Contents

About coronaviruses and SARS-CoV-2

Coronaviruses get their name because of their appearance under the microscope. There are many coronaviruses and, in general, they tend to cause respiratory infections in people and intestinal infections in animals.

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Coronaviruses naturally circulate in animals in the wild, such as bats and mice. Before they develop the ability to infect people, coronaviruses seem to first need what scientists call “an intermediate species” of animal. Different coronaviruses infect different intermediate species, including camels, cows, civets and pigs. Once the coronavirus has infected an intermediate species, it mutates and can develop the ability to infect people. A person who encounters an intermediate species can become infected and pass on the virus to other people. Until about two decades ago, scientists found that most coronaviruses that could infect people would generally cause mild respiratory illness in healthy adults.

SARS

However, in 2002 an outbreak of a new disease appeared—severe acute respiratory syndrome (SARS). A virus called SARS-coronavirus (SARS-CoV) caused this syndrome. The virus that caused SARS was likely spread from bats to palm civets and then to people. It caused a flu-like illness in people, including fever, cough and shortness of breath. In severely affected people it could cause a lethal form of pneumonia. Ultimately, SARS-CoV infected about 8,000 people worldwide, about 10% of whom died. There have been no further cases of SARS identified since that initial outbreak.

MERS

Middle East respiratory syndrome (MERS) is spread by a coronavirus called MERS-CoV, likely from bats to camels and then to humans. Cases of MERS were first documented in 2012 in the Middle East and still occur there from time to time. Initial symptoms of MERS are similar to SARS and COVID-19. Overall, MERS has caused about 2,500 infections and 774 deaths.

COVID-19

In late 2019, cases of severe pneumonia first appeared in Wuhan, China, and then quickly spread around the world. A virus called SARS-CoV-2 was isolated from affected people and identified as the cause of associated symptoms—coronavirus disease 2019 (COVID-19).

SARS-CoV-2 tends to cause either no symptoms or mild symptoms in most (80%) infected people. These symptoms are similar to a mild cold or flu. In other people, particularly the elderly and those with underlying conditions (such as heart disease, higher-than-normal blood pressure, chronic respiratory diseases, diabetes, kidney disease, obesity), symptoms of COVID-19 can be more severe. Such people can feel as if they have a severe cold or flu. A minority of people with severe COVID-19 can develop pneumonia and problems breathing and may require hospitalization.

Inside the lungs

One of the puzzles about infection with SARS-CoV-2 is: Why does infection cause severe disease only in a minority of people? A clue about this has emerged from experiments with lung tissue.

Scientists in Hong Kong have performed experiments with lung tissue and two viruses—SARS-CoV and SARS-CoV-2. They have found the following:

  • Both viruses infect several groups of critical cells in the lungs—the cells involved in absorbing oxygen and releasing carbon dioxide; the cells involved in producing mucus to help keep lung cells healthy; and the cells of the immune system that patrol the lungs on the lookout for germs.
  • SARS-CoV-2 infection of lung tissue subsequently resulted in the production of three-fold more viruses than SARS-CoV infection.
  • SARS-CoV-2 infection did not appear to trigger the production of interferon. Furthermore, this virus caused only low levels of inflammation in lung tissue, at least in the short term. The experiments lasted for 48 hours.

Bear in mind

The results from the Hong Kong scientists suggest that SARS-CoV-2 may have a way to subvert the immune system’s defenses, at least in the lungs in the short term.

Previous research with other coronaviruses suggests that this family of viruses can produce proteins that can suppress the immune system. However, as this issue of TreatmentUpdate goes to press, no scientific team has yet found such proteins associated with SARS-CoV-2.

Research issues

Since SARS-CoV-2 is new to science, there are many issues that are unresolved and will remain unresolved or unclear for months to come. Cases of COVID-19 have overwhelmed health systems in many countries and caused a public health emergency. As a result, the science of many aspects of clinical research on COVID-19 has not been, at least initially, as rigorous as it might have been with other chronic and well-established conditions. Many of the studies on people with COVID-19 are retrospective in nature; that is, data were collected for one purpose and then later analyzed for another purpose. Such methods can cause scientists to inadvertently draw biased conclusions about a set of findings. However, such is the nature of research when a pandemic suddenly occurs. Over time, the state of knowledge and research on COVID-19 will improve and issues will be clarified.

Clinical trials are underway to test potential treatments for COVID-19. As well, many companies have established teams to develop a vaccine against SARS-CoV-2. However, a safe, highly effective vaccine is unlikely to become available until sometime in 2021.

In this issue of TreatmentUpdate, we review key biological and clinical reports on SARS-CoV-2 and COVID-19. This will give readers some idea of what generally happens with this new disease as well as some relevant virus research. Many of the reports we highlight will have come from China and the United States.

A future issue of TreatmentUpdate will have information on emerging treatments.

—Sean R. Hosein

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