Analyzing COVID-19 with

Mixed Test-Type Data

Contagion trends with molecular and serological tests.
Israel Meléndez, II - UPDATED: May 24, 2020

Fig. 1: Puerto Rico’s COVID-19 raw data with mixed test results.

Purpose
To present United States of America states and its territories with an alternative to
graph and analyze combined COVID-19 test data.

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 Introduction
Knowing the daily growth of pathogen infections and its trend is of key importance to
measure the effectiveness of moderation and control measurements. Trends are not covered
in daily reports beyond a casual non-quantitative assessment, and most local COVID-19 test
results are delayed by days.
According to the CDC[A]:
“Using serology testing for surveillance to better understand how many infections with SARS-CoV-2
have occurred.

By using seroprevalence surveys, CDC can learn about the total number of people that have been infected,
including those infections that might have been missed. These surveys also can help estimate how much of
the population has not yet been infected, helping public health officials plan for future healthcare needs.
These surveys can also track how infections progress through the population over time. This is done by
taking “snap shots” of the percentage of people who have antibodies against SARS-CoV-2 (also called the
seroprevalence) at different time points.

Since it often takes about a week for symptoms to appear after getting infected with SARS-CoV-2,
antibodies could develop about 2-3 weeks after infection. This means serology tests may not detect current
SARS-CoV-2 infections and should not be used to diagnose current COVID-19.”

In the United States of America, COVID-19 test results include two test type results:
molecular and serological. Mixing molecular and serological test results introduces a
graphing and analysis error when used together without distinction. To estimate the current
daily growth rate and the spread of infection within our population requires representing
both test-type results in a timeline that reflects how the two types represent different
symptom onset date.

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 Analysis

Fig. 2: Trend analysis with mixed test types.

Fig.2 shows the current daily growth graph with mixed test types. The graph contains
unique cases made from a depurated patient list and test results assigned to the test date—
not the reported date. In this case, two apparent infection peaks are evident. It seemed
plausible due to a documented event before the second visible peak, but serology test results
mostly drive the second peak without symptom onset alignment.
In order to estimate the actual distribution, a symptom onset alignment is needed for
serology test results as these represent an infection onset older than those represented by
molecular test results.


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 (3.1)

(3.2) (3.3) (3.4)

Fig. 3: Proposed Timeline of Testing for SARS-CoV-2 [2]

Fig. 3 shows a proposed timeline for testing SARS-CoV-2 based on estimated time
intervals and rates of viral detection.
In Puerto Rico, patients with positive serology test results require a molecular test for
confirmation of an active infection. If the patient tests positive to the molecular test, the
serology test result is replaced with the molecular test result to avoid patient duplication and
make all results unique.
Therefore, all reported serology test results are within the (3.1) “PCR - Likely
negativeb” zone. Within that zone, unique IgM and IgM+IgG positive results should be

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within weeks 4(3.3) and 5 after symptom onset, equivalent to 3 weeks (21 days) after the PCR
detection peak(3.2).
Unique IgG positive results should be from near week 6(3.4) after symptom onset and on,
equivalent to 5 weeks (35 days) after the PCR detection peak.

Methodology

Fig. 4: Puerto Rico’s New Unique Covid-2 Cases Timeline [3]

Fig. 4 shows the actual Puerto Rico new unique case timeline without test type
alignment. A time-shift factor is required for each test type to chronological align serology
test results with the molecular test result. Based on Fig. 3’s estimated variation, a time-shift
alignment factor of -21 days for IgM and IgM+IgG, and -35 days for IgG unique positive
results can be applied to analyze molecular and serological data together.

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 Fig. 5: Puerto Rico’s Aligned New Unique Covid-2 Cases Timeline

Fig. 5 combines all test results after applying an alignment time-shift factor. A proper
time-shift factor should yield an alignment in test result trends. As validation, Fig. 5 shows
each test type peak (5.2, 5.3, and 5.4) and how their corresponding week aligns with the molecular
peek’s (5.1) week. Further validation would be the alignment of the sum of all serology results
with the molecular test results.

Fig. 6: Puerto Rico’s New Unique

Covid-2 Cases Time-Adjusted
Timeline by Test Type.

Fig. 6 shows the aligned test results

with a 7-day average trend.

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 Results
Implementing the proposed time-shift test-type strategy yields data presentation with
aligned molecular and serology tests.

Fig. 7: Puerto Rico’s Accumulated Cases and Trend as Currently Reported.

