This virus is really good at peek-a-boo

This article has been reviewed by Dr. Emily Bowman, one of our subject matter experts.

The paper that we’ll be demystifying can be found here, if you want to follow along. The research was conducted by Public Health–Seattle and King County and the CDC COVID-19 Investigation Team.

TL;DR

• Researchers conducted a point-prevalence survey of residents in a skilled nursing facility in King County
• More than half of the residents who tested positive (according to Ct values) were asymptomatic at the time of testing, meaning they showed NO symptoms for Covid-19.
• Ct values of asymptomatic and presymptomatic patients are similar to those found in symptomatic patients, meaning they had just as much virus in their samples.
• Transmission via asymptomatic and presymptomatic residents most likely played a role in how fast the virus spread in this facility.

Introduction

COVID-19, the disease caused by SARS-CoV-2, was first detected in the United States on January 20^th, 2020 in a resident of Snohomish County, Washington. In this post, let me take you to its neighbor, King County, where an outbreak was identified in a skilled nursing facility in early March. In this study, the researchers conducted a point-prevalence survey. 

To take a point-prevalence survey, imagine you take people at a specific grocery store at a specific moment in time and freeze them. Then you take note of how many people in that population (total number of people in the grocery store) are wearing green shirts. Next, you divide this number by the total population to get the prevalence of people wearing green shirts at this point in time. 

In essence, the researchers of this study did exactly this but swap out the grocery store for a specific skilled nursing facility, and swap out the green shirts for positive test for SARS-SoV-2. And of course, you can’t really freeze people in real life, although that would be a cool super power, so swap the specific the time for a specific day. 

Timeline of events that unfolded at this skilled nursing facility:

• February 29^th: due to the local awareness around the novel (new) virus, the facility increases its infection control measures. Nursing staff are assessed twice a day for signs and symptoms. All health care staff are assessed at the start of each shift. 
• March 1^st: A staff member who had worked in Unit 1 on February 26^th and 28^th tests positive.
• March 3^rd: A hospitalized resident is diagnosed with COVID-19. This patient first developed symptoms on March 2^nd
• March 5^th: The facility is informed of the diagnosis. Visitors are restricted and communal activities are cancelled. 
• March 6^th: Public Health – Seattle and King County (PHSKC) and Center for Disease Control and Prevention (CDC) conduct an outbreak investigation and provide infection prevention and control recommendations
• March 8^th: CDC and PHSKC offers testing to all residents in Unit 1. 13 of 15 residents are tested, 2 decline. Of these 13, 6 test positive, but only 4 show symptoms. 2 residents are classified as asymptomatic as they had not shown any symptoms in the previous 14 days. (ie. these people are indeed infected with SARS-CoV-2 but don’t show any symptoms)
• March 9^th (FULL LOCKDOWN, we need to put all assumptions at the door): The facility implements COVID-19 transmission-based precautions for all residents of Unit 1.

 

Methods

1. March 13^th 2020: The first survey is conducted on all residents who opt-in, including those that previously tested positive. Researchers take nose and throat swabs of all participants, in accordance to CDC guidelines. Of the 82 residents, 76 participate.
2. March 19-20^th 2020: The second survey is conducted on residents who test negative or positive with atypical or no symptoms in the first survey.

Symptom assessment

In order to determine the symptom status of a resident, a standardized symptom-assessment form was used. Based on this, residents were categorized into 4 groups:

1. Typical symptoms: fever greater than 37.8°C, cough or shortness of breath in the past 14 days
2. Atypical symptoms: only chills, fatigue, increased confusion, runny nose, nasal congestion, sore throat, muscle aches, dizziness, headache, nausea, or diarrhea in the past 14 days
3. Asymptomatic: no new symptoms or only stable chronic symptoms in the past 14 days
4. Presymptomatic: Asymptomatic residents were reassessed within 7 days. If they showed symptoms in this time, they were recategorized as presymptomatic. 

Laboratory testing

Researchers collected nose and throat samples from all participating residents and conducted real-time reverse transcriptase–polymerase chain reaction (rRT-PCR) on them. In essence this procedure takes viral RNA and converts it into DNA, which can be amplified over and over and over until you have enough to be detected by a machine because the original sample is much too small to work with. The machine counts how many cycles of doubling you go through before it’s able to detect it. This is the cycle threshold value (Ct); a Ct of below 40 means you have enough genetic material in your sample to produce a detectable amount in less than 40 cycles, therefore indicating a positive diagnosis of SARS-CoV-2. 

