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
BackgroundThe progression and severity of the COVID 19 pandemic have been measured based on the daily and total numbers of cases, hospitalisations and deaths. We focused on the nature of hospitalisations from 2020 to 2022. MethodsWe analysed the role played by SARS-CoV-2 in the pandemic in the UK; we lodged FOI requests to Public Health Wales (PHW), Scotland (PHS), and Northern Ireland (PHA NI), the UK Health Security Agency (UKHSA) and NHS England. We asked for all-cause hospital admission monthly numbers reported by days of positivity to SARS-CoV-2 since admission from March 2020. We grouped replies by respondents. We considered any positive tests acquired from day 8 post admission as evidence of in hospital transmission. ResultsPHW, PHS and PHA NI, provided data within two months. The proportion of people admitted who became positive after eight or more days was 33% in Northern Ireland, 24% in Scotland and 45% in Wales. There are seasonal fluctuations reflecting community admissions but no evidence that the proportion of those infected in hospitals reduced over time. No authorities had viral load or symptoms data relating to their datasets. Given the limitations in PCR reporting, it is impossible to know how many "positive" cases were active. UKHSA did not hold the data, and NHS England did not clarify the content of its website. ConclusionAggregate data of "cases of Covid" in hospitals should not be used to inform policy of decision-makers until coordination, and proper interpretation of the dataset are instigated.
Subject(s)
COVID-19ABSTRACT
Polymerase Chain Reaction (“PCR”) tests have been used to identify cases of COVID-19 during the course of the pandemic. Notably, PCR alone cannot differentiate between the presence of whole viruses (which can be transmitted and infect individuals) and small fragments of genetic material that are not infectious. A feature of PCR known as the cycle threshold (Ct) can be used to discriminate between these states, but the relationship between Ct and infectiousness is still poorly understood. This well-known limitation of the test compromises the identification of cases and their trends, and consequently those measures to interrupt transmission (such as isolation) that are undertaken on the basis of reliably identifying infectious individuals. Here, we interrogate the public authorities’ understanding of PCR testing for SARS-CoV-2 in the UK by accessing Freedom of Information requests submitted in 2020-21.We searched WhatDoTheyKnow and found 300 FOI requests , from over 150 individuals. We grouped their questions into four themes addressing the number of tests in use, the reporting of cycle thresholds (‘Ct’), the Ct values themselves, and the accuracy of tests. The number of validated tests in use in the UK is currently not clear: In FOI responses, Public Health England (PHE) report it may be “ 80 ” or “ 85 ”. However, European regulations suggest there could be over 400 different CE marked tests available on the market and available for use. Laboratories have a statutory duty to report positive cases to PHE, but they do not have to advise which tests they are using nor submit Ct values. Only two FOI responses provided answers on Ct values, indicating that in a set time span, 24–38% of the Ct values were over 30. The most common FOI asked if there was a cycle threshold for positivity. In those that responded, the Ct for a positive result varied from 30 to 45. We found limited information on the technical accuracy of the tests. Several responses stated there is no ‘static’, ‘specific’ or ‘standard’ cycle threshold. The current system requires significant changes to ensure it offers accurate diagnostic data to enable effective clinical management of SARS-CoV-2. PCR is an important and powerful tool, but its systematic misuse and misreporting risk undermining its usefulness and credibility.
