Reina Sikkema

Erasmus MC | Erasmus MC · Department of Virology

The transmission routes and risk factors for zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) infections are still unknown. We used the World Health Organization questionnaire for MERS-CoV case-control studies to assess risk factors for human MERS-CoV seropositivity at a farm complex in Qatar. Nine camel workers with MERS-CoV antibo...

Introduction The increase in emerging human infectious diseases that have a zoonotic origin and the increasing resistance of microorganisms to antimicrobial drugs have shown the need for collaborations between the human, animal and environmental health sectors. The One Health concept increasingly receives recognition from policy makers and research...

Assessing influenza A virus strains circulating in animals and their potential to cross the species barrier and cause human infections is important to improve human influenza surveillance and preparedness. We reviewed studies describing serological evidence of human exposure to animal influenza viruses. Comparing serological data is difficult due t...

The risk of infection with avian influenza viruses for poultry workers is relatively unknown in China, and study results are often biased by the notification of only the severe human cases. Protein microarray was used to detect binding antibodies to 13 different haemagglutinin (HA1-part) antigens of avian influenza A(H5N1), A(H7N7), A(H7N9) and A(H...

To the Editor: Avian influenza A(H5N6) influenza viruses have circulated among poultry in southern (Jiangxi, Guangdong) and western (Sichuan) provinces of China since 2013 (1,2). In 2014, outbreaks of H5N6 virus infection occurred among poultry in China, Laos, and Vietnam (1). In April 2014, the first case of highly pathogenic H5N6 infection among...

Climate change is one of several drivers of recurrent outbreaks and geographical range expansion of infectious diseases in Europe. We propose a framework for the co-production of policy-relevant indicators and decision-support tools that track past, present, and future climate-induced disease risks across hazard, exposure, and vulnerability domains...

In November 2021, seven western lowland gorillas and four Asiatic lions were diagnosed with COVID-19 at Rotterdam Zoo. An outbreak investigation was undertaken to determine the source and extent of the outbreak and to identify possible transmission routes. Interviews were conducted with staff to identify human and animal contacts and cases, complia...

In October 2020, a new lineage of clade 2.3.4.4b HPAI virus of the H5 subtype emerged in Europe, resulting in the largest global outbreak of HPAI to date, with unprecedented mortality in wild birds and poultry. The virus appears to have become enzootic in birds, continuously yielding novel HPAI virus variants. The recently increased abundance of in...

Background Healthcare facilities have been challenged by the risk of SARS-CoV-2 transmission between healthcare workers (HCW) and patients. During the first wave of the COVID-19 pandemic, infections among HCW were observed, questioning infection prevention and control (IPC) measures implemented at that time. Aim This study aimed to identify nosoco...

Drivers are factors that have the potential to directly or indirectly influence the likelihood of infectious diseases emerging or re-emerging. It is likely that an emerging infectious disease (EID) rarely occurs as the result of only one driver; rather, a network of sub-drivers (factors that can influence a driver) are likely to provide conditions...

Usutu virus (USUV) is a mosquito-borne zoonotic flavivirus causing mortality in Eurasian blackbirds (Turdus merula) in Europe. In dead blackbirds, avian malaria co-infection due to mosquito-borne hemosporidians (e.g., Plasmodium spp.) has been reported. In humans, a similar co-infection of a flavivirus, Dengue virus, and Plasmodium spp. is causing...

Introduction: In 2020, the first Dutch West Nile virus (WNV) infected birds were detected through risk-targeted surveillance of songbirds. Retrospective testing of patients with unexplained neurological disease revealed human WNV infections in July and August 2020. Bird ringers are highly exposed to mosquito bites and possibly avian excrements dur...

Modified vaccinia virus Ankara (MVA) is used as a vaccine against monkeypox virus (MPXV) and as a viral vaccine vector. MVA-MERS-S is a vaccine candidate against Middle East respiratory syndrome- associated coronavirus (MERS-CoV). Here, we report that cross-reactive MPXV nAbs were detectable in only a single subject after the first dose, 3 out of 1...

Background: Outbreaks of zoonotic emerging infectious diseases (EIDs) require rapid identification of potential reservoir hosts and mapping disease spread in these hosts to inform risk assessment and adequate control measures. Animals are often understudied when a novel EID is detected in humans and acquisition of animal samples is hampered by pra...

