COVID-19 Weekly Briefing for 1/3/22
COVID-19 Weekly Briefing for Monday, January 3, 2022, in summary:
Vaccines remain our strongest layer of protection and other reminders; the C19 pandemic will unfold in three phases and we are about to begin Phase II; how to use rapid antigen tests now that they are less sensitive to Omicron (new technique and time of day may matter); PCR tests are still working to detect Omicron; new vaccine data are mostly good news especially for kids; the number of cases is the highest it has ever been; Omicron looks to cause less severe lower respiratory illness but maybe not less severe upper respiratory or GI illness and no data yet on rate of progression to long-covid with Omicron infections; new isolation/quarantine guidelines from CDPH are closer to our office's strategy than the recent receommendations from CDC; C19 mortality in NY and CA compared to TX and FL; Moderna for babies 6 months up to kids 5 yrs likely to get FDA approval in Feb; infections with prior VOCs including Delta do not protect well against infection with Omicron but infections with Omicron do protect against infections with Delta and that has implications for where the things are heading in the near term.
1302 -1307. This week's briefing begins with a few important reminders. First, it is appropriate that we recalibrate our expectations of vaccines, boosters, and rapid tests to align with Omicron but we should avoid the false binary narrative that if these things are less effective then they are ineffective. Here are some national mortality rates that should help clarify the case for anyone whose vaccine-hesitancy derives from the false understanding that vaccines are ineffective:
Deaths among unvaccinated: 6.1 per 100K
Deaths among those with primary vaccination: 0.5 per 100K
Deaths among fully immunized (primary vax plus booster): 0.1 per 100K
Here in San Diego, we have seen a five-fold increase in infections, an 11-fold increase in hospitalizations, and a 13-fold increase in deaths among those who were unvaccinated or under-vaccinated compared to those who completed the initial primary vaccination (two shots of mRNA or 1 shot of Janssen). Those ratios skew much further in favor of vaccination if we compare only those who completed their primary vaccination or are fully immunized (boosted) to those who are unvaccinated. For example, according to the CDC, a person who is unvaccinated is 10 times more likely to test positive for C19 and 20 times more likely to die compared to a vaccinated (unboosted) person.
And here we see a graphic representation of hospitalizations comparing vaccinated against unvaccinated in NYC as we enter the era of Omicron (which implies, as a side note, that Omicron may not be less virulent than prior VOCs–at least with regard to upper respiratory illness):
Here are some big-picture concepts to keep in mind (all part of our practice protocols):
Being fully immunized is a strong layer of protection against infection and an extremely strong layer of protection against developing severe disease or dying.
Masking is another strong layer of protection against both infection and developing severe disease or dying. However, prevention against infection is only robust if it involves the use of a high-efficiency mask that is properly fit to the face with no loose gaps for air to go around the mask. A loose-fitting mask, even if it is high-quality, is minimally protective against infection as are cotton or nylon masks–even if they are well-fit. Surgical masks have better filtration than cotton or nylon but are not anatomically designed to create a close fit for most faces. How do even low-quality masks like surgical masks help prevent progression to severe disease/death if they are only minimally protective against infection? By lowering the viral inoculum (remember the early cruise-ship studies with high rates of asymptomatic and minimally symptomatic passengers who wore cotton masks presented during the briefings in spring of 2020).
Face shields offer an additional layer of protection when worn in addition to masks.
Outdoors and well-ventilated rooms are another strong layer of protection.
HEPA units are another layer of protection (we have one in every room of our clinic including bathroom, waiting room, and exam rooms).
Handwashing and avoiding touching one's face is another strong layer of protection.
Avoiding congregate settings is another layer of protection. Tricia and I only left our home over the holiday break to get food at the store or come into the office to take care of a couple of patients and do some housekeeping. WE WOULD NOT CONSIDER DINING OUTDOORS AT A RESTAURANT as this has been the number one cause of community outbreaks throughout the pandemic and Omicron, with its more efficient spread, is undoubtedly ripping across restaurant patios daily (the SDCDPH stopped collecting this data after Delta arrived when they effectively abandoned contact tracing). WE WOULD NOT CONSIDER attending a concert, play, or sporting event where people are packed together for prolonged periods of time, some unmasked, many/most under-masked, all cheering, shouting, talking, singing, etc.
