COVID-19: Prelude to a Pandemic

COVID-19 has traveled far and wide from the original outbreak zone in Wuhan China.  Currently, the outbreak has spread to 68 countries (+ 1 cruise ship).  As of March 1st, 2020, there are a total of 89,081 cases with 3,057 deaths.  The rate of new cases in China has steadily dropped, likely due to containment efforts. Last week, the trajectory of the COVID-19 outbreak suddently changed, when local spread began to be reported in South Korea (4,212 cases), Italy (1,701 cases) and Iran (978 cases).  With higher caseloads in these countries, it is only a matter of time that the outbreak will become a global pandemic.

It is possible that transmission will smolder in some countries, while it is surges in other countries.  The surges will increase the likelihood of further spread.  Thereafter, it could be introduced and lead to outbreak spikes in other countries.  There is some suspicion that the disease may already have penetrated into sites, while rigid case definitions and persons under investigation were used.  What is also incredible is the degree of measures that countries are taking to protect themselves from localized spread or introduced infections.

A few local, unconnected COVID-19 cases have already been confirmed in the United States.  Currently, the US has 87 confirmed cases, with several recent cases identified in Washington State, including within a care facility, with two deaths reported.  A recent case of a high school student in Snohomish County was found to have virus with a geneitc link to the first US case, that of a man in his 30s who had traveled to Wuhan and returned to Washington state several weeks prior – potentially six weeks of local spread.  On Friday February 28th, a case was confirmed in Oregon.  On Sunday, a second case was confirmed, who was a contact of the other.  Neither of them fit the original definition of a person at risk.  A surge in cases, particularly those unconnected to the original outbreak, raises the high likelihood that occult community spread is already occurring.  

Key Points:

The case fatality rate is one way of determining the severity of a disease.  It is specifically the total number of people who die from a disease over the number of those diagnosed with the disease.  This number is not always accurate because of assumptions on the reliability on the denominator.

Case fatality rate (%):       Number who die from disease

                                             ————————————————–                      X 100

                                              Number confirmed with disease

In epidemiology, a case definition often relies on syndrome lists, when tests to confirm diagnosis are not readily available.  Whereas death from a disease is usually more accurate, the number of people with a certain disease may be misrepresented.  Many people do not come to be assessed if they have mild disease.  Moreover, as with COVID-19, there was no readily available test in the beginning of the outbreak.  So, in an active epidemic, as more cases are determined with widespread, reliable diagnostic tests, the denominator becomes more accurate.  As is often the case, the case fatality rate tends to drift downward and closer to a reliable metric.

Based on the February 24th, 2020 JAMA article, of the 72,314 cases records, 44,672 were diagnosed with the viral nucleic acid test that was available (62%);  22% were suspected based on symptoms and exposures without testing; 15% were clinically diagnosed cases without testing; 1% were asymptomatic cases diagnosed with the nucleic acid testing.  This means that about 37% of the cases that go into the denominator were not confirmed with diagnostic testing.  Not to mention, how many more persons were not included, who didn’t seek care for likely milder disease and possibly, who died and the infection wasn’t considered.

Those with COVID-19 presented with mild (81% of cases), severe (14%) or critical disease (5%), of which almost 50% died.  The total case fatality rate (CFR) of confirmed cases was 2.3%.  Adjusting the CFR to age provides a more accurate picture of the impact of age.  From this, you can see that the infection is disproportionately more severe in the elderly.

About 35% of those who died from COVID-19 in this study had a known chronic disease:  10.5% had cardiovascular disease, 7.3% had diabetes, 6.3% had respiratory illness, 6% had hypertension and 5.6% had cancer.

Outside of Wuhan, case fatality rate is lower (0.7%).  It is expected that with the secondary outbreak sites, we will have a better understanding of both numerator and denominator, as well as other demographic information to better inform us on the impact of thise disease.

Behaviors have surfaced over the fears of COVID-19 “coming to a city near you,” some proactive and some not always thought out as well.  In one survey in Taiwan, 79.9% of the people questioned said that they were using masks to protect themselves from COVID-19.  The CDC currently does not recommend the use of facemasks or respiratorys (e.g. N-95) for the general public.  Masks or respirators likely do not provide any protection from general precautions such as handwashing or hand sanitizer use and avoiding touching your mouth, nose or eyes.

For the purpose of definition of “close contact spread”, this is when a person is in contact within 6 feet from an infected person for at least 1 hours of exposure.  The greatest at risk for infection with close contact spread are healthcare workers.  Like SARS and Ebola in the past, front-line healthcare workers face the biggest risk of becoming infected.  The sickening of healthcare workers would represent a strong blow toward our treatment capacity, and should be prevented.

