A Comprehensive Update on SARS-CoV-2 and COVID-19

Part II (continued)

Transmission Characteristics of SARS-CoV-2 and the CDC’s New Respiratory Virus Guidance

To refresh ourselves on this blog series, in Part I, we reviewed what we have learned about the biology of the SARS-CoV-2 virus. In Part II, we began the discussion of the many things we have learned about the transmission characteristics of SARS-CoV-2.

We first discussed the mode of transmission, namely aerosols, or what we would call airborne transmission, and I provided you some of the evidence gained that confirms that this is the dominant mode of transmission, as opposed to early reports by the WHO and CDC that the dominant mode of transmission was respiratory droplets. As I explained, this is not a minor difference. Airborne transmission poses far greater risks to more people than respiratory droplets and the mitigation measures are far different. In fact, the only way superspreader events occur, which we saw many examples of, is through airborne transmission.

We then discussed the incubation period determined at the beginning of the pandemic being between 2 – 14 days with the median being 5 days. I introduced the concept of the serial interval and how in the case of this virus, we can establish that infected people may transmit the virus for 1 – 2 days prior to the onset of symptoms. We also looked at how this data, plus the available data on viral shedding, served as the basis for the CDC’s isolation (infected person) guidelines of 10 days and the quarantine (exposed person) of 14 days.

We also discussed the revision of the isolation guidelines towards the end of 2021 as hospitals were facing the prospects of being overwhelmed and going on crisis standards of care during Delta and subsequently at the beginning of 2022 with Omicron, a problem that would be magnified if health care workers had to isolate for 10 days.

Finally, we looked at another aspect of transmission – nosocomial infection (infection of staff and patients in health care settings).

It just so happens that since the last blog post, the CDC has revised its isolation guidance again. This gives us the perfect opportunity while we are reviewing our accumulated knowledge and the science around the transmission characteristics of the virus, to evaluate the soundness of the new guidelines.

But, before we do, let’s review an article on viral load and viral shedding. Unfortunately, I am not aware of recent studies with the latest variants, but the few government or former government leaders of the pandemic response who have spoken on this issue have made the assertion that the science has not changed (personally, without more recent studies, I don’t know whether it has or not) and certainly, in the supporting document in which the CDC explains its rationale for this new guidance, no new evidence or studies are cited that I might have missed. Recall that the major way for us to determine whether someone remains infectious and for how long is to assess how long they shed virus (see the end of the very first blog post on transmission characteristics).

SARS-CoV-2 viral load and shedding kinetics | Nature Reviews Microbiology was published in December of 2022. As the authors point out, “SARS-CoV-2 viral load and detection of infectious virus in the respiratory tract are the two key parameters for estimating infectiousness.” Recall that viral load is the amount of virus one has (directly measured and expressed as the numbers of copies of virus per milliliter of transport fluid [the liquid in the tube that the nasal swab is inserted into] or indirectly measured and reported as the cycle threshold [CT value] on a PCR test), based on the principle that someone whose nose and throat are teeming with virus is much more likely to infect another in close contact than someone whose nose has very few copies of virus in it. Again, you can get a refresher on these tests in the first blog post of Part II of this blog series. Be sure not to get confused. The higher the direct measurement (copies of virus/ml), the higher the viral load, but the lower the indirect measurement (CT value), the higher the viral load [each cycle amplifies the amount of nucleic acid until it can be measured, so the fewer times the sample has to be amplified, the more virus you started with, hence the higher viral load).

By conducting serial determinations to detect infectious virus in a large group of infected subjects, it is then possible to provide a range for the “infectious period,” the time period following infection in which the infected person is able to transmit the virus and infect another person.

PCR (polymerase chain reaction) tests (these are the tests that were first available that you generally had to go to a doctor’s office, urgent care or hospital to get and that usually took days to get results back) can be used to confirm infection (as these tests have good sensitivity [will identify that you have the infection if you are infected] and good specificity [if the test is positive, it is highly likely that it is infection with SARS-CoV-2 and not something else], but we will discuss these tests in more detail later in the blog series when we get to the updated data on tests), and they can be used as surrogate measures of viral load, as explained above. These tests are of limited value for measuring viral shedding, because they cannot distinguish between infectious virus and viral debris remaining from the body’s immune attack on the virus and/or treatment with antivirals or monoclonal antibodies.

