Quantified impacts of non-pharmaceutical interventions on influenza circulation during the COVID-19 pandemic in 13 African countries, 2020-2022.

Nonpharmaceutical interventions (NPIs) for SARS-CoV-2 disrupted circulation of influenza. We used data from 13 African countries and generalized linear models to identify associations between levels of NPIs, using the Oxford Stringency Index, and seasonal influenza activity, using parameters derived from 2020-2022 seasonal influenza surveillance. We found that for each step increase in school closings, the average percentage of respiratory specimens testing positive for influenza across the influenza season dropped by 20% (95% CI: 1-38%); no other NPI was significant. These findings may inform interventions to slow influenza circulation in pandemics and possibly during seasonal epidemics.

Safety and immunogenicity of locally produced trivalent inactivated influenza vaccine (Tri Fluvac) in healthy Thai adults aged 18-64 years in Nakhon Phanom: A Phase III double blinded, three-arm, randomized, controlled trial.

BACKGROUND: Domestic influenza vaccine production facilitates a sustainable supply for mitigating seasonal influenza and improves national health security by providing infrastructure and experience for pandemic vaccine production, if needed. METHODS: A Phase III, double blind, randomized controlled trial was conducted from Sep 2019-Oct 2020 in healthy adults 18-64 years in Nakhon Phanom, Thailand. Randomization (3:3:1) compared study vaccine (Tri Fluvac), saline placebo, and an active comparator (licensed vaccine). Primary outcomes were superior efficacy compared to placebo based on RT-PCR-confirmed influenza virus infection within 12 months and non-inferiority compared to active comparator based on immunogenicity (HAI assay) at 28 days. Safety was also assessed. RESULTS: The trial enrolled 4,284 participants (Tri Fluvac = 1,836; placebo = 1,836; active comparator = 612). There were 29 RT-PCR positive influenza infections (10 Tri Fluvac, 5.5/1,000 PY; 19 placebo, 10.4/1,000PY; 0 comparator) for an absolute protective efficacy of 46.4 (95 % CI = -22.0-76.5) compared with placebo, but the power was 43.7 %. Seroconversion difference rates between Tri Fluvac and comparator at Day 28 were 1.74 (95 % CI: -2.77, 6.25), 2.22 (-2.40, 6.84), and -0.57 (-5.41, 4.27) for A(H1N1), A(H3N2), and B strains, respectively. Adverse and severe adverse events occurred in 175 (9.5 %) Tri Fluvac, 177 (10.8 %) placebo, and 66 (10.8 %) comparator arms (p-value = 0.437, Tri Fluvac vs. comparator) CONCLUSIONS: Tri Fluvac was well tolerated, and immunogenicity was non-inferior to the active comparator, meeting U.S. Food and Drug Administration (FDA) criteria for adult vaccine licensure. Few acute respiratory infections were reported during intense COVID-19 pandemic restrictions, resulting in insufficient power to evaluate clinical efficacy.

The role of asymptomatic infections in influenza transmission: what do we really know.

Before the COVID-19 pandemic, the role of asymptomatic influenza virus infections in influenza transmission was uncertain. However, the importance of asymptomatic infection with SARS-CoV-2 for onward transmission of COVID-19 has led experts to question whether the role of asymptomatic influenza virus infections in transmission had been underappreciated. We discuss the existing evidence on the frequency of asymptomatic influenza virus infections, the extent to which they contribute to infection transmission, and remaining knowledge gaps. We propose priority areas for further evaluation, study designs, and case definitions to address existing knowledge gaps.

Avian influenza A(H5) virus circulation in live bird markets in Vietnam, 2017-2022.