Subject(s)
COVID-19ABSTRACT
Death is a widely used outcome to assess the severity of pandemics. Accuracy in assigning the cause of death is of vital importance to define the impact of the agent, monitor its evolution, and compare its threat with those of other agents. Throughout the COVID-19 pandemic, there has been widespread reporting of aggregate death data with little attention paid to the accuracy of the assignment of causation. We aimed to analyse public authorities' understanding of the assignment of cause of deaths during the SARS-CoV-2 pandemic in the UK by accessing Freedom of Information requests posed in three periods in 2020-21. By public authorities, we mean NHS Health Trusts, laboratories, and government agencies such as Public Health England and the Department of Health and Social Care. We searched WhatDoTheyKnow using the terms "covid and death". We excluded those requests to bodies that cannot provide an answer (e.g. Councils) and those dealing with the effects of vaccines. We grouped questions into themes addressing the definitions and causes of death relevant to the pandemic. We looked at the responses to the questions of the definition of cause of death, the accuracy of the attribution, the role of other pre-existing pathologies and how these were reported and quantified. We found 800 requests from over 90 individuals. There was no consistency in the definition of cause of death or contributory cause of death across national bodies and in different bodies within the same nation. Nursing home providers, as well as medical practitioners, can assign a cause of death according to the Care Quality Commission. Post-mortem examinations were uncommon, the ONS did not incorporate their results in the summary of deaths by cause during the pandemic period. The meaning of the words "test" or "swab" was never clarified by any of the respondents. In care homes in England 1,304 out of 17,264 COVID-19 (7.6%, range 0% to 63%) mentioned COVID-19 in the absence of contributory or other factors in the death certificate, making it impossible to ascertain a chain of causality. The inconsistencies already noted hinder the ascertainment of the role of each factor leading to death and the quantification of the importance of infection. Some responses indicate that SARS-CoV-2 negative individuals or those whose death was not caused by COVID-19 were classified as "COVID-19 deaths". We found 14 different ways of attributing the causes of death mentioned by respondents. The overall lack of consistency has confused the public and likely led to erroneous conclusions. We are unable to separate the effects on deaths of SARS-CoV-2 from those of human interventions. A coherent process based on consistent definitions across the devolved nations is required. Furthermore, to enhance the accuracy of causation in pandemics a subset of deaths should be verified using autopsies with full medical documentation.
Subject(s)
COVID-19 , DeathABSTRACT
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 a protocol for a systematic review to assess fomite transmission in SARS-CoV-2. Our research questions are as follows: 1. Are fomite samples infectious? 2 If so, what proportion are infectious, and what is the distance and duration of infectiousness in the air? 3. What is the relationship between fomites, infectiousness and PCR cycle threshold (Ct)? 4. Is there evidence of a chain of transmission that establishes an actual instance of fomite transmission of SARS-CoV-2? We will include studies of any design (and in any setting) that investigate fomite transmission (defined as any inanimate object that, when contaminated with or exposed to infectious agents, can transfer the agent to a new host). We will only include studies that performed viral culture which assessed cytopathic effect and verification techniques to ensure the cultured virus is SARS-CoV-2. We will assess the risk of bias using a checklist modified from the QUADAS-2 criteria.
ABSTRACT
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
BackgroundVertical transmission of SARS-CoV-2 has been reported but does not appear to be common. This study aims to systematically review the evidence for vertical transmission of SARS-CoV-2. MethodsThis review is part of an Open Evidence Review on the transmission dynamics of SARS-CoV-2 and the role of intrauterine mother to fetus transmission. Literature searches were performed in the WHO Covid-19 Database, LitCovid, medRxiv, and Google Scholar for SARS-CoV-2 using keywords and associated synonyms, search date up to 20 December 2020, no language restrictions. ResultsWe included 106 studies assessing vertical transmission of SARS-CoV-2 from pregnant women to their neonates: these studies comprised 40 reviews (21 fulfilled systematic review methodology, including risk of bias assessment of included studies) and 66 primary studies including 32 case reports (of up to two cases) and 34 prospective and retrospective cohort studies, prospective and retrospective case series, observational studies (including asymptomatic screening), database studies and a quality improvement project. Almost all were conducted in a hospital setting. The 32 case reports were considered to be at 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 examined vertical transmission, which was not related to maternal symptomatology. For the cohort and case series studies, the percentage of positive neonates ranged from 0% to 22% across the studies. Twenty studies reported no positive vertical transmission. Three studies that reported the highest positivity rates of 11%, 15% and 22% had specifically selected neonates with a positive test (within up to 35 days) within the study population and were therefore more selective populations. Across the cohort and case series studies there were 65/2391 (2.7%) neonates born to mothers with a diagnosis of COVID-19 tested positive for SARS-CoV-2 within 24 hours of birth. No evidence correlated maternal symptomatology to vertical transmission. Mode of delivery did not correlate with rates of vertical transmission. Of 25 studies, 7 identified SARS-CoV-2 in placental tissue; some of these did not demonstrate vertical transmission to the neonate. No study reported the results of viral culture to detect SARS-CoV-2. ConclusionsThe results of these studies indicate that vertical transmission is possible, but is not frequent, and factors that influence when vertical transmission occurs are unknown. Further studies using standardised methods to establish viral infection are needed to establish vertical transmission rates and to assess clinical and other conditions affecting transmission.
