ABSTRACT
Background. The extent to which the oro-faecal route contributes to the transmission of SARS-CoV-2 is not established. Methods: We systematically reviewed the evidence on the presence of infectious SARS-CoV-2 in faeces and other gastrointestinal sources by examining studies that used viral culture to investigate the presence of replication-competent virus in these samples. We conducted searches in the WHO Covid-19 Database, LitCovid, medRxiv, and Google Scholar for SARS-CoV-2 using keywords and associated synonyms, with a search date up to 28th of November 2023. Results: We included 13 studies involving 328 COVID-19 subjects - providing 314 faecal or rectal swab SARS-CoV2 positive samples tested also with viral culture. The methods used for viral culture across the studies were heterogeneous. Three studies (2 cohorts and 1 case-series) reported observing replication-competent SARS-CoV-2 confirmed by quantitative RT-PCR (qPCR) and whole genome sequencing, and qPCR including appropriate cycle threshold changes. Overall, six (1.9%) of 314 faecal samples subjected to cell culture showed replication-competent virus. One study found replication competent samples from one immunocompromised patient. No studies were identified demonstrating direct evidence of oro-faecal transmission to humans. Conclusions: Our review found a relatively low frequency of replication-competent SARS-CoV-2 in faecal and other gastrointestinal sources. Although it is biologically plausible, more research is needed, using standardized cell culture methods, control groups, adequate follow-up and robust epidemiologic methods, including whether secondary infections occurred, to determine the role of the oro-faecal route in the transmission of SARS-CoV-2.
Subject(s)
COVID-19 , CoinfectionABSTRACT
Background: Vertical transmission of SARS-CoV-2 has been reported but appears uncommon. Objectives This study systematically reviewed the evidence on vertical transmission of SARS-CoV-2 from pregnant women to their neonates. Search strategy Literature searches in WHO Covid-19 Database, LitCovid, medRxiv, and Google Scholar for SARS-CoV-2 using keywords and associated synonyms, search date to 20 December 2020; no language restrictions. Selection criteria Studies of any design reporting transmission. Data collection and analysis Two reviewers independently assessed article eligibility and extracted data. Results were reported descriptively; no meta-analyses were possible. Main results 106 studies were included: 40 reviews and 66 primary studies, most conducted in hospitals. 32 case reports were assessed as high risk of bias, due to the study design; across the 34 remaining primary studies, risk of bias was low to moderate. Sixteen case reports described vertical transmission. In cohort studies and case series, 65/2391 (2.7%) neonates born to mothers with a COVID-19 diagnosis tested positive for SARS-CoV-2 within 24 hours of birth; the proportion of positive neonates ranged from 0% to 22%. Twenty studies reported no vertical transmission. Maternal symptomatology and mode of delivery were not correlated with vertical transmission. 7/25 studies of placental tissue identified SARS-CoV-2; vertical transmission was infrequent. No study reported the results of viral culture to detect SARS-CoV-2. Conclusions These findings indicate that vertical transmission is possible, but not frequent. Further high-quality studies are needed to understand vertical transmission. Funding World Health Organization: WHO registration No 2020/1077093.
Subject(s)
COVID-19ABSTRACT
Rationale for the review: COVID-19 treatment can worsen parasitic disease in patients with coinfection. Consequently, there is a need to investigate the infection with SARS CoV 2 and Strongyloides. We aim to systematically review clinical and laboratory features of COVID 19 and Strongyloides coinfection, to investigate possible interventions and outcomes in this pathology. Also, we aim to identify difficulties in managing the parasitic disease manifestations in this context and to emphasize research gaps requiring further attention. Methods: We will search two electronic databases (LitCOVID, and WHO COVID 19) and will include studies on SARS CoV 2 and Strongyloides coinfection. We will adapt the WHO UMC system for standardized case causality assessment to evaluate if using corticosteroids or other immunosuppressive drugs in COVID 19 patients determined acute strongyloidiasis manifestations. Expected results: We will present the evidence in three distinct packages: study description, methodological quality assessment and data extracted. We will summarize the evidence and will draw conclusions as to the quality of the evidence.