Daily rapid antigen tests (RATs) are another layer of protection. However, RATs must be performed correctly. Only in the US are we restricted to doing just nasal swabs and the virus probably grows migrates to the nose later in the disease course compared to the throat. A better technique is to combine throat and nose swabbing. Testing is probably better in the middle of the day when viral titers tend to peak. Finally, the best use of RATs is for daily surveillance (more about all of this below). Single-use RAT spot-checks is a weak strategy (on its own) but can be incorporated into a multilayered strategy as one of several barriers of protection.
The understanding we should all have fully internalized by this point but is nevertheless worth repeating is that no one layer by itself offers sufficient protection against infection but the degree of protection goes up with the addition of each layer. Whenever we let our guard down by choosing to not employ one or more of the layers, we increase our risk of infection. For example, eating lunch outdoors with coworkers who are not members of your household increases the risk for everyone involved. Throwing on a cloth or surgical mask rather than a high-efficiency N95 alternative to ‘just quickly run into the store’ increases the risk of that event substantially. The same goes for choosing not to open a window because it's cold/hot outside or attending a party because you don't want to disappoint family or friends. Full immunization (3 shots or 2 shots plus an infection) and masking are the two most important layers of protection. Everyone in our practice has been fully immunized but this is not the time to drop masking. We have about 6-8 weeks ahead of us during which time we should be taking maximum precautions–more about what to expect in the next section...
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Where are we now and where are we headed with C19?
It is not good scientific practice to make predictions without conclusive data. On the other hand, trying to predict what's coming is how we make strategy manage anxiety during times of stressful uncertainty. So, while I recommend we all continue to refrain from prognosticating with patients, within our team I think it is reasonable at this moment to share one version of what we could reasonably expect, at least in the near and medium-term, based on the accumulated and most current data–with the caveat that, because the covid-terrain is constantly changing, all predictions should be understood as ‘informed conjecture.’
In the last 2 weeks, many of us have had C19 enter our lives directly, with family, friends, and coworkers getting sick. When this happens, it is hard to know what to do and, along with questions about post-exposure or infection protocols, a number of general pandemic-related questions keep coming up, such as:
How bad will the Omicron wave get?
When will it be over?
When can I plan to start traveling again?
Will SARS-CoV-2 become an endemic virus like influenza that we all just learn to live with?
Is Omicron milder? Should I just expose myself to it and get it over with?
If so many people who are vaccinated are getting infected, why should I get vaccinated?
If the rapid tests aren't accurate, what's the point of using them?
Here is the big picture: According to my crystal ball, the pandemic will unfold in three phases as follows:
Phase I: This is the period in which the virus spreads like wildfire all over the world, catching governments and scientists off-guard and leading to a disorganized approach to mitigation that is ineffective. During this first phase, the virus keeps mutating to cause new variants with evolutionary pressure toward faster spread. Each new faster-spreading variant will displace the prior one until most of the world has developed a measure of immunity that begins to make the faster-spreading variants less successful at causing infection (‘herd immunity’). We should get to that point and transition into Phase II by the end of the Omicron wave (likely the end of Feb).
Phase II: Once most of the world has reached herd immunity, evolutionary pressure will push the virus to mutate mainly away from prior immunity. The new VOCs will mostly or completely evade the antibodies and, to a lesser extent, the cellular immunity induced by the first generation of vaccines tuned to the ancestral 'wild type' strain. They will also evade immunity caused by infections from prior variants. This level of mutation will likely come at some cost to the virus, making it perhaps less contagious, less efficient at replicating within infected cells, and/or less virulent (the latter is actually advantageous to the virus). Omicron, which replicates 10x more slowly in lung tissues compared to Delta is an example of how this more mutated variant may be becoming less likely to cause ARDS (severe pneumonia caused by the 'cytokine storm' that requires ICU/CCU care/ventilator). On the other hand, early data suggest that Omicron mutates 70x faster in the upper airways/mainstem bronchi. This may be part of why it's faster spreading than Delta. Omicron looks to me like a sort of transitional variant between Phases I and II, with faster spread and more immune evasion but lower virulence (causes less severe illness).