Subject(s)
COVID-19ABSTRACT
BackgroundVaccines are highly effective for preventing a range of childhood infections. However, there have been concerns about an alarming decline in vaccinations in 2020 due to the COVID-19 pandemic. MethodsWe performed a rapid review for studies that assessed childhood vaccination uptake during restrictive phases of the COVID-19 pandemic. ResultsWe found 35 published studies that compared changes in the pattern of childhood vaccinations before and during the pandemic. Thirteen were surveys; two mixed-methods surveys and interviews, three modelling studies and 17 retrospective cohort studies with historical controls. We also included ten reports by national or international agencies that had original data on vaccination uptake. Significant global disruptions to vaccine services were reported in Africa, Asia, America (including Latin America and the Caribbean) and Europe. We also found evidence of significant disruption to vaccine uptake for diphtheria tetanus pertussis, BCG, measles and polio. Countries where vaccination rates were already suboptimal had greater drops in uptake and there was evidence of smaller declines in younger children compared to older children. Children born to women who could not read and write were more likely to be incompletely immunized. Various initiatives were used to drive up vaccination rates post restrictions. ConclusionsObstacles to the delivery of vaccination services during the Covid-19 pandemic drove down immunisation rates, especially in disadvantaged people and poorer countries.
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
Subject(s)
COVID-19ABSTRACT
BackgroundHow SARS-CoV-2 is transmitted is of key public health importance. SARS-CoV-2 has been detected in the feces of some Covid-19 patients which suggests the possibility that the virus could additionally be transmitted via the orofecal route. MethodsThis review is part of an Open Evidence Review on Transmission Dynamics of Covid-19. We conduct ongoing searches using LitCovid, medRxiv, Google Scholar and Google for Covid-19; assess study quality based on five criteria and report important findings on an ongoing basis. Where necessary authors are contacted for further details or clarification on the content of their articles. ResultsWe found 59 studies: nine reviews and 51 primary studies or reports (one cohort study also included a review) examining the potential role of orofecal transmission of SARS-CoV-2. Half (n=29) were done in China. Thirty seven studies reported positive fecal samples for SARS-CoV-2 based on RT-PCR results (n=1,034 patients). Six studies reported isolating the virus from fecal samples of nine patients, one study isolated the virus from rectal tissue and one laboratory study found that SARS-CoV-2 productively infected human small intestinal organoids. Eleven studies report on fecal samples found in sewage, and two sampled bathrooms and toilets. ConclusionsVarious observational and mechanistic evidence support the hypothesis that SARS-CoV-2 can infect and be shed from the human gastrointestinal tract. Policy should emphasize the importance of strict personal hygiene measures, and chlorine-based disinfection of surfaces in locations where there is presumed or known SARS-CoV-2 activity.
