TL:DR for SARS-CoV-2 and COVID-19


What follows are the TL:DR snippets of information gathered from various scientific publications about the SARS-CoV-2 virus and COVID-19 disease, with attributes.



Why the Coronavirus Has Been So Successful

The Atlantic: Read the full article. [Note: this is an excellent article and dense with useful information. I’d suggest going to the source and reading it in its entirety.]

Published: March 20, 2020

In shape, it’s [SARS-CoV-2] essentially a spiky ball. Those spikes recognize and stick to a protein called ACE2, which is found on the surface of our cells: This is the first step to an infection. The exact contours of SARS-CoV-2’s spikes allow it to stick far more strongly to ACE2 than SARS-classic did, and “it’s likely that this is really crucial for person-to-person transmission,” says Angela Rasmussen of Columbia University. In general terms, the tighter the bond, the less virus required to start an infection.

To be clear, SARS-CoV-2 is not the flu. It causes a disease with different symptoms, spreads and kills more readily, and belongs to a completely different family of viruses. This family, the coronaviruses, includes just six other members that infect humans. Four of them—OC43, HKU1, NL63, and 229E—have been gently annoying humans for more than a century, causing a third of common colds. The other two—MERS and SARS (or “SARS-classic,” as some virologists have started calling it)—both cause far more severe disease.

There’s another important feature. Coronavirus spikes consist of two connected halves, and the spike activates when those halves are separated; only then can the virus enter a host cell. In SARS-classic, this separation happens with some difficulty. But in SARS-CoV-2, the bridge that connects the two halves can be easily cut by an enzyme called furin, which is made by human cells and—crucially—is found across many tissues. “This is probably important for some of the really unusual things we see in this virus,” says Kristian Andersen of Scripps Research Translational Institute.

most respiratory viruses tend to infect either the upper or lower airways. In general, an upper-respiratory infection spreads more easily, but tends to be milder, while a lower-respiratory infection is harder to transmit, but is more severe. SARS-CoV-2 seems to infect both upper and lower airways, perhaps because it can exploit the ubiquitous furin. This double whammy could also conceivably explain why the virus can spread between people before symptoms show up—a trait that has made it so difficult to control.

…of the 100-plus mutations that have been documented, none has risen to dominance, which suggests that none is especially important. “The virus has been remarkably stable given how much transmission we’ve seen,” says Lisa Gralinski of the University of North Carolina. “That makes sense, because there’s no evolutionary pressure on the virus to transmit better. It’s doing a great job of spreading around the world right now.”

(The virus might also be able to infect ACE2-bearing cells in other organs, including the gut and blood vessels.)

in extreme cases, the immune system goes berserk, causing more damage than the actual virus. For example, blood vessels might open up to allow defensive cells to reach the site of an infection; that’s great, but if the vessels become too leaky, the lungs fill even more with fluid. These damaging overreactions are called cytokine storms. They were historically responsible for many deaths during the 1918 flu pandemic, H5N1 bird flu outbreaks, and the 2003 SARS outbreak.

other factors—a person’s genes, the vagaries of their immune system, the amount of virus they’re exposed to, the other microbes in their bodies—might play a role too. In general, “it’s a mystery why some people have mild disease, even within the same age group,” Iwasaki says.

At the moment, the virus is tearing through a world of immunologically naive people, and that vulnerability is likely to swamp any seasonal variations. … the new virus is transmitting readily in countries like Singapore (which is in the tropics) and Australia (which is still in summer). And one recent modeling study concluded that “SARS-CoV-2 can proliferate at any time of year.”


COVID-19: How and Why the Virus Spreads Quickly

—From contributing editor for Scientific American magazine W. Wayt Gibbs in Washington state, March 22nd, 2020. (Read the entire article here.)

On March 10th, despite stern official warnings not to gather in groups, 56 people met for an event in Skagit County. All of them were apparently healthy at the time. But ten days later, 43 of those 56 people have either been confirmed to have COVID-19 or are showing symptoms of the disease. Experts suspect that one or more people in the group was a so-called “super-shedder,” someone who has yet to show symptoms but is transmitting lots of infectious virus.

