Timeline of SARS-CoV-2 Spread in Italy: Results from an Independent Serological Retesting
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
The massive emergence of COVID-19 cases in the first phase of pandemic within an extremely short period of time suggest that an undetected earlier circulation of SARS-CoV-2 might have occurred. Given the importance of this evidence, an independent evaluation was recommended by the World Health Organization (WHO) to test a subset of samples selected on the level of positivity in ELISA assays (positive, low positive, negative) detected in our previous study of prepandemic samples collected in Italy. SARS-CoV-2 antibodies were blindly retested by two independent centers in 29 blood samples collected in the prepandemic period in Italy, 29 samples collected one year before and 11 COVID-19 control samples. The methodologies used included IgG-RBD/IgM-RBD ELISA assays, a qualitative micro-neutralization CPE-based assay, a multiplex IgG protein array, an ELISA IgM kit (Wantai), and a plaque-reduction neutralization test. The results suggest the presence of SARS-CoV-2 antibodies in some samples collected in the prepandemic period, with the oldest samples found to be positive for IgM by both laboratories collected on 10 October 2019 (Lombardy), 11 November 2019 (Lombardy) and 5 February 2020 (Lazio), the latter with neutralizing antibodies. The detection of IgM and/or IgG binding and neutralizing antibodies was strongly dependent on the different serological assays and thresholds employed, and they were not detected in control samples collected one year before. These findings, although gathered in a small and selected set of samples, highlight the importance of harmonizing serological assays for testing the spread of the SARS-CoV-2 virus and may contribute to a better understanding of future virus dynamics.
Article activity feed
-
-
SciScore for 10.1101/2021.07.14.21260491: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: bioMILD, clinicaltrials.gov ID: NCT02247453) collected from July 14, 2018 until February 23, 2019, matched by date of collection, sex, age, smoking habits.
IRB: The Institutional Review Board and Ethics Committee of Fondazione IRCCS Istituto Nazionale dei Tumori of Milan approved the study.
Consent: All eligible subjects provided written informed consent.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources For the analysis and the graphic design the GraphPad Prism software (version 5.2) was adopted. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_0027…SciScore for 10.1101/2021.07.14.21260491: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: bioMILD, clinicaltrials.gov ID: NCT02247453) collected from July 14, 2018 until February 23, 2019, matched by date of collection, sex, age, smoking habits.
IRB: The Institutional Review Board and Ethics Committee of Fondazione IRCCS Istituto Nazionale dei Tumori of Milan approved the study.
Consent: All eligible subjects provided written informed consent.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources For the analysis and the graphic design the GraphPad Prism software (version 5.2) was adopted. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)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:We acknowledge some limitations in this re-test study related to the limited sample size, the highly specific selection of screening participants (heavy smokers ≥ 30 pack years and ≥55 years old), possibly not representative of the general population, and the intrinsic experimental variability of the immunoenzymatic assays employed in the different laboratories. Moreover, we cannot exclude that other confounding conditions, such as preexisting immunity against other agents, might have contributed to the SARS-CoV-2 positivity in our assays. Nonetheless, cross reactivity towards the most common HCoVs was ruled out. As pointed out in the recent WHO report (www.who.int) and in other commentaries (1,2), studies from different countries suggest that SARS-CoV-2 was growing under the surface for some time before the first diagnosed case in Wuhan. Suggestive evidence from our previous published study (10) and conflicting results from the current retesting exercise, despite adding important signals in this direction, do not allow us to accept or discard this hypothesis. Indeed findings of these studies are only partially confirmed due to the heterogeneity of methods utilized and the risk of non-specific signals in serological assays. Despite that, the report underlines the importance of investigating these potential early events, to solve the still unanswered questions about the origin and timing of the current pandemic and may contribute to a better understanding of the future virus c...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT03654105 Active, not recruiting Screening and Multiple Intervention on Lung Epidemics NCT02247453 Active, not recruiting Plasma microRNA Profiling as First Line Screening Test for L… 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.
Results from scite Reference Check: We found no unreliable references.
-