BACKGROUND: Highly pathogenic avian influenza A(H5) human infections are a global concern, with many A(H5) human cases detected in Vietnam, including a case in October 2022. Using avian influenza virus surveillance from March 2017-September 2022, we described the percent of pooled samples that were positive for avian influenza A, A(H5), A(H5N1), A(H5N6), and A(H5N8) viruses in live bird markets (LBMs) in Vietnam. METHODS: Monthly at each LBM, 30 poultry oropharyngeal swab specimens and five environmental samples were collected. Samples were pooled in groups of five and tested for influenza A, A(H5), A(H5N1), A(H5N6), and A(H5N8) viruses by real-time reverse-transcription polymerase chain reaction. Trends in the percent of pooled samples that were positive for avian influenza were summarized by LBM characteristics and time and compared with the number of passively detected avian influenza outbreaks using Spearman's rank correlation. RESULTS: A total of 25,774 pooled samples were collected through active surveillance at 167 LBMs in 24 provinces; 36.9% of pooled samples were positive for influenza A, 3.6% A(H5), 1.9% A(H5N1), 1.1% A(H5N6), and 0.2% A(H5N8). Influenza A(H5) viruses were identified January-December and at least once in 91.7% of sampled provinces. In 246 A(H5) outbreaks in poultry; 20.3% were influenza A(H5N1), 60.2% A(H5N6), and 19.5% A(H5N8); outbreaks did not correlate with active surveillance. CONCLUSIONS: In Vietnam, influenza A(H5) viruses were detected by active surveillance in LBMs year-round and in most provinces sampled. In addition to outbreak reporting, active surveillance for A(H5) viruses in settings with high potential for animal-to-human spillover can provide situational awareness.

Reported Global Avian Influenza Detections Among Humans and Animals During 2013-2022: Comprehensive Review and Analysis of Available Surveillance Data.

BACKGROUND: Avian influenza (AI) virus detections occurred frequently in 2022 and continue to pose a health, economic, and food security risk. The most recent global analysis of official reports of animal outbreaks and human infections with all reportable AI viruses was published almost a decade ago. Increased or renewed reports of AI viruses, especially high pathogenicity H5N8 and H5N1 in birds and H5N1, H5N8, and H5N6 in humans globally, have established the need for a comprehensive review of current global AI virus surveillance data to assess the pandemic risk of AI viruses. OBJECTIVE: This study aims to provide an analysis of global AI animal outbreak and human case surveillance information from the last decade by describing the circulating virus subtypes, regions and temporal trends in reporting, and country characteristics associated with AI virus outbreak reporting in animals; surveillance and reporting gaps for animals and humans are identified. METHODS: We analyzed AI virus infection reports among animals and humans submitted to animal and public health authorities from January 2013 to June 2022 and compared them with reports from January 2005 to December 2012. A multivariable regression analysis was used to evaluate associations between variables of interest and reported AI virus animal outbreaks. RESULTS: From 2013 to 2022, 52.2% (95/182) of World Organisation for Animal Health (WOAH) Member Countries identified 34 AI virus subtypes during 21,249 outbreaks. The most frequently reported subtypes were high pathogenicity AI H5N1 (10,079/21,249, 47.43%) and H5N8 (6722/21,249, 31.63%). A total of 10 high pathogenicity AI and 6 low pathogenicity AI virus subtypes were reported to the WOAH for the first time during 2013-2022. AI outbreaks in animals occurred in 26 more Member Countries than reported in the previous 8 years. Decreasing World Bank income classification was significantly associated with decreases in reported AI outbreaks (P<.001-.02). Between January 2013 and June 2022, 17/194 (8.8%) World Health Organization (WHO) Member States reported 2000 human AI virus infections of 10 virus subtypes. H7N9 (1568/2000, 78.40%) and H5N1 (254/2000, 12.70%) viruses accounted for the most human infections. As many as 8 of these 17 Member States did not report a human case prior to 2013. Of 1953 human cases with available information, 74.81% (n=1461) had a known animal exposure before onset of illness. The median time from illness onset to the notification posted on the WHO event information site was 15 days (IQR 9-30 days; mean 24 days). Seasonality patterns of animal outbreaks and human infections with AI viruses were very similar, occurred year-round, and peaked during November through May. CONCLUSIONS: Our analysis suggests that AI outbreaks are more frequently reported and geographically widespread than in the past. Global surveillance gaps include inconsistent reporting from all regions and human infection reporting delays. Continued monitoring for AI virus outbreaks in animals and human infections with AI viruses is crucial for pandemic preparedness.

