February 28th, 2022

The answer in my mind has been no for quite some time as it is well known that natural infection provides the best immunity over time, assuming that you survive and have no risk factors making natural infection a risk.

In an excellent opinion piece in the Lancet Rheumatology, Dr. McGonagle lays out a concise reason why.

"First, it is well established that for single stranded RNA viruses such as influenza, natural immunity after recovery from infection provides better protection than vaccination, which needs to be undertaken annually because of waning vaccine immunity. The same has been shown for SARS-CoV-2; in one study, individuals exposed to natural infection were ten-times less likely to be reinfected compared with vaccinated individuals without natural infection (adjusted hazard ratio 0·02, 95% CI 0·01–0·04 for previous infection vs 0·26, 0·24–0·28 for vaccination). Individuals exposed to natural infection were also less likely to be admitted to hospital with COVID-19.

Second, before the COVID-19 pandemic, it was a well-established principle that although systemic vaccination against viral respiratory tract pathogens protects vaccinees against serious infection, these individuals can still transmit virus to non-vaccinated individuals because of a lack of mucosal immunity. Therefore, individuals with immunity resulting from natural infection are probably less likely to transmit the infection to vulnerable patients (who should themselves be vaccinated) compared with those who are vaccinated but not naturally immune. Long-term immunity in the upper airway cannot be directly measured, and serum antibody levels are not a surrogate for mucosal immunity.

Third, numerous studies have shown that vaccination in individuals with previous natural SARS-CoV-2 infection induces so-called super-immunity (or hybrid immunity)—ie, higher antibody and T-cell responses compared with vaccination alone. This concept is often evoked in favour of vaccination, but this super-immune state has no proven long-term clinical correlates, and an increasing number of studies show marginal, if any, additional benefits of vaccination in individuals with natural immunity. Attributing higher serum antibody responses in vaccinated individuals to superiority over natural infection is erroneous, as considerable time might have elapsed since the natural infection with the expected waning of antibody levels.

Additionally, natural infection, with induction of strong interferon-dependent immunity in the upper airways, could lead to interferon-related influenza-like symptoms, but with the innate cytokine response preventing sufficient breach of the mucosal barrier for clinically significant antibody generation. Intramuscular vaccination will readily generate an antibody response, which is measurable as serum antibodies, albeit transiently. This phenomenon cannot be used to claim that vaccines are better than natural infection.

In some countries, including Germany, the voices of immunologists around the equivalence of natural immunity to vaccination are at least partly heard, since health-care workers who have recovered from natural SARS-CoV-2 infection are exempt from mandated vaccination for 90 days.

However, based on the history of viral pneumonia and natural immunity, the scientific basis of this time frame is unclear—arguably it should be indefinite.

There is an ongoing shortage of health-care workers in England, which a vaccine mandate would probably exacerbate; indeed, this seems to be the primary factor in the UK government's reconsideration of the policy. A strong component of averting a further crisis in health-care personnel should include making politicians aware of the power of natural immunity in individuals who have recovered from COVID-19."

Well said! We have to nuance vaccination need moving forward based on personal risk and prior infection history.

Dr. M

McGonagle Lancet Rheumatology


Repeated for their importance in case you missed it:

1) According to a study from Kaiser Permanente, the risk of death from Omicron is 91% less than Delta. The authors state: Our analyses included 52,297 cases with SGTF (Omicron) and 16,982 cases with non-SGTF (Delta [B.1.617.2]) infections, respectively. Hospital admissions occurred among 235 (0.5%) and 222 (1.3%) of cases with Omicron and Delta variant infections, respectively. Among cases first tested in outpatient settings, the adjusted hazard ratios for any subsequent hospital admission and symptomatic hospital admission associated with Omicron variant infection were 0.48 (0.36-0.64) and 0.47 (0.35-0.62), respectively. Rates of ICU admission and mortality after an outpatient positive test were 0.26 (0.10-0.73) and 0.09 (0.01-0.75) fold as high among cases with Omicron variant infection as compared to cases with Delta variant infection. Zero cases with Omicron variant infection received mechanical ventilation, as compared to 11 cases with Delta variant infections throughout the period of follow-up. Median duration of hospital stay was 3.4 (2.8-4.1) days shorter for hospitalized cases with Omicron variant infections as compared to hospitalized patients with Delta variant infections, reflecting a 69.6% (64.0-74.5%) reduction in hospital length of stay. (Lewnard et. al. 2022)

The study also noted 74% less ICU care needed and 54% less hospitalization. The reason behind these changes seems to be related to the mutations that made the Omicron variant more likely to infect the upper lung tissue and the nasopharynx leading to less tissue damage in the terminal lung tissue where oxygen and blood are exchanged. This appears to lead to less inflammation and downstream damage systemically. This is all good news overall.

