Viral transmission in asymptomatic cases of SARS-CoV-2 infection

Abstract

The COVID-19 pandemic has triggered an unprecedented demand for diagnostic tests. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is highly contagious in the presymptomatic period, when the viral load is high. In the effort to reduce transmission, for the first time in infection diagnostics history, testing is being aimed not only at symptomatic, but also at asymptomatic individuals, both in the health care setting and in the community.Shortages in PCR reagents and platforms, related to the demand for large-scale testing, fuelled the effort for alternative diagnostic solutions. We have read with interest the Journal of Infection (JoI) article, regarding the laboratory based assay chosen by the British government, for SARS-CoV-2 mass testing (Operation Moonshot), a loop mediated isothermal amplification (LAMP), produced by OptiGene. 1 , 2 The testing of saliva by OptiGene direct ORF1ab LAMP (with no RNA extraction), in newly built laboratories under the management of acute NHS Trusts, is costing the taxpayer over 400 million British pounds and has resulted in the movement of key staff away from essential roles in acute NHS Trust diagnostic laboratories, at short notice.The OptiGene assay on saliva samples is intended for the testing of asymptomatic NHS staff, to help prevent hospital acquired outbreaks. The assay however, failed to detect more than 50% of saliva positive cases in a pilot in Greater Manchester, when compared to a "gold standard" qPCR (polymerase chain reaction) assay. 2 In contrast, recently published data from the Department of Health and Social Care (DHSC) report 70% sensitivity for swabs and 79% for saliva for this assay. 2 To understand the performance in more detail, 86 PCR positive nose and throat swabs, with a variable viral load, collected from patients and symptomatic or asymptomatic members of hospital staff, were tested in parallel by direct LAMP and in-house CDC N1/N2 qPCR (Limit of Detection (LOD) 156 digital copies/mL or 2 • 6 digital copies per reaction, Qnostics) at the Southampton Specialist Virology Centre. These samples were stored at 4 °C, prior to being frozen at −80 °C within 36 h of sample collection. The SARS-CoV-2 Molecular Q Panel (SCV2MQP) from Qnostics was used to quantify the qPCR results in digital copies/mL.Consistent with results from the Manchester Regional Virus Laboratory, which evaluated freshly collected saliva samples from asymptomatic individuals, we have been unable to replicate the sensitivity (see Table 1 ) reported by the DHSC. For this reason, we would like to raise a number of points on which we seek clarity.A sample of > 10,0 0 0,0 0 0 ( > 10 7 ) digital copies/mL (dc/mL), collected from a symptomatic NHS staff member, swabbed on day one of symptoms, produced a negative result when tested by the OptiGene direct LAMP method. Similarly, a swab from an asymptomatic staff member, a target group for this assay, with 2,50 0,0 0 0 (2.5 × 10 6 ) dc/mL was missed. A false negative result, with a high viral load, is a patient safety risk, particul...

Incidence of spread of clinically relevant SARS-CoV2 infection between children in a tertiary emergency department: An evaluation

“…Grall and colleagues highlight that asymptomatic carriers are rarely potential viral transmitters in hospital. 1 Their study was in adults and to our knowledge spread in healthcare settings between children has not been reported. Leicester was the first area in the United Kingdom to undergo a localised lockdown with reports of relatively high numbers of children and young people affected.…”

Variation in microparasite free-living survival and indirect transmission can modulate the intensity of emerging outbreaks

“…Because of the identifiability problem 9,61,62 and a general lack of consensus regarding the mechanisms of transmission in various diseases, we caution against the overextrapolation of these findings to any particular epidemic. As of fall 2020, the evidence for widespread surface transmission of SARS-CoV-2 remains dubious [30][31][32][33][34][35][36][37][38][39][40][41] . Insofar as SARS-CoV-2 is not the last of the emerging infectious diseases, then we should remain vigilant about understanding how different routes of transmission may influence disease dynamics, as there remain other microparasites in human and nonhuman hosts that are transmitted via the environmental route and require our attention.…”

“…However, one feature of SARS-CoV-2 transmission that was validated in laboratory settings, but whose epidemiological role remains highly controversial, is SARS-CoV-2 free-living survival. Specifically, several laboratory and epidemiological findings offer conflicting evidence that indirect or environmental transmission (via free-living virus) may play a role in some settings [30][31][32][33][34][35][36][37][38][39][40][41] , and to our knowledge, none have fully investigated how this route of transmission may influence features of outbreaks. Several unknowns notwithstanding, the availability of SARS-CoV-2 data make it a valuable model for examining the particulars of indirect transmission in emerging outbreaks.…”