Timing of seasonal influenza epidemics for 25 countries in Africa during 2010-19: a retrospective analysis.

BACKGROUND: Using country-specific surveillance data to describe influenza epidemic activity could inform decisions on the timing of influenza vaccination. We analysed surveillance data from African countries to characterise the timing of seasonal influenza epidemics to inform national vaccination strategies. METHODS: We used publicly available sentinel data from African countries reporting to the WHO Global Influenza Surveillance and Response FluNet platform that had 3-10 years of data collected during 2010-19. We calculated a 3-week moving proportion of samples positive for influenza virus and assessed epidemic timing using an aggregate average method. The start and end of each epidemic were defined as the first week when the proportion of positive samples exceeded or went below the annual mean, respectively, for at least 3 consecutive weeks. We categorised countries into five epidemic patterns: northern hemisphere-dominant, with epidemics occurring in October-March; southern hemisphere-dominant, with epidemics occurring in April-September; primarily northern hemisphere with some epidemic activity in southern hemisphere months; primarily southern hemisphere with some epidemic activity in northern hemisphere months; and year-round influenza transmission without a discernible northern hemisphere or southern hemisphere predominance (no clear pattern). FINDINGS: Of the 34 countries reporting data to FluNet, 25 had at least 3 years of data, representing 46% of the countries in Africa and 89% of Africa's population. Study countries reported RT-PCR respiratory virus results for a total of 503 609 specimens (median 12 971 [IQR 9607-20 960] per country-year), of which 74 001 (15%; median 2078 [IQR 1087-3008] per country-year) were positive for influenza viruses. 248 epidemics occurred across 236 country-years of data (median 10 [range 7-10] per country). Six (24%) countries had a northern hemisphere pattern (Algeria, Burkina Faso, Egypt, Morocco, Niger, and Tunisia). Eight (32%) had a primarily northern hemisphere pattern with some southern hemisphere epidemics (Cameroon, Ethiopia, Mali, Mozambique, Nigeria, Senegal, Tanzania, and Togo). Three (12%) had a primarily southern hemisphere pattern with some northern hemisphere epidemics (Ghana, Kenya, and Uganda). Three (12%) had a southern hemisphere pattern (Central African Republic, South Africa, and Zambia). Five (20%) had no clear pattern (Côte d'Ivoire, DR Congo, Madagascar, Mauritius, and Rwanda). INTERPRETATION: Most countries had identifiable influenza epidemic periods that could be used to inform authorities of non-seasonal and seasonal influenza activity, guide vaccine timing, and promote timely interventions. FUNDING: None. TRANSLATIONS: For the Berber, Luganda, Xhosa, Chewa, Yoruba, Igbo, Hausa and Afan Oromo translations of the abstract see Supplementary Materials section.

Effect of neuraminidase inhibitor (oseltamivir) treatment on outcome of hospitalised influenza patients, surveillance data from 11 EU countries, 2010 to 2020.

BackgroundTimely treatment with neuraminidase inhibitors (NAI) can reduce severe outcomes in influenza patients.AimWe assessed the impact of antiviral treatment on in-hospital deaths of laboratory-confirmed influenza patients in 11 European Union countries from 2010/11 to 2019/20.MethodsCase-based surveillance data from hospitalised patients with known age, sex, outcome, ward, vaccination status, timing of antiviral treatment, and hospitalisation were obtained. A mixed effect logistic regression model using country as random intercept was applied to estimate the adjusted odds ratio (aOR) for in-hospital death in patients treated with NAIs vs not treated.ResultsOf 19,937 patients, 31% received NAIs within 48 hours of hospital admission. Older age (60-79 years aOR 3.0, 95% CI: 2.4-3.8; 80 years 8.3 (6.6-10.5)) and intensive care unit admission (3.8, 95% CI: 3.4-4.2) increased risk of dying, while early hospital admission after symptom onset decreased risk (aOR 0.91, 95% CI: 0.90-0.93). NAI treatment initiation within 48 hours and up to 7 days reduced risk of dying (0-48 hours aOR 0.51, 95% CI: 0.45-0.59; 3-4 days 0.59 (0.51-0.67); 5-7 days 0.64 (0.56-0.74)), in particular in patients 40 years and older (e.g. treatment within 48 hours: 40-59 years aOR 0.43, 95% CI: 0.28-0.66; 60-79 years 0.50 (0.39-0.63); ≥80 years 0.51 (0.42-0.63)).ConclusionNAI treatment given within 48 hours and possibly up to 7 days after symptom onset reduced risk of in-hospital death. NAI treatment should be considered in older patients to prevent severe outcomes.

