Siddharth Sridhar

The University of Hong Kong | HKU · Department of Microbiology

Uncovering how host metal(loid)s mediate the immune response against invading pathogens is critical for better understanding the pathogenesis mechanism of infectious disease. Clinical data show that imbalance of host metal(loid)s is closely associated with the severity and mortality of COVID-19. However, it remains elusive how metal(loid)s, which a...

The devastating Coronavirus Disease 2019 (COVID-19) pandemic indicates that early detection of candidates with pandemic potential is vital. However, comprehensive metagenomic sequencing of the total microbiome is not practical due to the astronomical and rapidly evolving numbers and species of micro-organisms. Analysis of previous pandemics suggest...

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day)...

Background & aims: Rat hepatitis E virus (Rocahepevirus ratti; HEV-C1) is an emerging cause of hepatitis E that is divergent from conventional human-infecting HEV variants (Paslahepevirus balayani; HEV-A). Validated serological assays for HEV-C1 are lacking. We aimed to develop a parallel enzymatic immunoassay (EIA) system that identifies individu...

Children infected by SARS-CoV-2 Omicron variant may develop neurological complications. To study the pathogenesis in the growing brain, we intranasally challenged newly-weaned or mature hamsters with SARS-CoV-2 Omicron BA.2, BA.5, or Delta variant. Omicron BA.2 and Delta infection produced a significantly lower viral load in the lung tissues of new...

ABSTRACT Accurate and simple diagnostic tests for coronavirus disease 2019 (COVID-19) are essential components of the pandemic response. In this study, we evaluated a one-tube reverse transcription–loop-mediated isothermal amplification (RT-LAMP) assay coupled with clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein...

Background & Aims: HEV variants such as swine genotypes within Paslahepevirus species balayani (HEV-A) and rat HEV (Rocahepevirus ratti; HEV-C1) cause chronic hepatitis E in immunocompromised individuals. There are few reliable and accessible small animal models that accurately reflect chronic HEV infection. We aimed to develop an immunocompromised...

Monitoring population protective immunity against SARS-CoV-2 variants is critical for risk assessment. We hypothesize that Hong Kong’s explosive Omicron BA.2 outbreak in early 2022 could be explained by low herd immunity. Our seroprevalence study using sera collected from January to December 2021 shows a very low prevalence of neutralizing antibodi...

Hepatitis E virus (HEV) infection in humans is primarily caused by genotypes within Paslahepevirus species balayani (HEV-A). Rocahepevirus species ratti (HEV-C1, otherwise known as rat HEV) can also infect humans. HEV grows poorly in cell culture. Recent studies have reported that hyper-confluent cell layers, amphotericin B, MgCl2, progesterone, an...

Background The role of SARS-CoV-2 in the pathogenesis of testicular damage is uncertain. Methods We investigated the virological, pathological, and immunological changes in testes of hamsters challenged by SARS-CoV-2 wild-type and its variants by intranasal or direct testicular inoculation using influenza virus A(H1N1)pdm09 as control. Results Be...

Background Previously, hepatitis E in humans was believed to be caused exclusively by species A variants of the Orthohepevirus genus (HEV-A) of the family Hepeviridae. However, we have previously demonstrated that Orthohepevirus species C (HEV-C), also known as rat hepatitis E virus, also causes hepatitis in humans. Due to high sequence divergence...

Background Wildtype mice are not susceptible to SARS-CoV-2 infection. Emerging SARS-CoV-2 variants, including B.1.1.7, B.1.351, P.1, and P.3, contain mutations in spike that has been suggested to associate with an increased recognition of mouse ACE2, raising the postulation that these SARS-CoV-2 variants may have evolved to expand species tropism t...

Background Hepatitis E virus (HEV) variants belonging to Orthohepevirus species A (HEV-A) are the primary cause of human hepatitis E. However, we previously reported that Orthohepevirus C (HEV-C1), a divergent HEV variant commonly found in rats, also causes hepatitis in humans. Here, we present a clinical-epidemiological investigation of human HEV-...

