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Background: In early 2022, there was a sudden surge of patients infected by the Omicron variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Hong Kong (HK), resulting in 9,163 deaths as of 29 May 2022. Many of the local population had not been vaccinated before this wave. The number of patients who developed coronavirus disease 2019 (COVID-19) related respiratory failure outnumbered the capacity of intensive care unit (ICU) beds. Some of these patients had to be supported with high flow nasal cannula (HFNC) therapy outside ICU setting. HK was in crisis situation. The primary objective of this study is to assess the 28-day mortality of this group of patients. The secondary objective is to explore any predictors of non-survivors to help clinical decision-making in future crisis. Methods: This is a retrospective observational study of patients suffering from COVID-19 related respiratory failure who received HFNC therapy in general medical wards of two hospitals during the period of 17 Mar to 30 Apr 2022. Survival and risk factors were reviewed. Results: Forty-nine patients were recruited. Twenty-six patients (53%) survived at 28-day after initiation of HFNC support. Three clinical parameters were found to be significantly associated with mortality at 28-day: (I) SpO2/FiO2 (SF) ratio <160 at 48 hours; (II) SF ratio <191 at 72 hours; (III) serial SF ratio at 48 or 72 hours showing no improvement over that at the time of initiation of HFNC therapy. Conclusions: Use of HFNC outside ICU setting showed benefit to patients suffering from COVID-19 related acute hypoxemic respiratory failure (AHRF). Serial SF ratio monitoring at 48 and 72 hours after therapy initiation might serve as predictors of outcome and thus guide clinical decision-making for medical resource allocation in outbreak situation.
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This study evaluates the association between antivirals (Molnupiravir and Nirmatrelvir-Ritonavir) and all-cause and respiratory mortality and organ dysfunction among high-risk COVID-19 patients during an Omicron outbreak. Two cohorts, Nirmatrelvir-Ritonavir versus control and Molnupiravir versus control, were constructed with inverse probability treatment weighting to balance baseline characteristics. Cox proportional hazards models evaluated the association of their use with all-cause mortality, respiratory mortality, and all-cause sepsis (a composite of circulatory shock, respiratory failure, acute liver injury, coagulopathy, and acute liver impairment). Patients recruited were hospitalized and diagnosed with the COVID-19 Omicron variant between February 22, 2022 and April 15, 2022, and followed up until May 15, 2022. The study included 17,704 patients. There were 4.67 and 22.7 total mortalities per 1000 person-days in the Nirmatrelvir-Ritonavir and control groups respectively before adjustment (weighted incidence rate ratio, - 18.1 [95% CI - 23.0 to - 13.2]; hazard ratio, 0.18 [95% CI, 0.11-0.29]). There were 6.64 and 25.9 total mortalities per 1000 person-days in the Molnupiravir and control groups respectively before adjustment (weighted incidence rate ratio per 1000 person-days, - 19.3 [95% CI - 22.6 to - 15.9]; hazard ratio, 0.23 [95% CI 0.18-0.30]). In all-cause sepsis, there were 13.7 and 35.4 organ dysfunction events per 1000 person-days in the Nirmatrelvir-Ritonavir and control groups respectively before adjustment (weighted incidence rate ratio per 1000 person-days, - 21.7 [95% CI - 26.3 to - 17.1]; hazard ratio, 0.44 [95% CI 0.38-0.52]). There were 23.7 and 40.8 organ dysfunction events in the Molnupiravir and control groups respectively before adjustment (weighted incidence ratio per 1000 person-days, - 17.1 [95% CI, - 20.6 to - 13.6]; hazard ratio, 0.63 [95% CI 0.58-0.69]). Among COVID-19 hospitalized patients, use of either Nirmatrelvir-Ritonavir or Molnupiravir compared with no antiviral use was associated with a significantly lower incidence of 28-days all-cause and respiratory mortality and sepsis.
