Modeling HCV elimination recovery following the COVID-19 pandemic in the United States: Pathways to regain progress.

BACKGROUND: As of 2019, the United States (US) was not on track to achieve targets for elimination, due to increasing incidence and treatment barriers. In 2020, the COVID-19 pandemic disrupted HCV services globally and in the US. As healthcare services normalize, there is an urgent need to reassess progress and evaluate scenarios that restore a pathway toward HCV elimination. METHODS: We updated a validated Markov model to estimate HCV-related morbidity and mortality in the US. Five scenarios were developed to bookend possible HCV outcomes in the wake of the pandemic. These included 1) return to pre-COVID-19 treatment forecasts; 2) achieve elimination targets through treatment and harm reduction; 3) long-term treatment disruptions; 4/5) achieve elimination targets through increased treatment without increased harm reduction, starting in either 2022 or 2025. FINDINGS: From 2014-2019, more than 1.2 million patients were treated for HCV in the US. Elimination targets in 2030 could be achieved in the US by treating an additional 3.2-3.3 million patients from 2020 to 2030, or by preventing new infections through expanded harm reduction programs and treating up to 2.7 million patients. Intervention scenarios could prevent over 30,000 HCC cases and over 29,000 liver-related deaths. INTERPRETATION: The US has made strides toward HCV elimination, but gains could be lost in the wake of the pandemic. However, it is still possible to avert nearly 30,000 deaths through increased harm reduction and increased treatment rates. This requires a coordinated effort from the entire HCV community.

Effectiveness of Remdesivir Treatment Protocols Among Patients Hospitalized with COVID-19: A Target Trial Emulation.

BACKGROUND: Remdesivir is recommended for certain hospitalized patients with COVID-19. However, these recommendations are based on evidence from small randomized trials, early observational studies, or expert opinion. Further investigation is needed to better inform treatment guidelines with regard to the effectiveness of remdesivir among these patients. METHODS: We emulated a randomized target trial using chargemaster data from 333 US hospitals from 1 May 2020 to 31 December 2021. We compared three treatment protocols: remdesivir within 2 days of hospital admission, no remdesivir within the first 2 days of admission, and no remdesivir ever. We used baseline comorbidities recorded from encounters up to 12 months before admission and identified the use of in-hospital medications, procedures, and oxygen supplementation from charges. We estimated the cumulative incidence of mortality or mechanical ventilation/extracorporeal membrane oxygenation with an inverse probability of censoring weighted estimator. We conducted analyses in the total population as well as in subgroups stratified by level of oxygen supplementation. RESULTS: A total of 274,319 adult patients met the eligibility criteria for the study. Thirty-day in-hospital mortality risk differences for patients adhering to the early remdesivir protocol were -3.1% (95% confidence interval = -3.5%, -2.7%) compared to no early remdesivir and -3.7% (95% confidence interval -4.2%, -3.2%) compared to never remdesivir, with the strongest effect in patients needing high-flow oxygen. For mechanical ventilation/extracorporeal membrane oxygenation, risk differences were minimal. CONCLUSIONS: We estimate that, among hospitalized patients with COVID-19, remdesivir treatment within 2 days of admission reduced 30-day in-hospital mortality, particularly for patients receiving supplemental oxygen on the day of admission.

COVID-19 therapeutics and outcomes among solid organ transplant recipients during the Omicron BA.1 era.

Treatment outcomes associated with the use of novel COVID-19 therapeutics in solid organ transplant recipients (SOTR) are not well described in the literature. The objective of this analysis was to characterize 30-day hospitalization and other key secondary endpoints experienced by outpatient SOTR with mild-moderate COVID-19 treated with nirmatrelvir/ritonavir (NR), sotrovimab, or no SARS-CoV-2 specific treatment. This IRB-approved, retrospective study included 154 SOTR with a documented positive SARS-CoV-2 infection between December 16, 2021 and January 19, 2022 (a predominant Omicron BA.1 period in New York City). Patients who received NR (N = 28) or sotrovimab (N = 51) experienced a lower rate of 30-day hospitalization or death as compared to those who received no specific treatment (N = 75) (p = .009). A total of three deaths occurred, all among patients who initially received no specific treatment prior to hospitalization. These results suggest a role for SARS-CoV-2 specific agents in the treatment of SOTR with COVID-19, and that there does not appear to be any difference in effectiveness when comparing NR versus sotrovimab.

