Transmission of SARs-CoV-2

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. 

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.

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.

Onakpoya I., Heneghan C., Spencer A E., Brassey, J.,  Rosca C E., Maltoni S., Plüddemann A., Evans H D., Conly M J., and Jefferson T.

Research questions we seek to answer: 

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?

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.

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)?'

 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.