Long title: Exhaled SARS-CoV-2 RNA viral load kinetics measured by facemask sampling associates with household transmission <sup>☆</sup>

Pan, Daniel; Williams, Caroline M; Decker, Jonathan W.; Fletcher, Eve; Sze, Shirley; Assadi, Sara; Haigh, Richard D; Saleem, Baber; Nazareth, Joshua; Garton, Natalie J.; Barer, Michael R.

doi:10.1016/j.cmi.2022.07.005

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Long title: Exhaled SARS-CoV-2 RNA viral load kinetics measured by facemask sampling associates with household transmission ^☆

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Author(s): Daniel Pan , MRCP ^a ^, ^b ^, ^∗ , Caroline M. Williams , PhD ^a ^, ^c , Jonathan Decker , MSc ^a , Eve Fletcher , MSc ^a , Shirley Sze , MD ^d , Sara Assadi , MBChB ^b , Richard Haigh , PhD ^a , Baber Saleem , PhD ^e , Joshua Nazareth , MRCP ^a ^, ^b , Natalie J. Garton , PhD ^a , Manish Pareek , PhD ^a ^, ^b ^, ¹ , Michael R. Barer , PhD ^a ^, ^c ^, ¹

Publication date (Electronic): 14 July 2022

Journal: Clinical Microbiology and Infection

Publisher: The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.

Keywords: Tirborne, Facemask, SARS-CoV-2 household, Transmission

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Abstract

Objectives

No studies have examined longitudinal patterns of naturally exhaled SARS-CoV-2 RNA viral load (VL) during acute infection. We report this using facemask sampling (FMS) and assessed the relationship between emitted RNA VL and household transmission.

Methods

Between December 2020 and February 2021, we recruited participants within 24 hours of a positive RT-qPCR on upper respiratory tract sampling (URTS) (day 0). Participants gave FMS (for 1 hour) and URTS (self-taken) on 7 occasions up to day 21. Samples were analysed by RT-qPCR (from sampling matrix strips within the mask) and symptom diaries recorded. Household transmission was assessed through reporting of positive URTS RT-qPCR in household contacts.

Results

Analysis of 203 FMS and 190 URTS from 34 participants showed that RNA VL peaked in the first five days following sampling. Concomitant URTS, FMS RNA VL and symptom scores however were poorly correlated, but a higher severity of reported symptoms was associated with FMS positivity up to day 5. Of 28 participants who had household contacts, 12 (43%) reported transmission. Frequency of household transmission was associated with the highest (peak) FMS RNA VL obtained (negative copies/strip: 0% household transmission; 1-1000 copies/strip: 20%; 1001 – 10,000 copies/strip: 57%; >10,000 copies/strip: 75%; p=0.048; age adjusted odds ratio of transmission per log increase in copies/strip: 4.97; 95% CI: 1.20-20.55, p=0.02) but this was not observed with peak URTS RNA VL.

Conclusions

Exhaled RNA VL measured by FMS is highest in early infection, can be positive in symptomatic patients with concomitantly negative URTS and is strongly associated with household transmission.

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Most cited references 23

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Respiratory virus shedding in exhaled breath and efficacy of face masks

Nancy Leung, Daniel Chu, Eunice Shiu … (2020)

We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.

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Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study

Michael Marks, Pere Millat-Martínez, Dan Ouchi … (2021)