…in a study out this week in the New England Journal of Medicine, researchers at a Montana biohazard lab run by the National Institutes of Health confirmed what many experts had feared: this coronavirus can also be infectious outside of a living body, in some cases for days.

The N.I.H. researchers tested whether the SARS-CoV-2 virus can spread via fomites (objects or materials which are likely to carry infection, such as clothes, utensils, and furniture). On cardboard, it took a good four hours before the amount of live virus started to fall significantly, and the surface remained quite infectious eight hours later. On stainless steel—think railings, shopping carts, gas pumps, jungle gyms—the coronavirus remained infectious for more than a day. And on plastic—so, our pens, our credit cards, our keyboards and keypads—it stayed viable for two to three days.

…can you catch COVID-19 from someone who hasn’t tested positive, or even from someone who may feel perfectly healthy? …yes. (emphasis added) In a paper that appeared on March 16th an international group of researchers … concluded that only 14% of COVID-19 infections were documented, meaning that 86%—that’s six out of seven cases—never showed up in the statistics as a confirmed case.

…one of the authors of that paper, said in a news briefing: “These undocumented infections were … about half as infectious per person as a documented case who has more severe symptoms and maybe shedding more. Because, however, there are many more of these undocumented cases, it’s the undocumented infections that are driving the spread and growth of the outbreak… Generally, you’re looking at about an order of magnitude more cases than have been confirmed.”

In a preprint article published on March 18th, researchers with the World Health Organization studied 94 COVID-19 patients in Guangzhou, China to determine when they became infectious—and when they stopped shedding the virus. … overall, the patients tended to become less infectious as their symptoms progressed. … Through some calculations, the scientists concluded that these coronavirus patients shed the most virus, and were probably most infectious to others, up to two days before they started feeling ill.

W.H.O. researchers estimate that around half of the people who caught this virus in Guangzhou got it from someone who was still feeling healthy at the time. …documented cases where patients have fully recovered from COVID-19 but continued to test positive for the virus for more than a week after their symptoms disappeared.

…these tests aren’t perfect. A number of studies, including one done by scientists at Wuhan University in February, have found that these RT-PCR tests we’re relying on today aren’t sensitive enough to reliably catch the infection in its early stages. So a negative test result is no guarantee that you’re not carrying the virus.

Elizabeth Halloran of the Fred Hutchinson Cancer Research Center explained at news briefing last week: “the basic reproductive number (R0)—that is the average number of people that an average person infects at the beginning—is estimated … to be about 2.5. And there are actually estimates that are higher. That’s before all this behavioral reduction and social distancing which would reduce it. But it’s going to be difficult even if it does go down somewhat seasonally in the summer to bring that down necessarily below one.”


Part 2: COVID-19: How and Why the Virus Spreads Quickly

—From contributing editor for Scientific American magazine W. Wayt Gibbs in Washington state, March 22nd, 2020. (Read the entire article here.)

Interview with: computational epidemiologist Lauren Ancel Meyers of the University of Texas

serial interval
the average number of days between someone catching the virus and passing it on to someone else

The model Neil Ferguson and his team at Imperial College developed actually used a slower serial interval of six and a half days, and it explored the effects of reproductive numbers ranging between 2 and 2.6.

…first simulated an imaginary, worst-case scenario in which we did none of those things and simply let COVID-19 rampage through the U.S. unchecked. The results from that simulation show why no country should contemplate taking a hands-off approach to this pandemic. The model predicts that without quarantines or social distancing, mortality from the pandemic would skyrocket for the new few months, peak in June or July, and then decline through September, in a steep bell curve. If we took no measures to flatten that bell curve, the model predicts that over 80 percent of the U.S. population would be infected, and fatalities would number in the millions.

