World Monitor Magazine, №1/2020 WM_March 2020_FOR WEB (12.03.) | Page 47

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cells using a key-lock principle, in which the virus presents the
key and the cell the lock that is complementary to the key to en-
ter the cell and replicate. For the SARS-Cov-2 virus, the viral sur-
face protein “Spike protein S” is the “key” and it must fit snugly
into the “lock” protein that is expressed (=molecularly presented)
on the surface of the host cells. The cellular lock protein that the
SARS-Cov-2 virus uses is the ACE2 protein FIG 6).
This cell surface enzyme normally has a cardio-pulmonal
protective function. ACE2 is expressed at higher levels in the
elderly, in people with chronic heart failure or with pulmonary
or systemic arterial hypertension. (Note that ACE2 expression
is “rate –limiting” because other host proteins whose pres-
ence is also needed for the virus to enter the cells, such as
proteases, are more abundantly and widely expressed). Cer-
tain blood pressure drugs (as now intensely discussed since
hypertension is a risk factor for progression to ARDS and
death in COVID-19), but also mechanical stress from ventila-
tion, ironically, can increase the expression of ACE2.
Figure 6. The SARS-Cov-2 enters the host cell by docking with
its Spike protein to the ACE2 (blue) protein in cell surfaces.
Technically, one could quantify by how much the reduction by
4-fold of the droplets that a person is exposed to, as achieved
by surgical masks, or by 3-fold, as achieved by makeshift tea-
cloth masks, contributes to a reduction of the “reproduction
rate” from the initial R0 to the effective Rt after mitigation
intervention at time t. Perhaps by 25%? Then one could, us-
ing SEIR-epidemiological models, compute to what extent a
partial reduction of R would substantially flatten the curve
–to the desired extent to avoid overwhelming the health care
system (see Figure 1).
But such “bottom up” calculation of R is complicated because
it would require knowledge of many mechanistic factors that
are not easy to quantify. For instance, we do not know to
what proportion COVID-19 is transmitted via large spray
droplets vs. small aerosols. Only in the latter case will the
advantage of N95 respirator masks over surgical masks be
fully realized! We also do not know how much social distanc-
ing alone contributes to reducing R.
Thus, let us have a look at the actual biology of transmission
which offers a way out of this problem and has also not been
considered by officials who claimed that “surgical masks are
not effective”.
III. THE BIOLOGY
The SARS-Cov-2 virus, like any virus, must dock onto human
Surprisingly, ACE2 expression in the lung is very low: it is lim-
ited to a few molecules per cell in the alveolar cells (AT2 cells)
deep in the lung. But a just published paper by the Human Cell
Atlas (HCA) consortium reports that ACE2 is highly expressed
in some type of (secretory) cells of the inner nose! (FIG. 7).
Combine this fact with the above explanation of the me-
chanics: The nasal expression of ACE2 protein suggests that
the SARS-Cov2 virus infects these cells. One can also infer
that transmission of the SARS-Cov2 virus will occur largely
via large cough or sneeze droplets, which comprise the vast
portion of the sprayed liquid in cough/sneeze and will land
in the nasopharynx due to their size — precisely where the
molecular locks for the virus are present, allowing viral at-
tachment and entry into the host cells. Obviously this route of
transmission could be effectively blocked by simple physical
barrier. (The proximal expression of ACE in the nasal cavity
also supports the transmission by surface droplets — hence,
indeed wash your hands).
In fact, Wölfel et al. now report that viral material can be
readily detected and isolated from nasal swabs, unlike in the
case of other airborne viral infections, such as the original
SARS. Compared to SARS (which also uses ACE2 to enter
cells) in the case of COVID-19, viral genomes (RNA) appear
earlier in nasal swabs and at much higher concentration, such
that detection is rather easy. In fact, the FDA just approved
swabs for tests taken from just from the front of the nose
through self-collection, instead of deep in the nasopharynx.
The molecular analysis also show that the SARS-Cov2 virus is
active and replicates already in the nasopharynx, unlike other
respiratory viruses that dwell in deeper regions of the lung.