COVID-19: Calculating Risks in the Midst of Confusion
"Take calculated risks. That is quite different from being rash."
- General George Patton
“I think the way [the new CDC guidelines] were released was very problematic.”
- Thomas Frieden, M.D., former CDC director
There has been considerable confusion about who’s at risk of Omicron, what isolating and quarantining entails, and what tests are best for making a diagnosis of COVID-19. Recently, there also has been discussion about a new way of thinking about COVID-19. In this Germ Gems post, I address these issues.
Who is at risk of SARS-CoV-2 Omicron infection? SARS-CoV-2 Omicron is everywhere—even in Antarctica. Everyone is at risk of getting infected.
Like all SARS-CoV-2 variants, Omicron causes asymptomatic infections. (Some studies suggest the asymptomatic infection rate of Omicron is 70% or greater.) Even though people without any symptoms can transmit SARS-CoV-2, what most people really care about is whether the virus will precipitate illness, especially severe or life-threatening disease.
Full vaccination (including a booster) with any of the three U.S. Food and Drug Administration-(FDA) approved vaccines dramatically reduces the risk of severe or fatal COVID-19 infection. Nonetheless, breakthrough infections do occur and they can be serious and, although rare, even fatal.
On January 7, 2022, the Center for Disease Control and Prevention (CDC) published a study that showed that of 1,228,664 adults who completed a primary COVID-19 vaccination, 0.015% developed severe COVID-19, and only 0.0033% died. All persons with severe outcomes had at least one risk factor.
In another recent study, researchers found that almost 80% of COVID-19-related deaths in fully vaccinated adults occurred in those who had at least four of the following risk factors: older age (65 and up), compromised immunity, chronic kidney, heart, pulmonary, neurologic, or liver disease, and diabetes. Interestingly, Pfizer and Johnson & Johnson vaccine recipients had comparable risks of severe outcomes, while the risk of severe disease was significantly lower in those who received the Moderna vaccine.
Thus, when you make decisions about engaging in activities that could put you at risk of acquiring a SARS-CoV-2 infection whether it be with Omicron or any of the other variants you need to calculate your risk of getting severe COVID-19. You clearly need to factor in your vaccination status and whether you have any comorbid medical conditions before you embark on any such activity.
Confusion over isolation and quarantine. The CDC defines the terms isolation and quarantine as follows:
Isolation separates sick people with a contagious disease from people who are not sick.
Quarantine separates and restricts the movement of people who were exposed to a contagious disease to see if they become sick.
In both instances, these procedures are meant to decrease the risk of transmission of the virus from people who are known to be infected (isolation) or who may be infected (quarantine). In its January 4, 2022 updated guidelines “What We Know About Quarantine and Isolation”, the CDC provided details regarding what constitutes an exposure as well as isolation and quarantining procedures.
At the end of 2021, the CDC issued updated guidelines that shortened its recommended period of isolation of SARS-CoV-2-infected patients from 10 days to 5 days. These revised guidelines weighed in the balance the highly disruptive costs of isolation to the economy and schooling versus the very small risk of transmission of the virus after 5 days of infection. To many experts, the revised guidelines made a lot of sense. They have now, however, become the target of some sharp criticism. For example, on January 5, the American Medical Association criticized the government’s guidelines on quarantine and isolation, saying the guidance was “confusing” and risked further spread of COVID-19.
On January 7, 2022, CDC director Rochelle Walensky, M.D., MPH, held a CDC-only media briefing to clarify the CDC’s isolation and quarantine guidance. In this briefing, she reminded everyone “The virus is . . . constantly throwing us curve-balls. As the virus changes, the science changes.” She reiterated that the CDC’s guidelines to come out of isolation after 5 rather than 10 days of infection applied only to people who no longer had any symptoms but that if you were still symptomatic, you should not leave isolation. She further explained that once you come out of isolation, you should wear a “well-fitting mask” from days 6-10 since the start of infection.
Experts agree that only a small amount of virus is being shed by day 5 after getting infected, and everyone agrees that isolation can be extremely disruptive. But many critics of the CDC’s guidelines believe that the lifting of isolation at 5 days should require a negative COVID-19 test result. Even though tests for SARS-CoV-2 aren’t approved for determining contagiousness, this requirement seems reasonable to me. I also agree, however, with the importance of tailoring quarantine and isolation periods to the circumstances of individual patients, as is suggested by Dr. Amesh Adaja in a January 7, 2022 article in MedPage Today, “COVID Isolation Should Not Be ‘One Size Fits All’.”
Testing for SARS-CoV-2. From the outset of the COVID-19 pandemic, testing for SARS-CoV-2 has been problematic. (The ongoing plight of finding tests and testing sites in Minnesota, for example, is highlighted by MinnPost writer Greta Kaul in a January 6, 2022 article, “Nearly two years into the pandemic, Minnesota still doesn’t have enough COVID-19 tests.”) The good news, however, is that the White House plans to buy and distribute 500 million free rapid tests by the end of this month. President Biden’s plan initially will involve providing eight at-home tests per person per month at certain pharmacies reimbursed via private insurance. (The details are currently being hammered out, including procedures for getting free test kits to hundreds of millions of Americans without insurance.)