Background: The effect of low environmental temperature on viral shedding and disease severity of COVID-19 is uncertain. Methods: We investigated the virological, clinical, pathological, and immunological changes in hamsters housed at room (21 oC), low (12-15 oC), and high (30-33 oC) temperature after challenge by 10 5 plaque-forming units of SA...

A multi-pronged carbapenemase-producing Enterobacteriaceae (CPE) screening strategy was implemented in Hong Kong West healthcare network. Of 199,192 fecal specimens from 77,194 patients screening from 1 July 2011 to 30 June 2019, the incidence of CPE per 1000 patient admission significantly increased from 0.01 (2012) to 1.9 (2018) (p<0.01). With ap...

Background: Post-vaccination myopericarditis is reported after immunization with COVID-19 mRNA-vaccines. The effect of accidental intravenous injection of this vaccine on the heart is unknown. Methods: We compared the clinical manifestations, histopathological changes, tissue mRNA expression and serum levels of cytokine/chemokine in Balb/c mice...

Non-conductive olfactory dysfunction (OD) is an important extra-pulmonary manifestation of coronavirus disease 2019 (COVID-19). Olfactory bulb (OB) volume loss and olfactory network functional connectivity (FC) defects were identified in two patients suffering from prolonged COVID-19-related OD. One patient received olfactory treatment (OT) by the...

Objectives: Sensitive molecular diagnostic assays are essential for COVID-19 diagnosis. We evaluated the Hecin Scientific SARS-CoV-2 nucleic acid test kit, a duplex real-time RT-PCR assay targeting the SARS-CoV-2 N and ORF1ab genes. Methods: The Hecin test kit’s diagnostic performance in detecting SARS-CoV-2 RNA was compared to the LightMix Modular...

Purpose: To evaluate the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in conjunctival secretions from patients without ocular symptoms. Methods: Conjunctival swabs were prospectively collected from laboratory-confirmed Coronavirus disease 2019 (COVID-19) patients without ocular symptoms for reverse transcription-polym...

Background & Aims Rat hepatitis E virus (Orthohepevirus species C; HEV-C1) is an emerging cause of viral hepatitis in humans. HEV-C1 is divergent from other HEV variants infecting humans that belong to Orthohepevirus species A (HEV-A). This study assessed HEV-C1 antigenic divergence from HEV-A and investigated the impact of this divergence on infec...

Without modern medical management and vaccines, the severity of the Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome(SARS) coronavirus 2 (SARS-CoV-2) might approach the magnitude of 1894-plague (12 million deaths) and 1918-A(H1N1) influenza (50 million deaths) pandemics. The COVID-19 pandemic was heralded by...

Background Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing amidst widespread transmission during the Coronavirus Disease 2019 (COVID-19) pandemic. Disease phenotypes of SARS-CoV-2 exposure occurring around the time of vaccine administration have not been described. Methods Two-dose (14 days apart) v...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted largely by respiratory droplets or airborne aerosols. Despite being frequently found in the immediate environment and faeces of patients, evidence supporting oral acquisition of SARS-CoV-2 is unavailable. Utilizing Syrian hamster model, we demonstrate that the severity of p...

Purpose of review: The Coronavirus Disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health threat associated with major socioeconomic disruptions. Understanding on the transmission characteristics of SARS-CoV-2 is crucial for optimizing preventive strategies. Recent find...

Currently available COVID-19 antibody tests using enzyme immunoassay (EIA) or immunochromatographic assay have variable sensitivity and specificity. Here, we developed and evaluated a novel microsphere-based antibody assay (MBA) for detecting immunoglobulin G (IgG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein (...

Objectives: Accurate assays for hepatitis C virus (HCV) quantitation and genotyping are important for the management of HCV infection. In this study, we evaluated the performance of cobas HCV and cobas HCV GT assays (Roche) for HCV quantitation and genotyping on the cobas 4800 System. Methods: We compared the performance of the cobas HCV assays...

Sensitive molecular assays are critical for coronavirus disease 2019 (COVID-19) diagnosis. Here, we designed and evaluated two single-tube nested (STN) real-time RT-PCR assays, targeting SARS-CoV-2 RdRp/Hel and N genes. Both STN assays had a low limit of detection and did not cross react with other human coronaviruses and respiratory viruses. Using...

