SARS-CoV-2/Covid-19 Pandemic Update and Commentary
By Kevin C. Maki, PhD, CLS, FNLA
Comments from our Chief Scientist, Epidemiologist Kevin C. Maki, PhD as of April 11, 2020
The toll produced by the global pandemic of novel coronavirus (SARS-CoV-2), which causes the Covid-19 disease, is enormous, both in human and economic terms. I am confident that we will be able to return gradually to a more normal existence but doing so will take time. Below are some thoughts on various issues related to the pandemic.
Epidemiology. Most of Asia, including Hubei Province where Wuhan, China is located, has returned to a relatively normal existence, punctuated by intensive surveillance efforts to identify new infections, isolate them and track their contacts to avoid community spread. Deaths per million population in countries and territories in Asia such as Hong Kong, Japan, Singapore and India have been 1 per million population or less. Even in China, the original epicenter country, the official number of deaths is 2 per million population, although there have been questions raised about the accuracy of their reporting.
Europe has been affected more severely. In the two hardest-hit countries, Spain and Italy, the current numbers of deaths per million population are 352 and 322, respectively. The good news is that most European countries appear to be past the peaks in their outbreaks. Public health efforts to institute social distancing, hand washing, surface disinfection, temperature monitoring and diagnostic testing have slowed the spread and most countries appear to be past the peak (apex) of the epidemic curve, and are experiencing declines in numbers of new infections, hospitalizations and deaths.
In the US, New York and New Jersey have been the epicenters. The best indicator of the number of new infections is new hospitalizations because it is less confounded by who gets tested. In New York state, the number of new hospitalizations has been trending down. As I write this, deaths per day have stopped increasing, and should show a clear decline soon, since deaths are, grimly, a lagging indicator. A decline in new hospitalizations should translate into a decline in new deaths after a lag of about 5-8 days. The peak in new hospitalizations in NY state, based on a 3-day rolling average, appears to have been April 2. It looks likely that the peak in new deaths per day occurred on April 8.
There are several sources of data that, together, suggest to me that the US is dramatically slowing the spread of the virus and should be at or near the apex in number of new infections. Italy peaked in number of new infections around March 21 and the US was behind Italy by roughly 16 days. Therefore, it is entirely possible that the peak in new infections has already occurred in the US as a whole (although not necessarily in every city). Hopefully we will see a decline in new US deaths very soon.
What are the case fatality and infection fatality rates for SARS-CoV-2/Covid-19 infection? The case fatality rate (or ratio) is the fraction of those who have symptoms that die. In the US, this has been estimated to be about 1.4%. Those who are older and have other conditions such as cardiovascular disease, diabetes, obesity, hypertension, asthma, and emphysema are at higher risk. Young people, especially children, appear to be at lower risk. Minority groups such as African Americans and Latinos have higher prevalence of conditions that increase risk for adverse outcomes with infection. Thus far, the available data suggest that these communities have been disproportionately affected by Covid-19 and have worse outcomes on average.
At present, the percentage of people who have very mild symptoms or are asymptomatic after infection is unknown. Preliminary data from the city of Heinsberg, Germany, which had a large outbreak, showed that about 15% of the population had antibodies, indicating a history of infection. Many of these people were asymptomatic or mildly symptomatic. The infection mortality rate, which is the percentage of those who have been infected who die from the infection, was 0.37%. This value is much lower than the case fatality rate, which has been similar in the US and Germany, around 1.4%. This would suggest that Covid-19 is somewhat more severe than influenza, which has an infection fatality rate of 0.13% based on the last 10 years of experience in the US, but not 10 times worse, as has been suggested by those referencing the case fatality rate of 1.4%. Extensive serology (antibody) testing will be needed to more clearly define the infection fatality rate.
What needs to happen for us to start returning to normal life? A gradual return toward a more normal existence should be possible in the coming weeks. However, we need several things to happen for that to be feasible.
- We need to see clear and sustained declines in hospitalizations in a region before restrictions can be eased, indicating that community spread has been contained.
- Active surveillance must be instituted, which means temperature and symptom monitoring with immediate testing and rapid result availability for those who show signs or symptoms consistent with infection. Those who test positive should be immediately isolated until the infection has passed. Communities that are showing an increase in the number of infections should be identified early through surveillance so that intensified efforts to stop the spread may be instituted.
- Methods need to be in place to identify and track contacts of those infected, who may have been exposed. In some countries, such as Singapore, this has been done through cell phone tracking. Although this does raise issues about privacy, one option may be for all Americans to be automatically enrolled for a period of time with an option to opt out. For contacts of those infected, a message can be sent advising that the individual seek testing.
- Ideally, data will be available from randomized clinical trials to demonstrate efficacy of one or more treatment modalities. Many such trials are underway in the US and in other countries. Results should be available for some very soon.
What treatments look most promising? The treatments that, in my view, are most promising are those involving antibodies. Antibodies can be created by mice with humanized immune systems. These can then be infused into people to help fight the infection, or possibly even to prevent infection in people at high risk, such as healthcare workers. The second way to use antibodies as a treatment is convalescent plasma. For those who have recovered, plasmapheresis can be used to harvest their antibodies. This plasma or a fraction of plasma (immunoglobulins) can be infused into an infected person. The challenge is that a single session of plasmapheresis takes 90-120 min and produces only 2-4 doses. Therefore, many plasma donors are needed in order to use this treatment on a large scale if proven effective in clinical trials.
A second category of treatment is antiviral drugs. The one that appears to be furthest along in development is remdesivir. This class of agent interferes with viral replication in cells. Similar agents, such as the drug Tamiflu® (oseltamivir), tend to be most effective if given early in the disease process. For example, oseltamivir, reduces flu symptoms by 3-4 days if given during the first 12 hours of symptoms, but only by about 1 day if given after 12 hours but within the first 48 hours.
Finally, there are medications used for other purposes for which there is some evidence that they may have actions that inhibit SARS-CoV-2 activity or ability to enter cells. These include hydroxychloroquine, which is used as an antimalarial drug as well as for rheumatoid arthritis and lupus, and ivermectin, which is used as a treatment for parasitic infections such as lice and scabies. In addition to these agents, the tuberculosis (bacille Calmette-Guérin or BCG) vaccine shows some promise as a means to increase the immune response to respiratory infections in general. People who have received this vaccine appear to have a 70-80% lower incidence of respiratory infections. Trials were already underway in Europe to evaluate the usefulness of this vaccine for reducing risk of respiratory infections in healthcare workers. Countries where BCG vaccination is required appear to have fewer Covid-19 infections and deaths.
Should we be optimistic? I am optimistic that we will be able to slow the spread of Covid-19 sufficiently to buy some time for effective treatments and, eventually, a vaccine, to become available. There is a great deal of work to do in order to prepare the US for a phased return to a more normal life. However, a tremendous amount of research is underway that I expect will provide critically important answers to the scientific, clinical and public health questions that will be keys to lifting some of the current restrictions that were instituted to slow transmission