ABSTRACT
Using the VA COVID-19 National Database, we created matched pairs of previously uninfected vaccinated (≥2 doses of an mRNA vaccine) and previously infected unvaccinated individuals. The incidence rate (per 1000 person-days) of breakthrough infection among vaccinated individuals (0.30, 95% CI 0.29-0.32) was similar to reinfection rate among unvaccinated individuals (0.31, 95% CI 0.30-0.32; p=0.5). The incidence rate of hospitalization/death was higher after reinfection (7.31, 95% CI 6.66-8.03) compared with rate after breakthrough infection (4.69, 95% CI 4.06-5.42; P<0.0001). Conclusion: The incidence of hospitalization/death is significantly higher after reinfection among unvaccinated individuals compared with breakthrough infection after vaccination.
ABSTRACT
Screening for hepatitis D virus (HDV) is recommended for all individuals with hepatitis B virus (HBV) infection. Coinfected individuals experience more severe liver-related outcomes. We determined the HDV testing and coinfection rates and all-cause mortality among those infected with HBV. We used the US Department of Veterans Affairs (VA) healthcare system's national databases to identify individuals with HBV infection. We determined the proportion of individuals referred to gastroenterologists/hepatologists, or infectious diseases providers, and the proportion screened and tested positive for HDV. We calculated the HBV treatment rates, defined as ≥ 3 months of continuous prescription with an approved drug. Finally, we calculated all-cause mortality stratified by HDV coinfection and HBV treatment status. Among 44,951 individuals with at least one positive HBsAg, HBeAg or HBV DNA test, 5964 (13.3%) were screened for HDV (180 [3.0%] tested positive), and 28,291 (62.9%) were referred to gastroenterology/hepatology or infectious diseases. Treatment for HBV was prescribed for 73 (40.5%) of HDV-coinfected and 2425 (41.9%) HDV-uninfected individuals. All-cause mortality rate per 100 person-years was lower among those without HDV coinfection (2.98 for untreated HBV, 2.53 for treated HBV; p < 0.001) compared with those with HDV coinfection (5.14 for untreated HBV, 3.0 for treated HBV; p = 0.02). Kaplan-Meier curves demonstrated a significantly higher mortality among HDV-coinfected individuals who were not treated for HBV (log-rank p < 0.0001). Screening rates for HDV among HBV-infected individuals are suboptimal. While HDV coinfection is associated with higher all-cause mortality, HBV treatment may confer a survival benefit.
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Background and Aims: Severe outcomes of COVID-19 are associated with advancing age and comorbidities. The specific aim of our study was to determine the impact of COVID-19 on the clinical course and outcome of patients with cirrhosis. Methods: We retrieved data from VA national repository and identified patients tested for SARS-CoV-2 RNA who had cirrhosis. Each virus positive patient was propensity-matched with virus negative subjects by demographics and comorbidities. Primary endpoint was death within 30 days of COVID-19 diagnosis and secondary endpoint was hospitalization within 14 days. Results: Among 1,115,037 individuals tested for SARS-CoV-2 RNA, 31,680 had cirrhosis. Of those patients, 4456 virus positive patients were propensity-matched with 8752 virus negative subjects. In this cohort of 13,208, median age was 67 years and 95% were male. Most had multiple comorbidities. Alcohol use, hepatitis C and MASH were the dominant etiologies of cirrhosis. At baseline, median MELD was 6% and 21% had hepatic decompensation. Advanced age was the most significant determinant of hospitalization and mortality. Comorbidities, alcohol use and MELD increased the likelihood of hospitalization whereas SARS-CoV-2 positivity had lower Day-14 hospitalization hazard. MELD was associated with higher mortality hazard whereas vaccination reduced the hazard of hospitalization and death. SARS-CoV-2 positivity increased the hazard of death at Day-30 by 72% and at Day-90 by 26%. Conclusion: Although patients with cirrhosis who developed COVID-19 were less likely to be hospitalized, they were more likely to die within 30 days compared to their virus negative counterparts. Vaccination was effective in reducing both hospitalization and death.
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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.