On the other hand, the rapid antigen tests (RATs) [these are the tests that the government would send to your house if you ordered them or that you could buy at the drug store] are a better (though not perfect) test for detecting infectious virus, but they don’t tell us much about viral load. As I mentioned in the first blog piece of Part II, the gold standard for determining infectiousness is actually growing the virus in cell culture from a patient sample or looking for evidence of cell infection when healthy cells are mixed with virus obtained from the patient in culture. However, these tests are only performed at highly specialized laboratories, under enhanced biosecurity measures, are more expensive to conduct, and take far more time to conduct.

At the beginning of the pandemic, viral load studies of patients with mild disease showed that the viral loads (and presumably infectiousness) were highest in the first 5 days of the illness, with the peak often occurring at the day of onset of symptoms, or even 1 – 2 days prior to the onset of symptoms. The viral load would most often continue to decline over the two weeks following the onset of symptoms, however, the preponderance of evidence suggested that, in immunocompetent individuals, who only had mild disease, infectious virus was rarely detected beyond day 10 following the onset of symptoms (hence the justification for the isolation guidelines that used 10 days).

Figure 1. Viral kinetics of the ancestral (wild-type; original) virus

Looking at Figure 1, we see the days since symptom onset along the x-axis (abscissa, horizontal axis). Day 0 is the day that symptoms first appeared. The viral load is plotted along the y-axis (ordinate, vertical axis).

Recall that at the beginning of the pandemic, the mean incubation period was 5 days (see first blog post of Part II of this series). Thus, at 5 days prior to onset of symptoms (-5), the designation of “infection” is made. This is the point, on average, at which the subjects being plotted out on this graph were exposed to an infected person and then became infected themselves.

The PCR test won’t become positive until the infecting virus is replicating in the nose and throat and producing enough copies of virus that the nucleic acid (the RNA sequence) of the virus can be detected with amplification on this test, which is often prior to the onset of symptoms and about a day before the rapid antigen tests will be able to detect the presence of viral antigens (proteins) [note that I use the more common reference to these tests as rapid antigen tests, but this paper uses the reference to these tests as antigen-detecting (rapid) diagnostic tests (Ag-RDT) – a reference that is less commonly used].

The symptom-onset falls within a window to reflect that in a population of people, some have incubation periods (infection-to-onset of symptoms) that is shorter (as short as 2 days) and others have incubation periods that can be much longer.

What this diagram illustrates is that the viral load (and the number of virus RNA copies and the amount of infectious virus) is generally highest right around the time of the onset of symptoms, however, note that the person may have high levels of infectious virus both a day or two prior to the onset of symptoms, as well as beyond the period of symptoms, though that level of infectious virus is declining as the symptomatic period is ending.

The duration of symptoms is highly variable. Some people (early estimates were 33 – 40% of all those infected) were asymptomatic, either because they had not yet developed symptoms by the time their infection was detected, or because they never developed symptoms, yet, they clearly could transmit the virus and infect others. Some people only had symptoms 1 – 2 days, and others might have lingering symptoms. The time period during which the rapid antigen tests remained positive reasonably well correlated with the period of infectiousness, however, the correlation to symptoms was not well correlated.

The elimination or clearance of infectious virus correlates with (remember that “correlates with” is not synonymous with “caused by”) the production of the body’s antibodies. Generally, antibodies are produced in response to a newly recognized antigen as early as in 5 days, but generally there is a maturation process in which these antibodies change type (we will discuss this in a later blog post when we explore the immune response) and also become higher-affinity antibodies (bind to their targets more tightly), which progresses over time, but becomes evident by around day 10.

The above data points displayed in Figure 1 are for immunocompetent persons with mild-moderate illness. We know that those who develop severe disease can have high viral loads extending into the second week of illness, which is generally when we see deterioration in those who develop severe disease, and we also know that immunocompromised persons can have extended periods (weeks to months) of persistent infectious virus.

What is unknown (at least to me because I have not found more recently conducted studies) is whether the infectious period has decreased with the priming of this immune response by either prior infection or vaccination or both, but that would seem to be a reasonable hypothesis. On the other hand, although there are few studies with limited data as to when the infectious period ends, based on that limited data displayed in Figure 2, I am not confident that my hypothesis is valid. Further adding to my doubt is vaccine studies that have tended to show that vaccinees develop lower viral loads with breakthrough infections, but do not have shorter durations of shedding of infectious virus.

Figure 2. Shedding kinetics for different variants.

Figure 2 illustrates that while there was a shortening of the incubation period for Delta (summer/fall 2021) and even more for Omicron (beginning of 2022 through today), and Delta tended to produce higher viral loads than either the ancestral or Omicron variants, there isn’t much support for the period of shedding of infectious virus being shortened significantly.

