COVID-19 Weekly Briefing for 1/10/22
COVID-19 Weekly Briefing for Monday, January 10, 2022, in summary:
Beware of bogus testing sites in San Diego; we should stick to the science and recommend > 5 days isolation for infected; it takes 3 additional days to test positive on nasal swabs compared to throat swabs; a Ct value of <29 on PCR means you're infectious; UCSD gets FDA EUA for their new PCR test; asymptomatic infections are high; Pfizer boosters are at 5 months post primary vaccinaton (PPV) per new CDC guidance; 3 shots now means 'up to date' with vaccination per new CDC nomenclature; the first viral vector vaccine in pill form, from Vaxart, works better than the current mRNA vaccines; the real case rate is 4-5 times higher than the official numbers; the CDC forecasts 20K+ hospital admissions/day in the next couple of weeks; cognitive dysfunction is present in 10% of post-covid and loss of smell/taste now estimated at 1.6M Americans; the US is not yet seeing as strong an uncoupling of cases from severe illness as other countries have seen because we are under-vax'd and obese; Omicron has a different way of gaining entry into the cell than prior variants; Paxlovid is enrolled into the Medicines Patents Pool; cool non-C19 study shows cataract removal can reduce the risk of dementia.
C19 Testing in San Diego
1323 - 1325. Adding to the confusion and frustration of healthcare providers and patients alike, bogus C19 field testing sites have been popping up in San Diego. Some are collecting personal data, likely for nefarious purposes, including insurance information, addresses, DOBs, and SS #s. Others are simply not performing the tests that they are charging for. Still others are serially billing insurance companies for additional tests not being performed. Patients getting tested at field-testing sites should ask which lab their samples are being sent to. If the people at the site don’t know, it’s probably a bogus test site. They should also confirm that the lab is certified by the CDPH by going here before getting tested. They should not pay for PCR tests (which are supposed to be free). They should ask the person taking swabs what their healthcare credentials are–C19 testing should not be performed by non-healthcare personnel. Any field-testing site that seems suspicious can be reported here.
We are not going to resume open testing for C19 at the office at this time. As you will read below, Omicron is causing the highest national and local case rates since the pandemic began. It is estimated to be more infectious than measles or smallpox and bypasses vaccination-induced immunity at an unacceptably high rate. In my estimation, we are taking on enough risk by continuing to see patients in the office, especially with the high estimated rate of minimally symptomatic and asymptomatic cases (see below) without performing throat swabs on sick or exposed patients upon request. Providers may still perform/order RATs or PCR tests at the office to meet the needs of special clinical circumstances at their discretion.
In terms of our office policy for team members, we will continue to require 5 days isolation from the date of a positive test followed by a negative PCR; or two consecutive days of negative RATs, beginning on day 6 post-diagnosis; or 10 days isolation with a negative RAT on day 10 for return to work in the clinic.
Our strategy is strictly safety-based; it does not address the discomfort felt by the entire team whenever someone is out sick. It is in contrast to the CDC guidance which recommends 5 days isolation followed by a return to work without the need for a negative test, followed by 5 days of masking. This guidance was likely created to address anticipated personnel shortages (especially in the hospitals which in some places are already being overwhelmed). It also differs a little from California DPH which last week recommended 5 days of isolation plus a negative 'test' to return to work but over last weekend, added an exclusion in the case of healthcare workers (HCWs) such that asymptomatic HCWs who test positive through Feb 1, 2022, need not isolate or do any further testing and those who were exposed need not quarantine or test but rather, in both scenarios, must wear N95 respirators for source control. There are no persuasive data showing that 5 days of isolation is a sufficient amount of time to avoid/stop the chain of transmission and very few people outside our office understand masking. If our practice gets overwhelmed we could consider taking a riskier approach.
Testing
1326. PCR tests detect Omicron at a lower Ct value (more easily) from oral swabs compared to nasopharyngeal swabs. The reverse was true for Delta. Oral (saliva) testing is more sensitive with Omicron (which now makes up > 95% of all cases in the US).