Background Scarce data are available on what variables affect the risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of symptomatic COVID-19, and, particularly, the relationship with viral load. We aimed to analyse data from linked index cases of COVID-19 and their contacts to explore factors associated with transmission of SARS-CoV-2. Methods In this cohort study, patients were recruited as part of a randomised controlled trial done between March 17 and April 28, 2020, that aimed to assess if hydroxychloroquine reduced transmission of SARS-CoV-2. Patients with COVID-19 and their contacts were identified by use of the electronic registry of the Epidemiological Surveillance Emergency Service of Catalonia (Spain). Patients with COVID-19 included in our analysis were aged 18 years or older, not hospitalised, had quantitative PCR results available at baseline, had mild symptom onset within 5 days before enrolment, and had no reported symptoms of SARS-CoV-2 infections in their accommodation or workplace within the 14 days before enrolment. Contacts included were adults with a recent history of exposure and absence of COVID-19-like symptoms within the 7 days preceding enrolment. Viral load of contacts, measured by quantitative PCR from a nasopharyngeal swab, was assessed at enrolment, at day 14, and whenever the participant reported COVID-19-like symptoms. We assessed risk of transmission and developing symptomatic disease and incubation dynamics using regression analysis. We assessed the relationship of viral load and characteristics of cases (age, sex, number of days from reported symptom onset, and presence or absence of fever, cough, dyspnoea, rhinitis, and anosmia) and associations between risk of transmission and characteristics of the index case and contacts. Findings We identified 314 patients with COVID-19, with 282 (90%) having at least one contact (753 contacts in total), resulting in 282 clusters. 90 (32%) of 282 clusters had at least one transmission event. The secondary attack rate was 17% (125 of 753 contacts), with a variation from 12% when the index case had a viral load lower than 1 × 106 copies per mL to 24% when the index case had a viral load of 1 × 1010 copies per mL or higher (adjusted odds ratio per log10 increase in viral load 1·3, 95% CI 1·1–1·5). Increased risk of transmission was also associated with household contact (3·0, 1·59–5·65) and age of the contact (per year: 1·02, 1·01–1·04). 449 contacts had a positive PCR result at baseline. 28 (6%) of 449 contacts had symptoms at the first visit. Of 421 contacts who were asymptomatic at the first visit, 181 (43%) developed symptomatic COVID-19, with a variation from approximately 38% in contacts with an initial viral load lower than 1 × 107 copies per mL to greater than 66% for those with an initial viral load of 1 × 1010 copies per mL or higher (hazard ratio per log10 increase in viral load 1·12, 95% CI 1·05–1·20; p=0·0006). Time to onset of symptomatic disease decreased from a median of 7 days (IQR 5–10) for individuals with an initial viral load lower than 1 × 107 copies per mL to 6 days (4–8) for those with an initial viral load between 1 × 107 and 1 × 109 copies per mL, and 5 days (3–8) for those with an initial viral load higher than 1 × 109 copies per mL. Interpretation In our study, the viral load of index cases was a leading driver of SARS-CoV-2 transmission. The risk of symptomatic COVID-19 was strongly associated with the viral load of contacts at baseline and shortened the incubation time of COVID-19 in a dose-dependent manner. Funding YoMeCorono, Generalitat de Catalunya. Translations For the Catalan translation of the abstract see Supplementary Materials section.

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Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults

Ben Killingley, Alex Mann, Mariya Kalinova … (2022)

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Author and article information

Contributors

Manish Pareek: Role: Prof

Michael R. Barer: Role: Prof

Journal

Journal ID (nlm-ta): Clin Microbiol Infect

Journal ID (iso-abbrev): Clin Microbiol Infect

Title: Clinical Microbiology and Infection

Publisher: The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.

ISSN (Print): 1198-743X

ISSN (Electronic): 1469-0691

Publication date PMC-release: 14 July 2022

Publication date (Electronic): 14 July 2022

Affiliations

[a ]Department of Respiratory Sciences, University of Leicester

[b ]Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust

[c ]Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust

[d ]Department of Cardiovascular Sciences, University Hospitals of Leicester NHS Trust

[e ]Deparment of Engineering, University of Leicester, United Kingdom

Author notes

[∗ ]Correspondence to:Dr Daniel Pan NIHR Doctoral Research Fellow in Infectious Diseases Department of Respiratory Sciences University of Leicester ; Tel.: +44(0)7726 226778.

[1]

Joint senior authors

Article

Publisher Item ID: S1198-743X(22)00369-X

DOI: 10.1016/j.cmi.2022.07.005

PMC ID: 9281452

PubMed ID: 35843566

SO-VID: 01a3f513-5cf4-4704-92f4-88a7b35e4547

License:

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

History

Date received : 30 April 2022

Date revision received : 6 June 2022

Date accepted : 7 July 2022

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