Phase II is also the period in which science and innovation steadily gain the upper hand over the virus. Over the last week, we have seen the approval of two antiviral medicines and we can expect more to come. Pfizer is already at work making Paxlovid in a nasal spray form. That will make it more effective as early treatment and an ideal prophylactic therapy for those who work in high-risk environments or have had a known exposure. By directing the medicine at the site of colonization (the nose/nasopharynx/throat/bronchi), intranasal Paxlovid could be able to stop Scov2 before it has time to penetrate into the body's interior to cause an infection. Intranasal antiviral therapy might prevent the virus from entering the brain to cause gray matter destruction.
We should also expect to see new vaccines tuned to the newly emerging variants (as we currently have with vaccines against influenza) and, more importantly, pan-coronavirus vaccines that offer protection against any/all human beta coronaviruses. We may even see these come to market as intranasal preparations. By spraying them into the nose, vaccines could engage the MALT, making protection against infection stronger by provoking high titers of IgA to patrol the nasal, oral, pulmonary, and gut mucosa in search of Scov2 (or other beta coronaviruses). Phase II will also likely see the coalescence of international cooperation into the beginnings of a permanent worldwide infrastructure of science, industry, and medicine with experts sharing knowledge in real-time and spreading the production of vaccines and medicines across the globe to address the issue of inequity of access to preventive and interventional therapies. This, of course, will require leadership from persons of great courage, persuasion, and intelligence...
Phase III: is the period in which international cooperation, innovation, and viral mutation all reach an equilibrium that is conducive to the establishment of something that looks like 'normal life' again. I imagine that travel and large congregate activities will be regulated from a public health perspective to greater and lesser degrees depending on disease prevalence.
A worldwide app that verifies a person's vaccination/immune status against C19 (and perhaps other diseases) will become a normal requirement for international travel and most countries will also have a similar domestic version required for entry into bars, restaurants, cultural events, and domestic travel, the way we currently need to show ID to get into many places to prove that we are of age or have a valid ticket.
In Phase III, we will have established a new science and medical model that enables better messaging and quicker response times to rapidly-changing data–something we have not seen from the CDC during this pandemic. The new public health organizations will be led by physicians, not lab scientists, and be more nimble, geared toward providing real-time sensemaking and guidance to fit the twists and turns of the public health story as it unfolds, rather than waiting until scientific thresholds for certainty are reached before offering guidance which, by that time, are in many instances already outdated. For example, rather than waiting until a mountain of evidence accumulates to prove beyond any shadow of a doubt that a pathogen is airborne, recommendations to use high-efficiency masks will be made when early evidence suggests airborne transmission.
Of course, some of these things are already happening and the phases will likely bleed into one other. Here's how I have been answering the above questions from patients, family, and friends:
How bad will the Omicron wave get and when will it be over? Omicron has already caused the highest number of daily cases in the US including here in San Diego (more than 3K cases/day confirmed by PCR) since the pandemic began. The current wave is made up of both Omicron and Delta but Omicron is now the dominant variant in most places since it spreads faster and is better able to evade prior immunity to cause breakthrough infections and reinfections. We should expect very high numbers for at least the next several weeks with the wave essentially over and a moderate persistent case rate thereafter, beginning in mid-February. This is based on the assumption that the Omicron wave will have a higher peak but a shorter duration compared to Alpha (last year at this time) or Delta (the wave that never crashed).
When can I plan to start traveling again? This question is a proxy for When will the constraints on 'normal life' be lifted? I think we should expect Phase I of the pandemic to be over after Omicron or after the variant that follows it. But things like travel, restaurant dining, bars, and concerts will not be truly safe until the middle/end of Phase II.
Unfortunately, Phase II will require the same vigilance and behavioral restrictions that were needed (but never universally adopted and hardly enforced) during Phase I. Omicron may be the last or one of the last variants to attain dominance based on having faster spread (higher replication rates, higher penetrance into cells, higher viral titers). Phase II will likely be driven by variants with significantly more immune escape (even compared to Omicron) rendering prior immunity minimally protective against infections.