Subject(s)
Antiviral Agents , COVID-19 Drug Treatment , COVID-19 , Cytidine , Disease Progression , Hospitalization , Hydroxylamines , Leucine , Ritonavir , SARS-CoV-2 , Humans , Male , Female , Ritonavir/therapeutic use , Middle Aged , Hydroxylamines/therapeutic use , Cytidine/analogs & derivatives , Cytidine/therapeutic use , COVID-19/mortality , COVID-19/epidemiology , Antiviral Agents/therapeutic use , Leucine/analogs & derivatives , Leucine/therapeutic use , Aged , SARS-CoV-2/isolation & purification , Proline/analogs & derivatives , Proline/therapeutic use , Indoles/therapeutic use , Adult , Pandemics , Risk Factors , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Pneumonia, Viral/drug therapy , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Betacoronavirus , Lactams , NitrilesABSTRACT
OBJECTIVE: To determine the association of nirmatrelvir/ritonavir (NMV/r) with hospitalization or death within 30 days as compared with untreated controls previously uninfected and nonhospitalized. METHODS: We used a matched cohort design using inverse probability of treatment weight (IPTW). Individuals prescribed NMV/r within 3 days of COVID-19 diagnosis were compared with IPTW-based untreated controls. Variables for IPTW included age, race, sex, body mass index, geographic location, vaccination status, and multiple comorbidities. Additional analyses were conducted on NMV/r-treated and propensity score-matched untreated controls. RESULTS: Among 7615 individuals prescribed NMV/r and 62 077 controls identified between 1 January 2022 and 25 February 2023, the risk of hospitalization/death was lower among NMV/r-treated persons vs untreated controls (243 vs 3468 events; absolute risk difference [ARD], -2.36 [95% CI, -2.57 to -2.14]). The difference was significant for those >60 and ≤60 years old (ARD, -3.86 [95% CI, -4.19 to -3.54] vs -0.27 [95% CI, -0.51 to -0.03]) and for persons asymptomatic and symptomatic (ARD, -7.09 [95% CI, -7.62 to -6.55] vs -1.46 [95% CI, -1.66 to -1.25]). Significant benefit was observed among individuals unvaccinated and vaccinated, with or without a booster dose. CONCLUSIONS: NMV/r is associated with a significant reduction in 30-day hospitalization or death among individuals previously uninfected and nonhospitalized.
Subject(s)
COVID-19 , Lactams , Leucine , Nitriles , Proline , Humans , Middle Aged , COVID-19 Drug Treatment , COVID-19 Testing , Cohort Studies , Ritonavir/therapeutic use , Hospitalization , Propensity Score , Antiviral Agents/therapeutic useABSTRACT
Background: Health-related quality of life is rapidly becoming recognized as an important indicator of how a disease affects patient lives and for evaluating the quality of care, especially for chronic conditions such as chronic kidney disease (CKD). Objectives: This study is an attempt to assess the quality of life in patients with chronic kidney disease at MMIMSR and also identify characteristics that may be associated with their worsening quality of life. Materials and Methods: This cross-sectional investigation was conducted at the in-patient department (IPD) of the MMIMSR hospital. This study included 105 CKD patients and used a systematic random sampling method for quantitative analysis. This study utilized a 36-item short-form SF-36 (v1.3) questionnaire to assess HRQoL in CKD patients. Descriptive statistics were employed at the baseline. Chi square and ANOVA were used to draw comparisons between two groups or more than two groups, respectively. Logistic regression analysis was utilized to identify the potential QoL determinants. A p value of 0.05 or lower was used to determine statistical significance. Results: Among a total of 105 participants, the mean (±standard deviation) age was found to be 54.53 ± 13.47 years; 48 were male patients, and 57 were female patients. Diabetes Mellitus (61.9%), hypertension (56.2%), chronic glomerulonephritis (7.6%), chronic pyelonephritis (6.7%), and polycystic kidney disease (5.7%) were identified to be the most frequent disorders associated with CKD. The current study also demonstrated that the HRQoL score domains such as symptom problem list, the effect of kidney disease, and the burden of kidney disease decline significantly and progressively as the patient advances into higher stages of CKD (p = 0.005). A similar pattern was observed in work status, sleep, and general health (p < 0.005). Additionally, a statistically significant difference was noted for cognitive function, quality of social interaction, overall health, dialysis staff encouragement, patient satisfaction, social support, physical functioning, role of physical health, pain, emotional well-being, role of emotional health, social functioning, and energy fatigue (p < 0.005). The mean difference for PCS and MCS based on CKD stages was found to be statistically significant (p < 0.005). The PCS and MCS showed a positive correlation with GFR (r = 0.521), and Hb (r = 0.378), GFR (r = 0.836), and Hb (r = 0.488), respectively. Conclusions: The findings of this study demonstrated that a significant decrease in HRQoL was observed among CKD patients, with a progressive deterioration of HRQoL dimensions as the patient advances to end-stage renal disease. This study also revealed that CKD imposes various restrictions on patients' day-to-day lives, particularly in terms of their physical and mental functioning, even in the initial stages of the disease.