Factors Associated With Readmission in the United States Following Hospitalization With Coronavirus Disease 2019.

BACKGROUND: Patients hospitalized for coronavirus disease 2019 (COVID-19) may experience complications following hospitalization and require readmission. In this analysis, we estimated the rate and risk factors associated with COVID-19-related readmission and inpatient mortality. METHODS: In this retrospective cohort study, we used deidentified chargemaster data from 297 hospitals across 40 US states on patients hospitalized with COVID-19 from 15 February 2020 through 9 June 2020. Demographics, comorbidities, acute conditions, and clinical characteristics of first hospitalization are summarized. Multivariable logistic regression was used to measure risk factor associations with 30-day readmission and in-hospital mortality. RESULTS: Among 29 659 patients, 1070 (3.6%) were readmitted. Readmitted patients were more likely to have diabetes, hypertension, cardiovascular disease (CVD), or chronic kidney disease (CKD) vs those not readmitted (P < .0001) and to present on first admission with acute kidney injury (15.6% vs 9.2%), congestive heart failure (6.4% vs 2.4%), or cardiomyopathy (2.1% vs 0.8%) (P < .0001). Higher odds of readmission were observed in patients aged >60 vs 18-40 years (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.48-2.50) and those admitted in the Northeast vs West (OR, 1.43; 95% CI, 1.14-1.79) or South (OR, 1.28; 95% CI, 1.11-1.49). Comorbidities including diabetes (OR, 1.34; 95% CI, 1.12-1.60), CVD (OR, 1.46; 95% CI, 1.23-1.72), CKD stage 1-5 (OR, 1.51; 95% CI, 1.25-1.81), and CKD stage 5 (OR, 2.27; 95% CI, 1.81-2.86) were associated with higher odds of readmission; 12.3% of readmitted patients died during second hospitalization. CONCLUSIONS: Among this large US population of patients hospitalized with COVID-19, readmission was associated with certain comorbidities and acute conditions during first hospitalization. These findings may inform strategies to mitigate risks of readmission due to COVID-19 complications.

Niacinamide May Be Associated with Improved Outcomes in COVID-19-Related Acute Kidney Injury: An Observational Study.

Background: AKI is a significant complication of coronavirus disease 2019 (COVID-19), with no effective therapy. Niacinamide, a vitamin B3 analogue, has some evidence of efficacy in non-COVID-19-related AKI. The objective of this study is to evaluate the association between niacinamide therapy and outcomes in patients with COVID-19-related AKI. Methods: We implemented a quasi-experimental design with nonrandom, prospective allocation of niacinamide in 201 hospitalized adult patients, excluding those with baseline eGFR <15 ml/min per 1.73 m2 on or off dialysis, with COVID-19-related AKI by Kidney Disease Improving Global Outcomes (KDIGO) criteria, in two hospitals with identical COVID-19 care algorithms, one of which additionally implemented treatment with niacinamide for COVID-19-related AKI. Patients on the niacinamide protocol (B3 patients) were compared against patients at the same institution before protocol commencement and contemporaneous patients at the non-niacinamide hospital (collectively, non-B3 patients). The primary outcome was a composite of death or RRT. Results: A total of 38 out of 90 B3 patients and 62 out of 111 non-B3 patients died or received RRT. Using multivariable Cox proportional hazard modeling, niacinamide was associated with a lower risk of RRT or death (HR, 0.64; 95% CI, 0.40 to 1.00; P=0.05), an association driven by patients with KDIGO stage-2/3 AKI (HR, 0.29; 95% CI, 0.13 to 0.65; P=0.03; P interaction with KDIGO stage=0.03). Total mortality also followed this pattern (HR, 0.17; 95% CI, 0.05 to 0.52; in patients with KDIGO stage-2/3 AKI, P=0.002). Serum creatinine after AKI increased by 0.20 (SEM, 0.08) mg/dl per day among non-B3 patients with KDIGO stage-2/3 AKI, but was stable among comparable B3 patients (+0.01 [SEM, 0.06] mg/dl per day; P interaction=0.03). Conclusions: Niacinamide was associated with lower risk of RRT/death and improved creatinine trajectory among patients with severe COVID-19-related AKI. Larger randomized studies are necessary to establish a causal relationship.

Early clinical experience with nirmatrelvir/ritonavir for the treatment of COVID-19 in solid organ transplant recipients.