As shown in Fig. 7, using a 7-days central moving average to avoid shifting, the
combined serology trend shows alignment with the molecular trend. As additional
validation, the data zone (7.2) close to the gray-zone (7.1)[4] shows parallelism before, during,
and after the event. The data zone (7.2) also shows a relatively constant asymptomatic to
symptomatic ratio denoted by the constant gap (7.3).
Align test type results can be used to interpret patterns throughout the COVID-19
pandemic. As an example, read from the aligned data, the disruption caused by the event (7.1)
[4] caused a trend inflection measurable seven days after its start.
It can also be estimated that 61% of patients were asymptomatic after the documented
event. (7.1)[4][6] It also took about one week of continued control (lockdown) measures to inflect
the trend (7.2) back to a downward trend.


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 Fig. 8: Puerto Rico’s Time-Adjusted Accumulated Cases and Trend.

As shown in Fig. 8, shows the estimated and confirmed accumulated cases and
accumulated related deaths with their respective trends[8]. When a time-shift factor is applied
to serological test results, the current contagion panorama changes to an estimated daily
growth of 0.33%. The latter is at a Control[5] level (<1%) while the unadjusted trend is at a
Moderation[5] (between 1% and 10%). This is a significant difference that can adversely affect
how governmental decisions are made when these are made assuming the incorrect current
status. The current growth rate based solely on molecular tests is 0.67%, at control. This
discrepancy is expected as the cumulative total from all test types is about double the
cumulative total from molecular test results. The discrepancy also presents a conundrum:
which metric to use and communicate?
The Estimated Total Unique Cases trend from Fig. 8 can be the best metric with low-
latency and real-time data, but that is not the case in Puerto Rico. With a lack of low-latency
and real-time data, the molecular trend can provide the best trend for measuring
performance and managing moderation and control measures as it represents active
confirmed infections with relatively low reporting latency. Real-time reporting will make this
data more useful and can shorten disruptive control measures.

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 Impact

Fig. 9: Puerto Rico’s Estimated COVID-19 Infections During the Holy Week Event.

Serological Time-Shifting analysis can be a useful tool in studying past events but also
delineating future actions to control spread. Fig. 9 shows the estimated infections during and
immediately after the Holy Week Event. The symptomatic-to-asymptomatic ratio observed
the week after averages about 4:6, 61% asymptomatic patients. This figure concurs with
published global estimates. [7] Because this period falls within the estimated serology test
results window for IgG positives at the time of publishing, the data may change, increasing
the asymptomatic portion of patients.


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 Conclusions
“By conducting random antibody sampling of the general public (known as a serosurvey), public
health bodies could better estimate the true levels of exposure   and resulting population
immunity. For COVID-19, this would be a game-changer, as true transmission and CFRs could be
calculated to forecast the intensity and longevity of the pandemic to direct decision-making.
Furthermore, by identifying potential geographical ‘hot-spots’ of low population immunity, health
systems could better allocate resources to prevent or manage transmission.”[1]

• Serologic test results should not be used with molecular test results without time-
shifting test dates to represent the actual contagion trend.
• Unique serology test results show alignment with molecular test results.
• Time-shifted serological test results can be used to recreate the total contagion
panorama in a region.
• Time-shifted serological test results can be used to estimate the symptomatic to
asymptomatic ratio.
• Molecular test results can be used for a conservative growth rate estimation of the
actual trend when it represents unique cases and all patients with positive serological
tests are subjected to the molecular tests to confirm or discard an active infection.
• For Puerto Rico:
• Holy Week’s shopping event created measurable effects about 7 days after its
start.
• One event appears to have significantly disrupted our downward trend.
• It took about 7 days of continued measures to inflect the trend back to a
downward trend I knew cases.
• About two thirds of the tested patients are estimated as asymptomatic. [6]
-o-

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Assumptions:
1. All tests represent unique patients without duplication among test types.

2. All test results are assigned to the test date and not to the report date.

3. Molecular assay tests were performed to symptomatic patients at the test detection peak to obtain an
alignment approximation with serology tests.

4. Most serological test results are performed to asymptomatic patients as part of public agencies and private
businesses back-to-work- initiatives.

References:
A. CDC; COVID-19 Serology Surveillance Strategy.

1. The Native Antigen Company; Why We Need Antigen and Antibody Tests for COVID-19.

2. Salim Rezale et al.; COVID-19: Screening, Testing, PUI, and Returning to Work.

3. Departamento de Salud de Puerto Rico; May 18, 2020

4. El Nuevo Día; Amanecen abarrotados los supermercados y grandes almacenes de suministros.

5. Gerard J. Tellis et al.; How Long Should Social Distancing Last? Predicting Time to Moderation, Control, and
Containment of COVID-19.

6. An estimated average of at least 61% of patients were asymptomatic during the period from day 35 through
day 40.

7. Carl Heneghan et al.; COVID-19: What proportion are asymptomatic?

8. Minute Physics, Aatish Bhatia et al.; How To Tell If We're Beating COVID-19

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