Results 

Residents

On March 13^th 2020, at the first point-prevalence survey, 76 residents were tested. 

• 23 tested positive. 
  • 11 were symptomatic
    • 9 showed typical symptoms
    • 2 showed atypical symptoms 
  • 12 showed no new symptoms 
    • 11 showed symptoms within the next 7 days: classified as presymptomatic
    • 1 showed no symptoms even after 7 days: classified as asymptomatic
• 52 tested negative
• 1 tested negative but had previously been tested positive

On March 19^th -20^th 2020, at the second point-prevalence survey, 49 of the 52 negative symptom residents were tested (3 left the facility before March 19^th 2020)

• 24 tested positive
  • 9 were symptomatic
    • 7 showed typical symptoms
    • 2 showed atypical symptoms 
  • 15 showed no new symptoms 
    • 13 showed symptoms within the next 7 days: classified as presymptomatic
    • 2 showed no symptoms even after 7 days: classified as asymptomatic
• 25 tested negative

Of total 27 (12+15) residents who showed no symptoms at testing, 24 (11+13) showed symptoms within 7 days of testing positive and were recategorized as presymptomatic. The average time to develop symptoms amongst these patients was 4 days. The most common symptoms were fever, cough and malaise.

Cycle threshold 

Ct values for the 47 residents who tested positive ranged from 13.7 to 37.9. The median Ct values of the 4 positive groups were:

• typical symptoms: 24.8
• atypical symptoms: 24.2 
• presymptomatic: 23.1 
• asymptomatic: 25.5

Prevalence and transmission in the facility

The doubling time (time it takes to double the number of cases) of COVID-19 cases in the facility among resident was estimated to be 3.4 days. This is in contrast to the 5.5 days doubling time of the surrounding King County. 

Amongst the staff, by March 13^th, 11 of the 138 full-time staff had tested positive for SARS-CoV-2. By March 26^th, 55 of the 138 reported symptoms. However, only 51 had been tested; of which 26 tested positive. Of these 26 staff members, 17 were nursing staff and 9 held other positions in the facility.

Discussion

Although the facility was quick to adopt infection-control measures, within 23 days of the first positive SARS-CoV-2 patient, the facility had a 64% prevalence among residents. Of importance here is that more than half of the residents who tested positive (according to Ct values) were asymptomatic at the time of testing, meaning they showed NO symptoms and may as well been mistaken for someone who does not have Covid-19. Also, the Ct values of asymptomatic and presymptomatic patients are similar to those found in symptomatic patients, meaning they had just as much virus in their samples. Therefore, transmission via asymptomatic and presymptomatic residents most likely played a role in how fast the virus spread. This is in line with other studies that have indicated evidence for transmission by presymptomatic persons. These findings indicate that the symptoms-based infection-control strategies that were initially adopted were not sufficient.

The doubling time observed in this facility was much faster than in the rest of King County, likely due to inadequately controlled transmission within the facility. Although this study did not investigate the effect of indirect contact transmission, we must also consider contaminated environmental surfaces and shared medical devices could have also played a role. 

Clearly, the recommended infection control measures were not effective due, at least in part, to viral transmission by asymptomatic or presymptomatic residents. Therefore, it is worth considering additional prevention measures such as increased testing to appropriately categorize and isolate high-risk patients. Testing large numbers of residents and staff quickly may help more effective and efficient infection control measures than symptoms-based infection-control strategies.

Limitations of this study

1. Some residents may have been misclassified based on symptoms due to the difficulty of symptom determination. To make up for this, the researchers used multiple sources of symptom data. Therefore, the rate of error at this facility would have been equal to that found in any other skilled nursing facility. Meaning that the results of this study can be generalized to other skilled nursing facilities.
2. This study was conducted on residents of a skilled nursing facility. Therefore it is unknown if these findings can be applied to the general public. 
3. Asymptomatic staff members were not tested. Therefore their role in transmission in this facility is unknown.

This study indicates that there is a high chance that presymptomatic and asymptomatic people may be a significant driver in the spread and speed of this pandemic. Either way, testing is the only way we’ll be able to identify who is truly negative and who is merely asymptomatic or presymptomatic. Infection prevention control measures that solely focus on the symptomatic are not sufficient. So the lesson of the story is…. Listen to health professionals and stay home unless absolutely necessary! That way, even if you are presymptomatic or asymptomatic, you won’t contribute to the spread of the virus and instead save lives!