Volume 12, Letter 17 Coronavirus Update 59 plus other stuff
April 11th, 2022
North Carolina like the rest of the country is still without much Covid related illness. A few cities are starting to see some cases. Salisbury Pediatrics is Covid testing between a zero and 2% positive rate week by week. Influenza remains relatively infrequent. All of these stats are the lowest since the pandemic began.
The 7 day moving average of cases for the US in recent weeks has plummeted from the highs of greater than 800,000 to less than 29,000 owing to Omicron's incredible activity and burn rate. Quick up and quick down.
The risk of death is 0.000033 once vaccinated with a two dose series or survived natural infection.
As it stands today, the United States has had 80.2 million known cases and almost 983,000 deaths. The case numbers will continue to underestimate true case volume by 3-4x as home kit positives are not being reported.
As with the first newsletter on this topic, keep solace with the fact that there is a 99+% chance of survival for all of us regardless of vaccination. However,
mathematically, you now have a 99.9998% chance of survival once vaccinated and the vaccine safety for the mRNA vaccines continues to look good.
Omicron now has three strains: newer variant BA.2 makes up 23 - 40% of current case volume based on different parts of the country while omicron BA 1.1 is at 60 +% and B 1.1.529 is the rest. Delta is no longer registering a blip at all. Disease remains mild compared to the tough Delta strain. If you had natural Omicron BA.1, like me, then you have a very small risk of getting BA.2 moving forward. The likelihood of significant illness if you are one of these rare individuals is very small unless you are already very unhealthy.
Omicron did its job for immunity according to the CDC. 95% of tested individuals had evidence of SARS2 infection in the past. (CDC link) BA.1 Omicron tore through the country leaving a wake of immune understanding in its path. We should be very well prepared now immunologically for any new exposures.
Little else to report here. (CDC Variants)
Europe is seeing a new wave of cases and many countries in Asia are seeing massive volumes based on little a priori immunity to SARS2. The lockdowns of the past finally come back to cause havoc. The US remains quiet - for now. If we do have another wave, it would be very surprising if hospitalization is significant after the massive omicron wave and the T cell immunity that followed.
There are lots of articles predicting a large new BA.2 wave. I doubt it, but time will tell.
Quick Hits and other musings -
1) Data from the SARS2 (delta) inoculation trial are out in Nature Medicine: From the abstract: 36 volunteers aged 18–29 years without evidence of previous infection or vaccination were inoculated with a wild-type virus intranasally in an open-label, non-randomized study (ClinicalTrials.gov identifier NCT04865237; funder, UK Vaccine Taskforce). After inoculation, participants were housed in a high-containment quarantine unit, with 24-hour close medical monitoring and full access to higher-level clinical care. The study’s primary objective was to identify an inoculum dose that induced well-tolerated infection in more than 50% of participants, with secondary objectives to assess virus and symptom kinetics during infection. Eighteen (~53%) participants became infected, with viral load (VL) rising steeply and peaking at ~5 days after inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log10 copies per milliliter. Viable virus was recoverable from the nose up to ~10 days after inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected participants, beginning 2–4 days after inoculation, whereas two (11%) participants remained asymptomatic (no reportable symptoms). Anosmia or dysosmia developed more slowly in 15 (83%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs present even in asymptomatic infection. All infected individuals developed serum spike-specific IgG and neutralizing antibodies. Results from lateral flow tests were strongly associated with viable virus, and modeling showed that twice-weekly rapid antigen tests could diagnose infection before 70–80% of viable virus had been generated. (Killingley et. al. 2022)
This is a fascinating study looking at the reality of SARS2 activity in healthy young adults. However, this data is only useful historically as Delta is gone and teenagers and young adults are not the only groups affected. They are limited in their value as immune activity changes dramatically with age and co morbid disease risk. All that said, this data is remarkable as a study of disease in real time controlled analysis.
2) From Cell Reports Medicine: The ongoing SARS-CoV-2 pandemic highlights the importance of determining the breadth and durability of humoral immunity to SARS-CoV-2 mRNA vaccination. Herein, we characterize the humoral response in 27 naïve and 40 recovered vaccinees. SARS-CoV-2-specific antibody and MBC responses are durable up to six months, although antibody half lives are shorter for naïve recipients. The magnitude of the humoral responses to vaccination strongly correlates with responses to initial SARS-CoV-2 infection. Neutralization titers are lower against SARS-CoV-2 variants in both recovered and naïve vaccinees, with titers more reduced in naïve recipients. While RBD is the main neutralizing target of circulating antibodies, Moderna-vaccinated naïves show a lesser reliance on RBD, with >25% neutralization remaining after depletion of RBD-binding antibodies. Overall, we observe that vaccination induces higher peak titers and improves durability in recovered as compared to naïve vaccinees. These findings have broad implications for current vaccine strategies deployed against the SARS-CoV-2 pandemic.
We have noted this response type before. Natural immunity followed by vaccination offers a broader and better response than a naive SARS2 person. This is unlikely to matter anymore as almost all of us have had this virus over the past 2 years. A booster now for anyone will provide a decent albeit short lived response. Boosters remain a necessity only for the high risk based on the literature to date.
