Should we test for past or present SARS- CoV-2 infection prior to vaccination?

The current CDC guidelines regarding SARS-CoV-2 vaccination state that almost every person age 16 and over (Pfizer mRNA vaccine) or 18 and over (Moderna mRNA vaccine and Janssen vaccine) can be immunized without knowledge of prior infection status, as long as the person is not known to be infected with SARS-CoV-2 at the time of vaccination. According to the CDC, “Viral testing to assess for acute SARS-CoV-2 infection or serologic testing to assess for prior infection for the purposes of vaccine decision-making is not recommended.” The CDC does not promote testing before vaccination, largely because it believes it is safe for the majority of the population, wants to simplify the vaccination rules, and instill confidence in vaccination in order to reach herd immunity and reduce loss of life.  However, the CDC outlines some examples of vaccine precautions and contraindications. Some physicians and researchers believe that testing to determine the status of infection and immunity prior to vaccination can be beneficial.

Complete information from the CDC regarding mRNA vaccinations can be found here.

Cases where testing for SARS-CoV-2 infection or immunity before vaccination may be beneficial:

1. Testing for SARS-CoV-2 infection before vaccination can help reduce the chance of post-vaccine inflammation exacerbation.

The CDC states: “Persons… who have had a known COVID-19 exposure should not seek vaccination until their quarantine period has ended to avoid potentially exposing healthcare personnel and other persons to SARS-CoV-2 during the vaccination visit. ”The purpose of this caution is to protect the spread of SARS-CoV-2 to health care personnel, and not to protect the infected individual, because the CDC deems it safe to receive a vaccination if infected. 

However, some physicians believe it is best to defer vaccination until SARS-CoV-2 infection has resolved for another reason:  a compounding effect of simultaneous inflammatory response to infection and the vaccine.  In other words, infection produces inflammation, and vaccination also produces inflammation.  The level and severity of inflammation resulting from infection and vaccination varies from person to person.  When infection and post-vaccination inflammation occur at the same time, the effect may exacerbate the inflammation response in the body.

Individuals tested for SARS-CoV-2 infection before vaccination can benefit from removing the possibility of vaccination inflammation exacerbating concurrent SARS-CoV-2 infection inflammation.

2.  Testing forSARS-CoV-2 infection before vaccination helps distinguish the cause of post-vaccination symptoms.

If a person is infected with SARS-CoV-2 at the time of vaccination, then it will not be clear whether symptoms that develop after vaccination arose as a result of infection (including symptoms that may require antiviral treatment), or whether symptoms that develop after vaccination arose as a result of vaccination side effects (which may be reportable and require different management than symptoms that arose from active illness).

Individuals tested for SARS-CoV-2 infection before vaccination can benefit from the ability to distinguish symptoms of vaccination from symptoms of illness.

3. Testing for SARS-CoV-2 infection and immunity before vaccination can help with vaccine risk-benefit assessment of patients considered at higher risk of serious side effects from the vaccine.

a. Anaphylaxis

Although no anaphylactic reactions were reported from either the Pfizer or Moderna vaccines during clinical trials, anaphylactic reactions have been reported following administration of the mRNA vaccines outside of the clinical trials.  Anaphylaxis after receiving an mRNA vaccine is approximately ten times more likely than anaphylaxis after flu vaccination, and up to 100 times more likely than anaphylaxis with other vaccines in general.  There is also a chance of anaphylaxis with the Janssen vaccine, although very small.

Although anaphylaxis after SARS-CoV-2 vaccination is more likely to occur in those who have experienced anaphylaxis or allergies in the past, it has also been reported in those without a history of allergies.  The CDC page “Managing Anaphylaxis” after mRNA vaccinations can be found here:

The CDC contraindicates vaccination for those who have a history of allergic reaction of any severity (including anaphylaxis) to a previous dose of a SARS-CoV-2 vaccine or any component of the vaccines, including polyethylene glycol (PEG) and polysorbate.  The CDC states: “Persons with a precaution to vaccination should be counseled about the unknown risks of experiencing a severe allergic reaction and balance these risks against the benefits of vaccination.”