At present good handwashing technique or the use of alcohol hand sanitizer and social distancing are probable the most helpful measures to protect the general population from infection.  If you are ill, please sneeze in your arm – not in your hands.

Spread of COVID-19 is mainly spread from person to person, when respiratory droplets containing virus come into contact with a mucus surface, such as the mouth, eyes or nose.  They can also spread on fomites, inanimate objects such as keys, doorknobs, money or phones, or on contaminated surfaces.  According to the CDC, “because of poor survivability of these coronaviruses on surfaces, there is likely very low risk of spread from products or packaging that are shipped over a period of days or weeks at ambient temperatures.

It is generally believed that viruses are relatively fragile and susceptible to desiccation (drying), if they are not in the host.  Smaller respiratory droplets evaporate and likely the virus particles on those droplets are not able to re-infect.  It is not clear whether COVID-19 virus particles on larger droplets would thrive longer.

A recent study in the Journal of Hospital Infection suggested that SARS, MERS and endemic (HCoV) coronaviruses could remain infectious on surfaces, including metal, glass or plastic, for up to nine days – at room temperature.  At a temperature of  30 degrees Celsius (86F) or greater, it is likely to survive a shorter duration.  The CDC is presently studying this concern for COVID-19.  The researchers commented that surface disinfectants such as 0.1% sodium hypochlorite or 62-71% ethanol readily decontaminated surfaces.

A speedy diagnosis has a lot of benefits.  While taking into account the timing to a positive test, symptomatic patients can be triaged into “confirmed” versus “possible” or “unlikely” groups, while other tests are employed (e.g. influenza and Respiratory virus panel PCR).  Those confirmed groups can be appropriately informed to stay home and avoid contact with others, bolstering containment strategies.

The ideal place for rapid diagnostic kits would be at the point-of-care, rather than at national or statewide public health departments.  Though the CDC has made test kits available to state public health departments recently, with confirmation of cases still managed centrally by the CDC.

The test for diagnosis of COVID-19 relies on nucleic acid (RNA in this case) and is referred to as a real-time reverse transcriptase-polymerase chain reaction (rRT-PCR).  A sample is taken from the nasopharynx (deep nose) or oropharynx (throat) is run on a testing apparatus known as a theramal cycler.  A hyperlink to the details of the procedure.

The test often has a high sensitivity (ability to detect a true positive) and high specificity (not detecting a true negative).

The use of a chest computed tomography (CT) can be another way to determine if someone has COVID-19.  A CT can demonstrate the effects of the lung tissue from the viral infection.  When using RT-PCR resulst as a reference, the CT scan for detecting COVID-19 related pneumonia was 97% sensitive and could show disease even before the RT-PCR turned positive.

In the last few days, several cases have been reported in the United States (e.g. California, with no clear epidemiologic connection to the original outbreak site.  Consequently, the CDC revised their criteria for a person under investigation (PUI), expanding the definition to include those with fever and cough and “no source of exposure identified.”  This leads to questions about the possibility of a smoldering epidemic already underway in some parts of the United States.

With a wider definition for PUI, it is expected that physicians will be able to test patients for COVID-19 who have more serious respiratory illnesses even without close epidemiologic connections.  They will be placed in standard, contact and airborne precautions and be isolated in special rooms that circulate the air out of the room (negative pressure), while they are being ruled out.

It is expected with a greater case burden, hospitals may be at the risk of exhausting their resources.  Presently, hospitals in the United States are coordinating efforts as entities and in conjunction with state and local health departments.  Particularly in light of the recent cases without connection to the initial outbreak area, hospitals are ramping up their vigilance in considering cases to be tested.  Signage, visual alerts and mask and alcohol sanitizer stations are placed at all entry points of the hospital.  Patients are being triaged in a way to avoid possibly infecting others in the waiting room or medical staff.

Patients who are ill with milder systems are being asked to stay home and not be seen in the clinic, rather than put others at risk for infection.

The uncertaintly of COVID-19 has led to a paralysis and sell-off in the stock market with a decline of 12% in one week.  Investors are being encourage to wait out this volatility.  Its unclear how this strategy will be affected by the uncertainty of the COVID-19 outbreak.

Why take your chances with face-to-face meetings during the COVID-19 outbreak?  Zoom conferencing along with 3M, the makers of surgical masks, were a few of the companies that were buffered from these declines – a sign of how fears can promote company investments.  If Zoom conferencing becomes the standard for the office meeting during the COVID-19 outbreak, they will likely achieve further gains.  Anyways, at least you don’t have to shake that guy who catches his cough or sneeze with his hands – or worse get sneezed on.

It is likely that there will be economic and sociopolitical reverberations as a fallout of this outbreak for some time.