https://www.medrxiv.org/content/10.1101/2021.12.22.21268246v1
***1327. 30 patients with Omicron received saliva PCR (29 showed SGTF) and RATs using nasal swabs. It took three additional days, on average, to get a positive result on the RATs after testing positive by PCR. Four out of those thirty patients spread the disease during the early part of the disease course when their RATs were as-yet negative. Important: the authors note that a Ct value of < 29 indicates sufficient viral load with Omicron to be infectious. I don't know where they got that data from but, as discussed in a prior briefing, it would be good for us to ask that that information be included by Quest and Labcorps when we order tests. People who are seeking to emerge from isolation could do so safely even if they have more robust test data like Ct values. PCR tests can continue to detect viral nucleic acids for up to a few weeks in some cases even though such people are, in most cases, likely well past their infectious periods. Such people would be likely to have a Ct value of 30 or more which we could use as a metric for the safe ending of isolation. Unfortunately, the labs are not communicating well with clinicians, and recent attempts to get additional information have been disappointing.
https://www.medrxiv.org/content/10.1101/2022.01.04.22268770v1.full-text
1328. FDA grants EUA for UCSD's new PCR test which can be collected at home and then sent into the lab.
1329. Dr. Fauci explains that the new CDC guidelines enabling infected people to break isolation after 5 days without a test were political, not scientifically-based. With the high level of cases expected during the Omicron wave, CDC did not want too many essential workers off duty. That explains it but is this the right role for CDC? Should scientists without political or economic expertise be making public health policy based on economic modeling?
1330. Meanwhile, in places like NYC, we are seeing that 50-65% of people being admitted to the hospital for non-covid reasons are testing positive for C19 (incidental cases), suggesting very high asymptomatic prevalence. Do we think these people will not spread it to their coworkers? I have not seen data supporting that there is a direct link between degree of illness and the degree of infectiousness.
https://www.nytimes.com/2022/01/04/health/covid-omicron-hospitalizations.html
Vaccines and Vaccinations
1331. CDC changes recommendations for Pfizer boosters from 6 months post-primary vaccination (PPV) to 5 months. My note: it should be a three-shot primary vaccination regimen as follows: second shot one month after the first; third shot four months after the second.
https://www.cdc.gov/media/releases/2022/s0104-Pfizer-Booster.html
1332 - 1333. Only about 1/4 of Americans have had third shots and third shots are needed if the goal is to prevent infections and shut down waves of transmission. But instead of changing the definition of 'fully vaccinated' to mean a three-shot primary vaccination regimen, the CDC has decided to add new terminology to the already confusing vaccination status discussion, referring to those who have had 3 shots of mRNA vaccine as 'up to date.' They make exceptions for immunocompromised children and adults ages 5 or older who got Pfizer and for moderately or severely immunocompromised adults 18 and older who got Moderna, for whom they now recommend "an additional primary shot.” These groups are also now recommended to get a fourth shot which the CDC is calling the 'booster.' So two shots of mRNA vaccine for non-immunocompromised or two shots plus a third "additional primary shot" for immunocompromised = fully vaccinated according to new CDC terminology. Three shots of mRNA vaccine for non-immunocompromised or four shots for immunocompromised = up to date. Inexplicably, those who got Janssen are not recommended to have even one additional primary shot despite the fact that we know it underperforms compared to Pfizer and Moderna. Everyone is encouraged to get an mRNA booster on top of their primary vaccination regimen to bring their vaccination status "up to date."
My take: the CDC should be working to license Novavax or VXA-CoV2-1 from Vaxart (see below) and phase out Janssen (the least effective vaccine and the only one currently in use in the US that has been causally linked to fatalities). In the meantime, as suggested by Dr. Fauci, they should update the term "fully vaccinated" to mean 3 shots of any of the vaccines (including mix/match protocols) or (my take) two shots plus an infection.
1334 - 1335. Dr. Fauci has recently argued in favor of the CDC changing the primary vaccination regimen (regardless of vaccine) to 3-shots and changing the definition of 'fully vaccinated' to mean those who have had 3 shots. However, fearing still more legal challenges to the Biden Administration's attempt to enforce vaccination mandates for businesses with 100 or more employees, the CDC has instead chosen to introduce new language that most people will likely find more confusing than clarifying.
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html
1336. The first oral vaccine from Vaxart (pill form) called VXA-CoV2-1 induces a 250% stronger T-cell response compared to mRNA vaccines as well as IgA in the MALT, making it better in every way compared to the best current vaccines. Oral tablets/suspensions and intranasal sprays are the future of vaccination and therapy for respiratory and GI infectious diseases and are a sign that we are entering into phase II of the pandemic. Vaxart's non-replicating adenovirus formulation with adjuvant targets both spike and (more epitopically conserved) nucleocapsid proteins. T cell responses against four other endemic HCoVs (including some cold viruses) were also induced by vaccination, so a single oral dose of VXA-CoV2-1 could be cross-protective against a wide array of known and emerging pandemic coronaviruses according to this small early clinical trial.
