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BackgroundOrgan 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. ObjectivesWe 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. MethodsWe 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. ResultsWe 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. ConclusionsViral 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.
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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.
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This is a protocol for a systematic review to assess fomite transmission in SARS-CoV-2. Our research questions are as follows: O_LIAre fomite samples infectious? C_LIO_LIIf so, what proportion are infectious, and what is the distance and duration of infectiousness in the air? C_LIO_LIWhat is the relationship between fomites, infectiousness and PCR cycle threshold (Ct)? C_LIO_LIIs there evidence of a chain of transmission that establishes an actual instance of fomite transmission of SARS-CoV-2? C_LI 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.
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BackgroundMaritime 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. MethodsWe 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 resultsWe 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.
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Few studies have assessed for infectious SARS-CoV-2 in multiple types of clinical and environmental samples. In almost 500 samples from 75 hospitalized and community cases, we detected infectious virus with quantitative burdens varying from 5.0 plaque-forming units/mL (PFU/mL) up to 1.0x106 PFU/mL in clinical specimens and up to 1.3x106 PFU/mL on fomites including facial tissues, nasal prongs, call bells/cell phones, dentures, and sputum deposits with confirmation by plaque morphology, PCR, immunohistochemistry, and sequencing. Expectorated sputum samples had the highest percentage of positive samples and virus titers (71%, 2.9x102 to 5.2x105 PFU/mL), followed by saliva (58%, 10 to 4.6x104 PFU/mL), and cough samples without sputum (19%, 5 to 1.9x103 PFU/mL). We also detected infectious SARS-CoV-2 from patients hands (28%, 60 to 2.3x102 PFU/mL) but no infectious virus was found in continuous speech samples despite finding high levels of infectious virus in the associated nasopharynx, throat, or saliva specimens. We demonstrated infectious virus stability in clinical samples, including those dried for prolonged periods of time. Infectious virus correlated with time since symptom onset with no detection after 7-8 days in immunocompetent hosts and with N-gene based Ct values [≤] 25 significantly predictive of yielding plaques in culture. One PFU was associated with [~]105 copies of N gene RNA across a diversity of samples and times from symptom onset. Clinical salivary isolates caused illness in a hamster model with a minimum infectious dose of [≤]14 PFU/mL. Our findings of high quantitative burdens of infectious virus, stability even with drying, and a very low minimal infectious dose suggest multiple modes of transmission are exploited by SARS-CoV-2, including direct contact, large respiratory droplet, and fomite transmission and in the context of a high binding avidity to human cellular receptors, offer an explanation of the high contagiousness of this virus. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched the literature for articles that reported on the presence of infectious SARS-CoV-2 in patients samples from clinical and environmental sources. We found several key primary studies and systematic reviews providing valuable background on the carriage of infectious virus and the correlation with cycle threshold (Ct) and/or RNA copies/mL on PCR testing. Clinical correlations with respect to underlying clinical conditions and details on the onset of illness were not commonly reported with respect to the timing of obtaining specimens for culture. Few studies carefully assessed the presence of infectious virus in cough samples, sputum, nasal secretions, hands, and common high touch surfaces. A few published works were found on factors which may be associated with shedding of infectious virus. Added value of this studyWe assessed the presence of infectious virus shedding in almost 500 specimens from 75 patients with COVID-19 in both the hospital and community setting. High titers of infectious virus were detected in multiple clinical and environmental samples. The longest duration of recovery of infectious virus in a fomite sample was from a dried facial tissue found at a patients bedside table, used at least 9 hours earlier. Cough specimens revealed infectious virus in 28% of specimens with infectious virus titers as high as 5.2x105 PFU/mL. Hand samples contained infectious virus with titers ranging from 55 to 2.3x102 PFU/mL. Infectious viral loads correlated with N-gene based Ct values and showed that Ct values [≤] 25 were predictive of yielding plaques in culture. These experiments also showed that infectious virus is most often recovered during a 7 to 8-day period following illness onset in immunocompetent persons, and during that time the ratio of RNA/PFU in these clinical specimens varies relatively little, with a ratio [~]160,000:1. Infectious virus may be recovered for weeks to several months in immunosuppressed persons. We also showed that virus recovered from saliva specimens, representing a commonly encountered fomite sample, caused infection in the Syrian hamster model, hence demonstrating the infectiousness of the virus sourced from this type of specimen. A challenge dose as low as 14 PFU/mL yielded infection in this model. Implications of all the available evidenceWe have shown that SARS-CoV-2 is relatively easy to culture when obtained early in the course of illness and there are high levels of cultivatable SARS-CoV-2 in multiple types of clinical specimens and common fomites, including high-touch surfaces and demonstrated their infectiousness in a mammalian host. Our results demonstrate the presence of high quantitative burdens of SARS-CoV-2 in sputum, saliva, and droplets from coughing, which would lend support to large respiratory droplet transmission, hands which would support direct contact transmission, and fomites which would promote indirect contact transmission. We were unable to detect any infectious virus in continuous speech samples which suggests that brief conversations, without coughing or sneezing, pose little risk of transmitting SARS-CoV-2. Our findings provide an explanation for the high contagiousness of this virus and support current public health measures and infection prevention and control guidelines including physical distancing, hand hygiene, masking, and cleaning and disinfection.
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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.
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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.
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BackgroundSARS-CoV-2 has been detected in wastewater and its abundance correlated with community COVID-19 cases, hospitalizations and deaths. We sought to use wastewater-based detection of SARS-CoV-2 to assess the epidemiology of SARS-CoV-2 in hospitals. MethodsBetween August and December 2020, twice-weekly wastewater samples from three tertiary-care hospitals (totaling >2100 dedicated inpatient beds) were collected. Wastewater samples were concentrated and cleaned using the 4S-silica column method and assessed for SARS-CoV-2 gene-targets (N1, N2 and E) and controls using RT-qPCR. Wastewater SARS-CoV-2 as measured by quantification cycle (Cq), genome copies and genomes normalized to the fecal biomarker PMMoV were compared to the total daily number of patients hospitalized with active COVID-19, confirmed cases of hospital-acquired infection, and the occurrence of unit-specific outbreaks. ResultsOf 165 wastewater samples collected, 159 (96%) were assayable. The N1-gene from SARS-CoV-2 was detected in 64.1% of samples, N2 in 49.7% and E in 10%. N1 and N2 in wastewater increased over time both in terms of amount of detectable virus and the proportion of samples that were positive, consistent with increasing hospitalizations (Pearsons r=0.679, P<0.0001, Pearsons r=0.728, P<0.0001, respectively). Despite increasing hospitalizations through the study period, wastewater analysis was able to identify incident nosocomial-acquired cases of COVID-19 (Pearsons r =0.389, P<0.001) and unit-specific outbreaks by increases in detectable SARS-CoV-2 N1-RNA (median 112 copies/ml) versus outbreak-free periods (0 copies/ml; P<0.0001). ConclusionsWastewater-based monitoring of SARS-CoV-2 represents a promising tool for SARS-CoV-2 passive surveillance and case identification, containment, and mitigation in acute-care medical facilities. Supplemental Material includedO_ST_ABSKey-points summaryC_ST_ABSSAS-CoV-2 RNA is detectable in hospital wastewater. Wastewater SARS-CoV-2 RNA increases in conjunction with COVID-19-related hospitalizations. Spikes in SARS-CoV-2 wastewater signal correspond to incident hospital-acquired cases and outbreaks, suggesting passive surveillance via wastewater has great promise for COVID-19 monitoring.
