tetano
Editor, Senior Moderator
Rev Med Virol
. 2022 Apr 2;e2342.
doi: 10.1002/rmv.2342. Online ahead of print.
Assessing severe acute respiratory syndrome coronavirus 2 infectivity by reverse-transcription polymerase chain reaction: A systematic review and meta-analysis
Alexey Fomenko[SUP] 1 [/SUP], Stephanie Weibel[SUP] 2 [/SUP], Helia Moezi[SUP] 2 [/SUP], Kristina Menger[SUP] 2 [/SUP], Christine Schmucker[SUP] 3 [/SUP], Maria-Inti Metzendorf[SUP] 4 [/SUP], Edith Motschall[SUP] 5 [/SUP], Valeria Falcone[SUP] 1 [/SUP], Daniela Huzly[SUP] 1 [/SUP], Marcus Panning[SUP] 1 [/SUP], Gerta Rücker[SUP] 5 [/SUP], Hartmut Hengel[SUP] 1 [/SUP]
Affiliations
Abstract
The cornerstone of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is reverse-transcription polymerase chain reaction (RT-PCR) of viral RNA. As a surrogate assay SARS-CoV-2 RNA detection does not necessarily imply infectivity. Only virus isolation in permissive cell culture systems can indicate infectivity. Here, we review the evidence on RT-PCR performance in detecting infectious SARS-CoV-2. We searched for any studies that used RT-PCR and cell culture to determine infectious SARS-CoV-2 in respiratory samples. We assessed (i) diagnostic accuracy of RT-PCR compared to cell culture as reference test, (ii) performed meta-analysis of positive predictive values (PPV) and (iii) determined the virus isolation probabilities depending on cycle threshold (Ct) or log[SUB]10[/SUB] genome copies/ml using logistic regression. We included 55 studies. There is substantial statistical and clinical heterogeneity. Seven studies were included for diagnostic accuracy. Sensitivity ranged from 90% to 99% and specificity from 29% to 92%. In meta-analysis, the PPVs varied across subgroups with different sampling times after symptom onset, with 1% (95% confidence interval [CI], 0%-7%) in sampling beyond 10 days and 27% (CI, 19%-36%) to 46% (CI, 33%-60%) in subgroups that also included earlier samples. Estimates of virus isolation probability varied between 6% (CI, 0%-100%) and 50% (CI, 0%-100%) at a Ct value of 30 and between 0% (CI, 0%-22%) and 63% (CI, 0%-100%) at 5 log[SUB]10[/SUB] genome copies/ml. Evidence on RT-PCR performance in detecting infectious SARS-CoV-2 in respiratory samples was limited. Major limitations were heterogeneity and poor reporting. RT-PCR and cell culture protocols need further standardisation.
Keywords: SARS-CoV-2; cell culture; infectivity; real-time polymerase chain reaction; systematic review.
. 2022 Apr 2;e2342.
doi: 10.1002/rmv.2342. Online ahead of print.
Assessing severe acute respiratory syndrome coronavirus 2 infectivity by reverse-transcription polymerase chain reaction: A systematic review and meta-analysis
Alexey Fomenko[SUP] 1 [/SUP], Stephanie Weibel[SUP] 2 [/SUP], Helia Moezi[SUP] 2 [/SUP], Kristina Menger[SUP] 2 [/SUP], Christine Schmucker[SUP] 3 [/SUP], Maria-Inti Metzendorf[SUP] 4 [/SUP], Edith Motschall[SUP] 5 [/SUP], Valeria Falcone[SUP] 1 [/SUP], Daniela Huzly[SUP] 1 [/SUP], Marcus Panning[SUP] 1 [/SUP], Gerta Rücker[SUP] 5 [/SUP], Hartmut Hengel[SUP] 1 [/SUP]
Affiliations
- PMID: 35366033
- DOI: 10.1002/rmv.2342
Abstract
The cornerstone of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is reverse-transcription polymerase chain reaction (RT-PCR) of viral RNA. As a surrogate assay SARS-CoV-2 RNA detection does not necessarily imply infectivity. Only virus isolation in permissive cell culture systems can indicate infectivity. Here, we review the evidence on RT-PCR performance in detecting infectious SARS-CoV-2. We searched for any studies that used RT-PCR and cell culture to determine infectious SARS-CoV-2 in respiratory samples. We assessed (i) diagnostic accuracy of RT-PCR compared to cell culture as reference test, (ii) performed meta-analysis of positive predictive values (PPV) and (iii) determined the virus isolation probabilities depending on cycle threshold (Ct) or log[SUB]10[/SUB] genome copies/ml using logistic regression. We included 55 studies. There is substantial statistical and clinical heterogeneity. Seven studies were included for diagnostic accuracy. Sensitivity ranged from 90% to 99% and specificity from 29% to 92%. In meta-analysis, the PPVs varied across subgroups with different sampling times after symptom onset, with 1% (95% confidence interval [CI], 0%-7%) in sampling beyond 10 days and 27% (CI, 19%-36%) to 46% (CI, 33%-60%) in subgroups that also included earlier samples. Estimates of virus isolation probability varied between 6% (CI, 0%-100%) and 50% (CI, 0%-100%) at a Ct value of 30 and between 0% (CI, 0%-22%) and 63% (CI, 0%-100%) at 5 log[SUB]10[/SUB] genome copies/ml. Evidence on RT-PCR performance in detecting infectious SARS-CoV-2 in respiratory samples was limited. Major limitations were heterogeneity and poor reporting. RT-PCR and cell culture protocols need further standardisation.
Keywords: SARS-CoV-2; cell culture; infectivity; real-time polymerase chain reaction; systematic review.