key: cord-0709240-10gakkv5
authors: Honore, Patrick M.; Redant, Sebastien; Preseau, Thierry; Kaefer, Keitiane; Barreto Gutierrez, Leonel; Attou, Rachid; Gallerani, Andrea; De Bels, David
title: A Study Revealed That a High Percentage of Patients With Severe COVID-19 With Viral RNAaemia Had Significantly Worse Outcomes, and This Is the First Report About the Risk Factors of Viral RNAaemia in Patients With COVID-19: We Are Not Sure!
date: 2021-07-07
journal: Chest
DOI: 10.1016/j.chest.2021.02.074
sha: f0fd9e1524e57fc10c21574cee648a4e51277818
doc_id: 709240
cord_uid: 10gakkv5

nan

Editor's Note: Authors are invited to respond to Correspondence that cites their previously published work. Those responses appear after the related letter. In cases where there is no response, the author of the original article declined to respond or did not reply to our invitation. 1 In fact, in a recent study, blood samples were collected. 2 The molecular testing indicated increased viral loads. 2 This increased viral RNAaemia was strongly correlated with the level of disseminated intravascular coagulation (DIC) as well the D-dimer levels and thus correlated with severity level. 2 Clearly the study from Li et al 1 is not the first to show a relationship between RNAaemia and level of severity. 2 Regarding pathophysiology, whether the virus itself is responsible for this direct damage is unclear in the study by Dumache et al. 2 Increased levels of RNAaemia inducing increase in DIC and D-dimers could induce more damage to various organs. 2 In another recent study, detection of viral subgenomic RNA correlated poorly with shedding of infectious virus. 3 These RNAs are produced only in actively infected cells and are not packaged into virions. 3 Subgenomic RNAs were still detected when virus cultures turned negative. 3 This could indicate that active replication continues in severely ill COVID-19 after seroconversion. 3 Possibly, infectious virions are produced but are directly neutralized by antibodies. 3 Conversely, the half-life of viral subgenomic RNAs is unknown in COVID-19 and may still be detected once replication has stopped. 3 In other words, in their evaluation, the level of RNAaemia is not related to severity, because less than 5% of this RNAaemia is able to be infective. 3 A very important issue raised by a new study was that digital polymerase chain reaction (PCR) more sensitive than quantitative PCR for the detection of SARS-CoV-2 RNAaemia in the plasma of the patients. 4 Unfortunately, in the study of Li et al, 1 they did used quantitative PCR and not digital PCR. 1 In addition, prolonged shedding of SARS-CoV-2 furthermore occurs regardless of disease severity or development of virus-neutralizing antibodies. 5 RNA viruses are capable of long-term persistence, possibly through poorly understood RNA structure-mediated effects on innate and adaptive host immune responses. 5 The assumption that resolution of COVID-19 and the appearance of anti-SARS-CoV-2 IgG antibodies represents virus clearance and protection from reinfection, implicit, for example, in the susceptibleinfected-recovered model used for epidemic prediction, should be rigorously reevaluated. 5 coagulation (DIC) and elevated d-dimer levels [Published online ahead of print January 

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, 1 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, 2 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, 3 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, 4 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. 5 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. 3 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.

Risk factors of viral RNAaemia and its association with clinical prognosis among patients with severe COVID-19

Molecular testing of SARS-CoV-2 infection from blood samples in disseminated intravascular

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Risk factors of viral RNAaemia and its association with clinical prognosis among patients with severe coronavirus disease 2019

SARS-CoV-2 viral load is associated with increased disease severity and mortality