Background: Coronavirus Disease 2019 (COVID-19) is primarily an acute respiratory tract infection. Distinctively, a substantial proportion of COVID-19 patients develop olfactory dysfunction of uncertain underlying mechanism which can be severe and prolonged. The roles of inflammatory obstruction of the olfactory clefts leading to conductive impair...

Background In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. Aim The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmenta...

Background The role of severe respiratory coronavirus virus 2 (SARS-CoV-2)-laden aerosols in the transmission of coronavirus disease 2019 (COVID-19) remains uncertain. Discordant findings of SARS-CoV-2 RNA in air samples were noted in early reports. Methods Sampling of air close to 6 asymptomatic and symptomatic COVID-19 patients with and without...

Background Posterior oropharyngeal saliva is increasingly recognised as a valid respiratory specimen for SARS-CoV-2 diagnosis. It is easy to collect and suitable for community-wide screening. The optimal timing of collection is currently unknown, and we speculate that an early morning specimen before oral hygiene and breakfast would increase the di...

Background Olfactory dysfunction (OD) has been reported in coronavirus disease 2019 (COVID-19). However, there are knowledge gaps about the severity, prevalence, etiology, and duration of OD in COVID-19 patients. Methods Olfactory function was assessed in all participants using questionnaires and the butanol threshold test (BTT). COVID-19 patients...

Many respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the...

Background The role of subclinical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in perpetuating the COVID-19 pandemic is unknown because population seroprevalence data are absent. We aimed to establish the sensitivity and specificity of our enzyme immunoassay and microneutralisation assay, and the seroprevalence of SARS-C...

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be mostly transmitted by medium-to-large sized respiratory droplets although airborne transmission is theoretically possible in healthcare settings involving aerosol-generating procedures. Exposure to respiratory dr...

Objective: Currently available COVID-19 antibody tests using enzyme immunoassay (EIA) or immunochromatographic assay have variable sensitivity and specificity. Here, we developed and evaluated a novel microsphere-based antibody assay (MBA) for the detection of immunoglobulin G (IgG) against SARS-CoV-2 nucleoprotein (NP) and spike protein receptor b...

Hepatitis E virus (HEV) is an important cause of hepatitis, which can be transmitted via the bloodborne route. However, risk of hepatitis E among persons who inject drugs (PWIDs) is poorly understood. This study aimed to elucidate whether PWIDs are at risk for hepatitis E. We performed HEV IgM, IgG and nucleic acid detection on a cohort of 91 PWIDs...

Background To describe the infection control strategy to achieve zero nosocomial transmission of symptomatic coronavirus disease (COVID-19) due to SARS-CoV-2 during the pre-pandemic phase (the first 72 days after announcement of pneumonia cases in Wuhan) in Hong Kong. Methods Administrative support with the aim of zero nosocomial transmission by r...

Background Rapid and sensitive diagnostic assays for SARS-CoV-2 detection are required for prompt patient management and infection control. The analytical and clinical performances of LightMix® Modular SARS and Wuhan CoV E-gene kit, a widely used commercial assay for SARS-CoV-2 detection, have not been well studied. Objective To evaluate the perfo...

Background Face mask usage by the healthy population in the community to reduce risk of transmission of respiratory viruses remains controversial. We assessed the effect of community-wide mask usage to control coronavirus disease 2019 (COVID-19) in Hong Kong Special Administrative Region (HKSAR). Methods Patients presenting with respiratory sympto...

Background A physiological small animal model that resembles COVID-19 with low mortality is lacking. Methods Molecular docking on the binding between angiotensin-converting enzyme 2 (ACE2) of common laboratory mammals and the receptor-binding domain of the surface spike protein of SARS-CoV-2 suggested that the golden Syrian hamster is an option. V...

We thank Dr. C. Adlhoch and Dr. SA Baylis for their comments on our study describing the impact of rat hepatitis E virus (Orthohepevirus C genotype 1 or HEV‐C1) on human health in Hong Kong. We concur with them that HEV‐C1 infection is currently a blind spot in hepatitis E diagnostic testing. As they point out, routinely used molecular assays for H...

