Corona Update 25 January 2021
I discovered a second immuno-compromised patient with accelerated
evolution by accident. I wanted to know whether the spontaneous mutations
occurring in the
first immuno-compromised patient
could also be found in the general human population. I searched for Spike
protein mutations in the NCBI SARS-CoV-2 sequence database. I selected all
sequences of 1269 AA (4 amino acids shorter than the standard 1273 Spike
protein). I added the standard Spike protein length of 1273 AA until I hit
the maximum number of 500 sequences that are allowed in one search. The
result: 27 sequences of length 1269 of which 16 showed the deletion
previous blog). Unexpectedly, two of them showed me the way to a second
immuno-compromised patient (Fig. 1).
|Fig 1. Two new sequences with the 141-144 deletion: QNQ32127; QNQ32151|
Fig 2. The publication that describes the virus sequence (source).
Usually the sequences in the database are a 'Direct Submission'. They are
not published. But the source of these new sequences (Fig.1) revealed that
they were part of a
'Case Study: Prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised cancer patient' .
That's how I discovered my second immuno-compromised patient.
Fig. 3. Long-term SARS-CoV-2 shedding  with within-patient
It is an immuno-compromised individual persistently testing positive for SARS-CoV-2. Remarkably: it is an asymptomatic individual! The virus mutated and created genetic diversity. This cannot be explained by contamination or secondary infection because the viral genomes of this patient cluster as a mono-phyletic clade*).
This strongly suggests evolution
The authors state: "Throughout the course of infection, there was marked
within-host genomic evolution of SARS-CoV-2. Deep sequencing revealed a
continuously changing virus population structure with turnover in the
relative frequency of the observed genotypes over the course of infection.
Potential factors contributing to the observed within-host evolution is
prolonged infection and the compromised immune status of the host,
possibly resulting in a different set of selective pressures compared
with an immune-competent host.
These differential selective pressures may have allowed a larger genetic
diversity with continuous turnover of dominant viral species throughout
the course of infection." ,.
The convalescent plasma therapy was not successful. But it is expected to
be a selective pressure on the virus.
Apart from demonstrating evolution, there is an important public health lesson: "an estimated 3 million people in the United States have some form of immuno-compromising condition, including individuals with HIV infection".
Fig. 4. Two deletions. red arrow: 21 nt. yellow: 12 nt. (click to
first row (black) shows nt, second row shows AA (colored)
Two in-frame*) deletions were observed in the Spike glycoprotein coding region:
1) A 21 nt in-frame deletion (residues 21,975–21,995) was found in the N-terminal domain (NTD) of S1, leading to a 7-amino-acid deletion (amino acids [AA] 139–145)
2) A 12 nt deletion (residues 21,982–21,993) was detected in the day 70 isolate, leading to a 4-AA deletion (AA 141–144) in the NTD.
As can be seen from Fig. 4 the two deletion strains disappear later.
Then there is the famous N501Y substitution which is found in the British and the South Africa variant (wikipedia). Isn't remarkable that this mutation originates independently and spontaneously in a single individual and at the same time in the world population? It could be that is a coincident, but also that it has a competitive advantage.
Abbr = abbreviations.
nt = nucleotides or bases. Three bases code for 1 AA.
AA = amino acids.
mono-phyletic clade = an evolutionary group of organisms with one common ancestor.
in-frame deletions = deletions in DNA/RNA that leave the codons (triplets) intact: for example a 3 or 6 base deletion which removes only intact codons. A 1 or 2 base deletion is out-of-frame and causes troubles.
viral shedding = the release of virus particles (in the air) (wikipedia)
The authors did not state explicitly, but these results could -just as
the patient in my previous blog- be compared with anti-biotic resistance
after an unsuccessful anti-biotic treatment.
- Case Study: Prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised cancer patient. 23 Dec 2020
There was no selection effect detected in in vitro experiments of
mutated virus strains.