For individuals with any history of anaphylaxis, the CDC lists considerations that can be used to conduct a risk assessment for SARS-CoV-2 vaccination, to be discussed with a physician.  This assessment should include a person’s risk of exposure to SARS-CoV-2, the person’s risk of severe disease or death from SARS-CoV-2 (depending on age and underlying medical conditions), and whether the person has previously been infected with SARS-CoV-2.

Although almost all cases of anaphylaxis can be treated in the medical setting, testing forSARS-CoV-2 infection and immunity prior to vaccination in individuals at higher risk for anaphylaxis could help assess an individual’s risk versus benefit of vaccination.

b.  Frail, elderly population

In mid-January 2021, as Norway began immunizing its population with the mRNA vaccine, almost 0.1% of the people who were in the initial wave of vaccines died.  The deaths occurred entirely in those age 75 and older.  After review, the World Health Organization determined that the deaths were expected in the population of frail, elderly individuals, and that the benefits of the vaccine outweighed the risks:

Despite these findings, the Norwegian government has since contraindicated the vaccine to people over the age of 75. 

Around the same time, the UK reported 143 deaths shortly after vaccination of elderly people and those with underlying illness, but the UK Medicines and Healthcare Products Regulatory Agency reported vaccination was not the cause:

Amid these occurrences, the CDC believes the mRNA vaccine is safe, but some physicians contraindicate the mRNA vaccine in the frail, elderly population.

Also, one of the main databases of post-vaccination side effects is from self-reported symptoms using a smartphone app called VSAFE.  However, the elderly population is unlikely to use this app, and so this database underestimates the number of side effects in the population, particularly among the elderly.

Testing for SARS-CoV-2 infection and immunity prior to vaccination of the frail, elderly population could help assess an individual’s risk versus benefit of vaccination.

C.  Guillain-Barre syndrome (GBS)

The CDC states that those with Guillain-Barre syndrome are not contraindicated from the SARS-CoV-2 vaccines.  However, some doctors believe that individuals with a history of post-influenza-vaccine GBS should not receive these vaccines, because they could stimulate a similar response.  Physicians of patients with a history of GBS can perform a risk assessment of the risk versus benefit of the vaccine. 

Testing for SARS-CoV-2 infectionand immunity prior to vaccination of those with a history of GBS could help assess an individual’s risk versus benefit of vaccination.

4. Testing for SARS-CoV-2 infection and immunity before vaccination can help with vaccine risk-benefit assessment of patients with conditions for which there is very little or no data.

a.  Pregnancy

There is very little data on the safety of the SARS-CoV-2 vaccines in pregnant or lactating women, although the CDC believes the risk may be low.  Pregnant or lactating women are allowed to choose if they receive a vaccine.  However, given that there are other vaccines that are contraindicated in pregnant and lactating women, and there is very limited data on SARS-CoV-2 vaccines in pregnant and lactating women, some physicians advise against it.

Those who have conditions where there is little to no vaccination data, such as pregnancy, could benefit from being tested for SARS-CoV-2 infection and immunity prior to vaccination, in order to help assess the risk versus benefit of vaccination.

b.  Other conditions for which there is little to no data

Other conditions for which there is very little to no SARS-CoV-2 vaccine study data, but for which the CDC believes are safe to take the vaccine, include the following:people with HIV or other immunocompromising conditions, people who take immunosuppressive medications, people with autoimmune conditions, people with Bell’s palsy, and people with dermal fillers.

Those who have underlying medical conditions where there is little to no vaccination data could benefit from being tested for SARS-CoV-2 infection and immunity prior to vaccination, in order to help assess the risk versus benefit of vaccination.

5. Testing for SARS-CoV-2 infection and immunity before vaccination can help conserve doses of vaccine for those with a greater immediate need and higher risk of infection.

The CDC states: “…while vaccine supply remains limited, persons with recent documented acute SARS-CoV-2 infection may choose to temporarily delay vaccination…”

The CDC states that it is not necessary to get a vaccine if you have been infected with SARS-CoV-2 in the past three months.  While various researchers have reported varying lengths of time of immunity, recent research indicates that infection can protect from re-infection for at least five months:

There has not yet been a sufficient length of time for the CDC to define the longevity of post-infection immunity, so currently, the general rule is three months.

Individuals who are tested prior to vaccination and confirmed to have SARS-CoV-2 infection or immunity could choose to delay vaccination, conserving the vaccine supply for those who have no immunity to the virus.