Background To describe the infection control preparedness for Coronavirus Disease (COVID-19) due to SARS-CoV-2 [previously known as 2019-novel coronavirus] in the first 42 days after announcement of a cluster of pneumonia in China, on 31 December 2019 (day 1) in Hong Kong. Methods A bundle approach of active and enhanced laboratory surveillance, e...

Background & aims: Hepatitis E virus (HEV) variants causing human infection predominantly belong to HEV species A (HEV-A). HEV species C genotype 1 (HEV-C1) circulates in rats and is highly divergent from HEV-A. It was previously considered unable to infect humans, but the first case of human HEV-C1 infection was recently discovered in Hong Kong....

Several commercial PCR kits are available for detection of herpes simplex virus (HSV) and varicella zoster virus (VZV), but the test performance of one CE-marked in vitro diagnostic kit—RealStar® alpha Herpesvirus PCR Kit—has not been well studied. This study evaluated the performance of RealStar® alpha Herpesvirus PCR Kit 1.0 on the LightCycler® 4...

Objective To report an outbreak of measles with epidemiological link between Hong Kong International Airport (HKIA) and a hospital. Methods Epidemiological investigations, patients’ measles serology, and phylogenetic analysis of the hemagglutinin (H) and nucleoprotein (N) genes of measles virus isolates were conducted. Results In total, 29 HKIA s...

Introduction: Plantar warts are associated with high transmissibility and morbidity. Among the available therapeutic options, none is uniformly effective or virucidal. Salicylic acid is the first-line therapy but approximately one-third of lesions could not resolve and become recalcitrant despite repeated treatment. Cryotherapy is widely accessibl...

Background & aims Transmission of human hepegivirus 1 (HHpgV-1), a novel human pegivirus, is closely associated with hepatitis C virus (HCV). The impact of HHpgV-1 viremia on HCV infection is unknown. This study aimed to a) evaluate impact of HHpgV-1 viremia on HCV viral load and liver injury and b) elucidate the clinical and molecular epidemiology...

We describe a nosocomial outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) ST59-SCCmec type V in a neonatal intensive care unit (NICU) in Hong Kong. In-depth epidemiological analysis was performed by whole-genome sequencing (WGS) of the CA-MRSA isolates collected from patients and environment during weekly surve...

Hepatitis E virus (HEV) genotype 4 (HEV-4) is an emerging cause of acute hepatitis in China. Less is known about the clinical characteristics and natural history of HEV-4 than HEV genotype 3 infections in immunocompromised patients. We report transmission of HEV-4 from a deceased organ donor to 5 transplant recipients. The donor had been viremic bu...

Background & aims: The aim of this study was to investigate the positive rate of hepatitis E virus (HEV) infection and the possible adverse outcomes in pregnant women of Qinhuangdao, China. Methods: Serum samples of 946 pregnant women were collected from July 2017 to October 2017 in Qinhuangdao First Hospital. All samples were tested for anti-HEV I...

Reusable blood collection tube holders are implicated in nosocomial hepatitis C virus transmission - Volume 40 Issue 2 - Vincent C. C. Cheng, Shuk-Ching Wong, Sally C. Y. Wong, Siddharth Sridhar, Cyril C. Y. Yip, Jonathan H. K. Chen, James Fung, Kelvin H. Y. Chiu, Pak-Leung Ho, Sirong Chen, Ben W. C. Cheng, Chi-Lai Ho, Chung-Mau Lo, Kwok-Yung Yuen

Human adenovirus type 4 (HAdV-E4), which is intriguingly limited to military populations, causes acute respiratory disease with demonstrated morbidity and mortality implications. This respiratory pathogen contains genome identity with chimpanzee adenoviruses, indicating zoonotic origins. A signature of these “old” HAdV-E4 is the absence of a critic...

It is estimated that one-third of the world population have been exposed to hepatitis E virus (HEV). In developed countries and China, zoonotic HEV strains are responsible for almost all acute and chronic HEV infection cases. It is always of immediate interest to investigate the zoonotic potential of novel HEV strains. In 2016, we discovered a nove...