Subject(s)
COVID-19ABSTRACT
Objectiveto review the evidence from studies comparing SARS-CoV-2 culture, the best indicator of current infection and infectiousness with the results of reverse transcriptase polymerase chain reaction (RT-PCR). MethodsWe searched LitCovid, medRxiv, Google Scholar and the WHO Covid-19 database for Covid-19 using the terms viral culture or viral replication and associated synonyms up to 10 September 2020. We carried out citation matching and included studies reporting attempts to culture or observe SARS-CoV-2 matching with cutoffs for RT-PCR positivity. One reviewer extracted data for each study and a second reviewer checked end edited the extraction and summarised the narratively by sample: fecal, respiratory, environment or mixed. Where necessary we wrote to corresponding authors of the included or background papers for additional information. We assessed quality using a modified QUADAS 2 risk of bias tool. This review is part of an Open Evidence Review on Transmission Dynamics of COVID-19. Summaries of the included studies and the protocol (v1) are available at: https://www.cebm.net/evidence-synthesis/transmission-dynamics-of-covid-19/. Searches are updated every 2 weeks. This is the fourth version of this review that was first published on the 4th of August and updated on the 21t of August ResultsWe included 29 studies reporting culturing or observing tissue invasion by SARS-CoV in sputum, naso or oropharyngeal, urine, stool, blood and environmental samples from patients diagnosed with Covid-19. The data are suggestive of a relation between the time from collection of a specimen to test, cycle threshold and symptom severity. The quality of the studies was moderate with lack of standardised reporting. Twelve studies reported that Ct values were significantly lower and log copies higher in samples producing live virus culture. Five studies reported no growth in samples based on a Ct cut-off value. These values ranged from CT > 24 for no growth to Ct [≥] 34. Two studies report a strong relationship between Ct value and ability to recover infectious virus and that the odds of live virus culture reduced by 33% for every one unit increase in Ct. A cut-off RT-PCR Ct > 30 was associated with non-infectious samples. One study that analysed the NSP, N and E gene fragments of the PCR result reported different cut-off thresholds depending on the gene fragment analysed. The duration of RNA shedding detected by PCR was far longer compared to detection of live culture. Six out of eight studies reported RNA shedding for longer than 14 days. Yet, infectivity declines after day 8 even among cases with ongoing high viral loads. A very small proportion of people re-testing positive after hospital discharge or with high Ct are likely to be infectious. ConclusionProspective routine testing of reference and culture specimens are necessary for each country involved in the pandemic to establish the usefulness and reliability of PCR for Covid-19 and its relation to patients factors. Infectivity is related to the date of onset of symptoms and cycle threshold level. A binary Yes/No approach to the interpretation RT-PCR unvalidated against viral culture will result in false positives with possible segregation of large numbers of people who are no longer infectious and hence not a threat to public health.
Subject(s)
COVID-19ABSTRACT
Abstract OBJECTIVE: To examine the effectiveness of eye protection, face masks, or person distancing on interrupting or reducing the spread of respiratory viruses. DESIGN: Update of a Cochrane review that included a meta-analysis of observational studies during the SARS outbreak of 2003. DATA SOURCES: Eligible trials from the previous review; search of Cochrane Central Register of Controlled Trials, PubMed, Embase and CINAHL from October 2010 up to 1 April 2020; and forward and backward citation analysis. DATA SELECTION: Randomised and cluster-randomised trials of people of any age, testing the use of eye protection, face masks, or person distancing against standard practice, or a similar physical barrier. Outcomes included any acute respiratory illness and its related consequences. DATA EXTRACTION AND ANALYSIS: Six authors independently assessed risk of bias using the Cochrane tool and extracted data. We used a generalised inverse variance method for pooling using a random-effects model and reported results with risk ratios and 95% Confidence Intervals (CI). RESULTS: We included 15 randomised trials investigating the effect of masks (14 trials) in healthcare workers and the general population and of quarantine (1 trial). We found no trials testing eye protection. Compared to no masks there was no reduction of influenza-like illness (ILI) cases (Risk Ratio 0.93, 95%CI 0.83 to 1.05) or influenza (Risk Ratio 0.84, 95%CI 0.61-1.17) for masks in the general population, nor in healthcare workers (Risk Ratio 0.37, 95%CI 0.05 to 2.50). There was no difference between surgical masks and N95 respirators: for ILI (Risk Ratio 0.83, 95%CI 0.63 to 1.08), for influenza (Risk Ratio 1.02, 95%CI 0.73 to 1.43). Harms were poorly reported and limited to discomfort with lower compliance. The only trial testing quarantining workers with household ILI contacts found a reduction in ILI cases, but increased risk of quarantined workers contracting influenza. All trials were conducted during seasonal ILI activity. CONCLUSIONS: Most included trials had poor design, reporting and sparse events. There was insufficient evidence to provide a recommendation on the use of facial barriers without other measures. We found insufficient evidence for a difference between surgical masks and N95 respirators and limited evidence to support effectiveness of quarantine. Based on observational evidence from the previous SARS epidemic included in the previous version of our Cochrane review we recommend the use of masks combined with other measures.