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Updated May 12, 2020

Authors:
Katherine Soreng, PhD, Director, Clinical and Scientific Resources, Siemens Healthineers
Connie Mardis, M.Ed., Head of Diagnostics Marketing Education, Siemens Healthineers

The Coronavirus Pandemic: What is COVID-19?

COVID-19 (coronavirus disease 2019) is the disease resulting from infection with a newly emerged coronavirus named SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Coronaviruses are a group of viruses usually found in animals. Most known animal coronavirus cannot directly infect humans, but sometimes the virus changes (mutates) and this can produce an ability to cause infection in people. Four commonly circulating coronaviruses associated with mild respiratory disease (the "common cold") with human transmission are well-known.

In 2003, the first SARS coronavirus (now called SARS-CoV) was identified in China and subsequently spread. It may have started in a bat and then spread to the civet (a small, nocturnal mammal) where it then transmitted to humans. Unlike previously identified coronaviruses, SARS-CoV was much more harmful to people. Like COVID-19, patients often presented initially with mild respiratory symptoms. Some would suddenly worsen, developing a severe acute respiratory syndrome that required critical intervention for the patient to breathe (such as placement on a ventilator). Mortality from the first SARS was estimated at about 5-10%. Unlike SARS-CoV-2, the first SARS virus did not appear to spread easily from human to human, and infection was successfully suppressed.

A related but even more dangerous coronavirus called MERS-CoV (Middle East respiratory syndrome coronavirus) outbreak occurred in 2012. While much more deadly (killing as many as 1 in 3 patients), it also did not spread easily between humans. This coronavirus may also have originated in bats, and then spread eventually to camels that subsequently transmitted infection to humans they came in contact with.

What sets the current SARS coronavirus apart (SARS-CoV-2) is its contagiousness, as it spreads readily from human to human, or from the environment to humans. Published data shows the virus can persist on surfaces and remain infective for hours or even days depending on surface and conditions, which is why disinfecting surfaces is a key recommendation. On average, someone with the COVID-19 virus is thought to infect two or more other people. This is considered a high rate of infectivity. For example, the infectivity rate of seasonal flu is typically less than 1.

Signs and Symptoms of COVID-19

The common signs and symptoms of COVID-19 overlap with other respiratory disease, including seasonal flu. Fever, cough, and fatigue are most common. The CDC has identified the percent of signs and symptoms observed in patients with confirmed COVID-19.

  • Fever (83–99%)
  • Cough (59–82%)
  • Fatigue (44–70%)
  • Loss of appetite (anorexia) (40–84%)
  • Shortness of breath (31–40%)
  • Sputum production (28–33%)
  • Muscle aches and pain (myalgias) (11–35%)

Importantly, many people with current infection may remain without any (asymptomatic) or only mild symptoms yet can transmit the virus. Testing of both symptomatic patients as well as individuals with known or highly likely exposure is urgently needed to reduce opportunities for transmission.

Accordion Title
Molecular Testing for COVID-19
  • Molecular tests can identify COVID-19 virus

    In order to confirm a diagnosis of COVID-19, testing for presence of the virus is necessary. This can be accomplished using molecular testing techniques that can recognize the genetic material of the virus (RNA), from samples such as sputum or throat/nasal swabs. While respiratory secretions are most likely to contain virus, it may be at an insufficient level to detect. Blood samples do not normally contain circulating SARS-CoV-2, so swab collections are typically used for molecular testing.

    As a truly new virus, tests had to be rapidly developed for the specific identification of COVID-19. The most common type of molecular test for COVID-19 uses a technique called RT-PCR (reverse transcription polymerase chain reaction). This technique can amplify a very small amount of genetic material millions of times, allowing detection. Related techniques include a method called isothermal amplification.

    Multiple labs and companies now offer molecular testing for COVID-19. Most tests require analysis in a lab, though a few can be conducted near the patient ("point of care" testing) by trained personnel. In some cases, tests results may require hours or days for the sample to be transported, the RNA isolated and amplified, and a test result obtained. Point-of-care testing may be more rapid, but typically can only run one to a few patient samples at a time. Data is limited on how the various methods compare for sensitivity, so all methods might not detect equivalently.

    Unfortunately, restrictions in the ability to obtain a molecular test when needed remain a challenge. Barriers have included both test reagent shortages (as manufacturers struggle to keep up with demand) and limitations in other supplies such as swabs and media needed to transport the swab to the lab.

  • Sample collection for molecular testing for COVID-19

    Initially, long swabs (nasopharyngeal swabs) capable of collecting a sample far back in the throat were used but required a medically trained professional. Other swab types have since been utilized and have the advantage of easier collection or even allowing a patient to self-collect. Presence of virus may vary with sample type collected or timepoint. Some data suggest the techniques may be similar in their ability to obtain virus. Importantly, a collected sample may or may not contain virus in all patients with COVID-19.

  • Can a person with COVID-19 test negative for the virus using a molecular test?

    A negative result in someone with a current infection is known as a false negative or FN. Repeat (serial) testing in COVID-19 patients reveal that a false negative can occur (some samples are positive and others negative with repeat testing in the same patient). False-negative results should be considered, especially if the patient is highly symptomatic and rules out for other respiratory disease such as flu. Reasons for false negatives include failure to have enough virus in the sample, improper storage of the sample, and limitations in test performance.

    In some cases, a presumptive rule-in for COVID-19 is clinically made in the absence of confirmed molecular testing for the virus. Approaches include testing suspect COVID-19 patients with other respiratory test panels. If negative, a presumptive diagnosis of COVID-19 may be made until diagnosis can be confirmed.