2) From MMWR: Among 1,228,664 persons who completed primary vaccination during December 2020–October 2021, severe COVID-19–associated outcomes (0.015%) or death (0.0033%) were rare. Risk factors for severe outcomes included age ≥65 years, immunosuppressed, and six other underlying conditions. All persons with severe outcomes had at least one risk factor; 78% of persons who died had at least four.

If you had a primary 2 dose vaccine series against SARS2, you have a 0.0033% chance of dying or 0.000033 which is 33 in 100,000 cases. If you add in the age and underlying comorbid disease risk, most of us have zero risk of dying. This data set is earily similar to initial data at the beginning of the pandemic. Age and comorbid disease is the route to a bad outcome in almost all cases. This data was all Delta variant related which means that the numbers are orders of magnitude smaller for Omicron. Keep it all in perspective.

Thus, again we sit here with data points for booster decisions. To vaccinate with boosters that are minimally effective against Omicron is a personal choice that is highly recommended by the medical community to protect the unvaccinated, the immune suppressed and the genetically at risk.

3) If you received a covid vaccine, the longer the time interval between the vaccine and a breakthrough infection was associated with better long term immunity. It appears that the later breakthrough infection occurs when the antibodies circulating against covid have waned significantly leading to the response to come from the memory long lived plasma cells. This also allows for a robust retraining through the lymph nodes germinal centers where antibody variations can occur to mimic the viral mutations.

From the article:"“It’s an interesting study,” says immunologist Jenna Guthmiller at the University of Chicago in Illinois. She cautions that the results are solely correlative, but adds that they are in line with immunologists’ general understanding of how antibody responses mature over time. Guthmiller explains that vaccination leads to an emergency blast of antibody production, as a natural infection would. If a person gets infected soon after vaccination, these antibodies are probably still circulating in the blood, where they’ll bind to the virus and quickly eliminate it. But when a person becomes infected months after vaccination, the antibodies that respond come from a new and improved batch made by long-lived cells that carry a memory of the pathogen. When the body encounters the pathogen again, these memory cells are called back to duty and have a chance to refine the antibodies, providing better protection against subsequent infections."(Sidik S. 2022)

This may be the exact mechanism behind the data showing that spacing out the vaccine interval was associated with better immune responses over time. Thus, if you had a Covid infection or vaccine recently, your immune response will be correspondingly less robust to generate new protective variant antibodies to the new variant exposure. I.e. if you recently had a vaccine and get Omicron within weeks, you will not get significant symptoms, but you will also not have a great long term immune response. My take on this data is hypothetical in that if you have a booster recently and then see Omicron, you will have minimal to no symptoms but will also have a weaker long term benefit. Therefore, will you need frequent boosters in the absence of natural infection? I think so. If the vaccine wanes in 3 to 4 months normally, then you will be set up for recurrent need. If you have a 0.0033% chance of dying once vaccinated, maybe it makes more sense to obtain natural disease if you are young and or older with no risk factors. Thinking out loud.

4) New data shows that vaccination with two doses of mRNA vaccines followed by natural infection is equivalent to natural infection followed by vaccination in providing super immune responses. "Current COVID-19 vaccines significantly reduce overall morbidity and mortality and are vitally important to controlling the pandemic. Individuals who previously recovered from COVID-19 have enhanced immune responses after vaccination (hybrid immunity) compared to their naïve-vaccinated peers; however, the effects of post-vaccination breakthrough infections on humoral immune response remain to be determined. Here, we measure neutralizing antibody responses from 104 vaccinated individuals, including those with breakthrough infections, hybrid immunity, and no infection history. We find that human immune sera following breakthrough infection and vaccination following natural infection, broadly neutralize SARS-CoV-2 variants to a similar degree. While age negatively correlates with antibody response after vaccination alone, no correlation with age was found in breakthrough or hybrid immune groups. Together, our data suggest that the additional antigen exposure from natural infection substantially boosts the quantity, quality, and breadth of humoral immune response regardless of whether it occurs before or after vaccination." (Bates et. al. 2022)

This is a vitally important study in the march toward understanding the long view on endemic Covid. Natural infection allows the T and B cell repertoire to see all pieces of the viral structure. Therefore, we make vastly different antibody responses to all of these differing structural proteins versus just a fragment of the vaccine seeded spike protein. This provides better long term immunity. The entire purpose of vaccinating in the first place was to prevent hospitalization and death. There was a fleeting belief that we could get a herd immunity this way. That ship sailed long ago. We are in a new endemic world now. Again, we sit at a place where logic dictates that the unvaccinated get vaccinated. The vaccinated with no risk factors will get great immunity with natural Omicron infection. Those with prior natural infection, no prior vaccination and waning immunity could get one dose of an mRNA vaccine to induce excellent immunity. Very logical and real time study based options here.

Dr. M