Subject(s)
Quality of Life , Renal Insufficiency, Chronic , Humans , Male , Female , Adult , Middle Aged , Aged , Quality of Life/psychology , Cross-Sectional Studies , Renal Dialysis , Renal Insufficiency, Chronic/psychology , HospitalsABSTRACT
BACKGROUND: Clinical benefit of molnupiravir (MPV) in coronavirus disease 2019 (COVID-19)-infected subpopulations is unclear. METHODS: We used a matched cohort study design to determine the rate of hospitalization or death within 30 days of COVID-19 diagnosis among MPV treated and untreated controls. Participants were nonhospitalized, previously uninfected Veterans with a first confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection between 1 January and 31 August 2022, who were prescribed MPV within 3 days of COVID-19 diagnosis, and matched individuals who were not prescribed MPV. RESULTS: Among 1459 matched pairs, the incidence of hospitalization/death was not different among MPV treated versus untreated controls (48 vs 44 cases; absolute risk difference [ARD], 0.27; 95% confidence interval [CI], -.94 to 1.49). No benefit was observed among those >60 or ≤60 years old (ARD, 0.27; 95% CI, -1.25 to 1.79 vs ARD, -0.29; 95% CI, -1.22 to 1.80), those with specific comorbidities, or by vaccination status. A significant benefit was observed in asymptomatic but not in symptomatic persons (ARD, -2.80; 95% CI, -4.74 to -.87 vs ARD, 1.12; 95% CI -.31 to 2.55). Kaplan-Meier curves did not show a difference in proportion of persons who were hospitalized or died among MPV treated compared with untreated controls (logrank P = .7). CONCLUSIONS: MPV was not associated with a reduction in hospitalization or death within 30 days of COVID-19 diagnosis. A subgroup of patients presenting without symptoms experienced a benefit.
Subject(s)
COVID-19 , Humans , Middle Aged , SARS-CoV-2 , COVID-19 Testing , Cohort Studies , HospitalizationABSTRACT
Importance: Patients from racially and ethnically minoritized populations, such as Black and Hispanic patients, may be less likely to receive evidence-based COVID-19 treatments than White patients, contributing to adverse clinical outcomes. Objective: To determine whether clinical treatments and outcomes among patients hospitalized with COVID-19 were associated with race. Design, Setting, and Participants: This retrospective cohort study was conducted in 130 Department of Veterans Affairs Medical Centers (VAMCs) between March 1, 2020, and February 28, 2022, with a 60-day follow-up period until May 1, 2022. Participants included veterans hospitalized with COVID-19. Data were analyzed from May 6 to June 2, 2022. Exposures: Self-reported race. Main Outcomes and Measures: Clinical care processes (eg, intensive care unit [ICU] admission; organ support measures, including invasive and noninvasive mechanical ventilation; prone position therapy, and COVID-19-specific medical treatments) were quantified. Clinical outcomes of interest included in-hospital mortality, 60-day mortality, and 30-day readmissions. Outcomes were assessed with multivariable random effects logistic regression models to estimate the association of race with outcomes not attributable to known mediators, such as socioeconomic status and age, while adjusting for potential confounding between outcomes and