Frequently Asked Questions on COVID-19
Frequently Asked Questions regarding COVID-19
What factors are responsible for the SARS-CoV-2 pandemic?
There are three main reasons:
- First, SARS-CoV-2 can easily infect and spread in humans. It's highly contagious and it seems to be transmitted for 1 or 2 days before people get sick, and some people have only very mild or subclinical infections.
- Second, none of us had any prior immunity to SARS-CoV-2 so the virus had plenty of opportunities to infect and replicate, even in older people would have developed immunity earlier in life if this virus had been circulating for many years.
- Thirdly, the outbreak occurred in a major business and travel hub in China and the virus was spread first to other regions of China, to other countries in Asia, also to Europe and the United States by travelers before countries were able to implement effective testing or other public health measures.
What diagnostic tests are currently available for the diagnosis of COVID-19 in humans and animals? What is the process for animal testing?
Currently the test that is being widely used for diagnosis of COVID in humans is the real-time PCR, which detects the virus nucleic acid in clinical specimens (mainly respiratory specimens – nasal or oropharyngeal swabs or sputum). This test does not show whether the virus is infectious or not, only the presence of viral RNA. Serological assays, which detect antibodies against the virus, are now becoming available. Those are still being evaluated, and include lateral flow assay that detects IgG and IgM antibodies, as well as several ELISA assays that are under development and a few are commercially available.
In animals testing is also performed by real-time PCR, which detects viral RNA. This assay was adapted to use animal-specific reagents and the clinical samples recommended for testing include nasal-, oropharyngeal- and rectal swabs. Currently there are ~20 Diagnostic laboratories across the country that are capable of performing the testing. Most of the states require approval from the state veterinarian prior to running the test and the test can only be requested by a Veterinarian. If the test is approved and run on regional VDLs, all presumptive positives need to be forwarded to the National Veterinary Services laboratory for confirmation.
What is the current status of the drugs being evaluated as antivirals against SARS CoV-2?
At this time, the NIH expert panel has stated that there is currently insufficient data to make the recommendation either for or against any antiviral or immunomodulatory therapy at any stage of SARS CoV-2 infection or COVID-19 disease. The NIH guidelines will be updated as required, and we expect them to be updated in short as the first clinical trials of remdesivir have just shown some efficacy. The most current ones can be found in this link: https://covid19treatmentguidelines.nih.gov
The FDA has now granted an Emergency Use Authorization for the use of remdesivir in COVID-19: https://www.fda.gov/media/137564/download
Several drugs are being both used and evaluated at the same time against SARS CoV-2. The most advanced one is remdesivir. Remdesivir was a pre-existing antiviral that had already been tested in humans against Ebola virus. During these tests, it proved to be safe for use in even critically ill patients. Remdesivir was known to be active against a variety of viruses, including the two previous zoonotic coronaviruses SARS CoV-1 and MERS, in culture and even in animal models. Early in the outbreak, remdesivir was shown activity against SARS CoV-2 in culture, and the first clinical trials were started almost immediately.
The first results of the first phase III (i.e., large scale) remdesivir clinical trials have just been made public on April 29. In an NIH placebo-controlled double blind trial, remdesivir treatment resulted in shortening the hospital stays by almost 1/3, from 15 to 11 days. Although this may not appear impressive, this effect would immediately lower hospital load by almost 1/3, leading to a significant improvement in the management of the outbreak. The number of deaths also decreased by about 1/3, but the numbers were (fortunately) very low in both groups (8% in remdesivir treated and 11.6% in placebo treated patients), and the differences are not statistically significant. Based on these results, the independent review board appears to have recommended halting the trial immediately and starting treating all patients. In a second clinical trial, “open label” and with no placebo group, 5 day treatment was shown to be equally as effective as 10 day treatment, with an aggregate mortality of 9.3%. These results make it possible to treat twice as many patients with the already existing remdesivir stocks. A third clinical trial in China, which was interrupted before completion because the outbreak was (fortunately) controlled and no new patients could be enrolled, produced in no statistical differences between remdesivir or placebo treated patients, but remdesivir treated patients recovered somewhat faster and sooner, consistently with the two USA-run clinical trials. In all three clinical trials, remdesivir proved safe and well tolerated. We think that it is realistic to expect an update to the NIH treatment guidelines as the FDA has already granted an Emergency Use Authorization approval for remdesivir.