3) From Scientific American: "According to Baric, Omicron is the first SARS-CoV-2 variant to evolve in the context of mounting immunity in the population—the result of vaccines and prior infection with other forms of the virus. Earlier variants, namely Alpha, Beta, Gamma and Delta, competed for dominance primarily on the basis of how well they infect human cells in high numbers and transit efficiently among people. But Omicron acquired the further advantage of being able to resist immune defenses against the variants that came before, thereby increasing the number of susceptible people in the population. The difference in neutralizing antibody responses against Omicron, compared with prior variants, “is massive,” Baric says. Neutralizing antibodies deflect SARS-CoV-2 from binding to ACE2 receptors, the virus’s entry point into human cells. “We’re talking about a 15- to 50-fold drop in antibody levels, depending on who runs the assay and how recently you’ve been infected or boosted,” Baric says." (Schmidt C. 2022)
BA.2 and the next wave of variants will use immune evasion by mutagenesis as the main strategy of infectivity. This is the new norm. The good news is that massive infectivity and rapid sequence increases population immunity in tandem leading to rapid up and rapid down in disease transmission. Keep yourself out of a high risk pool through lifestyle change decisions.
4) From the Cell Reports Medicine Journal: "The ongoing SARS-CoV-2 pandemic highlights the importance of determining the breadth and durability of humoral immunity to SARS-CoV-2 mRNA vaccination. Herein, we characterize the humoral response in 27 naïve and 40 recovered vaccinees. SARS-CoV-2-specific antibody and MBC responses are durable up to six months, although antibody half lives are shorter for naïve recipients. The magnitude of the humoral responses to vaccination strongly correlates with responses to initial SARS-CoV-2 infection. Neutralization titers are lower against SARS-CoV-2 variants in both recovered and naïve vaccinees, with titers more reduced in naïve recipients. While RBD is the main neutralizing target of circulating antibodies, Moderna-vaccinated naïves show a lesser reliance on RBD, with >25% neutralization remaining after depletion of RBD-binding antibodies. Overall, we observe that vaccination induces higher peak titers and improves durability in recovered as compared to naïve vaccinees. These findings have broad implications for current vaccine strategies deployed against the SARS-CoV-2 pandemic." (Mantus et. al. 2022)
The thrust of this report is that a vaccine booster is more beneficial if you had and survived natural disease first. This data set again leads me to a simple argument. If you had natural disease and survived with minimal issue, then one dose of vaccination could be prudent, however, in the Omicron era this is debatable based on disease severity and limited transmission protection. Unvaccinated and no disease history, vaccinate. Boosters only for high risk in my mind. More to come as the virus evolves.
5) More on Long Covid/PASC: "Patients with persistent cognitive impairment months after illness with mild COVID-19 have higher levels of inflammatory markers in their cerebrospinal fluid (CSF).
Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive post-acute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation." (Medscape Link)
More evidence that baseline inflammatory dysfunction or host genetic abnormalities are likely driving the PASC brain fog. I am convinced that individuals that suffer Long Covid are at baseline inflamed from poor lifestyle choices coupled to underlying host immune weaknesses for viral surveillance and killing. The fact that the immune markers are noted in the brain post illness is likely a sign that viral particles or remnants of the virus having penetrated a leaky brain barrier. This has lead to glial cells and other immune mediating immune cells to be angry in the CSF and brain. See 8 below for more.
Again, the answer remains, control what you can control. Eat, sleep, move and live cleanly.
6) Omicron did its job for immunity according to the CDC. 95% of tested individuals had evidence of SARS2 infection in the past. (CDC link) BA.1 Omicron tore through the country leaving a wake of immune understanding in its path. We should be very well prepared now immunologically for any new exposures.
7) Mensah and colleagues noted that reinfection rates closely followed community infection rates. The overall reinfection rate was 67 per 100,000. Adults had 73 per 100, 000 and children 22 per 100,000. The reinfection rate after primary infection was 0.68% overall, 0.73% in adults compared with 0.18% in children age younger than 5 years, 0.24% in those aged 5–11 years, and 0.49% in those aged 12–16 years. There were 109 children admitted to hospital with reinfection, 72% had co-morbidities. Intensive care admissions were rare. There were 0 deaths after reinfection. (Mensah et. al. 2022)
8) From a recent study in MedRxIV: Incubation of normal and tumor glial cells with the Pfizer-BioNTech COVID-19 mRNA vaccine (BNT162b2) led to alterations in the biochemical profile of various cell organelles.
The vaccine was shown to decrease concentrations of the oxidized form of cytochrome c in mitochondria, which decreases effectiveness of oxidative phosphorylation, reduces apoptosis, and decreases ATP production. Cytochrome c in the mitochondria of cells plays a key role in oxidative phosphorylation and apoptosis. These are key roles in cancer development. (Abramczyk et. al. 2022)
The authors of this paper note that their data hypothetically links covid vaccine to a potential association between cytochrome c activity, the immune system, and cancer development. This possibly could occur with natural disease as well, but I have not seen any data there. This research only bears being presented for the knowledge that this virus really messes with immune function and that tells me that we need to spend all of our efforts on maintaining quality immune activity.
A normal functioning repertoire of natural killer cells and TH1 cells will keep cancer cells at bay.
That's all this week,