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Background: Given effectiveness of SARS-CoV-2 vaccines and outpatient antiviral and monoclonal antibody therapy for reducing progression to severe COVID-19, we sought to estimate the impact of these interventions on risk of hospitalization following SARS-CoV-2 infection in a large US healthcare system. Method(s): All patients >=18 of age in the UNC Health system, with first positive SARS-CoV-2 RT-PCR test or U07.1 ICD-10-CM (diagnosis date) during 07/01/2021- 05/31/2022, were included. The outcome was first hospitalization with U07.1 ICD-10-CM primary diagnosis <=14 days after SARS-CoV-2 diagnosis date. SARS-CoV-2 vaccinations were included if received >=14 days prior to diagnosis. Outpatient therapies were included if administered after diagnosis date and before hospital admission. Age, gender, race, ethnicity, and comorbidities associated with COVID-19 (using ICD-10-CM, if documented >=14 days prior to diagnosis date) were also evaluated. Risk ratios for hospitalization were estimated using generalized linear models, and predictors identified using extreme gradient boosting using feature influence with Shapley additive explanations algorithm. Result(s): The study population included 54,886 patients, 41% men and 27% >=60 years of age. One-third of SARS-CoV-2 diagnoses occurred July-December 2021 and 67% December-May 2022 (predominantly Delta and Omicron variants, respectively). Overall 7.0% of patients were hospitalized for COVID-19, with median hospitalization stay of 5 days (IQR: 3-9). 32% and 12% of patients received >=1 SARS-CoV-2 vaccine dose and outpatient therapy, respectively. Unadjusted and age-adjusted hospitalization risk decreased with vaccination and outpatient therapy (TABLE). Comparing patients who received 3 vaccine doses versus none we observed a 66% relative reduction in risk, with stronger association for more recent vaccination. For patients who received nirmatrelvir/ ritonavir versus no therapy we observed a 99% relative reduction in risk. In predictive models, older age was the most influential predictor of being hospitalized with COVID-19, while vaccination and outpatient therapy were the most influential factors predicting non-hospitalization. Conclusion(s): The impact of recent SARS-CoV-2 vaccination and outpatient antiviral and monoclonal antibody therapy on reducing COVID-19 hospitalization risk was striking in this large healthcare system covering Delta and Omicron variant timeframes. SARS-CoV-2 vaccinations and outpatient therapeutics are critical for preventing severe COVID-19. Unadjusted and age-adjusted risk ratios for hospitalization among patients with SARS-CoV-2.
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Background. Eravacycline, a novel synthetic fluorocycline, is structurally similar to tigecycline. Cases of tigecycline associated hyperfibrinogenemia have been reported in the literature, however the mechanism is not currently well described. At this time it is unknown if this is a class effect. Methods. Two cases of patients on eravacycline for treatment of Mycobacterium abscessus (M.abscessus) who received regular fibrinogen monitoring are described. Results. Patient 1 received a kidney transplant (2010) and was admitted for acute hypoxic respiratory failure secondary to COVID-19. Their course was complicated by multiple infections including disseminated M.abscessus with positive cultures from the lung and blood. Eravacycline 1 mg/kg BID (80 mg) was started on D1 and continued through D24. Fibrinogen levels on D1 was 448 mg/dl and on D23 were 120 mg/dl. Eravacycline was stopped and fibrinogen returned to normal range (228 mg/dl) in 5 days. Eravacycline was re-trialed at 80 mg BID and fibrinogen level on D1 was 310 mg/dl and 147 mg/dl on D8. No repeat fibrinogen levels were obtained. Patient 2 was a lung transplant recipient (2019) admitted for treatment of M.abscessus skin and soft tissue infection. The patient was started on eravacycline 1 mg/kg BID (90 mg) due to concerns of hypofibrinogenemia from tigecycline. On D1 of eravacycline fibrinogen was 167 mg/dl , on D19 of therapy fibrinogen was 64 mg/dl and eravacycline was stopped. Fibrinogen level returned to normal 3 days after eravacycline discontinuation (212 mg/dl). Conclusion. Similar to tigecycline, we observed eravacycline related hypofibrinogenemia. Time to onset was variable in the two cases presented. Hypofibrinogenemia was readily reversible, within 3-5 days, with drug withdrawal and reproducible in one patient with re-challenge of eravacycline. Further analysis into eravacycline related hypofibrinogenemia and its impact on coagulation outcomes are warranted based on these reports.
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Purpose: Describe outcomes of patients (pt) with pre-tx COVID-19. Method(s): Multicenter study of SOT/HCT candidates who had a positive (pos) SARS-CoV-2 PCR pre-tx. Result(s): Pre-tx: Of 208 pt, median age was 56 (range 3-76). 87.8% were SOT candidates (40.5% kidney, 40.5% liver, 9.8% lung, 6.9% heart, 2.3% pancreas) and 13.9% were HCT candidates (54.2% allo, 45.8% auto). Pt underwent a median of 2 tests (range 1 - 14). In 41% of pt, > 1 neg PCR was required by the tx center before reactivation. Neg PCR was documented in 67.4% of pt at a median of 41 days (18-68) after pos PCR. Waitlist mortality was 11.0%;deaths were due to COVID-19 in 60% (12/20). Post-tx (all pt): 78 pt underwent tx at a median of 65.5 days (range 17-324) from COVID-19;71/78 have completed 4-weeks of follow-up. 24/78 (30.7%) pt were still PCR pos at time of tx (details below). 54/78 (69.2%) pt underwent routine PCR testing post-tx;62% were tested regularly for 8 weeks. Only 1 pt, who remained asymptomatic, developed recurrent pos PCR on surveillance testing 18 days post-tx. 1 pt had graft loss. There were no deaths at 4 weeks post-tx. Pt transplanted without a negative PCR: 24 pt with COVID-19 did not have neg PCR at time of tx: 9 (37.5%) kidney, 9 (37.5%) liver, 2 (8.3%) SLK, 1 (4.2%) lung, 1 heart (4.2%), 2 auto-HSCT (8.3%), 2 allo-HSCT (8.3%). Of 24 pt who were reactivated at a median of 21 days (range 8 - 38) from COVID-19 diagnosis, 7 underwent tx emergently (5 liver, 1 lung, 1 heart). 20/24 completed 4-weeks of follow-up;all were alive. PCR Cycle thresholds (Ct) increased over time, suggesting a reduction in SARS-CoV-2 viral loads with time elapsed since COVID-19 diagnosis. Conclusion(s): Short-term outcomes of transplantation in SOT/HCT candidates with prior COVID-19 were promising in this small cohort, even with a positive PCR going into transplant. Whether documentation of a negative PCR should be required for all tx candidates with a history of COVID-19 prior to transplantation should be investigated further, particularly among lung tx candidates. For certain tx candidates with COVID-19, relying time-based strategy instead of a test-based strategy may be safe.