mediators. Results: A total of 43â¯222 veterans (12â¯135 Black veterans [28.1%]; 31â¯087 White veterans [71.9%]; 40â¯717 [94.2%] men) with a median (IQR) age of 71 (62-77) years who were hospitalized with SARS-CoV-2 infection were included. Controlling for site of treatment, Black patients were equally likely to be admitted to the ICU (4806 Black patients [39.6%] vs 13â¯427 White patients [43.2%]; within-center adjusted odds ratio [aOR], 0.95; 95% CI, 0.88-1.02; P = .17). Two-thirds of patients treated with supplemental oxygen or noninvasive or invasive mechanical ventilation also received systemic steroids, but Black veterans were less likely to receive steroids (within-center aOR, 0.88; 95% CI, 0.80-0.96; P = .004; between-center aOR, 0.67; 95% CI, 0.48-0.96; P = .03). Similarly, Black patients were less likely to receive remdesivir (within-center aOR, 0.89; 95% CI, 0.83-0.95; P < .001; between-center aOR, 0.68; 95% CI, 0.47-0.99; P = .02) or treatment with immunomodulatory drugs (within-center aOR, 0.77; 95% CI, 0.67-0.87; P < .001). After adjusting for patient demographic characteristics, chronic health conditions, severity of acute illness, and receipt of COVID-19-specific treatments, there was no association of Black race with hospital mortality (within-center aOR, 0.98; 95% CI, 0.86-1.10; P = .71) or 30-day readmission (within-center aOR, 0.95; 95% CI, 0.88-1.04; P = .28). Conclusions and Relevance: These findings suggest that Black veterans hospitalized with COVID-19 were less likely to be treated with evidence-based COVID-19 treatments, including systemic steroids, remdesivir, and immunomodulatory drugs.
Subject(s)
COVID-19 , Veterans , Male , Humans , Aged , Female , COVID-19/therapy , SARS-CoV-2 , Retrospective Studies , Treatment Outcome , OxygenABSTRACT
BACKGROUND: Surgical randomized trials are difficult to accomplish. One major problem is recruitment of a sufficient number of patients to address the clinical problem. METHODS: We review the various ways patient recruitment in surgical RCTs can be promoted. We examine two landmark trials on the surgical treatment of temporal lobe epilepsy (TLE), one that was successful, and one which did not attain the target number of participants. DISCUSSION: Both designs of the Canadian and American trials of surgery for TLE included a benefit to participants: the Canadian trial gave a chance to have immediate access to investigation and treatment, as compared to a 1 year delay (considered 'standard care' in that center), while the American trial offered free surgical management to both arms. Patients were recruited and treatments randomly allocated prior to knowing for certain whether they were surgical candidates or not. This design choice may have helped circumvent the 'equipoise problem'. The Canadian trial offered participation to drug-resistant patients that were already routinely referred to surgical centers, while the success of the American trial which limited recruitment to the early period of drug resistance was dependent on a change of practice of referring clinicians which did not materialize. CONCLUSION: The surgical treatment of drug-resistant temporal lobe epilepsy has been validated using RCT methods. Ways to promote participation in surgical trials should be further investigated.