6. Testing for SARS-CoV-2 infection and immunity before vaccination may provide an option of receiving only one dose of the two-dose mRNA vaccine.

Although the CDC recommends two doses of the mRNA vaccine for almost everybody, some physicians and researchers think that one dose is sufficient for those who have been infected:

One argument against giving only one vaccine dose to those who were infected with SARS-CoV-2 is that it could provide a confusing precedent to the public. However, some physicians and researchers believe that a full course of vaccination is not necessary for those who have been infected and have immunity.

Individuals who are tested prior to vaccination and confirmed to have SARS-CoV-2 infection or immunity could decide with their health care provider to delay or forego immediate vaccination, thus reserving the supply of vaccines for those people who are at higher immediate risk of infection.

7. Testing for SARS-CoV-2 infection and immunity before vaccination can help prepare for the risk of side effects.

Approximately 85% of all people who receive the mRNA vaccines from Pfizer or Moderna experience at least one post-vaccination symptom, including but not limited to pain, swelling, erythema at the injection site, and localized axillary lymphadenopathy on the same side as the vaccinated arm.  Approximately 70% experience systemic symptoms such as fever, fatigue, headache, chills, myalgia, and arthralgia.  These symptoms are more frequent and severe following the second dose of the mRNA vaccine. 

According to the CDC and post-vaccination data, those who have recovered from SARS-CoV-2 infection prior to vaccination are more likely to have severe side effects to the first mRNA dose than those who have never been infected.  Those who have never been infected with SARS-CoV-2 are more likely to have severe side effects to the second mRNA dose than the first dose. 

Because mRNA vaccine side effects commonly include flu-like symptoms lasting a couple of days, it would be helpful for those getting vaccinated to prepare in advance for post-vaccine symptoms.  For example, hospital staff are advised to stagger vaccination of employees, so that there are not a significant number of people simultaneously calling out sick from work.

Side effects from the single-dose Janssen vaccine are possible, but typically shorter duration and less severe than the side effects from the vaccines of Pfizer and Moderna.

Individuals who are tested for SARS-CoV-2 infection and immunity prior to vaccination could benefit from knowing the chances of enduring more severe side effects after the first or second vaccine dose.

8.  Testing for SARS-CoV-2 cellular immunity before vaccination can provide valuable information regarding previous exposure to SARS-CoV-2 in the significant portion of the population that does not have detectable antibodies to SARS-CoV-2.

A weak antibody response that wanes quickly might be the reason why many people who tested positive for SARS-CoV-2 had no antibodies a few weeks or months later. A lack of antibodies doesn’t mean a person is not immune, because that person may have long term cellular immunity in the form of memory T cells.

A study published in Emerging Infectious Diseases found T cell immunity in 80% of patients who had been infected with SARS-CoV-2 but did not have detectable antibodies:

Individuals who are tested for SARS-CoV-2 cellular immunity prior to vaccination could benefit from knowing whether or not they have been exposed to SARS-CoV-2 and may have immunity not detectable by antibody tests.


With increasing information from SARS-CoV-2 post-vaccination data, some physicians and researchers are seeing the benefit of testing for SARS-CoV-2 infection and immunity prior to vaccination.  Testing need not delay vaccination more than a few minutes, as many tests for active infection (particularly antigen tests) and tests for immunity can be performed in 10-15 minutes, and can take place immediately prior to vaccination.  Although testing before vaccination is not a CDC recommendation for most people, same-day testing can provide a possible significant benefit to the patient.  Each person is an individual case with different risks and circumstances, and determining the status of infection and immunity prior to vaccination can help to provide information regarding vaccination timing, symptom response, risk assessment, vaccine dispersal, dosing, and preparation for vaccination side effects during this active pandemic.

Reduced COVID-19 Quarantine Options have been Provided by the CDC.

On December 2nd, the CDC provided options to reduce the quarantine period for those who have been exposed to SARS-CoV-2, the virus that causes the illness COVID-19. The purpose of the options is to reduce the amount of time that people must stay home from work, and also, the options may lessen the stress on the public health system.  This update results from increased knowledge of the SARS-CoV-2 incubation period, infectious period, and effective testing window.

