Transmission of SARs-CoV-2
Providing a rapid summary and evaluation of relevant data on the transmission of SARS-CoV-2, reporting important policy implications and highlighting areas of urgently needed research.
Our multidisciplinary team has considerable expertise in evidence synthesis and the evaluation of acute respiratory infections. Carl Heneghan and Tom Jefferson lead the research and have worked together for over a decade having been authors of the Tamiflu reviews. Both are Clinical Editors for the Cochrane Acute Respiratory Infections Group.
Transmission of SARS-CoV-2
We publish updates with recommendations for policy, and a series of hypotheses to be tested by further work. Our conclusions and expected outcomes are below the byline of each review.
The transmission areas include airborne, contact and droplet, orofecal, vertical, fomite and asymptomatic and presymptomatic transmission.
A Hierarchical Framework for Assessing Transmission Causality of Respiratory Viruses
Jefferson T., Heneghan C., Spencer E., Brassey J., Pluddemann A., Onakpoya, Evans D, and Conly J.
Abstract: 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. We review the history of causality assessment related to microbial etiologies with a focus on respiratory viruses and suggest a hierarchy of evidence to integrate clinical, epidemiologic, molecular, and laboratory perspectives on transmission. 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.
SARS-CoV-2 Exposures of Healthcare Workers and Acquisition of COVID-19 - commentary
Leal J., Jefferson T., Conly J.
Overview: Healthcare workers (HCWs) may be considered at higher risk given their frequent contact and exposure to SARS-CoV-2 infected patients. This pandemic has taught us the need for continuous risk assessment, adequate training of all HCWs in the principles of IPC, strict adherence to hand hygiene and the need for appropriate use of PPE in its totality. Real-time RCTs in IPC should be prioritized at the same level as trials in diagnostic testing, therapeutic interventions and vaccination.
Understanding COVID-19 admissions in the UK; Analysis of Freedom of Information Requests
Heneghan C., Brassey, J., and Jefferson T.
Abstract: The 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. Methods: We analysed the role played by SARS-CoV-2 in the pandemic in the UK.
Viral Cultures for Assessing Fomites Transmission of SARS-CoV-2: a Systematic Review
Research questions we seek to answer:
- Are fomite 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 fomites, infectiousness and PCR cycle threshold (Ct)?
Is there evidence of a chain of transmission that establishes an actual instance of fomite transmission of SARS-CoV-2?
Viral cultures, Polymerase Chain Reaction Cycle Threshold Values and Viral Load Estimation for SARS-CoV-2 Infectious Potential Assessment in Hematopoietic Stem Cell and Solid Organ Transplant Patients: A Systematic Review
Jefferson T., Spencer E A., Rosca E C., Maltoni S., Brassey J., Onakpoya T., Pluddemann A., Evans D., Conly J. and Heneghan C.
Conclusion: 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 avoid research waste and generate guidance based on an increasing evidence base.
Viral Cultures for Assessing Airborne Transmission of SARs-CoV-2: a Systematic Review Protocol (version 1)
Heneghan C., Spencer EA., Brassey J., Rosca EC., Plüddemann A., Evans DH., Conly JM., Maltoni S., Jefferson T., Onakpova I.
Abstract: The review will address a various research questions, such as, 'Are airborne samples infectious?', 'If so, what proportion are infectious, and what is the distance and duration of infectiousness in the air?' and, 'What is the relationship between infectiousness and airborne PCR cycle threshold (Ct)?'
Viral cultures, PCR Cycle threshold values and viral load estimation for COVID-19 infectious potential assessment in transplant patients: systematic review
Protocol Version 30 December 2021
Jefferson T., Spencer E., Maltoni S., Brassey J., Onakpoya I., Rosca E., Plüddemann A., Evans D., Conly J., Heneghan C.
Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) from pre and asymptomatic infected individuals. A systematic review update
T Jefferson, EA Spencer, J Brassey, DH Evans, JM Conly, C Heneghan.
Conclusion: High-quality studies provide probable evidence of SARS-CoV-2 transmission from presymptomatic and asymptomatic individuals, with highly variable estimated transmission rates.
Transmission of SARS-CoV-2 associated with cruise ship travel: protocol for a systematic review
Rosca E, Heneghan C, Spencer E, Brassey J, Plüddemann A, Onakpoya I, Evans D, Conly J, Jefferson T
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.
SARS-CoV-2 and the role of airborne transmission: systematic review
Heneghan C; Spencer EA; Brassey J; Plüddemann A; Onakpoya I; Evans D; Conly JM; Jefferson T. [version 1] F1000Research 2021, 52091.
Conclusion: SARS-CoV-2 RNA is detected intermittently in the air in various settings. Standardized guidelines for conducting and reporting research on airborne transmission are needed. The lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions over airborne transmission.
Transmission of SARS-CoV-2 from pre and asymptomatic infected individuals. A systematic review
T Jefferson, A Plüddemann, EA Spencer, J Brassey, EC Rosca, I Onakpoya, DH Evans, JM Conly, C Heneghan.
Conclusion: 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. More data and international standardisation of methods needed to further reduce uncertainty.