Subject(s)
Drug Resistant Epilepsy , Epilepsy, Temporal Lobe , Humans , Epilepsy, Temporal Lobe/drug therapy , Epilepsy, Temporal Lobe/surgery , Treatment Outcome , Canada , Randomized Controlled Trials as Topic , Temporal Lobe/surgeryABSTRACT
Background: Comparative effectiveness of coronavirus disease 2019 (COVID-19) vaccines across patient subgroups is poorly understood and essential to precisely targeting vaccination strategies. Methods: We used the US Department of Veterans Affairs COVID-19 Shared Data Resource to identify veterans who utilize VA health care and had no documented severe acute respiratory syndrome coronavirus 2 infection before December 11, 2020. Using a test-negative case-control design (TND), we used conditional logistic regression with adjustment for covariates to estimate vaccine effectiveness (VE) over time for veterans who received 2 doses of mRNA vaccines or 1 dose of Ad26.Cov2.S. Results: We identified 4.8 million veterans with a mean age of 64 years, of whom 58% had ≥1 chronic disease. Vaccine effectiveness for symptomatic infections, hospitalizations, and ICU admission or death declined over time and varied by the type of vaccine (P < 0.01). VE estimates against symptomatic infection during months 1 and 7 for mRNA-1273 compared with BNT162b2 were 89.7% (95% CI, 84.4%-93.0%) and 57.3% (95% CI, 48.4%-64.7%) vs 81.6% (95% CI, 75.9%-85.9%) and 22.5% (95% CI, 7.2%-35.2%) for individuals age <65 years and 78.4% (95% CI, 71.1%-83.9%) and 36.2% (95% CI, 27.7%-43.6%) vs 66.3% (95% CI, 55.7%-74.4%) and -23.3% (95% CI, -40.5% to -8.2%) in subjects age ≥65 years; against hospitalization 92.0% (95% CI, 76.1%-97.3%) and 83.1% (95% CI, 66.8%-91.4%) vs 85.6% (95% CI, 72.6%-92.4%) and 57.0% (95% CI, 31.2%-73.2%) in subjects age <65 years and 66.1% (95% CI, 45.3%-79.0%) and 64.7% (95% CI, 55.2%-72.3%) vs 61.0% (95% CI, 41.3%-74.2%) and 1.7% (95% CI, -22.0% to 20.8%) in those age ≥65 years; against ICU admission or death 89.2% (95% CI, 49.5%-97.7%) and 84.4% (95% CI, 59.0%-94.1%) vs 87.6% (95% CI, 61.0%-96.1%) and 66.4% (95% CI, 7.7%-87.8%) in subjects age <65 years and 75.4% (95% CI, 51.7%-87.5%) and 73.8 (95% CI, 62.9%-81.5%) vs 67.4% (95% CI, 32.6%-84.3%) and 29.3% (95% CI, 2.3%-48.9%) in subjects age ≥65 years, respectively (P interaction < .01 for all comparisons). Similarly, mRNA-1273 was more effective than BNT162b2 in veterans with >1 chronic disease. Conclusions: mRNA-1273 was more effective than BNT162b2 in older veterans and those with chronic diseases.
ABSTRACT
The SARS-CoV-2 Omicron variant is thought to cause less severe disease among the general population, but disease severity among at-risk populations is unknown. We performed a retrospective analysis using a matched cohort of United States veterans to compare the disease severity of subjects infected during Omicron and Delta predominant periods within 14 days of initial diagnosis. We identified 22,841 matched pairs for both periods. During the Omicron period, 20,681 (90.5%) veterans had mild, 1308 (5.7%) moderate, and 852 (3.7%) severe disease. During the Delta predominant period, 19,356 (84.7%) had mild, 1467 (6.4%) moderate, and 2018 (8.8%) severe disease. Moderate or severe disease was less likely during the Omicron period and more common among older subjects and those with more comorbidities. Here we show that infection with the Omicron variant is associated with less severe disease than the Delta variant in a high-risk older veteran population, and vaccinations provide protection against severe or critical disease.
Subject(s)
COVID-19 , Veterans , COVID-19/epidemiology , Cohort Studies , Humans , Retrospective Studies , SARS-CoV-2/genetics , Severity of Illness Index , United States/epidemiologyABSTRACT
BACKGROUND: The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may be less effective against the Omicron variant than against earlier variants. With recent resurgence of SARS-CoV-2 cases, the role of booster doses of the vaccine needs to be highlighted. METHODS: Using a retrospective cohort study design emulating a target trial, we determined the relative vaccine effectiveness (RVE) of a homologous booster dose of a SARS-CoV-2 messenger RNA (mRNA) vaccine compared with the primary vaccine series alone in preventing infection, hospitalization, and intensive care unit admission, and death in the Department of Veterans Affairs healthcare system in the United States. Among infection-free survivors who received 2 doses of a mRNA vaccine before 30 April 2021, we identified those who received a booster between 22 September and 25 December 2021 and matched them 1:1 with individuals who did not receive a booster. RESULTS: Among 2 384 272 previously uninfected persons with 2 doses of an mRNA vaccine by 30 April 2021, we identified 462 950 booster recipients between 22 September and 25 December 2021, who were matched 1:1 with non-booster recipients. The RVE (95% confidence interval) was 19% (17%-22%) for confirmed infection, 52% (46%-57%) for hospitalization, and 83% (65%-92%) for intensive care unit admission or death. Recipients of the mRNA-1273 vaccine had a lower cumulative incidence of infections and hospitalizations than recipients of the BNT162b2 vaccine (log-rank P <.001 for both comparisons). CONCLUSIONS: While the RVE of SARS-CoV-2 mRNA booster vaccine dose in preventing infection against the Omicron variant is low, it is substantial in preventing hospitalization and high in preventing the most severe/critical disease.