The CDC continues to endorse a quarantine of 14 days after the last known contact with a person infected with the virus, but now offers alternative, shorter options: 

A person who is exposed to SARS-CoV-2 but who remains asymptomatic may quarantine for 10 days instead of 14, without testing. 

Alternatively, a person may quarantine for only 7 days after exposure to SARS-CoV-2 if that person remains asymptomatic and receives a negative test result. The negative test result must occur on or after the fifth day of quarantine.

Because regional public health departments make the final decisions regarding length of quarantine, the revised CDC quarantine options may or may not be adopted by every region and institution.

The CDC guidelines regarding isolation of patients who are known to be infected with SARS-CoV-2 remain the same:

Isolate at least 10 days from the onset of symptoms, and at least 24 hours with no fever without fever-reducing medication.  Isolation can then be discontinued, but only if Covid-19 symptoms are improving. One exception is that loss or distortion of taste and smell may persist for weeks or months, but the patient does not need to remain in isolation or quarantine during recovery of those senses.

Those with severe Covid-19 illness that require hospitalization and those with weakened immune systems may need to isolate for 20 days after the onset of symptoms. This period of time is flexible, depending on the discretion of the patient’s doctor and the local health department.

If a person has tested positive for SARS-CoV-2 and has recovered from Covid-19 symptoms, that person should wait a minimum of three months before testing for the virus again, unless symptoms of Covid-19 develop again. (This does not preclude a person from serology testing during that time, to look for evidence of antibodies to the virus, as opposed to testing for an active viral infection.)

The CDC guidelines align with what scientists and doctors have learned about the incubation period and infectious period of the SARS-CoV-2 virus, the duration of illness that this virus causes, Covid-19, and the effective testing window of time. 

Most SARS-CoV-2 infections can be detected by PCR or antigen testing by the fifth day after infection.  

Most people infected with SARS-CoV-2 who become symptomatic will develop symptoms before the seventh day of exposure.

Most people infected with SARS-CoV-2 are not infectious beyond 10 days after the onset of Covid-19 symptoms.  (Exceptions include immunocompromised individuals and those with severe disease.)

It is not uncommon to continue to test positive for SARS-CoV-2 for an extended time after infection, because non-infectious viral particles may remain at detectable levels in the body for weeks or months after infection.  Unless a person has an immune system deficiency, a positive test result within three months after infection does not mean that person is still infectious to others.  Most likely, a person with a positive test result within three months of infection is not infectious to others and doesn’t need to quarantine unless symptoms reappear.

Immunity to SARS-CoV-2 is hypothesized to last at least one year in healthy individuals who are not immunocompromised.  This estimate is based upon the known length of immunity to SARS-CoV-1.


SARS-CoV-2 is the coronavirus that causes the disease Covid-19.

Covid-19 is the disease that is caused by the SARS-CoV-2 virus.

Quarantine:  A person who has been exposed to the SARS-CoV-2 virus must quarantine to stay away from others.  Quarantine after exposure to SARS-CoV-2 is most commonly done at home.

Isolation:  A person who is infected with the SARS-CoV-2 virus must isolate to stay away from others, even those living with them at home.


The quarantine update can be found at the CDC website here.

The isolation information can be found at the CDC website here.

The Million Dollar Question… Which COVID Test is Best?

One of the COVID tests currently used by Lookout Health is the Becton Dickinson BD Veritor system for the rapid detection of SARS-COV-2 virus. This is an FDA-authorized antigen test that detects current infection with the virus. The sample for this test is obtained via a nasal swab,and results are available in 15 minutes.

The data provided to the FDA by Becton Dickinson demonstrated an overall percent agreement (OPA) of 98% when compared to a three-hour polymerase chain reaction (PCR) which is currently considered the benchmark for evaluating new tests. The definition of overall percent agreement (OPA) is True Positives + True Negatives / Total Samples. In this same data set, the positive percent agreement (PPA) of the BD Veritor was reported as 84% and its negative percent agreement (NPA) as 100%. For the most part, people want to know if this means the BD Veritor is a “good test.” To address this question, it is helpful to understand the methods used for detecting viruses and other pathogens and how these methods have evolved over time.

