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Here’s Where Coronavirus Hides in Your Body
A new study provides the best look yet at how COVID-19 works—and how it might
be beaten.
David Axe
Updated Apr. 11, 2020 1:00PM ET / Published Apr. 08, 2020 4:07PM ET
https://www.thedailybeast.com/heres-where-coronavirus-hides-in-your-body
Summary followed by study.
The novel coronavirus can stow away in your throat without you knowing it, and every time you cough you’re broadsiding the people around you with the virus.
To stay healthy and contain SARS-CoV-2, stay home and keep your distance.
Population-wide efforts to control coronavirus might not be so straightforward,
however. The coronavirus is a clever, elusive, and tough little pathogen that could defy normal vaccines.
Those are two of the main takeaways from an important new study by a team of 18
scientists in Germany.
Working in two separate laboratories, the scientists carefully studied the spread of SARS-CoV-2 in the bodies of nine patients, taking daily measurements in order to understand each phase of the infection.
The team completed its study in early March and, published its findings in the journal Nature this month. “Active virus-replication in the upper respiratory
tract puts the prospects of COVID-19 containment in perspective,” the scientists wrote.
Close observers of coronavirus studies hailed the German team’s work. There’s “huge news” in the Nature paper, David Ostrov, a professor in the
Department of Pathology, Immunology and Laboratory Medicine at the University of Florida College of
Medicine, told The Daily Beast.
Some of the news is good.
SARS-CoV-2 starts replicating in the throat, not the lungs. For that reason, a simple throat swab is enough to test for the virus. There’s probably no need for an intrusive, unpleasant nasal swab.
The virus mostly spreads from people coughing on each other. It’s a lot less likely that you’ll catch the coronavirus by touching the same touchpad or toilet handle as an infected person.
It’s probably safe for a hospital to release a COVID-19 patient 10 days after
they start showing symptoms.
There’s bad news in the German study, too.
The antibodies our bodies produce in response to COVID-19 infection don’t actually destroy this virus. In that way, it is a lot like HIV.
That has implications for the high-stakes global effort to develop vaccines and
other treatments.
Besides containing important takeaways for doctors, scientists, and the public,
the German study also tells a story. One that helps to make sense of the pandemic.
Peter Kolchinsky, a virologist and biotech investor, summed up the Nature paper
on Twitter. The study, he wrote, “reveals a remarkable trick SARS-CoV-2 learned that makes it nastier than the first SARS,” which killed nearly 800 people during an
outbreak in 2003.
Viruses access our cells by interfacing with particular proteins. Once inside, they hijack our cells’ own mechanisms in order to make copies of themselves. When that happens, our bodies sometimes panic, mobilizing a powerful immune response that can go
too far… and make us sick or even kill us.
It turns out, SARS-CoV-2 prefers a spiky protein called ACE2.
“Think of it as a particular doorknob that the virus knows how to turn,” Kolchinsky explained in his summary of the German paper.
We’ve got a lot of those ACE2 proteins in our throats, which are great places
for a virus to hide out, replicate, and get ready to spread.
From the throat, the pathogen can spread inward to the lungs, where it becomes a lot more dangerous to the host. And with each cough it projects outward into the world. All without us even knowing it’s there.
Beating the coronavirus pandemic requires people to block the virus’ preferred method of travel—coughs—before they even know they have it. “There’s an evil genius to viruses that never ceases to amaze me,” Kolchinsky wrote.
Ostrov for his part focused on the German team’s findings on antibodies, which our bodies produce via a process called “seroconversion.”
“When aligned to viral load courses, it seems there is no abrupt virus elimination at the time of seroconversion,” the scientists wrote. “Rather, seroconversion early in week two coincides with a slow but steady decline of sputum viral load.”
“This means that the antibodies are not effective at clearing the virus,” Ostrov told The Daily Beast. “This is relevant when thinking about viruses and vaccines. HIV also stimulates production of antibodies that fail to clear the virus, as do many
other viruses, such as hepatitis virus C.”
“People have tried and failed to generate vaccines against such viruses, so we should not be overconfident that a vaccine strategy will work,” Ostrov added.