The rapid diagnostic tests for SARS-CoV-2 are the most useful in clinical decision-making for the management of COVID-19. In the January 7, 2022 issue of the New England Journal of Medicine, Dr. Paul Drain thoroughly reviewed this topic. Here are his “Key Clinical Points” on rapid diagnostic testing for SARS-CoV-2:
Rapid diagnostic tests (RDTs) that are authorized by the Food and Drug Administration to diagnose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are either nucleic acid amplification tests to detect genes or antigen-based immunoassays to detect proteins of SARS-CoV-2.
RDTs are approved for use in persons with symptoms of coronavirus disease 2019 (Covid-19) and in asymptomatic persons who are close contacts of a person with Covid-19 or who have been in a potential high-risk transmission setting.
Symptomatic persons should undergo testing as soon as possible, quarantine while awaiting test results, and consider retesting if they have a negative RDT, particularly if they have a high pretest probability of infection.
Asymptomatic persons with a known exposure to SARS-CoV-2 should undergo testing 5 to 7 days after exposure, and if the RDT is negative, they should undergo testing again 2 days later.
Persons with a known exposure to SARS-CoV-2 who are not fully vaccinated should quarantine while awaiting test results, and persons who test positive should isolate, contact a health care provider or public health department, and inform close contacts about the infection.
Rapid at-home antigen tests are quite accurate, especially if you have symptoms. “False-positive” results are very rare, but “false-negative” results do occur, especially if you have an asymptomatic infection. This is because antigen tests may not be able to pick up the low viral load of an early or waning COVID-19 infection. PCR (nucleic acid amplification) tests, on the other hand, are more sensitive and better at picking up asymptomatic, early, or waning infections. But the results of PCR tests usually take at least 24 hours.
The basis for false-negative antigen tests for Omicron is interesting. According to Matthew Herper in his January 7, 2022 article in STAT, “Scientists try to pinpoint why rapid Covid tests are missing some cases,” suggests growing evidence indicates that the Omicron variant collects in the throat, not in the nose, which may explain why nasal swabs aren’t detecting Omicron. Other scientists are showing that saliva tests may work better than nasal swabs suggesting that saliva or throat swabs may be preferred for testing for Omicron, even for PCR tests.
There is a growing number of anecdotal reports supporting the idea that saliva samples (throat swabs) are better for diagnosing COVID-19 in patients infected with Omicron. But on January 7 the FDA warned against using throat swabs for home COVID-19 testing as none of the studies of reliability of test kits used samples from the throat. (One strategy to increase sensitivity of the rapid tests may be by swabbing the throat and nose. In Israel, health officials have recommended that people swab their nose and throat to increase sensitivity. This strategy, however, is not endorsed by the FDA.)
The finding of Omicron in the upper airway (throat) may help explain why COVID-19 appears to be a milder disease than the disease inflicted by the Delta variant, which is more likely to infect cells in the lower airway (lungs) as well as in the nose. The higher levels of Omicron in saliva may also elucidate why this variant is so incredibly contagious and spread so readily when people talk, shout, cough, or sing.
Are we headed for a “new normal” COVID-19 pandemic strategy? Further confusion of the general public about what our public health and government officials are doing to combat the blizzard of COVID-19 Omicron cases was stirred up this past week. On January 6, 2022, six advisers to President Biden’s early COVID-19 transition team called for the President to adopt an entirely new COVID-19 strategy, that is, living with SARS-CoV-2 indefinitely. Their strategy, referred to as the “new normal” of living with the virus rather than trying to wipe it out, isn’t actually all that new. It reflects a reality expressed in my January 5, 2022 Germ Gem post, “COVID-19 Pandemic, Year 3—What will it bring?”, that COVID-19 isn’t going away but rather is going to settle down and become another endemic coronavirus infection. Like a long list of other endemic infections, most notably, influenza, this strategy requires new vaccines, including development of a universal vaccine that can prevent infections by all influenza viruses, and in the case of COVID-19, all coronaviruses.
In a January 6, 2022 article in the Journal of the American Medical Association, “A National Strategy for the ‘New Normal’ of Life with COVID,” three of these advisors wrote that the U.S. must avoid becoming stuck in a “perpetual state of emergency.” Another advisor, Dr. Rick Bright, chief executive of the Rockefeller Foundation’s Pandemic Prevention Institute, reminded everyone “that our vaccines are going to get weaker and eventually fail. . .we have to put a plan in place to continually update our vaccines, our diagnostics and our genomics so we can catch this early. Because the variants will come, and we should never be surprised and we should never underestimate this virus.”
Time will tell whether the CDC will adopt this strategy for living with COVID-19. If it does, it will be interesting to see what the CDC’s message about COVID-19 will be. Let’s hope it is simple and clear.