CID: Delayed Peak SARS-CoV-2 Viral Loads Relative to Symptom Onset and Implications for COVID-19 Testing Programs

#17,712

Over the past 45 months, not only has the SARS-COV-2 virus changed radically as it has evolved and diversified into thousands of variants, so have its most susceptible hosts; humans.  

Many of us have been infected one or more times by the original (D614G) version, or any of the variants that followed (e.g. Alpha, Delta, and a series of Omicron variants). Many have also received repeated COVID vaccines, based on distinct 3 formulations. 

From all of these exposures, changes to our immune systems are inevitable. In fact we count on it. The only way to get immunity to a novel virus is either from infection, or vaccination. 

But immunity isn't absolute, and for most people it has been far less robust and durable than hoped. 

The notion, pushed in 2020, that `once enough people had been infected, herd immunity would protect us', was both overly optimistic, and far from universally held (see COVID-19: From Here To Immunity).

By the end of 2020, the meme switched to `once enough people had been vaccinated, herd immunity would protect us'. While early protection from the vaccine was quite good, by the summer of 2021 we were seeing significant breakthrough infections, particularly with the new Delta variant. 

Immunity (regardless of how it was acquired) was increasingly redefined as a reduced risk for severe illness, hospitalization, or death.  Admittedly, the most important attributes for any vaccine. 

Gaining immunity, particularly from infection, is a double-edged sword. There is the obvious morbidity and mortality associated with acute infection, plus a significant percentage of survivors report long-lasting, and sometimes devastating, `Long COVID' sequelae.

But we are no longer an immunologically naive population, and the way that COVID impacts us is far different that what we saw in 2020, 2021, and even 2022.  For many (but not all), the illness is far milder than it used to be, and hospitalizations and deaths have clearly dropped. 

That could change, of course, should a new, antigenically distinct variant emerge. 

But for now - particularly for younger and healthier individuals - infection is less problematic than it was two years ago. Some of this is likely due to a less severe Omicron lineage, but some of it is also due to our repeated exposures and vaccine uptake.

But the severity of illness isn't the only change.  The time it takes the virus to overwhelm our immune defenses has increased as well.   

When we were immunologically naive, the virus could replicate rapidly, and the highest viral load normally occurred in the first day or two of symptomatic illness.  Early testing (both PCR and Rapid Antigen Test Kits) were more likely to return a positive result.

Today, with our immune systems mounting a delaying action, rapid antigen tests are less likely to show positive early in the illness.  That means that many people who test negative on day 1 or 2 of an illness will assume they are negative, when they aren't. 

A study published in late September in Clinical Infectious Diseases find that COVID viral levels now peak on Day 4 of symptomatic illness - while influenza A peaks on Day 1 or 2 - a variance that will require changes in our testing strategy, particularly as dual COVID/Flu test kits become more common. 

Due to copyright restrictions, I've just posted the link below, you find the full manuscript PDF available at this link.  I'll have a brief postscript after the break. 

The New Normal: Delayed Peak SARS-CoV-2 Viral Loads Relative to Symptom Onset and Implications for COVID-19 Testing Programs

Jennifer K Frediani, Richard Parsons, Kaleb B McLendon, Adrianna L Westbrook, Wilbur Lam, Greg Martin, Nira R Pollock

 
Clinical Infectious Diseases, ciad582, https://doi.org/10.1093/cid/ciad582
Published: 28 September 2023

 

We seem to enter  a `new normal' every few months when it comes to COVID, and further changes in how it impacts our lives are certainly possible.  For now, the FDA's advice on testing (updated Sept 29th) reads:

When You Should Test for COVID-19

• If you have symptoms, test immediately and then test again per the instructions if your first result is negative.
• If you were exposed to someone who has COVID-19 and you do not have symptoms, wait at least 5 full days after your exposure before testing. If you test too early, you may have an inaccurate result.
• If you are in certain high-risk settings, you may need to test as part of a screening testing program.
• Consider testing before coming into contact with someone who has a high risk for severe COVID-19; people who are older adults or immunocompromised, or have other medical conditions, especially if you are in an area with a medium or high COVID-19 Hospital Admission Level.

What Your At-Home OTC COVID-19 Test Result Means

• Most FDA-authorized at-home OTC COVID-19 tests are antigen tests. While not perfect, they provide a fast and convenient COVID-19 testing option to detect the virus, so you may know if you are infected and should stay at home and away from people to help reduce the spread of the virus.A positive result using an at-home COVID-19 antigen test means you likely have COVID-19. Anyone who tests positive for COVID-19, or who likely has COVID-19, should contact their health care provider and follow the CDC's guidelines for staying at home and away from people.
• A negative result using at-home COVID-19 antigen test means the test did not detect the virus that causes COVID-19, but it does not rule out COVID-19 because some tests may not detect the virus early in an infection. Always do a repeat test at minimum after 48 hours following a negative test result when using an antigen test. Use the following guidance to help interpret your negative test result and determine what steps to take next.

In addition to COVID-19 test results, and when determining the likelihood of having the virus, consider:

• Recent symptoms
• Close contact with someone who has COVID-19
• The level of COVID-19 in your community

What At-home COVID-19 Antigen Tests Do Not Tell You

• If you have an infection immediately after you are exposed to COVID-19 because it may take 2 to 5 days, and sometimes longer, for the virus to be detected by a COVID-19 antigen test. How long it takes before a test can detect the virus may vary between different COVID-19 variants and different tests.
• How contagious you are or if you can spread the virus to someone else. There are no tests that can tell you that. You could pass COVID-19 to others even before you get a positive result on a test.
• If you have another type of respiratory illness, such as flu or respiratory syncytial virus (RSV), unless it is a test specifically authorized for detection of these viruses. 

Delayed positive tests from rapid antigen tests not only increase the chance of people exposing others to the virus, it may also delay their ability to get an order for Paxlovid or other antivirals from their doctor.  

While I've ordered and received my new set of home test kits (they have an extended expiration date into late January 2024), and will use them if needed, I don't plan to put a lot of stock into any negative results. 

Instead, I've gotten the latest COVID vaccine, and will get the flu shot later this month. I'll wear a mask whenever in public, and will stay home if I'm `symptomatic', regardless of any test results.  

That's been my `new normal' for the past 3+ years, and I don't expect it to change anytime soon.