There’s some good news in these simulation results. It looks like closing schools, isolating confirmed cases and getting everyone to practice social distancing should drive the number of critical COVID-19 cases down to a level our health care systems can handle. … “it is difficult to be definitive about the likely initial duration of measures that will be required, except that it will be several months.”

But there’s also some bad news. In these simulations, infections start to shoot up quickly as soon as we let people congregate once again. The model predicts that within a few weeks of lifting the restrictions, we’re pretty much back where we started.

So until immunity to the disease becomes common, flattening the curve is like stepping on a balloon. You can change the shape of it by a lot, but the volume—the total number of people who will ultimately catch this virus—that is likely to remain about the same.

The researchers write: “To avoid a rebound in transmission, these policies will need to be maintained until large stocks of vaccine are available to immunise the population—which could be 18 months or more.”

Ira Longini of the University of Florida: “It’s probably only a vaccine that can really control the epidemic to a large extent by reducing the susceptibility of vaccinated people and also, if they do get infected, reducing the transmissibility to others.”

Numerous labs around the world are working at a breakneck pace to create and test vaccine. But no one has succeeded yet in making vaccines against the two other deadly coronaviruses that cause SARS and MERS.

“We need a serologic test (blood) that’s specific to this virus—and we don’t have one right now—so we could find out what proportion of the population was infected and how much herd immunity there may be out there, keeping in mind the caveat that immunity may not be durable.”

Researchers have already shown that people who are infected with this coronavirus do develop antibodies to it.

Researchers in China reported this week some encouraging results from a study on rhesus monkeys. Two weeks after the monkeys were infected with COVID-19, became sick and recovered, the scientists tried to reinfect the animals with the virus. The infection didn’t take. That was a small and short study, but it gives some reason to hope that the same will be true for people as well. We’ll know it isn’t if people who have recovered from COVID-19 start coming down with the disease a second time.



Energetic cost of building a virus

Gita Mahmoudabadia, Ron Milob, and Rob Phillipsa. Department of Bioengineering, California Institute of Technology, Pasadena, CA

Read the entire PDF here

…what is the energetic cost of a viral infection, and what is the energetic burden of a viral infection on the host cell?

The influenza virus is a eukaryotic virus infecting various animals, with an average burst size of 6,000, although note that the burst size depends upon growth conditions.

The influenza virus siphoned away only about 1 percent of its host cell’s energy but created about 6,000 new viruses.

[pG: “burst size” is the estimated number of viroids (individual virus’) ejected from a cell when it bursts.]


One Virus Particle Is Enough To Cause Infectious Disease

Wageningen University and Research Centre, March 14, 2009.

Read the entire article.

The experiment (using caterpillars) showed that exposure to a low dosage of virus particles resulted in a small number host infections (20%). The majority of these hosts (86%) turned out to be infected by a single virus genotype. In contrast, exposure to a high dosage of virus particles resulted in virtually all the hosts (99%) becoming infected.

…it can be derived that the virus particles have an independent effect, and that a single virus particle can indeed cause infection and/or disease.

If there are few virus particles that lead to an infection, the number of virus particles determines the degree of diversity that can be present within the host. … Until now, it was unclear whether a virus must be seen as an individual that can infect a host independently, or whether a cloud of viruses ‘cooperates’ to cause an infection. It is not yet known if the viruses that affect people can also act individually, but this research shows that it is possible.


Viral infections acquired indoors through airborne, droplet or contact transmission

Giuseppina La Rosa; Marta Fratini; Simonetta Della Libera; Marcello Iaconelli; Michele Muscillo. Dipartimento di Ambiente e connessa Prevenzione Primaria, Istituto Superiore di Sanità, Rome, Italy. 2013.

Read the full article.