All hepatitis E virus (HEV) variants reported to infect humans belong to the species Orthohepevirus A (HEV-A). The zoonotic potential of the species Orthohepevirus C (HEV-C), which circulates in rats and is highly divergent from HEV-A, is unknown. We report a liver transplant recipient with hepatitis caused by HEV-C infection. We detected HEV-C RNA...

Background Cytomegalovirus (CMV) mononucleosis is a manifestation of primary CMV infection. This study aims to establish the link between long-term population CMV seroepidemiological trends and incidence of CMV mononucleosis requiring hospitalization. Furthermore, by analyzing serial laboratory data of patients hospitalized with CMV mononucleosis,...

Background: Human adenoviruses are common causes of community-acquired respiratory tract and enteric infections. Severe disseminated infections with high mortality rates may be seen in immunocompromised individuals. An accurate and cost-effective quantitative assay is essential not only for laboratory diagnosis of adenoviral infections, but also f...

Background: Coxsackievirus A6 (CV-A6) represents the predominant enterovirus serotype in Hong Kong, but its epidemiology in our population was unknown. Objectives: To examine the clinical and molecular epidemiology of CV-A6 and detect emerging recombinant strains in Hong Kong. Study design: Nasopharyngeal aspirates (NPAs) from patients with fe...

Background A liver transplant recipient developed hospital-acquired symptomatic hepatitis C virus (HCV) genotype 6a infection 14 months post transplant. Objective Standard outbreak investigation. Methods Patient chart review, interviews of patients and staff, observational study of patient care practices, environmental surveillance, blood collect...

Hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Patients with chronic hepatitis B superinfected with HEV may progress to liver failure. Babao Dan (BD) is a traditional Chinese medicine widely used as an auxiliary option for the treatment of chronic hepatitis and liver cancer in China. This study aimed to evaluate the effect of BD...

I read with interest the work by Drave et al on the replication of hepatitis E virus (HEV) in neuronal cell lines (1). HEV is increasingly associated with a range of neurological manifestations including Guillain Barre Syndrome, neuralgic amyotrophy and encephalitis (2). Therefore, in‐vitro work on this subject is timely and important. This article...

Talaromyces marneffei, previously known as Penicillium marneffei, is the most important pathogenic thermally dimorphic fungus causing systemic mycosis in Southeast Asia. Traditionally, T. marneffei infection in human was mainly associated with acquired immunodeficiency syndrome caused by HIV infection. In recent years, there has been an increasing...

Japanese encephalitis virus (JEV) is a mosquitoborne virus endemic to China and Southeast Asia that causes severe encephalitis in <1% of infected persons. Transmission of JEV via blood transfusion has not been reported. We report transmission of JEV via blood donation products from an asymptomatic viremic donor to 2 immunocompromised recipients. On...

The Abbott RealTime HCV Genotype II assay (Abbott-RT-HCV assay) is a real-time PCR based genotyping method for hepatitis C virus (HCV). This study measured the impact of inter-genotypic recombination and probe cross-reactivity on the performance of the Abbott-RT-HCV assay. 517 samples were genotyped using the Abbott-RT-HCV assay over a one-year per...

Description of real-time reverse transcription PCR for detection of Japanese encephalitis virus.

Questionnaire given by Hong Kong Red Cross to blood donors.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in China. Recently, a shift in molecular epidemiology from hepatitis E genotype 1 (HEV-1) to hepatitis E genotype 4 (HEV-4) has been observed in Northern China, marking a switch from human-to-human transmission to zoonosis. However, similar data from cities in Southern China...

A new FDA-approved Xpert Xpress Flu/RSV assay has been released for rapid influenza virus detection. We collected 134 nasopharyngeal specimens to compare the diagnostic performance of the Xpert assay and the Alere i Influenza A & B assay for influenza A and B virus detection. The Xpert assay demonstrated 100% and 96.3% sensitivity to influenza A an...

There are two genotypes of swine hepatitis E causing foodborne zoonotic infections in humans – genotype 3 (HEV-3), which is prevalent in Europe and Japan, and genotype 4 (HEV-4) prevalent in China. HEV-3 has been established as a cause of chronic hepatitis in immunocompromised patients. However, the outcomes of HEV-4 infection, the most common caus...