We should expect these new highly immune-evasive variants to begin to emerge this spring or summer causing new waves of cases that will necessitate better interventions, better access to therapies, and better coordinated and enforced public health education and policy including enacting rigid vaccination and masking policies. Will we answer the call? My crystal ball says yes to the technological side but no to the part that requires political will and great leadership. The right combination of enforced public policies, new vaccines, and new medicines will enable Americans to begin to travel and attend congregate social and cultural activities with reasonable safety but a significant segment of society, animated by disinformation, will resist this approach, making the US once of the least safe places in the developed world with regard to C19 in 2022 and 2023. While some of us, by this time next year, armed with a combination of vaccines and oral and/or perhaps intranasal therapies, will be able to return to a more normal version of life, including the expectation of safe travel, many Americans will continue to contract C19.
Will SARS-CoV-2 become an endemic virus like influenza that we all just learn to live with? Yes. But we are not there yet. Endemic pathogens are, by definition, stable and Scov2 is anything but that as the new Omicron wave is about to demonstrate.
Most of us will be able to live well with C19 during Phase III, once it becomes clear to the vast majority of people that the only way out of this is through cooperation, trust, and unity. As an American of a certain age, I cannot help but remain somehow optimistic. I expect that within the next two to three years, we will all be adapted to a new normal that is not substantially informed by fear and frustration over C19 but looks a little different from the world we knew before the pandemic. Already I am struck when I watch movies from the pre-covid era by how normal it once was to share food, drinks, surfaces, and air–even with strangers or new acquaintances. The invention of clear masks that enable others to see one's entire face might be a permanent feature of human society in the future, worn widely during seasons of increased cold, flu, and C19. Better ventilation will become standard for new construction buildings and restaurants, schools, theaters, and bars will be required to make similar changes by retrofitting existing structures with high-efficiency HVAC/HEPA. A culture with less hugging/kissing and sharing of air, food, and surfaces will become normalized.
Is Omicron less virulent compared to prior VOCs? We don't yet know but there is a strong early signal from the data that Omicron is less likely to lead to ARDS because it replicates more slowly in lung tissue. Less ARDS means ICUs and CCUs are less likely to be overwhelmed by the large wave of Omicron-driven cases that we are now already seeing. But early reports of mild illness with a milder flu-like clinical syndrome of aches, pains, fever, runny nose, fatigue, and GI misery are, I think, less persuasive proof that Omicron is truly less virulent as is probably, at least somewhat explained by the high level of prior immunity from vaccination and prior infections.
For example, when we look at the hospitalization rate among unvaccinated v. vaccinated in NYC (see 1304 above) it does not appear that Omicron is less virulent with regard to upper airway and GI disease compared to prior variants. And of course, if you've been following these briefings, you know that I have been concerned about the long-term effects of (even mild) SARS-CoV-2 infections. Will Omicron cause more, less, or the same amount of long-covid? Will it enter the brain as frequently to destroy grey matter in the areas of the cortex that mediate smell, taste, and memory? What effect will it have on kidneys, liver, testes, ovaries, endothelium, fat, pancreas, heart, etc.?
My take: What seems likely to be true based on the current evidence is that lower rates of replication in the lungs should drive a lower incidence of pneumonia which means less pulmonary scarring and less pulmonary-based long-covid. Early reports of significantly lower incidence of loss of smell might be a sign that Omicron may cause less neurotropism and therefore, perhaps, less long-covid brain fog and less grey matter destruction. These ideas are purely hypothetical. Let's wait and see. In the meantime, yes, Omicron is probably less virulent but no, it's not safe to contract C19.
If so many people who are vaccinated are getting infected, why should I get vaccinated? The answer is simple: vaccinated people get infected far less often and when they do get infected, they get less sick compared to unvaccinated people. That means vaccinated people are less likely to develop long-covid or experience organ tissue injury that might cause serious delayed-onset health problems later in life. Seatbelts and airbags don't eliminate the risk of being injured in an accident, but they lower it. Vaccination does not eliminate risks associated with C19 but it lowers them.
