Predicting Infectious Severe Acute Respiratory Syndrome Coronavirus 2 From Diagnostic Samples

Abstract

Background RT-PCR has become the primary method to diagnose viral diseases, including SARS-CoV-2. RT-PCR detects RNA, not infectious virus, thus its ability to determine duration of infectivity of patients is limited. Infectivity is a critical determinant in informing public health guidelines/interventions. Our goal was to determine the relationship between E gene SARS-CoV-2 RT-PCR cycle threshold (Ct) values from respiratory samples, symptom onset to test (STT) and infectivity in cell culture. Methods In this retrospective cross-sectional study, we took SARS-CoV-2 RT-PCR confirmed positive samples and determined their ability to infect Vero cell lines. Results Ninety RT-PCR SARS-CoV-2 positive samples were incubated on Vero cells. Twenty-six samples (28.9%) demonstrated viral growth. Median TCID50/ml was 1780 (282-8511). There was no growth in samples with a Ct > 24 or STT > 8 days. Multivariate logistic regression using positive viral culture as a binary predictor variable, STT and Ct demonstrated an odds ratio for positive viral culture of 0.64 (95% CI 0.49-0.84, p<0.001) for every one unit increase in Ct. Area under the receiver operating characteristic curve for Ct vs. positive culture was OR 0.91 (95% CI 0.85-0.97, p<0.001), with 97% specificity obtained at a Ct of >24. Conclusions SARS-CoV-2 Vero cell infectivity was only observed for RT-PCR Ct < 24 and STT < 8 days. Infectivity of patients with Ct >24 and duration of symptoms >8 days may be low. This information can inform public health policy and guide clinical, infection control and occupational health decisions. Further studies of larger size are needed.

Long-distance airborne dispersal of SARS-CoV-2 in COVID-19 wards

“…There is accumulating evidence that COVID-19 contagiousness peaks shortly prior to symptom onset 16 . This implies that the patients in this study may be in a less contagious phase of COVID-19 disease, which is consistent with the ndings that SARS-CoV-2 infectivity appears to be low eight days after symptom onset 17,18 . Nevertheless, during dispersal from a patient to ventilation, and over considerable distances, the virus may still retain infective capability.…”

Epidemiological and clinical characteristics of COVID-19 in Indian children in the initial phase of the pandemic: A cross-sectional study

“…As performing a viral culture is di cult and requires advanced laboratory facilities, using GeneXpert platform with Ct values ≥ 24 may also be bene cial for predicting lack of infectivity. 35 Recently an alarming rise in the number of Pediatric and adolescent Kawasaki Disease and a multisystemic hyper-in ammatory syndrome associated with COVID-19 requiring admission to intensive care units have been reported in Europe as well as North America as the pandemic has progressed. 36,37,38 An acute onset illness accompanied by a hyperin ammatory syndrome, leading to multi-organ failure and shock has been described.…”

Transcriptional response modules characterise IL-1β and IL-6 activity in COVID-19

“…Severe Coronavirus Disease 2019 (COVID-19) typically occurs over a week from symptom onset, when viral titres have diminished, suggesting an unregulated host inflammatory response may be driving the pathogenesis of severe disease (1)(2)(3). Elevated IL-1 and IL-6 responses have each been associated with disease severity (1,(4)(5)(6)(7)(8).…”