1337. Italy mandates vaccination as well as proof of vaccination to get into work in the public or private sector. Violators will be fined 600 Euros. That will be hard to achieve in the US where political disinformation is unregulated and about one-third of Americans are under the sway of anti-vax conspiracy theories. It doesn't help that the CDC has entered into the political arena with muddy messaging poorly calibrated to avoid angering these people.
https://www.theguardian.com/world/2022/jan/05/italy-makes-covid-vaccinations-compulsory-for-over-50s
1338. Seroprevalence of anti-Scov2 antibodies among adults in Gauteng, South Africa prior to Omicron = 80%–one reason that Omicron infections appear to be causing less clinically severe disease. Another reason is that it replicates more slowly in the lungs and therefore, causes less ARDS. Of note: only about 18% of the 7K study participants had been vaccinated so the vast majority of their prior immunity came from infections. My note: If Omicron replicates more slowly in the lungs and possibly in the nose as well, and if the viral titers it creates are not higher, why is it so much more transmissible, even compared to Delta? One reason may involve its different cell entry pathway (see 1353 below). Another might be the Omicron, by several accounts, seems to cause significantly higher mucous production. This may be a function of the virus or it might be the result of prior immunity (runny nose is a symptom of immunity). Symptomatically infected people with runny noses are likely causing a higher rate of fomite transmission (transmission through touch) than we saw during prior waves of C19 that had dry upper airway disease.
https://www.medrxiv.org/content/10.1101/2021.12.20.21268096v1
1339. Vaccines tuned to the Scov2 ancestral 'wild type' strain's spike built 2 years ago have preserved efficacy of 88% against severe disease with a 3rd shot, even with the highly mutated Omicron variant. Unfortunately, the US lags well behind other advanced countries in getting third shots (less than 25%):
Why? Disinformation from political actors combined with confusing and sometimes non-science-based messaging on the part of the CDC have left many smart people confused about which tests to use and when to use them, therapies, the risks of delayed onset illness and long-covid, masking, and vaccinations/boosters. Helping patients understand that 'fully vaccinated' should mean three shots (even if the CDC is afraid to say so explicitly) is one of the most important jobs that we have as healthcare professionals at this moment.
Epidemiology During Omicron
1340. Columbia epidemiologist Jeffrey Shaman estimates the actual number of current C19 infections is 4-5x higher than the reported number. Too many people assume they have colds, are taking at-home rapid tests that do not get reported to the DPH, are not getting tested at all because based on guidance from their doctors who are telling many patients to just isolate and not test, or are asymptomatic and don't know they’re infected. Many of these people are undoubtedly spreading the disease.
https://www.washingtonpost.com/health/2021/12/30/how-long-will-omicron-last/
1341. CDC forecasts hospitalizations in the US to rise to 20K+/day in the next couple of weeks.
1342. In most places, we are seeing a strong decoupling of case rates from hospitalization and death rates (signaling that we are approaching herd immunity and/or Omicron is less virulent) as this graph of the current wave in London shows:
1343. But in the US, we are seeing more than a million cases/day with 1 out of every 100 Americans infected in the last week by official counts (think 4-5 times higher than that as the actual incidence rate) and child hospitalizations for C19 are soaring.
https://www.medscape.com/viewarticle/965941?src=soc_tw_220104_mscpedt_news_mdscp_milestone&faf=1
1344. And in places like NYC, we are seeing significant rises in hospitalizations d/t C19:
However, with the high rate of asymptomatic infections, at least some of these are most likely to represent incidental infections.
1345 - 1348. The US has a relatively low vaccination rate of about 62% and a much lower rate of boosted ('up to date' per the new CDC nomenclature as discussed above) of just 23%. The country that invented most of the vaccines and was best supplied with them ranks 66th in the world with regard to primary (CDC nomenclature = 2 shots) vaccination. Since we need 3 shots to build strong immune defenses and since we have the highest rate of obesity in the world among developed nations along with extremely high rates of obesity-related chronic illness, it is not surprising that we are also seeing higher hospitalization rates which jumped from about 40K nationally in late Nov to 65K on Christmas eve to > 110K by the end of last week. With an estimated up to 20% of healthcare workers infected or expected to be infected, this is undoubtedly one factor the CDC took into consideration when relaxing its recommendations for quarantine and isolation. Shortages of healthcare personnel in the context of rising hospitalizations is a disaster scenario we have been working to avoid throughout the pandemic.