If the rapid tests aren't accurate, what's the point of using them? RATs are less sensitive against Omicron but that is likely because in the US, we use only a nasal swab and it looks like Omicron may cause viral titers to rise in the nose much later in the disease course compared to the throat. Sensitivity is better if we perform a combined throat and nose swab, rather than just a nose swab.
Remember, with most people now having prior immunity, C19 symptoms should be expected much earlier following infection compared to prior variants. RATs should be performed later, ideally beginning 2-3 days after onset of symptoms (OOS) or 5 days after exposure, and continue for at least 3 days. RATs are best performed between 11 AM and 3 PM when viral titers tend to reach their daily peak.
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1308 - 1309. The FDA releases data showing that some/many/all (?) of the rapid antigen tests are less sensitive to Omicron compared to prior VOCs. Which tests are working better or worse compared to the others? They don't say. PCR tests are still reliable (at least the ones being performed at Labcorps and Quest are). Here is the model we had been working from (no longer valid):
What does this mean for us? It underscores that the best use of rapid antigen tests (RATs) is as a surveillance tool. RATs are best performed around the middle of the day (between 11 AM and 3 PM) when viral titers tend to be at their highest. They should be performed by collecting the sample using a combined throat and nasal swab. They will likely be most accurate 2-3 days post-OOS or 5-6 days post-exposure.
It also underscores that a negative RAT should not be interpreted to mean that there is not an infection. Recently we read in the news about a study that showed that while RATs are less sensitive and therefore, can lead to more false negatives with Omicron, those false negatives were consistently correlated with lower viral titers. One interpretation of this finding was that a false negative RAT can still (quite usefully) correctly predict whether or not a person is currently contagious. If you can't culture virus from the sample, then you're not contagious, right? But we should be careful not to embrace such an interpretation too quickly. We know that with Omicron, viral replication/titers are much slower/lower in the lungs but faster/higher in the mainstem bronchi compared to Delta. We do not know how fast Omicron is replicating in the nose, the area from which rapid tests samples are harvested but early signals show the virus likely migrates gradually from the throat to the nose over several days. Low viral titer in the nose does not negate the likely high infectiousness caused by fast replication taking place in the bronchi. This understanding is consistent with what the epidemiologists are telling us. In the past, it had been established that Scov2 is most transmissible 1-2 days prior to OOS through 2-3 days following OOS. With Omicron, it is reasonable to shift our testing timetable to the right, beginning daily testing 2 days post-OOS.
1310. This study of 382 hospitalized patients with known C19, testing was performed with both nasal and saliva swabs; the nasal swabs successfully caught all of the Delta cases but missed 15% of those with Omicron while the saliva caught all of the omicron cases (PCR). This suggests that live virus is less likely to be cultured from the nose early in the disease course but is nevertheless present in the upper airway.
https://www.medrxiv.org/content/10.1101/2021.12.22.21268246v1?s=09
***1311. Actually, while in the US RATs and PCR tests are only performed from nasal or nasal-pharyngeal swabs, nearly every other country in the world is using saliva, throat swabs, or a combination of throat and nasal swabs. Here is a video from NHS England showing how to perform a home rapid test using a combined throat and nasal swab technique. We use this technique at the office and should advise our patients to do the same.
1312. There have been numerous reports of rapid tests being negative when performed by nasal swab but positive with a throat swab. In some reports, a positive throat swab confirms the diagnosis of C19 after a negative RAT performed using the US-recommended nasal swab technique. Recent studies show that nasal swabs performed serially several times per day do not turn positive until 36 or 48 hours after the throat swab does. This suggests slower viral replication in nasal tissues (like we see in lung tissue cells) compared to the throat, trachea, and bronchi or delayed migration of the virus from the throat to the nose.
Michael Mina, who has been at the forefront of using daily RATs to control the pandemic chimes in as follows:
The bottom line is that we must be careful not to rely on a negative RAT as proof that someone is not infected or is not infectious and we should always perform the combined nasal/throat swab technique when using rapid tests.
1313. Meanwhile, PCR tests, two of which used platforms that were problematic for detection of Omicron, have been fixed and now all PCR tests offered in the US are reliable again (the ones being used at Quest and Labcorps never had the problem).