Nirmatrelvir/ritonavir (NR) use has not yet been described in solid organ transplant recipients (SOTRs) with mild COVID-19. The objective was to evaluate outcomes among SOTR and describe the drug-drug interaction of NR. This is an IRB-approved, retrospective study of all adult SOTR on a calcineurin inhibitor (CNI) or mammalian target of rapamycin inhibitor who were prescribed NR between December 28, 2021 and January 6, 2022. A total of 25 adult SOTR were included (n = 21 tacrolimus, n = 4 cyclosporine, n = 3 everolimus, n = 1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of NR: hold tacrolimus or mTOR inhibitor or reduce cyclosporine dose to 20% of baseline daily dose. Four patients (16%) were hospitalized by day 30; one for infectious diarrhea and three for symptoms related to COVID-19. No patients died within 30 days of receipt of NR. Median tacrolimus level pre- and post-NR were 7.4 ng/ml (IQR, 6.6-8.6) and 5.2 (IQR, 3.6-8.7), respectively. Four patients experienced a supratherapeutic tacrolimus concentration after restarting tacrolimus post-NR. Our results show the clinically significant interaction between NR and immunosuppressive agents can be reasonably managed with a standardized dosing protocol. Prescribers should carefully re-introduce CNI after the NR course is complete.

Patient Characteristics and Outcomes of 11 721 Patients With Coronavirus Disease 2019 (COVID-19) Hospitalized Across the United States.

BACKGROUND: As coronavirus disease 2019 (COVID-19) disseminates throughout the United States, a better understanding of the patient characteristics associated with hospitalization, morbidity, and mortality in diverse geographic regions is essential. METHODS: Hospital chargemaster data on adult patients with COVID-19 admitted to 245 hospitals across 38 states between 15 February and 20 April 2020 were assessed. The clinical course from admission, through hospitalization, and to discharge or death was analyzed. RESULTS: A total of 11 721 patients were included (majority were >60 years of age [59.9%] and male [53.4%]). Comorbidities included hypertension (46.7%), diabetes (27.8%), cardiovascular disease (18.6%), obesity (16.1%), and chronic kidney disease (12.2%). Mechanical ventilation was required by 1967 patients (16.8%). Mortality among hospitalized patients was 21.4% and increased to 70.5% among those on mechanical ventilation. Male sex, older age, obesity, geographic region, and the presence of chronic kidney disease or a preexisting cardiovascular disease were associated with increased odds of mechanical ventilation. All aforementioned risk factors, with the exception of obesity, were associated with increased odds of death (all P values < .001). Many patients received investigational medications for treatment of COVID-19, including 48 patients on remdesivir and 4232 on hydroxychloroquine. CONCLUSIONS: This large observational cohort describes the clinical course and identifies factors associated with the outcomes of hospitalized patients with COVID-19 across the United States. These data can inform strategies to prioritize prevention and treatment for this disease.

Association of Search Query Interest in Gastrointestinal Symptoms With COVID-19 Diagnosis in the United States: Infodemiology Study.

BACKGROUND: Coronavirus disease (COVID-19) is a novel viral illness that has rapidly spread worldwide. While the disease primarily presents as a respiratory illness, gastrointestinal symptoms such as diarrhea have been reported in up to one-third of confirmed cases, and patients may have mild symptoms that do not prompt them to seek medical attention. Internet-based infodemiology offers an approach to studying symptoms at a population level, even in individuals who do not seek medical care. OBJECTIVE: This study aimed to determine if a correlation exists between internet searches for gastrointestinal symptoms and the confirmed case count of COVID-19 in the United States. METHODS: The search terms chosen for analysis in this study included common gastrointestinal symptoms such as diarrhea, nausea, vomiting, and abdominal pain. Furthermore, the search terms fever and cough were used as positive controls, and constipation was used as a negative control. Daily query shares for the selected symptoms were obtained from Google Trends between October 1, 2019 and June 15, 2020 for all US states. These shares were divided into two time periods: pre-COVID-19 (prior to March 1) and post-COVID-19 (March 1-June 15). Confirmed COVID-19 case numbers were obtained from the Johns Hopkins University Center for Systems Science and Engineering data repository. Moving averages of the daily query shares (normalized to baseline pre-COVID-19) were then analyzed against the confirmed disease case count and daily new cases to establish a temporal relationship. RESULTS: The relative search query shares of many symptoms, including nausea, vomiting, abdominal pain, and constipation, remained near or below baseline throughout the time period studied; however, there were notable increases in searches for the positive control symptoms of fever and cough as well as for diarrhea. These increases in daily search queries for fever, cough, and diarrhea preceded the rapid rise in number of cases by approximately 10 to 14 days. The search volumes for these terms began declining after mid-March despite the continued rises in cumulative cases and daily new case counts. CONCLUSIONS: Google searches for symptoms may precede the actual rises in cases and hospitalizations during pandemics. During the current COVID-19 pandemic, this study demonstrates that internet search queries for fever, cough, and diarrhea increased prior to the increased confirmed case count by available testing during the early weeks of the pandemic in the United States. While the search volumes eventually decreased significantly as the number of cases continued to rise, internet query search data may still be a useful tool at a population level to identify areas of active disease transmission at the cusp of new outbreaks.