The evidence on transmission dynamics of COVID-19 from pre- and asymptomatic cases: protocol for a systematic review (Version 2)
T Jefferson, A Plüddemann, EA Spencer, J Brassey, EC Rosca, I Onakpoya, DH Evans, JM Conly, C Heneghan.
Expected results: We intend to present the evidence in three distinct packages: study description, methodological quality assessment and data extracted. We intend on summarising the evidence and drawing conclusions as to the quality of the evidence.
SARS-CoV-2 and the role of vertical transmission from infected pregnant women to their fetuses: systematic review
Annette Plüddemann, Elizabeth A. Spencer, Carl J. Heneghan, Jon Brassey, Igho J.Onakpoya, Elena Cecilia Rosca, David H. Evans, John M. Conly, Tom Jefferson.
Conclusion: The 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.
SARS-CoV-2 and the role of fomite transmission: systematic review
Onakpoya I; Heneghan C; Spencer EA; Brassey J; Plüddemann A; Evans D; Conly JM; Jefferson T. [version 3] F1000Research 2021
Conclusion: The majority of studies report the identification of SARS-CoV-2 RNA on inanimate surfaces; however, the lack of positive viral cultures creates uncertainty about fomites as a mode of transmission. The late timing of sample collection with respect to the illness onset and the variability in reported cycle thresholds and the relatively high values precludes drawing any firm conclusions. Heterogeneity in study designs and methodology prevents comparisons of findings across studies. Standardized guidelines for conducting and reporting research on fomite transmission is warranted.
Transmission of SARS-CoV-2 associated with aircraft travel: a systematic review (Version 1)
EC Rosca, C Heneghan, EA Spencer, J Brassey, A Plüddemann, IJ Onakpoya, DH Evans, JM Conly, T Jefferson.
Conclusion: 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.
SARS-CoV-2 and the role of close contact in transmission: systematic review
Onakpoya I; Heneghan C; Spencer EA; Brassey J; Plüddemann A; Evans D; Conly JM; Jefferson T. [version 1] F1000Research 2021
Conclusion: The evidence from published studies demonstrates that SARS-CoV-2 can be transmitted via close contact settings. The risk of transmission is greater in household contacts. There was wide variation in methodology. Standardized guidelines for reporting transmission in close contact settings should be developed to improve the quality reporting.
SARS-CoV-2 and the role of orofecal transmission: systematic review
Heneghan C; Spencer EA; Brassey J; Plüddemann A; Onakpoya I; Evans D; Conly JM; Jefferson T. [version 1] F1000Research 2021, 51592
Conclusions: Varied observational and mechanistic evidence suggests SARS-CoV-2 can infect and be shed from the human gastrointestinal tract, including some limited data demonstrating viral culture in fecal samples. Future studies should test this hypothesis rigorously to allow the development of appropriate public health measures.
Our SYSTEMATIC REVIEWS
Impact on healthcare policy
Reference WHO registration No 2020/1077093.
The World Health Organisation funded reviews were the first phase of our project. Its objective is to undertake a series of living systematic searches and appraisal of evidence on SARS-CoV-2 modes of transmission and its related updates are informing WHO guidance and scientific documents. CH, AP and ES also receive funding support from the NIHR SPCR Evidence Synthesis Working Group project 390.
The WHO updates interim guidance (12 July 2021) on infection prevention and control (IPC) during health care when coronavirus disease (COVID-19) is suspected or confirmed, and cites CEBM work on airborne, finite and close contact transmission as well as non pharmaceutical interventions.
Intended for health workers, including managers and IPC teams at facility, national and district/provincial levels, this guidance summarizes evidence on infection prevention and control strategies and measures associated with the care for suspected or confirmed cases of COVID-19 in health facilities.
Viral cultures for COVID-19
Complete live viruses are necessary for transmission, not the fragments identified by PCR. Prospective routine testing of reference and culture specimens and their relationship to symptoms, signs and patient co-factors should be used to define the reliability of PCR for assessing infectious potential. Those with a high cycle threshold are unlikely to have infectious potential.
Read the research: Viral cultures for COVID-19 infectious potential assessment – a systematic review.
What did we do?
We systematically reviewed the evidence from studies relating SARS-CoV-2 culture with the results of RT-PCR and other variables which may influence the interpretation of the test, such as time from symptom onset
PCR testing cannot distinguish between the shedding of live virus or of viral fragments with no infectious potential. Although viral culture is difficult, time-consuming and requires specialised facilities it potentially represents the best indicator of infection and infectious potential.
21st Aug: It’s a mistake to think all positive Covid tests are the same Carl Heneghan, Tom Jefferson
14th Sep: What does a case of COVID-19 really mean? Carl Heneghan, Tom Jefferson
7th Sep: Covid-19 and the end of clinical medicine as we know it Carl Heneghan, Tom Jefferson
John Conly, Professor of Medicine, Department of Medicine (Infectious Diseases), Cumming School of Medicine, University of Calgary and Alberta Health Services
David Evans, Professor, Department of Medical Microbiology & Immunology Chair
Elena Cecilia Rosca, Associate Professor, Department of Neurology, Victor Babes University of Medicine and Pharmacy of Timisoara
Jefferson T. et al, (2020)
Jefferson T. et al, (2021), Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 73, e3884 - e3899