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
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Abstract
Background
Organ transplant recipients are at increased vulnerability to SARS-CoV-2 due to immunosuppression and may pose a continued transmission risk especially within hospital settings. Detailed case reports including symptoms, viral load and infectiousness, defined by the presence of replication-competent viruses in culture, provide an opportunity to examine the relationship between clinical course, burden and contagiousness, and provide guidance on release from isolation.
Objectives
We performed a systematic review to investigate the relationship in transplant recipients between serial SARS-CoV-2 RT-PCR cycle threshold (Ct) value or cycle of quantification value (Cq), or other measures of viral burden and the likelihood and duration of the presence of infectious virus based on viral culture including the influence of age, sex, underlying pathologies, degree of immunosuppression, and/or vaccination on this relationship.
Methods
We searched LitCovid, medRxiv, Google Scholar and WHO Covid-19 databases, from 1 November 2019 until 31 December 2021. We included studies reporting relevant data for transplantees with SARS-CoV-2 infection: results from serial RT-PCR testing and viral culture data from the same respiratory samples. We assessed methodological quality using five criteria, and synthesised the data narratively and graphically.
Results
We included 10 case reports and case series reporting on 38 transplantees. We observed a relationship between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Two individuals shed replication-competent viruses over 100 days after infection onset. Lack of standardisation of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, most transplantees stopped shedding competent viruses when the RT-PCR cycle threshold was above 30 despite differences across platforms.
Conclusions
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 standardise guidance based on an increasing evidence base.
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SciScore for 10.1101/2022.03.01.22271684: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. 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 Search Strategy: We searched the following electronic databases: LitCovid, medRxiv, Google Scholar and the WHO Covid-19 database from November 2019 until December 31, 2021. Google Scholarsuggested: (Google Scholar, RRID:SCR_008878)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:Limitations …
SciScore for 10.1101/2022.03.01.22271684: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. 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 Search Strategy: We searched the following electronic databases: LitCovid, medRxiv, Google Scholar and the WHO Covid-19 database from November 2019 until December 31, 2021. Google Scholarsuggested: (Google Scholar, RRID:SCR_008878)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:Limitations include the small number of studies with viral culture and serial viral load estimates among transplant patients, high variability in study design and reporting and impossibility to pool results due to the well-known variability in sensitivity across essays21. Case series are conventionally considered low in the evidence hierarchy, as they may entail inherent bias in the selection of study participants and therefore have limited generalisability; however, here they are essential in providing the detailed reports needed for this unusual patient group. The case reports included here comprise some of the most detailed longitudinal reports of this patient group for whom data are needed. The evidence base is limited, however, by heterogeneous design and reporting within the studies with, for example, different observation windows for reporting of viral burden and culturability or clinical characteristics of patients. In addition to providing appropriate care for the individual patient, ongoing transmission of SARS-CoV-2 is a concern, and immunosuppressed individuals may pose a challenge by experiencing prolonged carriage of the virus that could lead to forward transmission. Based on our findings we would offer the following general guidance to clinicians: Physicians who are experienced with these immunosuppressed patient populations should work with public health to direct their isolation and quarantine requirements. Patients with immunosuppressive treatment following ...
Results from TrialIdentifier: No clinical trial numbers were referenced.
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.
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