Monitoring of SARS-CoV-2 in wastewater (WW) is a promising tool for epidemiological surveillance, correlating not only viral RNA levels with the infection dynamics within the population, but also to viral diversity. However, the complex mixture of viral lineages in WW samples makes tracking of specific variants or lineages circulating in the popula...

We aimed to assess SARS-CoV-2 contamination of air and surfaces to gain insight into potential occupational exposure in a large meat processing plant experiencing COVID-19 clusters. Methods: Oro-nasopharyngeal SARS-CoV-2 screening was performed in 76 workers. Environmental samples ( n = 275) including air, ventilation systems, sewage, and swabs of...

SARS-CoV-2 prevention and control measures did not only impact SARS-CoV-2 circulation, but also the timing and prevalence of other seasonal respiratory viruses. Especially in children, information on exposure and infections to seasonal coronaviruses as well as SARS-CoV-2 in the first year of the pandemic is largely lacking. Therefore, we set up a o...

In some areas in temperate Europe, genomic analyses of mosquito-borne virus outbreaks have revealed the presence of similar virus strains over several years, indicating local overwintering of these viruses. However, it remains unclear how mosquito-borne viruses can persist in winter, when conditions are generally unfavourable for virus circulation....

Rabies virus (RABV) has a broad host range and infects multiple cell types throughout the infection cycle. Next-generation sequencing (NGS) and minor variant analysis are powerful tools for studying virus populations within specific hosts and tissues, leading to novel insights into the mechanisms of host-switching and key factors for infecting spec...

Spread and emergence of West Nile virus (WNV) in Europe have been very different from those observed in North America. Here, we describe key drivers by combining viral genome sequences with epidemiological data and possible factors of spread into phylodynamic models. WNV in Europe has greater lineage diversity than other regions of the world, sugge...

Wild birds are reservoirs of several zoonotic arboviruses including West Nile virus (WNV) and Usutu virus (USUV), and are often monitored as indicators for virus introduction and spread. To optimize the bird surveillance for arboviruses in the Netherlands and to explore the possibilities for citizen science in surveillance, we investigated the suit...

SARS-CoV-2 outbreaks on 69 Dutch mink farms in 2020 were studied to identify risk factors for virus introduction and transmission and to improve surveillance and containment measures. Clinical signs, laboratory test results, and epidemiological aspects were investigated, such as the date and reason of suspicion, housing, farm size and distances, hu...

Background To understand the dynamics of infectious diseases, genomic epidemiology is increasingly advocated, with a need for rapid generation of genetic sequences during outbreaks for public health decision making. Here, we explore the use of metagenomic sequencing compared to specific amplicon- and capture-based sequencing, both on the Nanopore a...

In the Netherlands, 69 of the 126 (55%) mink farms in total became infected with SARS‐CoV‐2 in 2020. Despite strict biosecurity measures and extensive epidemiological investigations, the main transmission route remained unclear. A better understanding of SARS‐CoV‐2 transmission between mink farms is of relevance for countries where mink farming is...

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) break through infection- or vaccine-induced immunity is not well understood. We analyzed 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to...

Novel safe, immunogenic, and effective vaccines are needed to control the COVID-19 pandemic, caused by SARS-CoV-2. Here, we describe the safety, robust immunogenicity, and potent efficacy elicited in rhesus macaques by a modified vaccinia virus Ankara (MVA) vector expressing a full-length SARS-CoV-2 spike (S) protein (MVA-S). MVA-S vaccination was...

Here we describe a SARS-CoV-2 variant with diminished amplification of the ORF ORF1ab target in the Cobas® dual-target SARS-CoV-2 assay resulting in a discrepancy of Ct-values (Ct-value 20.7 for the E-gene and Ct-value 30.2 for ORF1ab). Five unique nucleotide mutations were identified in ORF1ab: C11450A (nsp10) C14178 T (RdRp), G15006 T (RdRp), G18...

p>In order to assess the risk of SARS-CoV-2 infection, transmission and reservoir development in swine, we combined results of an experimental and two observational studies. First, intranasal and intratracheal challenge of eight pigs did not result in infection, based on clinical signs and PCR on swab and lung tissue samples. Two serum samples retu...

