Effects of strict public health measures on seroprevalence of anti-SARS-CoV-2 antibodies during pregnancy.

INTRODUCTION: A substantial number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic throughout the course of infection. Nearly half of pregnant women with coronavirus disease 2019 (COVID-19) are asymptomatic upon diagnosis; these cases are not without risk of maternal morbidity. Here, we investigated the seroprevalence of anti-SARS-CoV-2 antibodies in an unselected sample of pregnant women in Hong Kong. METHODS: This prospective cohort study included pregnant women who presented for routine Down syndrome screening (DSS) between November 2019 and October 2020; all women subsequently delivered at the booking hospitals. Serum antibodies against SARS-CoV-2 were analysed using a qualitative serological assay in paired serum samples taken at DSS and delivery for all participants. RESULTS: In total, 1830 women were recruited. Six women (0.33%) were seropositive at the DSS visit; this seropositivity persisted until delivery. Of the six women, none reported relevant symptoms during pregnancy; one reported a travel history before DSS and one reported relevant contact history. The interval between sample collections was 177 days (range, 161-195). Among women with epidemiological risk factors, 1.79% with travel history, 50% with relevant contact history, and 0.77% with community SARS-CoV-2 testing history, were seropositive. CONCLUSION: The low seroprevalence in this study suggests that strict public health measures are effective for preventing SARS-CoV-2 transmission. However, these measures cannot be maintained indefinitely. Until a highly effective therapeutic drug targeting SARS-CoV-2 becomes available, vaccination remains the best method to control the COVID-19 pandemic.

Piloting a partially self-financed mode of human immunodeficiency virus pre-exposure prophylaxis delivery for men who have sex with men in Hong Kong.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg is a proven strategy for preventing human immunodeficiency virus (HIV) transmission in men who have sex with men (MSM). This study aimed to test the feasibility and acceptability of PrEP delivered at a pilot clinic for MSM in Hong Kong, where PrEP service is currently unavailable. METHODS: Partially self-financed PrEP was provided to HIV-negative adult MSM with high behavioural risk of HIV transmission after excluding hepatitis B infection and renal insufficiency. Participants received daily TDF/FTC for 30 weeks at 13.3% of the drug cost. Adherence and behaviours were monitored through questionnaires while creatinine and HIV/STI (sexually transmitted infection) incidence were monitored with point-of-care and laboratory tests. Preference for continuing with PrEP was evaluated at the end of the prescription period. RESULTS: Seventy-one PrEP-naïve MSM were included in the study, of whom 57 (80%) were retained at the end of 28 weeks. Satisfactory adherence and self-limiting adverse events were reported, while none of the participants contracted HIV. Risk compensation was observed, with an STI incidence of 3.17 per 100 person-years. At the end of the prescription period, a majority (89%) indicated interest in continuing with PrEP. Preference for PrEP was associated with age ≥28 years and peer influence (P=0.04), while stigma was a concern. Price was a deterrent to self-financed PrEP, and only half (51%) considered a monthly cost of ≤HK$500 (US$1=HK$7.8) as reasonable. CONCLUSIONS: A partially self-financed mode of PrEP delivery is feasible with good retention in MSM in Hong Kong.

High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections.

BACKGROUND: Better understanding of complications and outcomes of adults hospitalized with respiratory syncytial virus (RSV) infection is necessary. METHODS: A retrospective cohort study was conducted on all adults (≥ 18 years) admitted to 3 acute care general hospitals in Hong Kong with virologically confirmed RSV infection during 2009-2011 (N = 607). Adults hospitalized for seasonal influenza during the period were used for comparison (n = 547). Both infections were prospectively diagnosed following a standard protocol. Independent reviews of chest radiographs were performed by radiologists. Main outcome measures were all-cause death, respiratory failure requiring ventilatory support, and hospitalization duration. Cox proportional hazards models were used for analyses. RESULTS: The mean age of RSV patients was 75 (SD, 16) years; 87% had underlying conditions. Lower respiratory and cardiovascular complications were diagnosed in 71.9% (pneumonia, 42.3%; acute bronchitis, 21.9%; chronic obstructive pulmonary disease/asthma exacerbation, 27.3%) and 14.3% of patients, respectively; 12.5% had bacterial superinfections. Supplemental oxygen and ventilatory support were required in 67.9% and 11.1%, respectively. Crude all-cause mortality was 9.1% and 11.9% within 30 days and 60 days, respectively; mean length of stay of survivors was 12 (SD, 13) days. Advanced age, radiographic pneumonia, requirement for ventilation, bacterial superinfection, and elevated urea level and white blood cell count were independently associated with poorer survival. Systemic corticosteroid use was associated with longer hospitalization and secondary infections. The overall outcomes of survival and length of stay were not significantly different from those in influenza. CONCLUSIONS: RSV can cause severe lower respiratory complications in older adults, resulting in respiratory failure, prolonged hospitalization, and high mortality similar to seasonal influenza. Corticosteroids did not seem to improve outcomes. The unmet need for antiviral therapy and vaccination against RSV in adults should be promptly addressed.