Leveraging International Influenza Surveillance Systems and Programs during the COVID-19 Pandemic.

A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential.

All-cause versus cause-specific excess deaths for estimating influenza-associated mortality in Denmark, Spain, and the United States.

BACKGROUND: Seasonal influenza-associated excess mortality estimates can be timely and provide useful information on the severity of an epidemic. This methodology can be leveraged during an emergency response or pandemic. METHOD: For Denmark, Spain, and the United States, we estimated age-stratified excess mortality for (i) all-cause, (ii) respiratory and circulatory, (iii) circulatory, (iv) respiratory, and (v) pneumonia, and influenza causes of death for the 2015/2016 and 2016/2017 influenza seasons. We quantified differences between the countries and seasonal excess mortality estimates and the death categories. We used a time-series linear regression model accounting for time and seasonal trends using mortality data from 2010 through 2017. RESULTS: The respective periods of weekly excess mortality for all-cause and cause-specific deaths were similar in their chronological patterns. Seasonal all-cause excess mortality rates for the 2015/2016 and 2016/2017 influenza seasons were 4.7 (3.3-6.1) and 14.3 (13.0-15.6) per 100,000 population, for the United States; 20.3 (15.8-25.0) and 24.0 (19.3-28.7) per 100,000 population for Denmark; and 22.9 (18.9-26.9) and 52.9 (49.1-56.8) per 100,000 population for Spain. Seasonal respiratory and circulatory excess mortality estimates were two to three times lower than the all-cause estimates. DISCUSSION: We observed fewer influenza-associated deaths when we examined cause-specific death categories compared with all-cause deaths and observed the same trends in peaks in deaths with all death causes. Because all-cause deaths are more available, these models can be used to monitor virus activity in near real time. This approach may contribute to the development of timely mortality monitoring systems during public health emergencies.

The role of non-pharmaceutical interventions on influenza circulation during the COVID-19 pandemic in nine tropical Asian countries.

BACKGROUND: Low global influenza circulation was reported during the coronavirus-19 pandemic. We explored relationships between non-pharmaceutical interventions (NPIs) and influenza in tropical Asian countries. METHODS: Using World Health Organization (WHO) surveillance data from 2015 to 2019 and the WHO shiny app, we constructed expected seasonal influenza epidemic curves from March 2020 to June 2021 and compared the timing, and average percent positivity with observed data. We used multivariate regression to test associations between ordinal NPI data (from the Oxford Stringency Index) 4 weeks before the expected 2020/21 epidemics and present adjusted incidence rate ratio (IRR) or relative proportion ratio (RPR) and 95% confidence intervals (CI). RESULTS: Data from nine countries predicted 18 seasonal epidemics; seven were observed. Five started 6-24 weeks later, and all were 4-21 weeks shorter than expected. Five epidemics had lower maximum peak values (percent positivity), and all but one had lower average percent positivity than expected. All countries implemented NPIs. Each increased level of school closure reduced risk of an epidemic by 43% (IRR = 0.57, CI: 0.34, 0.95). Each increased level of canceling public events reduced the average percent positivity across the season by 44% (RPR = 0.56, CI: 0.39, 0.82) and each increased level in restricting internal movements reduced it by 41% (RPR = 0.59, CI: 0.36, 0.96). Other NPIs were not associated with changes. CONCLUSIONS: Among nine countries, the 2020/21 seasonal epidemics were delayed, shorter, and less intense than expected. Although layered NPIs were difficult to tease apart, school closings, canceling public events, and restricting internal movements before influenza circulation seemed to reduce transmission.