Chloroquine and hydroxychloroquine are commonly used, too, and the FDA has issued an “emergency use authorization” for their use in COVID-19. There are no published results of high quality controlled clinical trials yet and therefore their actual effectiveness is still unknown – they may be associated with significant side effects. The NIH has now launched a trial and we can expect to know the actual usefulness of these drugs in the coming months.
HIV drugs, so called “protease inhibitors” have also been used, although there is no clinical evidence showing that they are active against COVID-19. Early in the outbreak, oseltamivir was tried, but it resulted in no obvious benefits.
Besides the antiviral therapy, immunomodulators are being used to manage the disease, with a particular emphasis on so called “IL-6” inhibitors. There are ongoing clinical trials evaluating the efficacy of this approach, but uncontrolled studies suggest it has positive impact.
Corticoids are often used to manage respiratory distress and have been used also in COVID-19, although the CDC discourages this practice unless required to manage comorbidities.
What is being done in the search for new antivirals against SARS CoV-2?
A lot! Almost every research group or pharmaceutical company working on antivirals has re-focused on SARS CoV-2. Very large numbers of compounds are being evaluated against this virus, at a pace never seen before. There are several ongoing approaches in the search for COVID-19 antivirals, some of which are more advanced than others.
The most advanced compounds are inhibitors of the replication of the viral genome. One of these compounds, “NHC”, has shown good activity in culture and in animal models against the two previous zoonotic coronaviruses, SARS CoV-1 and MERS. The three dimensional structure of the main viral enzyme in charge of replicating the genome has been solved, which allows the rational design and optimization of specific inhibitors. The development of inhibitors of the viral replication enzymes is a mature approach that has resulted in many of the antivirals currently used against other viruses such as HIV and HCV. SARS CoV-2 also encodes for a viral protease, and viral proteases are another of the major targets for antivirals against other viruses, such as HIV and HCV. The workflow to identify and optimize protease inhibitors is thus mature and the three dimensional structure of the SARS CoV-2 protease has also been resolved. As another approach, there are a number of groups screening large number of different compounds for their potential ability to inhibit the replication of the virus, in culture. This is also a very mature approach that, for example, has recently resulted in one of the key groups of antivirals against HCV, the so-called “NS5A inhibitors”. One of the groups at the Baker Institute is starting a medium size screen for inhibitors of replication of SARS CoV-2 and other coronavirus, with the goal of contributing to the development of a drug against the current pandemic but more importantly to have a drug ready before the next outbreak ever occurs.
Beyond these traditional approaches, there are also great efforts being made to identify inhibitors of other viral functions, such as the primary attachment of the virus to the cell or its subsequent fusion to the cell membranes, as well as inhibitors of cellular functions required for viral replication. The efforts on antiviral development against SARS CoV-2 are enormous and proceeding at a mesmerizing pace, never seen before in the development of any antivirals. The urgency is real, and the responses are concordant with it.
Key links for more information:
ISAR - https://www.isar-icar.com/Coronavirus/
CDC - https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html
Do you foresee this corona virus mutating as it crosses species?
All viruses mutate due to random errors resulting from their replication, but of those only be a small number of mutations change the viral properties of SARS-CoV-2. Many viral genome sequences are being obtained and examined, so mutations will be quickly identified. It is still hard to predict whether any mutation might have an effect on the viral properties, but it is not expected that those will cause issues in the next year or so that would affect the control programs.
Many of my clients purchase their food online or otherwise have it delivered. How long can the virus live on cardboard boxes and what should I tell my clients about any precautions they should take?
Our current understanding of the virus that causes COVID-19 is that risk is highest from human-to-human transmission through aerosols and droplets between people who are in relatively close proximity (hence, social distancing is being mandated to reduce transmission). These aerosols and droplets may contaminate the environment, including on common materials we come in contact with. Researchers (NIH, UCLA, Princeton) have studied the decay of viruses on various surfaces. They largely find that the virus survives a few hours in air, up to a day on cardboard, and maybe upwards of 3 days on plastics and steel when in a cool, damp dark environment. While this environmental transmission is likely low risk, good hygiene and care can reduce it further. Wash your hands regularly, particularly after touching any item that originated outside your home. Disinfect items and surfaces with soap or disinfecting wipes. Where you can, leave items to sit for longer durations to allow any virus decay. The CDC has a set of guidelines on their webpage: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/cleaning-disinfection.html
My clients are concerned their animals can carry this virus on their fur if touched by someone out of their isolation group. Is this virus viable on fur and for how long? Is that known?