Subject(s)
COVID-19 , Vaccines , Humans , SARS-CoV-2 , 2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , Retrospective Studies , Vaccine Efficacy , RNA , RNA, Messenger , COVID-19 VaccinesABSTRACT
BACKGROUND: Knowledge of the vaccine effectiveness (VE) of a third or booster vaccine dose in preventing SARS-CoV-2 infection or its consequences is critical in developing recommendations for their use. We determined relative VE of 3 vs 2 doses of an mRNA vaccine in preventing symptomatic SARS-CoV-2 infection, hospitalization, and severe/critical disease. METHODS: Among veterans who had received 2 doses of an mRNA vaccine by 30 April 2021, we identified those who received a third dose of the same vaccine between 22 September and 24 November 2021 and 1:1 matched controls who had not received their third dose by then. Using Cox proportional hazards model, we calculated adjusted hazards ratios for symptomatic infection, hospitalization, and intensive care unit (ICU) admission or death after SARS-CoV-2-positive test. RESULTS: Among 2â 321â 366 veterans who received 2 doses of Pfizer BNT-162b2 or Moderna mRNA-1273 vaccine by 30 April 2021, we matched 395â 686 persons who received a third dose of the same vaccine between 22 September and 24 November 2021 to controls who did not receive a third dose. Adjusted HRs (95% CI) were .15 (.11-.21) for symptomatic infection and .18 (.13-.26) for hospitalizations for 3 vs 2 doses, corresponding to relative VE of 85% and 82%. Five ICU admissions or deaths were observed (4 among recipients of 2 doses). There was no difference in VE between BNT162b2 versus mRNA-1273 recipients. CONCLUSIONS: A third dose of a SARS-CoV-2 mRNA vaccine is associated with high VE against symptomatic infection, hospitalization, and critical disease in the pre-Omicron era.
Subject(s)
COVID-19 , Viral Vaccines , 2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2 , Vaccine Efficacy , Vaccines, Synthetic , mRNA VaccinesABSTRACT
BACKGROUND: Persons on chronic hemodialysis have a significantly diminished humoral immune response to SARS-CoV-2 vaccines. Whether this translates to reduced vaccine effectiveness (VE) is unknown. METHODS: We used the US Department of Veterans Affairs COVID-19 Shared Data Resource to identify all veterans who were tested for SARS-CoV-2 between 26 January and 31 August 2021. Using International Classification of Diseases, 10th edition, codes and attendance at a dialysis clinic/center, we identified those who were on chronic hemodialysis. We used a test-negative, case-control design using a doubly robust logistic regression model to determine the VE of the BNT-162b2 (Pfizer) or mRNA-1273 (Moderna) vaccines in preventing confirmed SARS-CoV-2 infection. RESULTS: Among 847 199 veterans tested for SARS-CoV-2 between 26 January and 31 August 2021, there were 6076 veterans on chronic hemodialysis. Among those, we identified 1270 cases (580 fully vaccinated) and 2959 controls (2120 fully vaccinated). The overall VE >14 days after the second dose in preventing documented infection was 68.2% (95% CI: 62.6-72.9%). VE was 68.9% (95% CI: 61.9-74.7%) for Pfizer BNT-162b2 and 66.7% (95% CI: 58.9-73.0%) for Moderna mRNA-1273 vaccine. There was no difference in VE by age (<70 vs >70 years), race, or sex. There were no events recorded in persons with a Charlson's comorbidity index score <2. CONCLUSIONS: VE of 2 doses of current mRNA vaccines in preventing SARS-CoV-2 infection in persons on chronic hemodialysis is lower than historic VE rates in the general population. Effects of additional doses in improving VE in this special population need further study.