First human infection of avian influenza A(H5N6) virus reported in Lao People's Democratic Republic, February-March 2021.

In March 2021, Lao People's Democratic Republic (Laos) reported an avian influenza A(H5N6) virus infection in a 5-year-old child identified through sentinel surveillance. This was the first human A(H5N6) infection reported outside of China. A multidisciplinary investigation undertook contact tracing and enhanced human and animal surveillance in surrounding villages and live bird markets. Seven Muscovy ducks tested positive for highly pathogenic avian influenza A(H5N6) viruses. Sequenced viruses belonged to clade 2.3.4.4h and were closely related to viruses detected in poultry in Vietnam and to previous viruses detected in Laos. Surveillance and coordinated outbreak response remain essential to global health security.

Spotlight influenza: Laboratory-confirmed seasonal influenza in people with acute respiratory illness: a literature review and meta-analysis, WHO European Region, 2004 to 2017.

BackgroundAcross the World Health Organization European Region, there are few estimates of the proportion of people seeking medical care for influenza-like illness or acute respiratory infections and who have laboratory-confirmed seasonal influenza infection.MethodsWe conducted a meta-analysis of data extracted from studies published between 2004 and 2017 and from sentinel data from the European surveillance system (TESSy) between 2004 and 2018. We pooled within-season estimates by influenza type/subtype, setting (outpatient (OP)/inpatient (IP)) and age group to estimate the proportion of people tested who have laboratory-confirmed and medically-attended seasonal influenza in Europe.ResultsIn the literature review, the pooled proportion for all influenza types was 33% (95% confidence interval (CI): 30-36), higher among OP 36% (95% CI: 33-40) than IP 24% (95% CI: 20-29). Pooled estimates for all influenza types by age group were: 0-17 years, 26% (22-31); 18-64 years, 41% (32-50); ≥ 65 years, 33% (27-40). From TESSy data, 33% (31-34) of OP and 24% (21-27) of IP were positive. The highest proportion of influenza A was in people aged 18-64 years (22%, 16-29). By subtype, A(H1N1)pdm09 was highest in 18-64 year-olds (16%, 11-21%) whereas A(H3N2) was highest in those ≥ 65 years (10%, 2-22). For influenza B, the highest proportion of infections was in those aged 18-64 years (15%, 9-24).ConclusionsLaboratory-confirmed influenza accounted for approximately one third of all acute respiratory infections for which medical care was sought during the influenza season.

Spotlight influenza: The 2019/20 influenza season and the impact of COVID-19 on influenza surveillance in the WHO European Region.

BackgroundAnnual seasonal influenza activity in the northern hemisphere causes a high burden of disease during the winter months, peaking in the first weeks of the year.AimWe describe the 2019/20 influenza season and the impact of the COVID-19 pandemic on sentinel surveillance in the World Health Organization (WHO) European Region.MethodsWe analysed weekly epidemiological and virological influenza data from sentinel primary care and hospital sources reported by countries, territories and areas (hereafter countries) in the European Region.ResultsWe observed co-circulation of influenza B/Victoria-lineage, A(H1)pdm09 and A(H3) viruses during the 2019/20 season, with different dominance patterns observed across the Region. A higher proportion of patients with influenza A virus infection than type B were observed. The influenza activity started in week 47/2019, and influenza positivity rate was ≥ 50% for 2 weeks (05-06/2020) rather than 5-8 weeks in the previous five seasons. In many countries a rapid reduction in sentinel reports and the highest influenza activity was observed in weeks 09-13/2020. Reporting was reduced from week 14/2020 across the Region coincident with the onset of widespread circulation of SARS-CoV-2.ConclusionsOverall, influenza type A viruses dominated; however, there were varying patterns across the Region, with dominance of B/Victoria-lineage viruses in a few countries. The COVID-19 pandemic contributed to an earlier end of the influenza season and reduced influenza virus circulation probably owing to restricted healthcare access and public health measures.

