Rectally shed SARS-CoV-2 lacks infectivity: time to rethink faecal-oral transmission?

We read with interest the Perspective by Guo et al. (Guo, M. et al. Potential intestinal infection and faecal–oral transmission of SARS-CoV-2. Nat. Rev. Gastroenterol. Hepatol. 18, 269–283 (2021))[1], on the potential faecal–oral transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A comprehensive list of reasons to substantiate that such a transmission route is probable was presented, including the well-documented shedding of viral RNA in faeces, epidemiological reports, and laboratory and animal tests. Viral debris and RNA are often found in large quantities in faeces from patients with COVID-19 as most of the viral material produced in the airways is cleared through swallowing. Furthermore, as argued by Guo et al.[1], studies indicate that intestinal infection by SARS-CoV-2 might contribute to the viral material shed in faeces.

In either case, it is important to emphasize that for the rectally shed virus to transmit to other humans it must retain its infectivity when it leaves the body. Proof in support of this property is obtained by successful isolation of the virus; that is, successful propagation of the sampled virus in laboratory cell culture. Guo et al.[1] refer to four studies in support of infectious virus particles being successfully isolated from patient’s faeces[2-5]. However, three of these studies base their conclusion of successful propagation of SARS-CoV-2 on microscopy observations alone[2-4], which is inadequate as it requires additional substantiation by quantitative analysis (such as reverse transcription PCR, RT-PCR) to conclude that virions have increased in number upon culturing[6,7]. All three papers use electron microscopy to show what appears to be intact SARS-CoV-2 particles in culture supernatants[2-4], but identifying SARS-CoV-2 in complex specimens in this way is difficult and error prone[8,9], and, even if visually intact virions are identified, it does not provide evidence for infectious capacity. Notably, only Zhou et al. confirmed viral propagation by RT-PCR[5]; a result that was obtained for a single faecal sample[5] and is, to the best of our knowledge, the only valid evidence reported in the literature that supports retained infectivity of rectally shed SARS-CoV-2.

One additional study has attempted culturing of rectally shed SARS-CoV-2 with the use of confirmatory RT-PCR. The comprehensive study by Wölfel et al. analysed 13 faecal samples from four patients during their course of COVID-19 and concluded that none of the samples contained culturable virus[10]. Results from our hospital are in line with this outcome as we have, to date, not been able to culture rectally shed SARS-CoV-2 from patients with COVID-19 of varying disease course (R.M.P., D.S.T., L.L.B., L.W.M., M.N.S., T.G.J., I.S.J. and T.E.A., unpublished data).

The potential existence of a faecal–oral transmission route has gained widespread attention. We would like to add to this discussion that the evidence in support of the key property that allows such a transmission, that rectally shed SARS-CoV-2 is infectious, remains weak and in our view inconclusive. New data to support this capacity have not emerged since the early reports on this topic, overall questioning whether such transmission is plausible and plays a substantial part in the dissemination of the virus.

There is a reply to this letter by Guo, M. et al. Reply to: Rectally shed SARS-CoV-2 lacks infectivity: time to rethink faecal–oral transmission? Nat. Rev. Gastroenterol. Hepatol. 10.1038/s41575-021-00503-8 (2021).