That doesn’t mean we don’t try to develop a coronavirus vaccine. Vaccines might end up working.
If they don’t, scientists might consider switching up their strategy. Instead
of leaning on vaccines to inoculate us, doctors could treat SARS-CoV-2 infections like they do HIV. With a cocktail of drugs that manages, but does not eliminate, the
infection.
[] STUDY FORMATTED FOR TEXT []
PDF Version
https://www.nature.com/articles/s41586-020-2196-x_reference.pdf
Virological assessment of hospitalized patients with COVID-2019
Roman Wölfel, Victor M. Corman, Wolfgang Guggemos, Michael Seilmaier, Sabine Zange,
Marcel A. Müller, Daniela Niemeyer, Terry C. Jones, Patrick Vollmar, Camilla Rothe,
Michael Hoelscher, Tobias Bleicker, Sebastian Brünink, Julia Schneider, Rosina
Ehmann,
Katrin Zwirglmaier, Christian Drosten & Clemens Wendtner
This is a PDF file of a peer-reviewed paper that has been accepted for publication.
Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our
authors
and readers. The text and figures will undergo copyediting and a proof review before
the paper is published in its final form.
ACCELERATED ARTICLE PREVIEW
transmission 6–8.
There is an urgent need for information on body site-specific virus replication, immunity, and infectivity. Here we provide a detailed virological analysis
of nine cases, providing proof of active virus replication in upper respiratory
tract
tissues. Pharyngeal virus shedding was very high during the first week of symptoms
(peak at 7.11 × 108 RNA copies per throat swab, day 4). Infectious virus was readily
isolated from throat- and lung-derived samples, but not from stool samples, in spite of
high virus RNA concentration. Blood and urine never yielded virus. Active replication
in the throat was confirmed by viral replicative RNA intermediates in throat samples.
Sequence-distinct virus populations were consistently detected in throat and lung
samples from the same patient, proving independent replication. Shedding of viral
RNA from sputum outlasted the end of symptoms. Seroconversion occurred after
7 days in 50% of patients (14 days in all), but was not followed by a rapid decline in viral
load. COVID-19 can present as a mild upper respiratory tract illness. Active virus
replication in the upper respiratory tract puts the prospects of COVID-19 containment
in perspective. described9,10 these observations do not address principal differences
between SARS and COVID-19 in terms of clinical pathology.
The here-studied patients were enrolled because they acquired their
infections upon known close contact to an index case, thereby avoiding representational biases due to symptom-based case definitions. All
patients were treated in a single hospital in Munich, Germany. Virological testing was done by two closely-collaborating laboratories using the
same standards of technology for RT-PCR and virus isolation, confirming
each other’s results based on almost all individual samples. Due to extremely high congruence of results, all data are presented together.
11. The present study uses samples taken during
the clinical course in the hospital, as well as from initial diagnostic testing before admission. In cases when this initial diagnostic testing
was done by other laboratories, the original samples were retrieved
and re-tested under the rigorous quality standards of the present study. RT-PCR sensitivity, sites of replication, and correlates
of infectivity based on aggregated data
To first understand whether the described clinical presentations are
solely caused by SARS-CoV-2 infection, samples from all patients were
tested against a panel of typical agents of respiratory viral infection, including HCoV-HKU1, -OC43, -NL63, -229E; Influenza virus A and B,
Rhinovirus, Enterovirus, Respiratory syncytial virus, Human Parainfluenza virus 1-4, Human metapneumovirus, Adenovirus, and Human
bocavirus. Interestingly, no co-infection was detected in any patient.
1B). The earliest swabs were taken on day
1 of symptoms, with symptoms often being very mild or prodromal.
All swabs from all patients taken between days 1 and 5 tested positive.
The average virus RNA load was 6.76x105 copies per whole swab until
day 5 (maximum, 7.11X108 copies/swab). Swab samples taken after day
5 had an average viral load of 3.44x105 copies per swab and a detection
rate of 39.93%. The last positive-testing swab sample was taken on day
28 post-onset. Average viral load in sputum was 7.00 x 106 copies per
mL (maximum, 2.35x109 copies per mL).
