This is a very interesting paper! It is a detailed virological and immunological study of 9 patients with COVID-19, presenting from Jan 23 – 27, 2020, all with mild upper respiratory symptoms (not requiring ICU admission or ventilators) in Germany.
I will try to summarize it.
- Pharyngeal virus shedding (from the back of the throat) was very high during the 1st week of symptoms, peaking at day 4 although earlier time points were often not available.
- During the 1st week after onset of symptoms, infectious virus (able to infect cells in a test tube) was present in throat (swab) and lung (sputum) samples (16% of swab samples; 83% of sputum samples), but not in stool samples. There was no infectious virus after day 8 of symptoms. Viral RNA sometimes lingered in the stools for weeks but there was no infectious virus
- Active viral replication in the throat was confirmed by a nifty assay which detects RNA intermediates that are only present with active replication (subgenomic viral RNA transcripts). By comparison SARS-CoV, the virus that causes SARS, does not replicate in the upper respiratory tract, but only in the lungs (lower respiratory tract).
- Shedding of viral RNA (RT-PCR tests detect this) in sputum outlasted the end of symptoms
- Seroconversion (the appearance of IgG and IgM antibodies to the virus) occurred after 7-14 days, but was not followed by a rapid decline in viral RNA
- there were no co-infections – they tested at least 16 other common viral respiratory infections
- the titers of viral RNA (swab tests) were highest on day one of symptoms and then gradually decreased. This was when symptoms were still minimal and “prodromal”. The peak viral loads were at least 1000 fold higher than in SARS.
- A rise in antibody titers was not closely correlated with clinical improvement
- antibodies showed cross-reactivity to 4 endemic human corona viruses (viruses that cause the common cold).
- The COVID-19 virus replicates big time in the nose/throat and very early on, often before symptoms – it is probably VERY infectious
- Because RT-PCR tests for viral RNA can persist for as long as 20+ days after initial symptoms appear, one must remain concerned about current recommendations for a 14-day quarantine. Is it really long enough?
- The antibody response was poorly correlated with getting better. Since antibodies are but one of several arms of the immune response, I would guess that CD8 cells, subsets of CD4 cells and perhaps cells of the innate immune system all participate in overcoming the viral infection. A prior paper documented the response of these cells in a single patient.
- Should therapeutic interventions such as anti-viral drugs or even convalescent plasma transfer focus on the earliest stages of the infection when symptoms have just appeared? That is when the virus is replicating massively. Currently, these therapeutic interventions are focused on the sickest patients in the ICU and on ventilators, at a much later stage of the disease. Paradigm shift?
- The utility of EARLY testing for viral RNA is obvious by either throat or nasal swab or expectorated sputum
- It will be interesting to compare these results (from patients with a milder disease course) to those of patients with severe disease.
PS: 17.9% of persons with COVID-19 are asymptomatic (have no symptoms what so ever) and are still producing virus and infecting others. That is 1 in 5 infected people have no symptoms. Think about it.