Viruses are small (20-400 nm)… Droplet transmission occurs when viruses travel on relatively large respiratory droplets (> 10 µm) that people sneeze, cough, or exhale during conversation or breathing (primary aerosolization). A single cough can release hundreds of droplets, a single sneeze thousands (up to 40 000) at speeds of up to 50-200 miles per hour, each droplet containing millions of viral particles (although the number varies greatly in the course of infection). Aerosol droplets travel only short distances (1-2 meters) before settlings on surfaces, where viruses can remain infectious for hours or days.

The flushing of a toilet, for example, can aerosolize significant concentrations of airborne viruses

Crowded indoor environments, especially when poorly ventilated, represent greater risks for viral transmission. Hospitals in particular, are environments where viral aerosol can be particularly hazardous, since patients tend to be especially prone to infection due to preexisting illness.


About 50% of all infections may be asymptomatic. Asymptomatic patients however, shed virus and can transmit the disease, thus creating a reservoir for the virus.

In most cases, the influenza virus is transmitted by droplets, through the coughing and sneezing of infected persons, but it can also be transmitted by airborne droplet nuclei as well as by contact, either through direct skin-to-skin contact or through indirect contact with contaminated environments.

In clinical studies, virus-laden particles within the respirable aerosol fraction have been detected in exhaled breaths of patients with influenza and in the air samples from healthcare settings during seasonal peak [9]. Moreover, the scientific literature presents evidence in support of a contribution of aerosol transmission to the spread of influenza A, including the prolonged persistence of infectious aerosolized influenza virus at low humidity.

…while the virus can survive on surfaces for hours or even days, it cannot survive on hands for longer than five minutes

Schools are known to have an important role in influenza transmission in a community since children have a higher influenza attack rate than adults (children get the flu twice as often as adults). This is why school closures can be effective in reducing the impact of influenza on a community

CORONAVIRUS (note: this is not specifically about COVID19 since this paper was published in 2013.)

The most common mode of transmission is through water droplets generated when an infected person coughs or sneezes. Transmission is thus most likely to occur in close proximity to someone who is infected or by touching a contaminated surface [47]. Current studies in different indoor environments, however, indicate that SARS may be transmitted through the airborne route as well [48]. Several clusters of infection have been reported, which point to a likely transmission by this route, including transmission in an aircraft from an infected person to passengers located 7 rows of seats ahead [49], a cluster of cases among guests sharing the same floor of a hotel [50], and another, counting more than 1000 persons, in an apartment complex in Hong Kong [51]. A detailed investigation on the latter outbreak linked it to aerosol generated by the building’s sewage system.


New coronavirus may spread through poop

LiveScience: By Yasemin Saplakoglu – Staff Writer February 20, 2020

Read the full article.

There are currently more cases of COVID-19 (the disease caused by the virus SARS-CoV-2) than would be expected if the virus were spreading only through respiratory droplets and contact with infected patients, according to a report published Feb. 15 by the Chinese Center for Disease Control and Prevention (China CDC).

…They isolated the coronavirus from one patient who had severe pneumonia and examined the virus under an electron microscope. They found that the coronavirus was viable. “This means that stool samples may contaminate hands, food, water, etc.,” the China CDC wrote in the report. People who use the bathroom and then don’t wash their hands could spread the virus to others, for instance.

China CDC recommends washing your hands frequently, disinfecting surfaces, maintaining personal hygiene, avoiding the consumption of raw food, boiling water before drinking it


What is COVID-19, and what do we know so far about its clinical presentation?

Published: February 28, 2020

Read the full article.

The virus responsible for COVID-19, SARS-CoV-2, is in the species SARS-like corona viruses. At 125?nm, it is slightly larger than influenza, SARS and MERS viruses. It is almost certainly a descendant from a bat corona virus of which there are many. The closest is a virus that originated from the Rhinolophus bat which is >?96% homologous with the current SARS-CoV-2 virus. It is only 79% homologous with the original SARS CoV.

The near identical gene sequences of 90 analysed cases from outside of China suggests it has likely emerged after a solitary species jump in early December 2019 from an unknown (likely mammalian) intermediate host.


