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Authors: Roman Woelfel et al.

Link to paper: https://www.nature.com/articles/s41586-020-2196-x_reference.pdf

Journal/ Pre-Print: Nature

Key Words: Virus replication, virology, throat, lung, stool, mild disease course

Research Highlights 

1. Live and potentially infectious virus isolated from throat swabs and lung specimens of mild hospitalised SARS-COV2 cases (1000x higher viral RNA than SARS-CoV1), as well as high viral RNA isolation from corresponding stool specimens.

2. Sequence distinct virus populations detected in throat and lung from the same patient and sgRNA analysis support independent and active replication at both sites- a key difference to SARS-COV1.

3. No live virus detected 8 days after symptom-onset.

Summary 

In this study the clinical course of SARS-COV2 in young to middle-aged professionals without significant underlying disease was virologically analysed. Live and therefore potentially infectious virus was isolated from throat and lung specimens of patients, however not from stool samples despite high virus RNA concentrations. In addition to live viral isolation from throat swabs, viral sequencing showed distinct virus genotypes in throat and lung of one patient and viral subgenomic messenger RNAs (sgRNA) strongly suggesting independent viral replication in the throat of patients rather than merely passive viral shedding from the lung and likely replication in the intestine. This resembles a striking difference to SARS-COV1, for which such live viral isolation was rarely successful. Live virus was not isolated 8 days after symptom onset from any patient or specimen, leaving room to discuss potential early hospital discharge for mild SARS-COV2 cases which will relieve overburdened hospitials/healthcare systems.

Impact for SARS-CoV2/COVID19 research efforts

Understand the virology of SARS-CoV2/COVID19:

· Pinpointing location and load of viral RNA alongside live virus in patients during disease course

Develop diagnostic tools for SARS-CoV2/COVID19:

· Examination of throat swabs, sputum(lung) and stool specimens

Inhibit of SARS-CoV2/COVID19 transmission:

· Assessment of viability and genotype of virus in different body fluids during disease course

Study Type

· Patient Case study

Strengths and limitations of the paper

Novelty: Active virus replication in upper respiratory tract (throat) of patients

Standing in the field: Not controversial

Appropriate statistics: Only 9 patients, statistical power lacking.

Viral model used: SARS-CoV2 infected patients

Translatability: In-depth virological characterisation makes earlier patient discharge possible and could relieve hospitals and overall healthcare systems. Data support efforts to control droplet transmission.

Main limitations: Patient cohort size (n=9), did not contain any severe cases. Samples to culture virus from stool were not taken before seroconversion, leaving fecal-oral transmission an open question.

The definition of mild is somewhat subjective given the variability of symptoms seen in Table 2.

Minor: More info re. The index case