Subject(s)
COVID-19 , Strongyloidiasis , Severe Acute Respiratory Syndrome , Parasitic DiseasesABSTRACT
Systematic reviews of 591 primary studies of the modes of transmission for SARS-CoV-2 show significant methodological shortcomings and heterogeneity in the design, conduct, testing and reporting of SARS-CoV-2 transmission. While this is partly understandable at the outset of a pandemic, evidence rules of proof for assessing the transmission of this virus are needed for pre-sent and future pandemics of viral respiratory pathogens. We review the history of causality as-sessment related to microbial etiologies with a focus on respiratory viruses and suggest a hierar-chy of evidence to integrate clinical, epidemiologic, molecular and laboratory perspectives on transmission. The hierarchy, if applied to future studies, should narrow the uncertainty over the twin concepts of causality and transmission of human respiratory viruses. We attempt to address the translational gap between the current research evidence and the assessment of causality in the transmission of respiratory viruses with a focus on SARS-CoV-2. Experimentation, consistency and independent replication of research alongside our proposed framework provide a chain of evidence that can reduce the uncertainty over the transmission of respiratory viruses and increase the level of confidence in specific modes of transmission, informing the measures that should be undertaken to prevent transmission.
ABSTRACT
Background Organ transplant recipients are at increased vulnerability to SARS-CoV-2 due to immunosuppression and may pose a continued transmission risk especially within hospital settings. Detailed case reports including symptoms, viral load and infectiousness, defined by the presence of replication-competent viruses in culture, provide an opportunity to examine the relationship between clinical course, burden and contagiousness, and provide guidance on release from isolation. Objectives We performed a systematic review to investigate the relationship in transplant recipients between serial SARS-CoV-2 RT-PCR cycle threshold (Ct) value or cycle of quantification value (Cq), or other measures of viral burden and the likelihood and duration of the presence of infectious virus based on viral culture including the influence of age, sex, underlying pathologies, degree of immunosuppression, and/or vaccination on this relationship. Methods We searched LitCovid, medRxiv, Google Scholar and WHO Covid-19 databases, from 1 November 2019 until 31 December 2021. We included studies reporting relevant data for transplantees with SARS-CoV-2 infection: results from serial RT-PCR testing and viral culture data from the same respiratory samples. We assessed methodological quality using five criteria, and synthesised the data narratively and graphically. Results We included 10 case reports and case series reporting on 38 transplantees. We observed a relationship between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Two individuals shed replication-competent viruses over 100 days after infection onset. Lack of standardisation of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, most transplantees stopped shedding competent viruses when the RT-PCR cycle threshold was above 30 despite differences across platforms. Conclusions Viral burden is a reasonable proxy for infectivity when considered within the context of the clinical status of each patient. Standardised study design and reporting are essential to standardise guidance based on an increasing evidence base.
Subject(s)
COVID-19ABSTRACT
This is a protocol for a systematic review that aims to evaluate the role of viral cultures for assessing airborne transmission of SARS-CoV-2. The review will address the following research questions: Are airborne samples infectious? If so, what proportion are infectious, and what is the distance and duration of infectiousness in the air? What is the relationship between infectiousness and airborne PCR cycle threshold (Ct)? Is there evidence of a chain of transmission that establishes an actual instance of airborne transmission of SARS-CoV-2? What circumstances might facilitate infectious viruses being airborne over long distances? We will search LitCovid, medRxiv, Google Scholar, and the WHO Covid-19 database to identify relevant studies. We will include studies reporting airborne transmission attempting viral culture or serial qRT-PCR with or without genomic sequencing. Predictive or modelling studies will be excluded. We will assess the quality of included studies using previously published criteria.