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COVID-19 , Sepsis , Humanos , Tratamiento Farmacológico de COVID-19 , Insuficiencia Multiorgánica , Ritonavir/uso terapéutico , SARS-CoV-2 , Sepsis/tratamiento farmacológico , Sepsis/epidemiología , Antivirales/uso terapéuticoRESUMEN
Background: Real-world data is currently limited on the association between oral antiviral therapy and healthcare system burden in patients with mild-to-moderate COVID-19. This study aims to evaluate the clinical and cost effectiveness of Molnupiravir and Nirmatrelvir-ritonavir use in reducing mortality in this population. Methods: This is a retrospective cohort study involving 54,355 COVID-19 patients during February 22-March 31,2022 in Hong Kong. Inverse probability of treatment weighting (IPTW) was used to adjust patient characteristics. Our exposure of interest was Molnupiravir/Nirmatrelvir-Ritonavir prescription, with all-cause mortality as the primary outcome. IPTW-adjusted multivariate regressions were used to estimate treatment impact on clinic re-attendance and unplanned admissions. Finally, attributed cost and incremental cost-effectiveness ratios (ICER) were estimated. Findings: In the outpatient cohort (N = 33,217, 61.1%), 16.1% used Molnupiravir and 13.4% used Nirmatrelvir-Ritonavir, while in the inpatient cohort (N = 21,138, 38.9%), 3.8% used Molnupiravir and 1.3% used Nirmatrelvir-Ritonavir. IPTW-adjusted Cox model estimated that Molnupiravir (hazard ratio (HR)(95%CI)=0.31 (0.24-0.40), P< 0.0001) and Nirmatrelvir-Ritonavir (HR=0.10 (95%CI 0.05-0.21), P< 0.0001) were significantly associated with a reduced mortality hazard. In the outpatient cohort, both antiviral prescriptions were associated with reduced odds for unplanned hospital admissions (Molnupiravir: odds ratio (OR) =0.72 (0.52-0.98), P=0.039; Nirmatrelvir-Ritonavir: OR=0.37 (0.23-0.60), P<0.0001). Among hospitalised patients, both antiviral prescriptions were associated with significant reductions in the odds ratios for 28-days readmission (Molnupiravir: OR=0.71 (0.52-0.97), P=0.031; Nirmatrelvir-Ritonavir: OR=0.47 (0.24-0.93), P=0.030). ICERs for death averted for Molnupiravir stood at USD493,345.09 in outpatient settings and USD2,629.08 in inpatient settings. In outpatient settings, Nirmatrelvir-ritonavir cost USD331,105.27 to avert one death, but saved USD5,502.53 to avert one death in comparison with standard care. Interpretation: In high-risk patients in Hong Kong with mild-to-moderate COVID-19, Molnupiravir and Nirmatrelvir-Ritonavir prescriptions were associated with reduced all-cause mortality and significant cost savings. Funding: Centre for Health Systems & Policy Research is funded by The Tung's Foundation; and The Laboratory of Data Discovery for Health Limited(D24H) is funded the AIR@InnoHK platform administered by the Innovation and Technology Commission of Hong Kong. Funders did not have any role in study design, data collection, data analysis, interpretation and writing of this manuscript.
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Systemic heparinisation is required for extracorporeal membrane oxygenation therapy, to prevent clotting of circuit and formation of thrombus in patient. Activated clotting time (ACT) or activated partial thromboplastin time (aPTT) has been the mainstay of monitoring of heparin dose. Thromboelastogram (TEG) is increasingly being used again in recent years with the advancement in technology. Its clinical usefulness in the monitoring of anticoagulation of ECMO therapy is demonstrated in the case presented. Our patient suffered from severe hemoptysis due to active microscopic polyangiitis and respiratory failure. Heparin infusion was given at the initiation of ECMO support without further aggravation of hemoptysis. Dose of heparin was adjusted successfully with the integration of the clotting profile and TEG results.
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A 41-year-old man from the emergency department presented with fever for 2 weeks, sore throat, dry cough and generalized umbilicated skin lesions (face (Fig. 1), and chest (Fig. 2)). HIV antibody was positive, CD4+ count was 2/µL. His skin swab, sputum and blood culture all yielded Talaromyces (Penicillium) marneffei (Fig. 3). Talaromyces marneffei is an important cause of morbidity and mortality in HIV-infected and other immunosuppressed patients who live in or are from endemic areas especially Southeast Asia. Amphotericin B or Itraconazole should be initiated as soon as possible for patients with talaromycosis.
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Electrolyte disturbances are known to cause acquired Long QT syndrome (LQTS) and Brugada syndrome. While a reduction in INa due to SCN5A mutation is implicated as the underlying mechanism in Brugada syndrome, hyponatremia, which can give rise to a reduced INa, has never been reported in literature as a cause or precipitating factor in this syndrome. We detailed a case in which concomitant-acquired LQTS and Brugada syndrome were associated with severe hypokalemia and hyponatremia following indapamide use for treatment of hypertension and highlighted the potential role of hyponatremia in the pathogenesis of the acquired form of Brugada syndrome.