SARS13,14, we analyzed the first paired swab and sputum samples
taken on the same occasion from seven patients. All samples were taken
between 2 and 4 days post-onset. In two cases, swab samples had clearly
higher virus concentrations than sputum samples, as indicated by a
difference greater than 3 in threshold cycle (Ct) value. The opposite
was true in two other cases, while the remaining 5 cases had similar concentrations in both sample types.
None of 27 urine samples and none of 31 serum samples were tested
positive for SARS-CoV2 RNA.
multiple occasions from clinical samples (Figure 1D). Whereas virus was readily isolated during the first week of symptoms from a considerable fraction of samples (16.66% in swabs, 83.33% in sputum samples), no
isolates were obtained from samples taken after day 8 in spite of ongoing
high viral loads.
laboratory based infectivity criteria for discharge of patients
1). The presence of separate genotypes in throat swabs
and sputum strongly supported our suspicion of independent virus replication in the throat, rather than passive shedding there from the lung.
Virus shedding, antibody response, and clinical
correlation in individual courses
2), viral RNA remained detectable in throat swabs well into
the second week. Stool and sputum samples remained RNA-positive
over three weeks in six of the nine patients, in spite of full resolution
of symptoms.
2F, G). Of note, four of nine patients showed loss of taste and
olfactory sensation, and described this loss to be stronger and more long-lasting than in common cold diseases.
2D). Results on differential
recombinant immunofluorescence assay indicated cross-reactivity or cross-stimulation against the four endemic human coronaviruses in
several patients (Table S1).
Conclusions
Whereas proof of replication by histopathology is awaited, extended
tissue tropism of SARS-CoV-2 with replication in the throat is strongly supported by our studies of sgRNA-transcribing cells in throat swab
samples, particularly during the first 5 days of symptoms. Striking
additional evidence for independent replication in the throat is provided
by sequence findings in one patient who consistently showed
a distinct virus in her throat as opposed to the lung. In addition, the disturbance of gustatory and olfactory sense points at upper respiratory
tract tissue infection.
Critically, the majority of patients in the present study seemed to be
already beyond their shedding peak in upper respiratory tract samples
when first tested, while shedding of infectious virus in sputum continued through the first week of symptoms. Together, these findings
suggest a more efficient transmission of SARS-CoV-2 than SARS-CoV
through active pharyngeal viral shedding at a time when symptoms
are still mild and typical of upper respiratory tract infection. Later in
the disease, COVID-19 then resembles SARS in terms of replication
in the lower respiratory tract. Of note, the two patients who showed
some symptoms of lung affection showed a prolonged viral load in
sputum. Our study is limited in that no severe cases were observed.
Future studies including severe cases should look at the prognostic
value of an increase of viral load beyond the end of week 1, potentially indicating aggravation of symptoms.
Further studies should therefore address whether SARS-CoV-2
shed in stool is rendered non-infectious though contact with the gut environment. Our initial results suggest that measures to contain viral
spread should aim at droplet-, rather than fomite-based transmission.
The prolonged viral shedding in sputum is relevant not only for hospital infection control, but also for discharge management. In a situation characterized by limited capacity of hospital beds in infectious diseases wards, there is pressure for early discharge following treatment. Based
on the present findings, early discharge with ensuing home isolation
could be chosen for patients who are beyond day 10 of symptoms with
less than 100,000 viral RNA copies per ml of sputum. Both criteria predict that there is little residual risk of infectivity, based on cell culture.
We have here
developed a particularly sensitive plaque reduction neutralization
assay. Considering the titers observed, a simpler microneutralization
test format is likely to provide sufficient sensitivity in routine application and population studies.
When aligned to viral load courses, it seems there is no abrupt virus elimination at the time of seroconversion. Rather, seroconversion early
in week 2 coincides with a slow but steady decline of sputum viral load. Whether certain properties such as glycosylation pattern at critical
sites of the glycoprotein play a role in the attenuation of neutralizing antibody response needs further clarification. In any case, vaccine
approaches targeting mainly the induction of antibody responses
should aim to induce particularly strong antibody responses in order
to be effective.
.
Virus isolation
Virus isolation was done in two laboratories on Vero E6 cells. 100 µl of
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