53% of claims; 50% inappropriate), followed by Pediatrics (18.6% of claims; 36% inappropriate) and Internal Medicine (14.1% of claims; 44% inappropriate). CONCLUSIONS: There is a high rate of inappropriate antibiotic prescription for acute URTIs in the private health care sector in the State of Qatar. Further studies are needed to determine the population-based rates across the country. Interventions to decrease inappropriate use in such settings are urgently needed.

Prolonged Stay of Stroke Patients in the Emergency Department May Lead to an Increased Risk of Complications, Poor Recovery, and Increased Mortality.

BACKGROUND AND AIM: Following an acute stroke (AS), patients are at an increased risk of developing complications that may affect prognosis. With overcrowding in the emergency department (ED), patients stay longer hours to days before transfer to a proper stroke ward. The aim of this study was to evaluate the effect of increasing length of stay (LOS) in the ED on the risk of stroke-related complications. METHODS: We analyzed data from our stroke registry of patients admitted with AS during 2014. Stay in ED was divided into 2 groups: less than 8 hours and more than 8 hours. Data regarding demographics, stroke type, severity of stroke, ED (LOS) in hours, total LOS in hospital, number and types of complications, and prognosis were collected. RESULTS: Mean age was 54.8 years and 78.9% were males (total n = 894). Prior to ward admission, 265 (29.5%) patients remained in the ED for less than 8 hours and 629 (70.4%) remained for more than 8 hours. There was no significant difference in comorbidities or the severity of stroke at admission between the 2 groups. An ED LOS of less than 8 hours was associated with reduced risk of complications (14.3% versus 19.2%, P = .06), reduced LOS in hospital, better prognosis at discharge (72.5% versus 57.6% had modified Rankin Scale of ≤2, P = .001) and at 90 days (89% versus 78.8%, P = .007) and lower in-hospital mortality (1.5% versus 5.4 %, P = .004). CONCLUSION: Delays in transferring AS patients from the ED may lead to an increase in complications resulting in an increased LOS and slower recovery.