As we critically examine the new CDC guidance, an important issue will be the correlation between symptoms and infectiousness. I already provided my observation above. Let’s look at what the authors of this study state:

“Considering that high viral loads can be detected in the URT (upper respiratory tract) of infected individuals regardless of their clinical manifestations, the presence of symptoms is an unreliable indicator of infectiousness. (emphasis added) Notably, individuals infected with SARS-CoV-2 can be infectious before the onset of symptoms, and it was estimated that about half of secondary transmissions take place in the pre-symptomatic phase.”

At this point, you should have a good understanding of the mode of transmission (airborne; aerosols), the incubation period (the time from exposure and infection until the onset of symptoms), the concepts of viral load (the amount of virus in their nose and throat), the period of viral shedding (the time during which there is the continued presence of virus detected in the nose and/or throat), and how we make determinations as to whether that virus is infectious (replication competent) virus. We are now ready to examine the new CDC isolation guidelines.

As usual, the changes are not easy to find or in one consolidated post, and they are not the model of clarity for science communication. Let’s start with CDC on X: “CDC’s updated guidance streamlines recommendations for dealing with a range of common respiratory viral illnesses. The updated recommendations continue to protect those most at risk for severe illness. See more details: https://t.co/HWwSqyLTXB” / X (twitter.com)

1. “CDC’s updated guidance streamlines recommendations for dealing with a range of common respiratory viral illnesses.”

My first reaction is that the CDC is perpetuating a troublesome analogy that COVID-19 is able to be treated like (and by implication, is analogous to) other “common respiratory viral illnesses.” The problems with this include:

1. Most “common respiratory viral illnesses” are seasonal. COVID-19 is not, and I will have an upcoming blog post with the evidence to demonstrate that it is not. This is dangerous because many people will let their guard down during the majority of the year that is not respiratory virus season if they subscribe to this thinking. Much more on this in upcoming blog posts.
2. Most experts who have studied the SARS-CoV-2 virus and the disease it causes realized more than a couple of years ago that COVID-19 is not limited to the upper respiratory tract like many common respiratory viruses, or even to the lungs, as in the case of more severe respiratory viruses. SARS-CoV-2 is much more of a systemic viral illness, characterized by endothelial cell damage, potentially serious neurologic manifestations, a much higher rate of post-viral syndrome (in this case, Long COVID or PASC) than is seen with other viruses, and many other long-term health consequences that we will review in depth in upcoming blog posts.
3. “The updated recommendations continue to protect those most at risk for severe illness.” We’ll discuss this after we look at the specific recommendations so that you can draw your own conclusion, however, I am worried that this will do exactly the opposite.

Let’s look at the actual guidance: Respiratory Virus Guidance (cdc.gov)

1. So, once again, we see the effort to blend SARS-CoV-2 in with other “common respiratory viruses” like “flu” and RSV: “Each year, respiratory viruses are responsible for millions of illnesses and thousands of hospitalizations and deaths in the United States. In addition to the virus that causes COVID-19, there are many other types of respiratory viruses, including flu and respiratory syncytial virus (RSV).”

What are the public health challenges with lumping SARS-CoV-2 in with other common respiratory viruses?