In the first wave of the COVID-19 pandemic (April 2020), SARS-CoV-2 was detected in farmed minks and genomic sequencing was performed on mink farms and farm personnel. Here, we describe the outbreak and use sequence data with Bayesian phylodynamic methods to explore SARS-CoV-2 transmission in minks and humans on farms. High number of farm infection...

Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal...

The current coronavirus disease 2019 (COVID-19) pandemic is the first to apply whole-genome sequencing near to real time, with over 2 million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole-genome sequences generated and shared through the GISAID platform. This genomic resource informed public health decision-making throughout th...

Assays to measure SARS-CoV-2-specific neutralizing antibodies are important to monitor seroprevalence, to study asymptomatic infections and to reveal (intermediate) hosts. A recently developed assay, the surrogate virus-neutralization test (sVNT) is a quick and commercially available alternative to the “gold standard” virus neutralization assay usi...

Objective Unprecedented SARS-CoV-2 infections in farmed minks raised immediate concerns regarding transmission to humans and initiated intensive environmental investigations to assess occupational and environmental exposure. Methods Air sampling was performed at infected Dutch mink farms, at farm premises and at nearby residential sites. A range o...

The Usutu virus (USUV) is a mosquito-borne zoonotic flavivirus. Despite its continuous circulation in Europe, knowledge on the pathology, cellular and tissue tropism and pathogenetic potential of different circulating viral lineages is still fragmentary. Here, macroscopic and microscopic evaluations are performed in association with the study of ce...

In the first wave of the COVID-19 pandemic (April 2020), SARS-CoV-2 was detected in farmed minks and genomic sequencing was performed on mink farms and farm personnel. Here, we describe the outbreak and use sequence data with Bayesian phylodynamic methods to explore SARS-CoV-2 transmission in minks and related humans on farms. High number of farm i...

Background: People on ships are at high risk for outbreaks of infectious diseases including coronavirus disease 2019 (COVID-19). A rapid and well-coordinated response is important to curb transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We studied an outbreak on an industrial ship to improve outbreak control for ships...

Worldwide exceptionally many COVID-19 clusters were observed in meat processing plants. Many contributing factors, promoting transmission, were suggested, including climate conditions in cooled production rooms favorable for environmental transmission but actual sampling studies are lacking. We aimed to assess SARS-CoV-2 contamination of air and su...

Animals like mink, cats and dogs are susceptible to SARS-CoV-2 infection. In the Netherlands, 69 out of 127 mink farms were infected with SARS-CoV-2 between April and November 2020 and all mink on infected farms were culled after SARS-CoV-2 infection to prevent further spread of the virus. On some farms, (feral) cats and dogs were present. This stu...

Objectives To obtain insight in SARS-CoV-2 clustering and transmission routes during outbreaks in the predominantly migrant workforce of the fruit and vegetable packaging industry of South Holland, the Netherlands, May to July 2020. Design This mixed methods study applied direct observation and interviews, epidemiologic investigation, source and c...

Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal...

Assays to measure SARS-CoV-2-specific neutralizing antibodies are important to monitor seroprevalence, to study asymptomatic infections and to reveal (intermediate) hosts. A recently developed assay, the surrogate virus-neutralization test (sVNT) is a quick and commercially available alternative to the 'gold standard' virus neutralization assay usi...

Background Sars-CoV-2 outbreaks resulted in a high case fatality rate in nursing homes (NH) worldwide. It is unknown to which extent presymptomatic residents and staff contribute to the spread of the virus. Aims To assess the contribution of asymptomatic and presymptomatic residents and staff in SARS-CoV-2 transmission during a large outbreak in a...

Background The Dutch province of Limburg borders the German district of Heinsberg, which had a large cluster of COVID-19 cases linked to local carnival activities before any cases were reported in the Netherlands. However, Heinsberg was not included as an area reporting local or community transmission per the national case definition at the time. I...

SARS-CoV-2 transmission in indoor spaces, where most infection events occur, depends on the types and duration of human interactions, among others. Understanding how these human behaviours interface with virus characteristics to drive pathogen transmission and dictate the outcomes of non-pharmaceutical interventions is important for the informed an...