The virus appears to be less stable on fibrous and porous materials (i.e. pet fur) so that it would be an unlikely source of transmission, although should be considered low-risk surface. Again, in general, practicing good hygiene is the best solution - wash your hands before and after interacting with a pet that was outside. Keep your pet well groomed, wash bowls and bedding regularly. The AVMA has resources at their website here: https://www.avma.org/resources-tools/animal-health-and-welfare/covid-19
I have clients who live alone and they want to know if they should try to foster their pets if they become infected?
From the CDC https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/animals.html: “If you are sick with COVID-19 (either suspected or confirmed), you should restrict contact with pets and other animals, just like you would around other people. Although there have been no reports of pets becoming sick with COVID-19 in the United States, it is still recommended that people sick with COVID-19 limit contact with animals until more information is known about the virus. This can help ensure both you and your animals stay healthy.”
Will the tiger that was tested pose a threat of transmission to other animals or humans?
Public health officials believe the large cats at the Bronx Zoo were infected by a zoo worker who was COVID-19-positive and shedding virus. Laboratory studies of infected cats have confirmed the potential for cat-to-cat transmission, prompting standard protocols of reducing transmissible diseases between animals. There is currently no evidence that animals can transmit SARS-CoV-2 to humans. Out of an abundance of caution, though, public health officials are recommending reduced contact between infected individuals and animals and hand washing after contact with animals.
Since cold viruses seem to mutate very easily, why not expect that this will happen with this virus SARS-CoV-2?
In truth, all viruses ‘mutate’ and RNA viruses that include rhinoviruses (colds), influenza viruses (flu), and coronaviruses (colds and COVID-19 agent) more readily acquire mutations due to their inherent biology of genome replication. The difference of concern lies in, 1) how fast do mutations arise, and 2) where do mutations arise in the genome. Through cooperation of labs around the world, we have thousands of sequences of SARS-CoV-2 that can be compared and tracked over time. Analysis finds that the rate of mutation is rather slow and in line with what we expect for these types of viruses. In influenza viruses, the concern of mutations comes from the selection by our own immune systems. The myriad of antibodies against past seasons of flu and vaccinations ‘selects’ for rapid mutations in flu that evade these barriers and drive the success of new seasonal variants. However, for SARS-CoV-2, there are no past antibodies. Indeed, data to date show no obvious mutations associated with modeled antigenicity. Researchers are optimistic that variants that can evade our immune response or a likely vaccine candidate are unlikely. This helpful video by Dr. Vaughn Cooper at the University of Pittsburg gives a great explanation: https://www.youtube.com/watch?v=MHRGPzoFyEM
What is the ‘cytokine storm’ that is associated with disease?
Cytokine Storm is a term for an observed system of immune overreaction. Cytokines are small proteins of the innate immune system involved in signaling between cells and tissues to activate inflammation. Cytokine storms have been observed in infectious disease (severe influenza strains, SARS, MERS) but also in chronic conditions such as multiple sclerosis and pancreatitis, and was observed in trials of immune-modulating pharmaceuticals. The pathophysiology of COVID-19 is still being evaluated, but there is a clear link with the levels of some particular cytokines, IL-6, IL-10 and sIL2R, whereas others like IL-1 are not increased. Levels of IL-6 are directly associated with disease progression, and IL-6 is being targeted with available drugs (humanized monoclonal antibodies) in the management of the disease.
I have read that re-exposure after recovery can lead to an exaggerated and serious immune-mediated reaction. Is that a likely (vs. rare) concern?
Antibody-dependent enhancement (ADE) is a mechanism by which non-neutralizing antibodies (often generated from past exposure) target a pathogen and promote infection into host cells. This mechanism has been observed in some flaviviruses – primarily in Dengue, also less frequently in Zika virus infections. This mechanism, however, is not generally observed in coronavirus infections in humans. The related emergent coronaviruses SARS-CoV-1 and MERS-CoV cause strong neutralizing seroconversion in patients that is protective. Leading coronavirologists cannot rule out the possibility, but it is more likely that the protective effects of neutralization outweigh the risks of potential ADE.