Over the years, the strategies for detecting infections have progressed immensely. Just two decades ago, the medical community primarily relied on cultures to determine whether or not infections were present. Cultures were considered the gold standard but could be finicky and often took days. With this method, samples were placed in petri dishes and needed time to grow before one could ascertain whether or not a particular bacteria or virus was present. Some pathogens grew quickly and others more slowly, so the amount of time it took to receive results actually depended on the organism itself. For some infections, there was a high rate of false negatives due to sampling and processing difficulties. It was accepted that many cultures did not have an accuracy (or sensitivity) of greater than 75%.

Then, Polymerase Chain Reaction (PCR) technology was created, and throughout the 1990’s and early 2000’s, this method was customized and adapted to detect a wide variety of pathogens, including viruses. This was a true technological breakthrough for diagnosing infections, as clinicians could detect the presence of a pathogen by identifying a specific fragment of its DNA as opposed to requiring it to grow in culture. PCR was soon found to have superior sensitivity to cultures and became universally utilized by clinicians. These tests are also known as molecular or nucleic acid tests.

Paralleling the growth of PCR technology was yet a third method used to diagnose activeinfections, and this was the antigen test. These tests detect the presence of proteins on the surface of a pathogen as opposed to its genetic material. Prior to the development of COVID antigen tests, such methodology was used for the diagnosis of influenza, tuberculosis, and strep, among other infections. Unlike PCR tests, antigen tests don’t require complex laboratories. With these tests, antigens are identified by antibodies located within a test cartridge. When the antigens from the pathogen are present, a strip on the cartridge signals that fact.

The two types of tests routinely used for detecting active COVID infections are PCR and antigen tests. The FDA has issued Emergency Use Authorizations for over 200 COVID diagnostic tests that fall into these categories, so it is impossible to address each specific test, but as the number of COVID cases rise and communities increasingly engage, it might make sense to ask the question which type of test is best? And the answer to that is… it depends.

PCR tests amplify genetic sequences, making it possible to identify small amounts of virus. This makes PCR tests for the SARS-CoV-2 virus very sensitive and very specific, meaning almost all active infections are detected, and only rarely will an uninfected person receive a positive result. Antigen tests don’t amplify their protein signal, and because of this they are less sensitive when compared to PCR. The trade-off is that antigen tests have results in minutes and can be read in an ambulatory setting, whereas PCR tests take several hours and require the complexity of a laboratory. Still, given that antigen tests have lower sensitivity, does this mean PCR tests are superior despite the time needed to obtain results Well, maybe not.

To control the spread of COVID, it is important to find people who are asymptomatic yet are shedding virus in great enough numbers to be infectious. It is also important to identify these individuals in a timely manner. A highly sensitive PCR test may find virus in a sample, but that doesn’t necessarily mean that the person has a high enough viral load to infect others. PCR tests can remain positive for weeks after someone is no longer infectious, as a small amount of viral genetic material can still be present. This lesson was learned years ago when PCR was first used to diagnose Chlamydia. At that time, clinicians would often repeat tests two weeks after treatment to ensure that the treatment was effective. When PCR was used for these repeat tests, treated patients could still be positive weeks later. At the time, it was thought that this indicated a treatment failure or recurrent infection, but as it turned out, that was not true. The majority of those patients were adequately treated and not at risk for spreading infection to others, but their Chlamydia PCR tests continued to be positive because those tests were detecting genetic material from dead bacteria. This is now an understood drawback of nucleic acid tests as opposed to cultures, which by definition require a pathogen that can multiply and grow.

This scenario shows that higher sensitivity isn’t always better. The best test would be one that can identify individuals who pose a risk to others and can do that quickly. It may be that the sensitivity of rapid antigen tests is ample for this purpose, and asymptomatic patients who may be detected by PCR but not captured by antigen tests do not have enough live virus to transmit the disease. Anecdotal evidence from the University of Arizona supports this notion, as they have been using rapid antigen tests for their screening and have avoided major outbreaks thus far. The viral load at which one is infectious and the ability of rapid antigen tests to identify truly infectious individuals is an important area for additional research. It is already clear that the speed and ease of antigen tests makes them a compelling tool in the armamentarium against COVID. If it is also shown that they are sensitive enough to unequivocally identify persons who are most at risk for transmitting the disease, one could make the case for considering these tests to be the best for many scenarios.