Subject(s)
COVID-19ABSTRACT
This is the protocol for a systematic review focussing on people receiving solid organ or hematopoietic stem cell transplants. Our research questions are as follows: What is the relationship between serial PCR Ct value or other measures of viral burden, and the likelihood and duration of the presence of infectious virus from viral culture, among transplant recipients with SARS-CoV-2 infection? What is the influence of age, sex, underlying pathologies, degree of immunosuppression, vaccination status, COVID-19 symptoms and COVID-19 disease course on viral burden and the likelihood of presence of infectious SARS-CoV-2? We will include single studies reporting serial Cts from sequential rt-PCR testing or other measures of viral burden such as RNA gene copies of respiratory samples (from nasopharyngeal specimens) along with viral culture data on the same samples, from patients about to receive a transplant or who are post transplant with SARS-CoV-2 infection.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Background: Maritime and river travel, including cruise ships, have been implicated with spreading viruses through infected passengers and crew. Given the novelty of the SARS-CoV-2 infection, early cruise ship travel transmission models of spread are based on what is known of the dynamics of other respiratory viral infections. Our objective is to provide a rapid summary and evaluation of relevant data on SARS-CoV-2 transmission aboard cruise ships, report policy implications, and highlight research gaps requiring attention. Methods: We will search LitCovid, medRxiv, Google Scholar, and the WHO Covid-19 database using COVID-19, SARS-CoV-2, transmission, and cruise ship appropriate synonyms. We will also search the reference lists of included studies for additional relevant studies. We will include studies reporting onboard SARS-CoV-2 transmission from passengers and/or crew to passengers and/or crew. We will consider any potential transmission mode. We will assess study quality based on five criteria and report important findings. The outcome will consist of the onboard cruise ships transmission of SARS-CoV-2. We will provide a narrative summary of the data and report the outcomes, including quantitative estimates where feasible and relevant. Where possible, compatible datasets may be pooled for meta-analysis. Expected results: We will present the evidence in three distinct packages: study description, methodological quality assessment and data extracted. We will summarize the evidence and will draw conclusions as to the quality of the evidence.
Subject(s)
COVID-19 , Respiratory Tract Infections , Pasteurellosis, PneumonicABSTRACT
Background The transmission role of SARS-Cov-2 infected persons who develop symptoms post testing (pre symptomatics) or not at all throughout the course of positivity (asymptomatics) is unknown. We carried out a systematic review of available evidence to determine whether they were infectious or not and if so for how long and their probable contribution to the pandemic spread of SARS-CoV-2. Methods We searched LitCovid, medRxiv, Google Scholar and the WHO Covid-19 databases and reference lists of included studies. Search terms were COVID-19, SARS-CoV-2, transmission, asymptomatic, presymptomatic and appropriate synonyms. Searches were carried out to 31 March 2021. We included studies on people exposed to SARS CoV-2 within 2-14 days (incubation time) of close contact or suspected community or institutional exposure to index asymptomatic (at the time of observation) infected individuals, as defined in the study. We included studies with a proven or hypothesised chain of transmission with secondary case infected based on fulfilling a confirmed or probable case definition and confirmation of infectiousness and transmission outcome based either on serial PCR cycle threshold readings or viral culture or gene sequencing or any combination thereof and adequate follow up. We assessed the reliability of symptom and sign survey compatible with contemporary knowledge and extracted documentation of the likelihood of transmission, presence of replicating virus and/or documentation of phylodynamics (genetic sequence lineage) and/or adequate follow-up and reporting of symptoms and signs. We wrote to all included studies corresponding authors to request further details and assessed likelihood of transmission using adapted causality criteria. Results We included 18 studies from a variety of settings. Because of the current lack of standardized methodology and clear reporting criteria there was substantial methodological variation in transmission studies. Asymptomatic prevalence at the time of initial testing varied from 12.5% to 100% and of these 6% to 100% were pre-symptomatic cases, depending on the setting and the methods of case ascertainment and the population. Nursing/care home facilities reported high rates of presymptomatic: 50% - 100% (n=3 studies). Fifteen studies were classified as high risk and three studies at moderate risk of symptom ascertainment bias. In practice, this assessment means that high-risk studies may be less likely to distinguish between pre-symptomatic and asymptomatic cases. Six of the asymptomatic studies and four presymptomatic studies reported growing infectious virus although the data was too sparse to determine duration of infectiousness. Three studies were judged as providing possible and three of probable/likely evidence of asymptomatic transmission of SARs-CoV-2. Five studies provided evidence of possible and two of probable/likely presymptomatic transmission of SARs-CoV-2. Author response rate was 100%. Conclusions Reliable studies included here provide probable evidence of transmission of SARS-CoV-2 from presymptomatic and asymptomatic individuals. Single point in time estimates and binary PCR testing alone cannot provide reliable information on symptom status and information on infectivity. The number of studies and asymptomatic and presymptomatic cases eligible for inclusion was low, with more data and international standardisation of methods needed to further reduce uncertainty.