Subject(s)
COVID-19 , Viral Vaccines , 2019-nCoV Vaccine mRNA-1273 , Aged , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Renal Dialysis , SARS-CoV-2 , Vaccines, Synthetic , mRNA VaccinesABSTRACT
BACKGROUND: Breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections after vaccination have been reported. Outcomes among persons with breakthrough infection are poorly understood. METHODS: We identified all veterans with a confirmed SARS-CoV-2 infectionâ >14 days after the second dose of an mRNA vaccine between 15 December 2020 and 30 June 2021 and propensity score-matched unvaccinated controls with SARS-CoV-2 infection. The primary outcome was severe/critical disease, defined as admission to an intensive care unit, need for mechanical ventilation, or death within 28 days of diagnosis or during index hospitalization. RESULTS: Among 502 780 vaccinated and 599 974 unvaccinated persons, there were 2332 (0.5%) breakthrough infections in the vaccinated group and 40 540 (6.8%) infections in the unvaccinated group over a follow-up period of 69 083 person-days in each group. Among these groups, we identified 1728 vaccinated persons with breakthrough infection (cases) and 1728 propensity score-matched unvaccinated controls with infection. Among the former, 95 (5.5%) persons met the criteria for severe/critical disease, while 200 (11.6%) persons met the criteria among the latter group. The incidence rate for severe/critical disease per 1000 person-days (95% confidence interval [CI]) was .55 (.45-.68) among vaccinated persons with breakthrough infection and 1.22 (1.07-1.41) among the unvaccinated matched controls who developed infection (Pâ <â .0001). Risk was higher; the hazard ratio (95% CI) with increasing age per 10-year increase was 1.25 (1.11-1.41); for those withâ >4 comorbidities, it was 2.85 (1.49-5.43), while being vaccinated was associated with strong protection against severe/critical disease (HR, 0.41; 95% CI: .32-.52). CONCLUSIONS: The rate of severe/critical disease is higher among older persons and those withâ >4 comorbidities but lower among fully vaccinated persons with breakthrough infection compared with unvaccinated controls who develop infection.
Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/prevention & control , Hospitalization , Humans , Risk Factors , Vaccination , Vaccines, Synthetic , mRNA VaccinesABSTRACT
New precise, responsive and selective univariate and multivariate chemometric spectrophotometric methods were developed and validated for determination of vandetanib (VTB), dasatinib (DTB), and sorafenib (SFB) in pure form, tablets, spiked human (plasma and urine). Determination of these drugs is essential because of their therapeutic benefits. These methods included double divisor ratio spectra derivative univariate method and chemometric multivariate method including partial least-squares (PLS) and principal component regression (PCR). A novel univariate method was developed for the estimation of these drugs. This method depends on the UV-Spectrophotometric data for simultaneous analysis of a ternary overlapped mixture. The Double divisor ratio spectra derivative absorption minima at 358.4 nm was used for quantification of VTB, absorption maxima at 300.3 nm for quantification of DTB and absorption maxima at 259.8 nm for quantification of SFB. This method shown a linearity in the extent of 2-9 µg/mL for VTB and DTB and over the concentration range of 3-9 µg/mL SFB within correlation coefficient (r2) of 0.9999. This method was successfully applied to pure form, tablet dosage form, spiked human (urine and plasma). Chemometric PLS and PCR models were found to be linear in the range of 2-9, 2-9, and 3-9 µg/mL for VTB, DTB and SFB, respectively. These models were estimated using eighteen mixtures as calibration set and seven mixtures as validation set. In the original data, the minimum root mean square error of prediction (RMSEP) was 0.11, 0.09 and 0.09 for VTB, DTB and SFB by PLS and 0.05, 0.04 and 0.03 by PCR while in the derivative data, the RMSEP was 0.09, 0.10 and 0.09 by PLS and 0.06, 0.06 and 0.03, by PCR for VTB, DTB and SFB, respectively. These methods were applied for the determination of the drugs in pure form and dosage form. Updating PLS model permitted the determination of the VTB, DTB and SFB in spiked human urine, plasma and drug-dissolution test of their tablet.