1. To the general public, when you mention the phrase common respiratory viruses, the majority are going to think of cold viruses, something that kids and most adults don’t worry about, don’t take any precautions to avoid, and don’t associate with any long term health consequences.
2. We have four “common cold” coronaviruses, and this new guidance promotes the prevailing notion among the public that viruses inevitably evolve to become milder (a rule that numerous viruses don’t follow – e.g., HIV; hepatitis A, B and C viruses; influenza viruses, Ebola virus, SARS-CoV, MERS-CoV, and measles virus to name only a few) and thus many will see this message as reinforcing the notion that the SARS-CoV-2 has evolved to become a fifth common cold coronavirus.
3. This will also perpetuate another popular misunderstanding among the public that the SARS-CoV-2 is now a seasonal respiratory virus like the other common cold viruses that the public is familiar with, and particularly because the CDC decided to explicitly mention two respiratory viruses that are clearly seasonal – influenza (except during influenza pandemics) and RSV. An upcoming blog post will provide the current evidence for why SARS-CoV-2 is not a seasonal virus. This will likely result in many people relaxing their precautions outside of the late fall and early winter months, and not testing and in appropriate cases not seeking antiviral treatment for a “summer cold” or assuming that their symptoms in March, May or July must be allergies.
4. We already have trouble getting people to take the influenza vaccines, and this messaging that associates SARS-CoV-2 with other seasonal respiratory viruses may further impede public health messages to get vaccinated. For example, during the 2020 – 2021 influenza season, at time when we were going through the first year of the COVID-19 pandemic, when COVID vaccines were not yet broadly available, a time when one would think interest in influenza vaccines might be among the highest, the CDC reports that vaccination coverage with ≥1 dose of flu vaccine was 58.6% among children 6 months through 17 years, a decrease of 5.1 percentage points from the 2019–20 flu season, and flu vaccination coverage among adults ≥18 years was 50.2%, an increase of 1.8 percentage points from the prior season. https://www.cdc.gov/flu/fluvaxview/coverage-2021estimates.htm.
5. Let’s compare just one of the public health impacts of COVID-19 and “common respiratory viruses” – Deaths:
   1. Influenza (2010 season – 2019 season) – the lowest number of influenza-related deaths in the U.S. was 12,000 in the 2011 season and the highest number of deaths was 51,000 in both 2014 and  2017. https://www.cdc.gov/flu/about/burden/past-seasons.html.
   1. RSV – the CDC reports that in an average year, roughly 6,000 – 10,000 people in the U.S. will die from RSV. https://www.cdc.gov/rsv/research/index.html.
   1. COVID-19 – the CDC reports (and a later blog post will explain why these numbers understate the actual number of COVID-19 deaths) 1,181,607 COVID-19 deaths in the U.S. since the start of the pandemic (2020 – now). If we look at the most recent full year of data (2023), a time when the CDC is saying that this is no longer the emergency that it once was in that we have much higher levels of immunity due to vaccination, prior infection or both, we still lost 75,232 Americans to COVID-19. https://covid.cdc.gov/covid-data-tracker/#trends_weeklydeaths_select_00.
6. Another challenge is that instead of providing focused guidance for the prevention of COVID-19, they now lump all the prevention guidance together. Hygiene and Respiratory Viruses Prevention | Respiratory Illnesses | CDC. This is problematic because while some of the advice that is appropriate for common cold viruses such as hand hygiene, cleaning surfaces, and covering coughs and sneezes is good general advice, it is wholly inadequate in preventing the transmission of COVID-19. I still have people inquiring as to whether they should wear gloves or wipe down packages because they remain confused about the transmission mode of SARS-CoV-2 based on earlier CDC messaging concerning it. To understand how inadequate these measures are, review the first part of the Part II blog post in which I discuss the mode of transmission for this virus.

I do want to commend the CDC on their section on air handling: Taking Steps for Cleaner Air for Respiratory Virus Prevention | Respiratory Illnesses | CDC. This is a topic that does not get enough attention. I will go into far more detail than the CDC does in a future blog post.

The CDC in essence eliminates the isolation guidance and replaces it with:

“You can go back to your normal activities when, for at least 24 hours, both are true:

• Your symptoms are getting better overall, and
  • You have not had a fever (and are not using fever-reducing medication).”

One immediate criticism I have is that the CDC does not define what a fever is, or if they do, I didn’t see it. Secondly, we don’t have very good data on this, especially with newer variants, but even at the beginning of the pandemic, we only saw fever in 81 – 82% of patients with mild – moderate COVID. I certainly have the impression from many of the people who have consulted with me about their infection or a family member’s infection recently, that number may be less now. Further, all the examples they provide are ones in which the patient has fever. Fever does not correlate well with the infectious period, so it seems unwise to place so much focus on that one sign and potentially inadvertently send the message that if they don’t have fever, then they may have a mild case (none of the case definitions for severity of illness include fever as a criterion) and might suggest to them that they are not infectious.

So, one can look back at Figure 1 so that you can draw your own conclusion, however, here is my critique of this advice as applied to the case of COVID-19:

Many people’s symptoms with COVID-19 are the worst on the 1^st day – day 0 in the figure. On day 1, the majority of people will feel “better.” However, look at where we are on day 1 in terms of infectious virus and the levels of infectious virus for the next week. Thus, a lot of employers may expect their employees to return to work the next day or two after symptoms begin, and a lot of employees and students may believe it is fine for them to return to work or school then, yet they may remain infectious for just over a week. And, let’s face it, few employers and schools have implemented the air handling guidance I commended above.

