Response.

To the Editor:

In the battle against COVID-19, scientists all over the world are doing their best to fight. From January 24, 2020, when the SARS-CoV-2 cases were first reported, to today (February 16, 2021), more than 100,000 related articles have been published. These scientific discoveries have enabled us to better understand our enemies.

In the research article published in CHEST, we enrolled the first 192 patients with severe COVID-19 from the Lotus study (Lopinavir Trial for Suppression of SARS-Cov-2, Chinese Clinical Trial Register number, ChiCTR2000029308), which was conducted from January 18, 2020, through February 3, 2020. Longitudinal samples including plasma, oropharyngeal swabs, and anal swabs were collected, and viral RNA was detected with reverse transcription polymerase chain reaction (PCR). Risk factors of patients complicated with viral RNAaemia were analyzed, and its association with clinical prognosis was assessed. With the spread of the epidemic, new cases have emerged worldwide, and increased amounts of evidence suggested that viral RNAaemia was associated with worse outcomes of patients with COVID-19, but the risk factors for RNAaemia are not clear.

Viral RNAaemia, which might result from live virus particles in the blood and debris of virus-infected cells, does not equal viremia. Although it has been proved that viral RNA of SARS-CoV-2 could be detected in the blood of patients with COVID-19, no success at isolating live virus particles has been reported. In vitro study showed that SARS-CoV-2 could infect capillary organoids and produce progeny virus, but whether it was the case in vivo remained uncertain. Isolation of live virions from blood was influenced by a series of factors, such as the presence of neutralizing antibodies and viral load. Furthermore, viral RNA, as a potent trigger of immune response, might also be involved in the pathogenesis of COVID-19. Therefore, no live virion successful isolation does not mean no harm.

Future basic research work is needed to understand the causes of viral RNAaemia and its role in disease pathogenesis. We agree that droplet digital PCR has higher sensitivity than quantitative PCR, and it could detect samples with low levels of nucleic acids. However, it still could not distinguish viral RNAaemia from viremia.