Subject(s)
Quinazolines , Calibration , Dasatinib , Humans , Least-Squares Analysis , Piperidines , Sorafenib , SpectrophotometryABSTRACT
BACKGROUND: Breakthrough infections after SARS-CoV-2 infection have been reported. Clinical outcomes among persons with breakthrough infection are not known. METHODS: We retrospectively identified all Veterans with a confirmed SARS-CoV-2 infection >14 days after the second dose of either Pfizer-BNT-162b2 or Moderna-mRNA-1273 vaccine between December 15, 2020 and March 30, 2021, and age, race, sex, body mass index, Charlson comorbidity index, geographical location, and date of positive test matched unvaccinated controls with SARS-CoV-2 infection. Our primary endpoint was the rate or severe disease defined as hospitalization, mechanical ventilation, or death in both groups. FINDINGS: Among 258,716 persons with both doses of vaccines and 756,150 without any vaccination, we identified 271 (0.1%) vaccinated persons with breakthrough infection and 48,114 (6.4%) unvaccinated matched controls with infection between December 15, 2020 and March 30, 2021. Among 213 matched pairs, symptoms were present in 33.3% of those with breakthrough infection and 42.2% of the controls. A total of 79 persons met the definition of severe disease or death (42 in the breakthrough infection group and 37 in the control group). Rate of severe disease or death per 1,000 person-days (95% CI) was 4.08 (2.64,5.31) among those with breakthrough infection and 3.6 (2.53,4.73) among the controls (P = 0.58). Rate was similar among both groups regardless of age-group, race, BMI or presence of comorbidities. Among persons with breakthrough infection and matched controls with infection, vaccination was not associated with a lower risk of severe disease or death in the main analyses but was associated with a lower risk when matching did not include geographic location (HR 0.62, 95% CI 0.43,0.91). INTERPRETATION: Demographic or clinical factors are not associated with a lower risk of severe disease or death in persons with breakthrough SARS-CoV-2 infection. FUNDING: None.
ABSTRACT
BACKGROUND: With the emergency use authorization of multiple vaccines against SARS-CoV-2 infection, data are urgently needed to determine their effectiveness in a real-world setting. OBJECTIVE: To evaluate the short-term effectiveness of vaccines in preventing SARS-CoV-2 infection. DESIGN: Test-negative case-control study using conditional logistic regression. SETTING: U.S. Department of Veterans Affairs health care system. PARTICIPANTS: All veterans who had testing for SARS-CoV-2 infection between 15 December 2020 and 4 March 2021 and no confirmed infection before 15 December 2020. INTERVENTION: SARS-CoV-2 vaccination with either the BNT-162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine as part of routine clinical care. MEASUREMENTS: Effectiveness of vaccination against confirmed SARS-CoV-2 infection. RESULTS: Among 54 360 persons who tested positive and 54 360 propensity score-matched control participants, the median age was 61 years, 83.6% were male, and 62% were White. Median body mass index was 31 kg/m2 among those who tested positive and 30 kg/m2 among those who tested negative. Among those who tested positive, 9800 (18.0%) had been vaccinated; among those who tested negative, 17 825 (32.8%) had been vaccinated. Overall vaccine effectiveness 7 or more days after the second dose was 97.1% (95% CI, 96.6% to 97.5%). Effectiveness was 96.2% (CI, 95.5% to 96.9%) for the Pfizer-BioNTech BNT-162b2 vaccine and 98.2% (CI, 97.5% to 98.6%) for the Moderna mRNA-1273 vaccine. Effectiveness remained above 95% regardless of age group, sex, race, or presence of comorbidities. LIMITATIONS: Predominantly male population; lack of data on disease severity, mortality, and effectiveness by SARS-CoV-2 variants of concern; and short-term follow-up. CONCLUSION: Currently used vaccines against SARS-CoV-2 infection are highly effective in preventing confirmed infection in a high-risk population in a real-world setting. PRIMARY FUNDING SOURCE: None.