Now, I don’t want to just criticize. I will explain what I would believe the current state of the science (though I admit it is inadequate and not updated, but it all any of us have to go on) would support: returning to work or school when your symptoms (perhaps other than fatigue) are largely resolved (as opposed to improving) and a rapid antigen test is negative.

Now, to be fair, the CDC’s guidance goes on in the next paragraph to state:

“When you go back to your normal activities, take added precaution over the next 5 days, such as taking additional steps for cleaner air, hygiene, masks, physical distancing, and/or testing when you will be around other people indoors.”

I have already commended the CDC for the “steps for cleaner air” and criticized the “hygiene” guidance at least to the application to COVID-19. How about masks?

When you click on that page, you are presented with this picture:

At this point, all of the aerosol scientists have just fallen out of their chairs and had a seizure. We have known for years now that surgical/procedural masks are wholly inadequate to protect their wearer or others from highly transmissible airborne viruses. Like the hand-washing and cleaning of surfaces, this will make people feel like they are doing something, but not protect anyone. We will do a deep dive into what we have learned about masks in an upcoming blog post, but you can see from this picture a number of problems, but I will point out just a few. The SARS-CoV-2 virus is much smaller than the diameter of one of the hairs making up his beard. Look at the bridge of his nose. See any gaps that are wider than the diameter of a hair? Keep in mind, when breathing through his nose, air will be preferentially directed through the path of least resistance – the gap around the bridge of his nose. See any gaps on the side of his face or under his chin? Do you suppose that his beard prevents the mask from getting a good seal to the skin of the face? (the answer is yes). When he breathes through his mouth, air will be directed through those gaps on the sides of his face and under his chin. The reverse is also true. As he exhales virus into the air, they are exiting through those gaps. Much more on all of this in that future blog post.

Again, to be fair, the CDC does provide some good information further down the page about masks and respirators, but in my opinion, the damage is done when people see the picture above, which does not promote the best and most consistent messaging about masks in the prevention of transmission of SARS-CoV-2.

Again, instead of just criticizing, what would I have done? I would have selected a picture of someone with an N95 mask, or at least a KN95.

To again give the CDC credit where I can, they do provide information on testing, however, they describe it as an “additional” strategy, instead of a whole-hearted endorsement to test prior to returning to work or to school. Further, once again, the picture you land on when clicking on that guidance is a bad choice in that it demonstrates poor testing technique.

Finally, I was disappointed to see that the CDC put all of the burden for protecting those who are immunocompromised, disabled and pregnant on those people.

I understand that the CDC finds itself in a tough spot. No matter what their guidance, large groups of people are likely to be unhappy.

Here are my final thoughts and recommendations:

1. It is my impression that this got rushed. While I knew this was coming, I was under the impression that this would be coming in April, until I got a call last week from someone providing input to the CDC on this guidance asking for my advice. I have only had the chance to speak to one local public health professional and it appears they were blind-sided by this guidance, as well.

Recommendation #1. The CDC would be better served to seek input from those on the front lines – state and local public health departments – prior to issuing new guidance.

• As I think back on the guidance throughout the pandemic, there has repeatedly been poor messaging. Here is just one example from the FAQs: “It (the Respiratory Virus Guidance) should not replace specific guidance for viruses that transmit through the air and require special control measures, such as measles.” The science is overwhelming that the mode of transmission for SARS-CoV-2 is airborne, and the CDC acknowledges this fact in some parts of its website, so why would the CDC make a statement like this that suggests that Influenza and SARS-CoV-2 are not viruses that are “transmit(ted) through the air?”

Recommendation #2. Have some people who are knowledgeable, but not necessarily experts review the materials to provide you with advice on where better word choices can be made, what portions are confusing, whether all of the information is easily accessible and understandable, where words are being used (like fever) that might mean different things to different people and therefore need to be defined, and whether things like the pictures selected actually reinforce the intended messages.

Recommendation #3. Start out with a clear message of what you are trying to accomplish. Why are you changing the previous guidance? Why now? What has changed? What is your public health goal? As I explained to the expert who asked for my advice, if I was the White House COVID advisor and the President asked me to draft a plan to manage the pandemic, my first question would be, “what is the outcome you are trying to achieve?” If he said I don’t want deaths to be in the news every day, then I would formulate a plan that would likely have much more focus on things like vaccination of staff and residents of nursing homes, for example. If he said, I don’t want kids to be out of school, then my plan would focus on childhood vaccination and school air handling. If he said, we just got these vaccines and I want to make sure they are still working when the next election comes around, then  my plan is going to be more focused on preventing widespread transmission and infection of immunocompromised persons. Hopefully, you see my point. The CDC should be clear as to what is their goal. My own personal goal would be to prevent the long-term health consequences of repeated infections, but the CDC barely mentions this.