Animals like mink, cats and dogs are susceptible to SARS-CoV-2 infection. In the Netherlands, 69 out of 127 mink farms were infected with SARS-CoV-2 between April and November 2020 and all mink on infected farms were culled after SARS-CoV-2 infection to prevent further spread of the virus. On some farms, (feral) cats and dogs were present. This stu...

We investigated the sources of infection among healthcare workers (HCWs) and patients in a teaching hospital during the early stages of the COVID-19 pandemic with epidemiological and whole genome sequencing data. This retrospective study is performed in a Dutch teaching hospital with nursing facilities located in Rotterdam and Schiedam with around...

Uncontrolled SARS-CoV-2 infections in farmed minks raised immediate concerns regarding human health which initiated intensive environmental investigations. Air sampling was performed in infected mink farms, at farm premises and at residential sites. A range of other environmental samples were collected from minks' housing units. Inside the farms, h...

The first highly pathogenic (HP) influenza A/H7N9 was reported in Guangdong in January 2017. To investigate the emergence and spread of HP A/H7N9 in Guangdong province, we sequenced 297 viruses (58 HP A/H7N9, 19 low pathogenic (LP) A/H7N9 and 220 A/H9N2) during 2016-2017. Our analysis showed that during the 5th wave, three A/H7N9 lineages were co-c...

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 was accompanied by uncertainty about its epidemiological and clinical characteristics Once camelus dromedarius was found to be the natural reservoir of the virus public health systems across the Arabian Peninsula came under unprecedented pressure to control its transmi...

Two-way transmission on mink farms Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoonotic virus—one that spilled over from another species to infect and transmit among humans. We know that humans can infect other animals with SARS-CoV-2, such as domestic cats and even tigers in zoos. Oude Munnink et al. used whole-genome sequenc...

Background An outbreak of coronavirus disease 2019 (COVID-19) in a nursing home in the Netherlands, following an on-site church service held on 8 March 2020, triggered an investigation to unravel sources and chain(s) of transmission. Methods Epidemiological data were collected from registries and through a questionnaire among church attendees. Sym...

Background: The Dutch province of Limburg borders the German district of Heinsberg, which had a large cluster of COVID-19 cases linked to local carnival activities in February, before any cases were reported in the Netherlands. However, Heinsberg was not included as an area reporting local or community transmission per the national case definition...

On 22 August, a common whitethroat in the Netherlands tested positive for West Nile virus lineage 2. The same bird had tested negative in spring. Subsequent testing of Culex mosquitoes collected in August and early September in the same location generated two of 44 positive mosquito pools, providing first evidence for enzootic transmission in the N...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background This study aimed to assess the contribution of asymptomatic and presymptomatic residents and staff in SARS-CoV-2 transmission during a large outbreak in a Dutch nursing home. Methods Observational study in a 185-bed nursing home with two consecutive testing strategies: testing of symptomatic cases only, and weekly facility-wide testing o...

In late December 2019, a cluster of cases of pneumonia of unknown etiology were reported linked to a market in Wuhan, China1. The causative agent was identified as the species Severe acute respiratory syndrome-related coronavirus and was named SARS-CoV-2 (ref. 2). By 16 April the virus had spread to 185 different countries, infected over 2,000,000...

The zoonotic origin of the SARS-CoV-2 pandemic is still unknown. Animal experiments have shown that non-human primates, cats, ferrets, hamsters, rabbits and bats can be infected by SARS-CoV-2. In addition, SARS-CoV-2 RNA has been detected in felids, mink and dogs in the field. Here, we describe an in-depth investigation of outbreaks on 16 mink farm...

Understanding the coronavirus (CoV) antibody landscape in relation to disease and susceptibility is critical for modelling of steps in the next phase during the current covid-19 pandemic. In March 2020, during the first month of the epidemic in The Netherlands, we performed cross sectional studies at two time points amongst patients of the Erasmus...

Background An outbreak of COVID-19 in a nursing home in the Netherlands, following an on-site church service held on March 8, 2020, triggered an investigation to unravel sources and chain(s) of transmission.Methods Epidemiological data were collected from registries and through a questionnaire among church visitors. Symptomatic residents and health...