1349. South Africa showed a high spike but a short wave with a drop to pre-wave levels after about 6 weeks. Will we see that elsewhere? In this graph showing some of the countries hit hardest by Omicron, note that only SA and Israel (where they are now giving out fourth shots of Pfizer) have seen a return in case rates to pre-wave levels (at least so far). Let's remember that the same thing was predicted about Delta after we saw the huge spike drop quickly in India. But in the UK and here in the US, while there was a precipitous drop from the peak, the numbers never came back down to anything close to pre-Delta levels and in fact, we (and the UK) continued to have rolling waves of Delta throughout the fall and early winter. My take: it's still a bit too early to tell but we should expect longer ‘tails’ to this wave in the US than in better vaccinated, healthier countries.
Long Covid
1350. Among 2K participants between ages 18-54, the presence of cognitive dysfunction assessed via an abbreviated form of the Barkley Deficits in Executive Functioning Scale (BDEFS) was seen at a much higher frequency among those who had C19 compared to controls, regardless of the severity of acute illness. The degree of cognitive impairment, however, was linked to the severity of the acute infection and it was higher among men, and also among younger adults. Overall approximately 10% of those who had been infected had demonstrable impairment of executive function.
https://www.medrxiv.org/content/10.1101/2022.01.01.22268614v1.full-text
1351 - 1352. As of last October, an estimated 1.6 million Americans are suffering from post-covid chronic loss of smell/taste beyond 6 months which has been associated with diminished quality of life, impaired food intake, inability to detect harmful odors such as smoke, enhanced worries about personal hygiene, diminished social well-being, and the onset of symptoms of depression. Fortunately, according to the ZOE Project, anosmia/ageusia is significantly less common with Omicron infections compared to prior VOCs. The most common symptoms of Omicron, according to several sources, appear to be: sore throat, runny nose, coughing/sneezing, headache/backache, and fatigue. My note: lower rates of anosmia/ageusia could turn out to be a sign that the olfactory nerve is not as vulnerable to infection with Omicron as it was with prior variants. That may have to do with Omicron’s different cell-entry mechanics (see 1353 below).
https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2786433
Virology
****1353. Immunity against Omicron was superior post-infections compared to post-primary vaccinations (2 shots) but inferior compared to 3 shots. Moderna is more protective than Pfizer which in turn was more protective than Oxford/AstraZeneca. Strikingly, Omicron exhibits a shift in Scov2's cell entry pathway from cell surface membrane fusion triggered by TMPRSS2 (all prior VOCs used TMPRSS2 to aid in cell membrane fusion which the virus needs to gain entry into cells) to cathepsin-dependent fusion within the endosomal membrane. In other words, Omicron is brought into cells like a nutrient. This fundamental shift in viral mechanics could inform the clinical expression of Omicron, including its ability to replicate in different tissues and therefore, the nature and severity of the disease it causes. Route 1 below shows how Scov2 has gained entry into cells to cause infections with all prior variants; route 2 shows how Omicron gains entry. If we see this carry over into the new, more highly immune evasive VOCs that I expect we’ll see beginning this spring, that will reinforce the understanding that Omicron is, in fact, the transitional variant between Phases I and II of the pandemic (as previously defined).
https://www.medrxiv.org/content/10.1101/2022.01.03.21268111v1
1354. Omicron made up 8.0% of cases one month ago, the week ending 12/11/21; 38% of cases the week ending 12/18; 77% of cases the week ending 12/25; and 95% of cases the week ending 1/1/22. At this point, all new cases should be considered Omicron.
https://covid.cdc.gov/covid-data-tracker/#variant-proportions
Therapies
1355. Paxlovid will cost (the federal government) $530 and Molnupiravir $712 per treatment course but both Pfizer and Merck have joined the Medicines Patent Pool (MPP) for their treatments. MPP encourages Big Pharmas to voluntarily cut deals that allow generic manufacturers to produce and sell a company’s drugs or vaccines at steep discounts in agreed-upon regions of the world (poor/underdeveloped). Generic manufacturers are expected to cut the cost of both medicines to about $20/treatment course in low-income countries. MPP started with the goal of making antiretrovirals for HIV more accessible to low-income countries and then later branched out to include drugs for hepatitis C and tuberculosis. The expansion of programs like this one to include Scov2 will be a critical feature of Phase III of the pandemic (according to my crystal ball).
Non-Covid
1356. Patients who undergo cataract-removal surgery have a 30% reduced risk of developing dementia including Alzheimer's. Loss of vision leads to social isolation which accelerated dementia. Interesting read.
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2786583