• Follow the science. It is incredibly important to restore the trust in the CDC. If it bends to political or business interests, that may benefit it in the short-term, but the science doesn’t change, and eventually it will become clear that the CDC abdicated its duty and the loss of trust will be very difficult to overcome, especially since we are not likely far off from the next pandemic threat. One problem is that we don’t have current science for these new variants, as you could see from my review of the science above. The CDC and the NIH should be pushing for these kinds of studies so that we would have current data when the CDC needs to reevaluate its guidance and so it can use that science to support its recommendations.

Recommendation #4. Promote the studies necessary to equip the CDC with the science to support changing guidance.

Recommendation #5. Provide technical briefings that review the science and how the CDC is applying the science to the goal for the guidance. Instead, the FAQ that was issued, Respiratory Virus Guidance Update FAQs | CDC, doesn’t include any science of evidence to support the recommendations.

• Please stop trying to analogize COVID-19 to influenza, RSV and common cold viruses. This is not science or evidence-based and further undermines your credibility. The science and facts should never be tortured in such a way as to comport with political or business objectives.

Stick with the science and the facts and make recommendations accordingly, and then allow politicians to implement them or not.

Also, be more precise. In the FAQs, you state: “COVID-19 health impacts are now increasingly similar to other respiratory viruses.” This is not even close to being an accurate statement. While there are certainly other post-viral syndromes, most common respiratory viruses don’t cause them to any significant extent, and even those that do, don’t appear with anywhere near the prevalence of PASC. Further, most respiratory viruses don’t cause the serious impacts we have seen to pregnant women and their unborn babies, nor the extent of the cardiovascular and neurological sequelae we are seeing with COVID-19. The public may not care about or wish to take the actions necessary to avoid these other health consequences, but failing to acknowledge these risks and issues and educate the public, deprives the public of being able to make informed and educated decisions as to their own personal health risks and those for their children and to weigh taking additional steps according to their own level of risk tolerance.

Recommendation #6. Stop trying to fit COVID-19 into a common respiratory virus category. Perhaps one day it will be, but it is not today. Misleading the public to consider COVID like the flu, RSV or a common cold is disrespectful to the millions of Americans suffering from PASC (Long Covid) and other long-term health consequences and potentially places more Americans at risk for developing these health problems.

Recommendation #7. Focus instead on how COVID is different from the flu and common cold. Provide Americans with the emerging science and warnings from it about the increasing risks with repeat infections, with the concerns that are being raised with infants being infected, with the concerning evidence for neurological sequelae from COVID-19.

• Show more respect, more empathy and more attention to the disabled and the immunocompromised. Don’t gaslight them by stating that you are going to treat COVID like a seasonal common respiratory virus and that this will help protect these groups of Americans. They aren’t falling for it, and it is clear to any of us who care for these folks that you have placed all of the burden to protect them on themselves.

Recommendation #8. Acknowledge those who are immunocompromised and otherwise disabled and their legitimate concerns. Advocate for safe essential services for them – dentists, doctors, hospitals, etc. Don’t state that “we have more and better tools” to prevent and treat COVID-19 when vaccines provide limited benefit, if any, for some of those with primary immunodeficiencies, when all of the previously available monoclonal antibody treatments are now ineffective due to widespread transmission of the virus and subsequent mutations and recombinations that have conferred immune evasion and when these patients used to have the protection of long-lasting antibodies through Evusheld, but that is no longer available. Immunocompromised patients have many fewer options to prevent and treat COVID, and this point needs to be acknowledged.  

This concludes Part II of the blog series and the topic of transmission characteristics of the SARS-CoV-2 virus. The upcoming Part III will deal with whether SARS-CoV-2 is a seasonal virus or whether COVID-19 has become a seasonal disease (spoiler alert – the answer to both is no). We have learned a lot more about the evolutionary biology of SARS-CoV-2, the traits that contribute to its viral fitness and some of the factors that determine when waves or surges occur. We will review all of that next.

Later topics will review COVID-19 vaccines, therapeutics, tests, the immune response to COVID-19, Long COVID or PASC, COVID-19 in children, and excess deaths, among others. As we get into these topics, we will also examine some of the claims made by doctors and others on the fringe or as part of the intensifying anti-science movement that Dr. Peter Hotez has written so much about. We will see whether and how well some of their claims have held up.