    Confirming current infection is important for the diagnosis in a patient with signs and symptoms and for people potentially exposed to that individual. If a person with a known exposure tests positive but has no or mild/moderate symptoms, he or she can self-isolate to limit infecting other people. Identifying and testing people with known or suspected exposure to someone with confirmed COVID-19 is known as contact tracing. This is an important method to help reduce viral spread but requires both trained personnel and enough access to testing. Even without testing, asymptomatic persons with confirmed exposure can self-isolate to help limit potential transmission. As tests for COVID-19 become more broadly available, contact tracing may prove imperative to help limit viral transmission.

Accordion Title
COVID-19 Antibody Testing
  • Serology testing for COVID-19 antibody

    Infection with a pathogen (“path” from the Greek root meaning "disease" and "gen" from the Greek root meaning "that which produces") such as a virus or bacteria causes the immune system to create antibodies. Antibodies are specific proteins produced by certain immune cells called B-cells. Antibodies can often (but not always) help fight off infection, and tests for antibodies can be highly useful to identify an immune response to a specific pathogen. A blood sample is typically used to identify antibody.

    Antibody testing in COVID-19 should provide significant insight into who has been previously infected, a process known as surveillance. This will be especially useful to identify asymptomatic infections, as antibody should be present in recovered individuals. Antibody tests may also prove useful to help identify an immune response to an existing infection, though they are less sensitive than molecular tests as it takes time for antibodies to develop. This period when antibody tests can be negative is known as the seroconversion window. Once antibodies become detectable, the person is said to have seroconverted.

    Often a molecular test can confirm presence of the virus during the seroconversion period. The "antibody blind" window with COVID-19 is variable and remains to be established but appears to average 2-14 days from symptom onset (but is also dependent on test sensitivity). Combining both molecular and antibody testing may be useful to identify infection and the immune response.

  • Antibody specificity for COVID-19

    Like all tests (including molecular ones), antibody tests for COVID-19 will need to have good specificity. Good specificity in a lab test means it is unlikely to falsely identify someone without the disease as having the disease. This is also known as false-positive or FP. If antibody to COVID-19 results in immunity (see below), it will be important to have good specificity, so patients aren't incorrectly identified as immune. Without sufficiently high specificity, a strategy to screen asymptomatic individuals for the determination of immune status will not be appropriate.

    While many different antibody tests rapidly became available for SARS-CoV-2, analysis produced uncertainty in performance, with false positive, false negative, and inconsistent results obtained. The FDA has subsequently enacted performance criteria and test oversight for antibody testing for SARS-CoV-2. As reliable antibody tests will be critical, this will be an important addition to testing.

  • COVID-19 antibody and immunity

    In many types of infections, antibody produced can help protect against reinfection after a person has recovered. This is a form of immunity. Many vaccines are designed to stimulate antibodies and produce immunity, so a person is protected from infection if exposed. This works extremely well for some infectious disease but not all. Some pathogens can re-infect, despite the presence of an immune response. In some infections, antibody alone is insufficient to protect, and other elements of the immune system must be utilized.

    Sometimes, partial immunity with antibody occurs following infection or vaccination. This incomplete immunity may result in infection with less severe symptoms. While full or at least partial protection with antibodies to COVID-19 is hoped for, it remains to be confirmed if sustained immunity to subsequent reinfection is seen with recovery from COVID-19.

    If immunity with antibody is confirmed, antibody testing may help identify individuals who are at low risk if exposed to people with current infection. This could be extremely useful in supporting our first responders or selecting those who can safely return to work. Patient data shows that both antibody and virus can coexist in patients, so a positive test for antibody does not mean the infection is resolved.

  • Antibody in early vs. late/resolved infection

    The body makes different types of antibodies, some which tend to occur early and others later. A type of antibody called IgM (immunoglobulin M) is typically the first antibody seen with seroconversion. The second antibody typically seen is called IgG (immunoglobulin G). Eventually, IgM disappears, and IgG remains detectable. In COVID-19, this typical seroconversion pattern is not seen in most patients, as IgM and IgG appear closely with each other, though IgG does persist after IgM eventually disappears. So unlike antibody testing in many infectious diseases, IgM alone cannot indicate acute infection nor can IgG alone indicate resolved infection. Instead, conversion to antibody-positive indicates an immune response to infection with SARS-CoV-2 but doesn't tell if the virus is still present.

    Some IgG is known as neutralizing antibody (because it can "neutralize" the ability of the pathogen to infect). Neutralizing antibody is important for viral immunity. If viruses can't infect cells they can't replicate and cause infection. Available serology tests for COVID-19 include "Total" tests that identify both IgG and IgM and single tests for either IgM or IgG. If a specific neutralizing (protective) antibody is ultimately identified for COVID19, testing for that specific type antibody will have important implications. These could include assessment for immunity or possibly screening of plasma from recovered patients (should the use of convalescent plasma prove a useful therapy). Protective levels of antibody may persist or wane with time. Further research should help define if COVID-19 antibody is protective and at what levels and for how long if so.

Conclusion

Testing is essential to both confirm current COVID-19 infection as well as identify those with evidence of an immune response to infection. Molecular and antibody testing will provide useful information in the management of COVID-19.

For more information on the progression, testing and treatment of COVID-19, you can download this brochure.

COVID-19 Patient Brochure

Patient Awareness Articles are created by and paid for sponsors and advertisers. The views expressed in these articles do not necessarily represent Lab Tests Online or AACC’s views, and their inclusion in Lab Tests Online is not an endorsement by AACC.

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