ABSTRACT
BACKGROUND: Solid organ and haematopoietic stem cell transplant recipients are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) than non-transplant recipients 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: To investigate the relationship between serial SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) value or cycle of quantification value, 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, in transplant recipients. METHODS: LitCovid, medRxiv, Google Scholar and the World Health Organization COVID-19 database were searched from 1st November 2019 to 26th October 2022. Studies reporting relevant data (results from serial RT-PCR testing and viral culture data from the same respiratory samples) for transplant recipients with SARS-CoV-2 infection were included in this systematic review: Methodological quality was assessed using five criteria, and the data were synthesized narratively and graphically. RESULTS: Thirteen case reports and case series reporting on 41 transplant recipients (22 renal, five cardiac, one bone marrow, two liver, one bilateral lung and 10 blood stem cell) were included in this review. A relationship was observed between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Three individuals shed replication-competent viruses for >100 days after symptom onset. Lack of standardization of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, the majority of transplant recipients stopped shedding replication-competent viruses when the Ct value was >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. Standardized study design and reporting are essential to standardize guidance based on an increasing evidence base.
Subject(s)
COVID-19 , Organ Transplantation , Humans , COVID-19/diagnosis , SARS-CoV-2 , Viral Load , Hematopoietic Stem CellsABSTRACT
BACKGROUND: The role of fomites in the transmission of SARS-CoV-2 is unclear. AIM: To assess whether SARS-CoV-2 can be transmitted through fomites, using evidence from viral culture studies. METHODS: Searches were conducted in the World Health Organization COVID-19 Database, PubMed, LitCovid, medRxiv, and Google Scholar to December 31st, 2021. Studies that investigated fomite transmission and performed viral culture to assess the cytopathic effect (CPE) of positive fomite samples and confirmation of SARS-CoV-2 as the cause of the CPE were included. The risk of bias using a checklist modified from the modified Quality Assessment of Diagnostic Accuracy Studies - 2 (QUADAS-2) criteria was assessed. FINDINGS: Twenty-three studies were included. The overall risk of bias was moderate. Five studies demonstrated replication-competent virus from fomite cultures and three used genome sequencing to match fomite samples with human clinical specimens. The mean cycle threshold (CT) of samples with positive viral culture was significantly lower compared with cultured samples that returned negative results (standardized mean difference: -1.45; 95% confidence interval (CI): -2.00 to -0.90; I2 = 0%; P < 0.00001). The likelihood of isolating replication-competent virus was significantly greater when CT was <30 (relative risk: 3.10; 95% CI: 1.32 to 7.31; I2 = 71%; P = 0.01). Infectious specimens were mostly detected within seven days of symptom onset. One study showed possible transmission of SARS-CoV-2 from fomites to humans. CONCLUSION: The evidence from published studies suggests that replication-competent SARS-CoV-2 is present on fomites. Replication-competent SARS-CoV-2 is significantly more likely when the PCR CT for clinical specimens and fomite samples is <30. Further studies should investigate the duration of infectiousness of SARS-CoV-2 and the frequency of transmission from fomites.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Fomites , COVID-19/diagnosisABSTRACT
Particular regions of the X and Y chromosomes share DNA sequence homology to the extent that cross hybridisation occurs. Thus, chromosome painting with a whole Y chromosome probe consistently results in fluorescence on specific regions of the X chromosome as well as the complete Y chromosome. This phenomenon has been exploited to elucidate the structure of unusual X chromosome rearrangements, without Y involvement, in two females.