A prospective intervention study on higher-dose oseltamivir treatment in adults hospitalized with influenza a and B infections.

BACKGROUND: It is unclear if higher-dose oseltamivir provides benefit beyond the standard dose in influenza patients who require hospitalization. METHODS: A prospective intervention study was performed in 2 acute care general hospitals in Hong Kong over 4 seasonal peaks (2010-2012). Adults (≥18 years) with laboratory-confirmed influenza (85 A/H3N2, 34 A/H1N1pdm09, 36 B) infections who presented within 96 hours were recruited. Study regimen of either 150 mg or 75 mg oseltamivir twice daily for 5 days was allocated by site, which was switched after 2 seasons. Subjects with preexisting renal impairment (creatinine clearance, 40-60 mL/minute) received 75 mg oseltamivir twice daily. Viral clearance by day 5 and clinical responses were compared between groups. Plasma steady-state trough oseltamivir carboxylate (OC) concentration was measured by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Altogether, 41 and 114 patients received 150 mg and 75 mg twice-daily oseltamivir, respectively; their enrollment characteristics (mean age, 61 ± 18 vs 66 ± 16 years) and illness severity were comparable. Trough OC levels were higher in the 150-mg group (501.0 ± 237.0 vs 342.6 ± 192.7 ng/mL). There were no significant differences in day 5 viral RNA (44.7% vs 40.2%) or culture negativity (100.0% vs 98.1%), RNA decline rate, and durations of fever, oxygen supplementation, and hospitalization. Results were similar when analyzed by study arm (all cases and among those without renal impairment). Subanalysis of influenza B patients showed faster RNA decline rate (analysis of variance, F = 4.14; P = .05) and clearance (day 5, 80.0% vs 57.1%) with higher-dose treatment. No oseltamivir resistance was found. Treatments were generally well tolerated. CONCLUSIONS: We found no additional benefit of higher-dose oseltamivir treatment in adults hospitalized with influenza A, but an improved virologic response in influenza B. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, NCT01052961.

Outcomes of adults hospitalised with severe influenza.

BACKGROUND: The aim of this study was to investigate factors affecting clinical outcomes of adults hospitalised with severe seasonal influenza. METHODS: A prospective, observational cohort study was conducted over 24 months (2007-2008) in two acute, general hospitals. Consecutive, hospitalised adult patients were recruited and followed once their laboratory diagnosis of influenza A/B was established (based on viral antigen detection and virus isolation from nasopharyngeal aspirates collected per protocol). Outcomes studied included in-hospital death, length of stay and duration of oxygen therapy. Factors affecting outcomes were analysed using multivariate Cox proportional hazards models. Sequencing analysis on the neuraminidase gene was performed for available H1N1 isolates. RESULTS: 754 patients were studied (influenza A, n=539; >75% H3N2). Their mean age was 70+/-18 years; co-morbidities and serious complications were common (61-77%). Supplemental oxygen and ventilatory support was required in 401 (53.2%) and 41 (5.4%) patients, respectively. 39 (5.2%) patients died; pneumonia, respiratory failure and sepsis were the causes. 395 (52%) patients received antiviral (oseltamivir) treatment. Omission of antiviral treatment was associated with delayed presentation or negative antigen detection results. The mortality rate was 4.56 and 7.42 per 1000 patient-days in the treated and untreated patients, respectively; among those with co-morbidities, it was 5.62 and 11.64 per 1000 patient-days, respectively. In multivariate analysis, antiviral use was associated with reduced risk of death (adjusted HR (aHR) 0.27 (95% CI 0.13 to 0.55); p<0.001). Improved survival was observed with treatment started within 4 days from onset. Earlier hospital discharge (aHR 1.28 (95% CI 1.04 to 1.57); p=0.019) and faster discontinuation of oxygen therapy (aHR 1.30 (95% CI 1.01 to 1.69); p=0.043) was associated with early treatment within 2 days. Few (n=15) H1N1 isolates in this cohort had the H275Y mutation. CONCLUSIONS: Antiviral treatment for severe influenza is associated with reduced mortality and improved clinical outcomes.

Virological response to peramivir treatment in adults hospitalised for influenza-associated lower respiratory tract infections.

An open-label trial on intravenous peramivir was conducted among adult patients hospitalised for influenza-associated lower respiratory tract complications (LRTCs). Virus culture and quantitative reverse transcription PCR (qRT-PCR) were performed serially until Day 10. Peramivir treatment was associated with viral RNA decline as well as culture and RNA negativity, which occurred at rates comparable with those of oseltamivir: by Day 5, viral load decline -2.5 log10 copies/mL [ßinteraction -0.071, standard error (SE) 0.121, 95% confidence interval (CI) -0.309 to 0.167]; culture-negative, 94% (vs. 95%); and RNA-negative, 44% (vs. 36%). Extended treatment of >5 days was required in 69% of cases because of slow clinical resolution and viral clearance in LRTCs. Peramivir was well tolerated. These data are useful for future trial design in this unique population.