Subject(s)
COVID-19ABSTRACT
BackgroundAir travel may be associated with the spread of viruses via infected passengers and potentially through in-flight transmission. Given the novelty of the SARS-CoV-2 virus, transmission associated with air travel is based on what is known about the dynamics of transmission of other respiratory virus infections, especially those due to other coronaviruses and influenza. Our objective was to provide a rapid summary and evaluation of relevant data on the transmission of SARS-CoV-2 aboard aircraft, report important policy implications, and highlight research gaps requiring urgent attention. MethodsThis review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We searched LitCovid, medRxiv, Google Scholar, and the WHO Covid-19 database from 1 February 2020 to 27 January 2021 and included studies on the transmission of SARS-CoV-2 aboard aircraft. We assessed study quality based on five criteria and reported important findings. ResultsWe included 18 studies on in-flight transmission of SARS-CoV-2, representing 130 unique flights and two studies on wastewater from aircraft. The overall quality of reporting was low. Two wastewater studies reported PCR-positive SARS-CoV-2 samples, but with relatively high Cycle threshold values ranging from 36 to 40. The definition of an index case was very heterogeneous across the studies. The proportion of contacts traced ranged from 0.68% to 100%. In total, the authors successfully traced 2800/19729 passengers, 140/180 crew members, and 8/8 medical staff. Altogether, 273 index cases were reported, with 64 secondary cases. No secondary cases were reported in three studies, each investigating one flight. The secondary attack rate among the studies that followed up >80% of the passengers and crew (including data on 10 flights) varied between 0% and 8.2%. The included studies reported on the possibility of SARS-CoV-2 transmission from asymptomatic, pre-symptomatic, and symptomatic individuals. Viral cultures were performed in two studies, with 10 positive results reported. Genomic sequencing and phylogenetic analysis were performed in individuals from four flights, with the completeness of genomic similarity ranging from 81-100%. ConclusionCurrent evidence suggests that SARS-CoV-2 can be transmitted during aircraft travel, but the published data do not permit any conclusive assessment of the likelihood and extent. Furthermore, the quality of evidence from most published studies is low. The variation in study design and methodology restricts the comparison of findings across studies. Standardized guidelines for conducting and reporting future studies of transmission on aircrafts should be developed.
Subject(s)
COVID-19ABSTRACT
Background The role of cases of SARS-CoV-2 who remain without symptoms throughout the active phase of the disease (asymptomatics) and those who have not developed symptoms yet when surveyed (pre-symptomatics) is at present unclear, despite the important role that they may play in infecting third parties. There is also a lack of clarity on the role of pauci-symptomatic persons with COVID-19 and the degree to which they may be associated with transmission compared to fully symptomatic persons. Methods We will search LitCovid, medRxiv, Google Scholar and the WHO Covid-19 database using Covid-19, SARS-CoV-2, transmission, and appropriate synonyms as search terms. We will also search the reference lists of included studies are searched for additional relevant studies. We will include studies of people exposed to SARS CoV-2 within 2-14 days (incubation time) of close contact or suspected community or institutional exposure to index asymptomatic infected individuals, as defined in each study with secondary case(s) infected. We will only include studies which provide microbiological proof of transmission outcome (culturable virus and /or genic sequencing). The inclusion of higher-quality evidence should overcome the methodological shortcomings of lower quality studies. We will assess quality of the chain of transmission evidence, microbiological proof and adequacy of follow up and symptom monitoring. Expected results We intend to present the evidence in three distinct packages: study description, methodological quality assessment and data extracted. We intend summarising the evidence and drawing conclusions