Development and external validation of a prediction risk model for short-term mortality among hospitalized U.S. COVID-19 patients: A proposal for the COVID-AID risk tool.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) has created unprecedented medical challenges. There remains a need for validated risk prediction models to assess short-term mortality risk among hospitalized patients with COVID-19. The objective of this study was to develop and validate a 7-day and 14-day mortality risk prediction model for patients hospitalized with COVID-19. METHODS: We performed a multicenter retrospective cohort study with a separate multicenter cohort for external validation using two hospitals in New York, NY, and 9 hospitals in Massachusetts, respectively. A total of 664 patients in NY and 265 patients with COVID-19 in Massachusetts, hospitalized from March to April 2020. RESULTS: We developed a risk model consisting of patient age, hypoxia severity, mean arterial pressure and presence of kidney dysfunction at hospital presentation. Multivariable regression model was based on risk factors selected from univariable and Chi-squared automatic interaction detection analyses. Validation was by receiver operating characteristic curve (discrimination) and Hosmer-Lemeshow goodness of fit (GOF) test (calibration). In internal cross-validation, prediction of 7-day mortality had an AUC of 0.86 (95%CI 0.74-0.98; GOF p = 0.744); while 14-day had an AUC of 0.83 (95%CI 0.69-0.97; GOF p = 0.588). External validation was achieved using 265 patients from an outside cohort and confirmed 7- and 14-day mortality prediction performance with an AUC of 0.85 (95%CI 0.78-0.92; GOF p = 0.340) and 0.83 (95%CI 0.76-0.89; GOF p = 0.471) respectively, along with excellent calibration. Retrospective data collection, short follow-up time, and development in COVID-19 epicenter may limit model generalizability. CONCLUSIONS: The COVID-AID risk tool is a well-calibrated model that demonstrates accuracy in the prediction of both 7-day and 14-day mortality risk among patients hospitalized with COVID-19. This prediction score could assist with resource utilization, patient and caregiver education, and provide a risk stratification instrument for future research trials.

SARS-COV-2 infection (coronavirus disease 2019) for the gastrointestinal consultant.

The current pandemic due to the severe acute respiratory syndrome coronavirus 2 has caused an extreme burden for health care systems globally, and the number of cases is expected to continue to increase, at least in the immediate future. The virus is estimated to have infected more than 1.5 million individuals. The available reports suggest that gastrointestinal (GI) involvement in coronavirus disease 2019 (COVID-19) is common and in some cases the GI symptoms may precede the respiratory symptoms. In addition to direct effects of severe acute respiratory syndrome coronavirus 2, the infected patients remain at risk for the complications commonly managed by gastroenterology and hepatology consultants. The most commonly reported GI manifestation of COVID-19 is diarrhea, which is reported in a third to up to more than half of the patients. Mild to moderate elevation of the liver enzymes are also common, although no case of acute liver failure has been reported so far. Many of the medications used for treatment of COVID-19 can also be associated with GI symptoms or liver injury and can be included in the differential diagnosis in these patients. Although the diagnosis of the infection is currently based on RNA analysis in respiratory samples, the available literature on fecal shedding of this virus suggests that fecal RNA testing might prove to be a useful diagnostic test. It is reasonable to delay all non-urgent endoscopic procedures during the peak of the pandemic and use additional protective equipment such as N95 respirators during endoscopy while most patients can be considered high risk for having been exposed to the virus.

COVID-19 in solid organ transplant recipients: Initial report from the US epicenter.

Solid organ transplant recipients may be at a high risk for SARS-CoV-2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty-six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual-organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty-two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non-rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID-19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID-19 has the potential to severely impact solid organ transplant recipients.