1314. In South Africa, Omicron infections showed a 17% lower risk of leading to hospitalization compared (contemporaneously) to Delta. However, once a person was hospitalized with either Omicron or Delta, their odds of progression to severe disease were the same. https://www.medrxiv.org/content/10.1101/2021.12.21.21268116v1
1315. C19 vaccines are incredibly safe for children ages 5-11.
https://www.cdc.gov/mmwr/volumes/70/wr/mm705152a1.htm?s_cid=mm705152a1_w
1316. How well are the C19 Vaccines working to prevent hospitalization in kids 12 - 17YO?
72% of hospitalizations among vaccine eligible seen in unvaccinated
0.4% of hospitalizations among vaccine eligible in vaccinated (2-doses)
That's a 180-fold reduction in hospitalizations among vax'd kids compared to unvax'd.
https://www.cdc.gov/mmwr/volumes/70/wr/mm705152a3.htm?s_cid=mm705152a3_w
1317. Protection against infection is lower and wanes more quickly against Omicron but boosters lower the risk of progression to hospitalization by 88%.
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron_severity_update.pdf
1318. California DPH doesn't agree with the new CDC recommendations for people infected with Scov2 to isolate for 5 days followed by 5 days of mask-wearing. CDPH recommends 5 days isolation plus a negative test, performed on Day 5, before they can end isolation. The CDC’s recommendations don’t ask for a follow-up negative test but only that those ending isolation continue wearing a mask around other people for 5 additional days. How could that possibly be reliable and responsible public health messaging?
CDPH recommends fully-immunized (boosted) who have had exposure to quarantine for 5 days followed by a negative test taken on day 5 to end the quarantine. They do not identify which test must be used but I think we can all agree that only a positive RAT on day 5 of quarantine would demand prolonging the quarantine. My note: If RATs are performed correctly on days 5 and 6 of quarantine and are both negative, that seems reasonable assurance that an infection did not occur. A negative PCR test performed on days 4, 5, or 6 offers similar reassurance.
CDPH offers 10 days isolation/quarantine as an alternative for those who do not want to/can't get tested on day 5. This strategy is consistent with the available data while the new CDC guidelines are not. I hope the CDC will retract/update their latest recommendations ASAP.
https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/COVID-19/Guidance-on-Isolation-and-Quarantine-for-COVID-19-Contact-Tracing.aspx
1319. New York and California state governmental authorities pushed harder than most states with regard to requiring masking and vaccinations while Florida and Texas pushed back just as forcefully against any masking or vaccination mandates. How did each of these states fare compared to the national average? Unsurprisingly, Florida and Texas registered significantly higher per capita death rates compared to the national average while New York’s and California's death rates were significantly lower (among those under age 65).
1320. Moderna is likely to be the first to get EUA for C19 vaccine for babies 6 months to children aged 5 yrs. Expected to get approval by late Feb. No myocarditis yet in pediatric trials for 6 months to 5YOs (so far).
https://www.wsaw.com/2021/12/30/moderna-vaccine-trial-young-children-nears-finish-line/
1321. Although infection with delta does not produce strong neutralizing antibody protection against Omicron, infection with Omicron does elicit neutralizing antibody protection against Delta. We should expect Delta to therefore more or less disappear as Omicron continues to take over and offer high protection against infection with Delta (especially among those who were vaccinated and then had an Omicron breakthrough).
https://www.ahri.org/wp-content/uploads/2021/12/MEDRXIV-2021-268439v1-Sigal_corr.pdf
Non-Covid
1322. Kittens and cats show the same bonding and distress behaviors toward their human 'parents' as human babies and children do toward their biological parents. Once thought only seen in humans and dogs, it now appears that cats share similar distinct attachment styles with their human caregivers that human babies do. 60% of kittens displayed a secure attachment style. They were distressed when their caregiver left the room and relieved and behaviorally appropriate when they came back. Roughly 30% of the kittens displayed an insecure attachment style, remaining stressed upon reunion displaying excessive contact, avoidance, or some disorganized mix. These specific behaviors as well as the 60/30 split of secure/insecure attachment styles mirrors that found in the literature for human children.