Human Infection with Avian Influenza A(H9N2) Virus, Cambodia, February 2021.

In February 2021, routine sentinel surveillance for influenza-like illness in Cambodia detected a human avian influenza A(H9N2) virus infection. Investigations identified no recent H9N2 virus infections in 43 close contacts. One chicken sample from the infected child's house was positive for H9N2 virus and genetically similar to the human virus.

Changes in Influenza and Other Respiratory Virus Activity During the COVID-19 Pandemic - United States, 2020-2021.

The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities.

Comparison of Non-Tumoral Portal Vein Thrombosis Management in Cirrhotic Patients: TIPS Versus Anticoagulation Versus No Treatment.

BACKGROUND: There is a lack of consensus in optimal management of portal vein thrombosis (PVT) in patients with cirrhosis. The purpose of this study is to compare the safety and thrombosis burden change for cirrhotic patients with non-tumoral PVT managed by transjugular intrahepatic portosystemic shunt (TIPS) only, anticoagulation only, or no treatment. METHODS: This single-center retrospective study evaluated 52 patients with cirrhosis and non-tumoral PVT managed by TIPS only (14), anticoagulation only (11), or no treatment (27). The demographic, clinical, and imaging data for patients were collected. The portomesenteric thrombosis burden and liver function tests at early follow-up (6-9 months) and late follow-up (9-16 months) were compared to the baseline. Adverse events including bleeding and encephalopathy were recorded. RESULTS: The overall portomesenteric thrombosis burden improved in eight (72%) TIPS patients, three (27%) anticoagulated patients, and two (10%) untreated patients at early follow-up (p = 0.001) and in seven (78%) TIPS patients, two (29%) anticoagulated patients, and three (17%) untreated patients in late follow-up (p = 0.007). No bleeding complications attributable to anticoagulation were observed. CONCLUSION: TIPS decreased portomesenteric thrombus burden compared to anticoagulation or no treatment for cirrhotic patients with PVT. Both TIPS and anticoagulation were safe therapies.

Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS: We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS: Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION: Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

Comparison of common acute respiratory infection case definitions for identification of hospitalized influenza cases at a population-based surveillance site in Egypt.

BACKGROUND: Multiple case definitions are used to identify hospitalized patients with community-acquired acute respiratory infections (ARI). We evaluated several commonly used hospitalized ARI case definitions to identify influenza cases. METHODS: The study included all patients from a population-based surveillance site in Damanhour, Egypt hospitalized for a broad set of criteria consistent with community acquired ARIs. Naso- and oropharyngeal (NP/OP) swabs were tested for influenza using RT-PCR. Sensitivity, specificity and PPV for influenza identification was compared between the 2014 WHO Severe Acute Respiratory Infection (SARI) definition (fever ≥38°C and cough with onset within 10 days), the 2011 WHO SARI definition (fever ≥38°C and cough with onset within 7 days), the 2006 PAHO SARI definition, the International Emerging Infections Program (IEIP) pneumonia case definition, and the International Management of Childhood Illness (IMCI) case definitions for moderate and severe pneumonia. RESULTS: From June 2009-December 2012, 5768 NP/OP swabs were obtained from 6113 hospitalized ARI patients; 799 (13.9%) were influenza positive. The 2014 WHO SARI case definition captured the greatest number of ARI patients, influenza positive patients and ARI deaths compared to the other case definitions examined. Sensitivity for influenza detection was highest for the 2014 WHO SARI definition with 88.6%, compared to the 2011 WHO SARI (78.2%) the 2006 PAHO SARI (15.8%) the IEIP pneumonia (61.0%) and the IMCI moderate and severe pneumonia (33.8% and 38.9%) case definitions (IMCI applies to <5 only). CONCLUSIONS: Our results support use of the 2014 WHO SARI definition for identifying influenza positive hospitalized SARI cases as it captures the highest proportion of ARI deaths and influenza positive cases. Routine use of this case definition for hospital-based surveillance will provide a solid, globally comparable foundation on which to build needed response efforts for novel pandemic viruses.