Features, Evaluation and Treatment Coronavirus (COVID-19)

Marco Cascella; Michael Rajnik; Arturo Cuomo; Scott C. Dulebohn; Raffaela Di Napoli.

Updated: March, 20, 2020

Read the full article.

Like other CoVs, it is sensitive to ultraviolet rays and heat. Furthermore, these viruses can be effectively inactivated by lipid solvents including ether (75%), ethanol, chlorine-containing disinfectant, peroxyacetic acid and chloroform except for chlorhexidine.

SARS-CoV-2. Its single-stranded RNA genome contains 29891 nucleotides, encoding for 9860 amino acids.

Based on data from the first cases in Wuhan and investigations conducted by the China CDC and local CDCs, the incubation time could be generally within 3 to 7 days and up to 2 weeks as the longest time from infection to symptoms was 12.5 days

The pathogenic mechanism that produces pneumonia seems to be particularly complex. Clinical and preclinical research will have to explain many aspects that underlie the particular clinical presentations of the disease. The data so far available seem to indicate that the viral infection is capable of producing an excessive immune reaction in the host. In some cases, a reaction takes place which as a whole is labeled a ‘cytokine storm’. The effect is extensive tissue damage. The protagonist of this storm is interleukin 6 (IL-6).

The case studies of Li et al. published in the New England Journal of Medicine (NEJM) on January 29, 2020, encapsulates the first 425 cases recorded in Wuhan. … the overall case-fatality rate (on confirmed cases) was 2.3%. Of note, the fatal cases were primarily elderly patients, in particular those aged ? 80 years (about 15%), and 70 to 79 years (8.0%). Approximately half (49.0%) of the critical patients and affected by preexisting comorbidities such as cardiovascular disease, diabetes, chronic respiratory disease, and oncological diseases, died. While 1% of patients were aged 9 years or younger, no fatal cases occurred in this group.

On the other hand, in younger subjects and in those who do not have basic respiratory impairments or other comorbidities, dyspnea (Difficult or labored breathing.) may appear later. In these patients experiencing worsening inflammatory-induced lung injury, there is a decrease in oxygen saturation (<93%). This seems to be the crucial phase of the disease, from this point onwards, there may be a rapid deterioration of respiratory functions. The scenario is truly incredible because for patients who are paucisymptomatic and slightly hypoxic, the first therapeutic approach is oxygen therapy. Although this strategy is effective, worsening of respiratory failure may occur in some patients. With the drive preserved, the next step, according to logic, is the NIV. This therapy has a rapid success by increasing the P/F. In some patients, however, there is a sudden, unexpected worsening of clinical conditions. Patients collapse under the operator’s eyes and require rapid intubation and invasive mechanical ventilation. However, after 24-48 hours the patient can have a rapid improvement with an increase in P/F. Operators are therefore tempted to proceed with weaning. But very often, after an initial success there is a new worsening of respiratory conditions, such as to require a new invasive therapy. Therefore, mechanical ventilation has also been suggested for 1-2 weeks.


Study highlights ease of spread of COVID-19 viruses

Published: Mar 09, 2020

Read the full article.

Virus concentrates quickly, sheds efficiently:
Led by researchers in Germany, the virologic study, which has not yet been peer-reviewed, found that the novel coronavirus quickly begins producing high viral loads, sheds efficiently, and grows well in the upper respiratory tract (nose, mouth, nasal cavity, and throat).

“Shedding of viral RNA from sputum outlasted the end of symptoms,” the authors wrote. “These findings suggest adjustments of current case definitions and re-evaluation of the prospects of outbreak containment.”

Throat swabs showed very high viral shedding during the first week of symptoms.

The findings contrasted starkly with those from the 2003 outbreak of SARS in terms of viral load. “In SARS, it took 7 to 10 days after onset until peak RNA concentrations (of up to 5×105 copies per swab) were reached. In the present study, peak concentrations were reached before day 5, and were more than 1,000 times higher.”

Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota: “The findings confirm that COVID-19 is spread simply through breathing, even without coughing, They also challenge the idea that contact with contaminated surfaces is a primary means of spread.”

The researchers estimated the median incubation period at 5.1 days (95% confidence interval [CI], 4.5 to 5.8 days). They found that 97.5% of patients who have symptoms do so within 11.5 days of infection (CI, 8.2 to 15.6 days).


New blood tests for antibodies could show true scale of coronavirus pandemic Read full article.

Published: Mar. 19, 2020

Some viral diseases, such as dengue, can cause more serious symptoms if a person has been previously exposed to a related strain of the virus and already has partial immunity. Existing antibodies can react to the related invader and trigger a dangerous overreaction, a phenomenon known as an antibody-dependent enhancement (ADE). Some researchers have suggested ADE might explain why the virus is more deadly in the elderly and less so in children, who have had less exposure to other coronaviruses.

Relatively few cases have been diagnosed among children, but it isn’t clear whether that’s because they don’t get infected or because their infections are generally so mild that they go unnoticed. Testing children for SARS-CoV-2 antibodies should resolve that.

Longer term antibody tests will also help researchers understand how long immunity to the virus lasts, a key issue for any future vaccine. For other coronaviruses, Krammer notes, immunity after an infection is strong for several months, but then begins to wane.


Researchers rush to test coronavirus vaccine in people without knowing how well it works in animals

Published: March 11, 2020 Read the full article.

Regulators require that a manufacturer show a product is safe before it goes into people, and while it isn’t enshrined in law, researchers almost always check that a new concoction is effective in lab animals before putting human volunteers at potential risk. “This is very unusual,” explained Akiko Iwasaki, a Yale University microbiologist who studies the immune response to viruses. “It reflects the urgency to develop vaccines to counter the Covid-19 pandemic.”

Mark Feinberg, president and CEO of the International AIDS Vaccine Initiative: “The traditional vaccine timeline is 15 to 20 years. That would not be acceptable here,” said Mark Feinberg, president and CEO of the International AIDS Vaccine Initiative. … When you hear predictions about it taking at best a year or a year and a half to have a vaccine available … there’s no way to come close to those timelines unless we take new approaches.”

The question is complicated by the newness of the science at play. The technology that has allowed Moderna to craft an experimental vaccine so fast has not yielded a single immunization that’s made it to market so far. It’s a trendy idea: Instead of injecting people with a weakened pathogen or proteins from the surface of a pathogen, so that our bodies will learn to fight off such infections in the future, scientists are betting on a kind of genetic hack, a lab-made concoction that gets the body to produce its own virus-like bits which it will then train itself to combat.

At the center of it all is a molecule called messenger RNA, or mRNA. Inside of us, its normal function is to transmit the instructions contained within our DNA to the cellular protein-making factories that carry them out. In Moderna’s recipe, the mRNA is synthetic, programmed with the goal of getting our inner machinery to produce certain coronavirus-like proteins — the very proteins that the pathogen uses to gain entry into our cells. Once those homemade dummy virus particles are there, the thinking goes, our bodies will learn to recognize and clobber the real thing.

The trouble is, your average lab mouse doesn’t seem susceptible to the new virus. While the bug behind Covid-19 has no trouble co-opting molecules on human cells to get inside and start multiplying, it isn’t so good at latching onto the mouse equivalent.

These pathogen-susceptible rodents were specially engineered in the wake of another coronavirus outbreak: SARS, in the early 2000s. To make them easier to infect, scientists adorned their cells with the human molecule that allows certain coronaviruses to slip inside. … “Those mice in the U.S. are being bred so that the colony can be enlarged,” explained Graham, adding, that they “will be available for experiments within the next few weeks.”

Covid-19 may well simply be a test case for other outbreaks to come. As Feinberg, of the International AIDS Vaccine Initiative put it, “This is a world where we’re going to see infectious diseases we’ve never seen before, and we need to get really good at developing vaccines against them quickly.”

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