Clinical and microbiological assessments of COVID-19 in healthcare workers: a prospective longitudinal study

  1. Antonin Bal
  2. Karen Brengel-Pesce
  3. Alexandre Gaymard
  4. Grégory Quéromès
  5. Nicolas Guibert
  6. Emile Frobert
  7. Maude Bouscambert
  8. Mary-Anne Trabaud
  9. Florence Allantaz-Frager
  10. Guy Oriol
  11. Valérie Cheynet
  12. Constance d’Aubarede
  13. Amélie Massardier-Pilonchery
  14. Marlyse Buisson
  15. Julien Lupo
  16. Bruno Pozzetto
  17. Pascal Poignard
  18. Bruno Lina
  19. Jean-Baptiste Fassier
  20. Florence Morfin-Sherpa
  21. Sophie Trouillet-Assant

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Abstract

A comprehensive assessment of COVID-19 in healthcare workers (HCWs) including the investigation of viral shedding duration is critical.

Methods

A longitudinal study including 319 HCWs was conducted. After SARS-CoV-2 screening with RT-PCR assay, other respiratory pathogens were tested with a multiplex molecular panel. For SARS-CoV-2 positive HCWs, the normalized viral load was determined weekly; viral culture and virus neutralization assays were also performed. For 190 HCWs tested negative, SARS-CoV-2 serological testing was performed one month after the inclusion.

Findings

Of the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; two of them developed severe COVID-19. The proportion of smell and taste dysfunction was significantly higher in SARS-CoV-2 positive HCWs than in negative ones (38.8% vs 9.5% and 37.3% vs 10.7%, respectively, p<0.001). Of the 67 positive patients, 9.1% were tested positive for at least another respiratory pathogen ( vs 19.5%, p=0.07). The proportion of HCWs with a viral load > 5.0 log 10 cp/ml (Ct value <25) was less than 15% at 8 days after symptom onset; 12% of them were still positive after 40 days (Ct >37). More than 90% of culturable virus had a viral load > 4.5 log 10 cp/ml (Ct < 26) and were collected within 10 days after symptom onset. From HCWs tested negative, 6/190 (3.2%) exhibited seroconversion for IgG antibodies.

Interpretation

Our data suggest that the determination of normalized viral load (or its estimation through Ct values) can be useful for discontinuing isolation of HCWs and facilitating their safe return to work. HCWs presenting mild COVID-19 are unlikely infectious 10 days after symptom onset.

Funding

Fondation des Hospices Civils de Lyon. bioMérieux provided diagnostic kits.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.11.04.20225862: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: Written informed consent was obtained from all participants and approval was obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France; ID RCB 2020-A00932-37).
    IRB: Written informed consent was obtained from all participants and approval was obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France; ID RCB 2020-A00932-37).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serological investigations: The presence of anti-SARS CoV-2 antibodies was evaluated on serum samples using the Wantai SARS-CoV-2 Ab ELISA kit (Wantai, Beijing, China), which detects total antibodies, and the VIDAS® SARS-COV-2 IgG test (bioMérieux, Lyon, France), according to the manufacturers’ instructions.
    anti-SARS CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    RT-PCR positive NPS were inoculated on confluent Vero cells (ATCC CCL-81) with Eagle’s Minimum Essential Media (EMEM) supplemented with 2% penicillin-streptomycin, 1% L-glutamine, and 2% inactivated fetal bovine serum.
    Vero
    suggested: None
    Briefly, gag/pol and luciferase plasmids were co-transfected with a SARS-CoV-2 full length S plasmid in HEK293T cells and pseudoviruses were harvested after 72h.
    HEK293T
    suggested: None
    Serial dilutions of human serum were incubated with pseudoviruses at 37°C for 1 h, then transferred onto HeLa-ACE2 cells in 96-well plates at 10 000 cells/well (Corning).
    HeLa-ACE2
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The present study has several limitations. First, the inclusion period between April to June corresponded to the second half of the first wave in France and led to a limited number of enrolled patients. Furthermore, the national lockdown may have had a substantial impact on the circulation of other respiratory viruses and the rate of co-infection is possibly underestimated. In addition, the date of symptom onset can be difficult to determine accurately. As asymptomatic HCWs were not screened, the prevalence of SARS-CoV-2 infection among HCWs was certainly underestimated in our cohort [4,7,32]. Finally, the results of viral culture must be considered with caution as this method can lack sensitivity, with its performance being highly dependent on the proper collection, transport, and rapidity of inoculation of samples on cells. In conclusion, we confirm the high prevalence of SARS-CoV-2 infection among HCWs who developed mainly mild COVID-19. Our data suggest that true quantitative viral load measured by RT-PCR or, at least, Ct values can be useful for appreciating the infectiousness of infected HCWs. In addition, we show that these patients are unlikely infectious 10 days after symptom onset, despite a high viral load. Taken together, these data could be very helpful for defining rules for discontinuing isolation of HCWs and facilitating their safe return to work.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04341142RecruitingAssessment of Serological Techniques for Screening Patients …

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.11.04.20225862 on medRxiv