Real-world evidence of adaptive immunity from vaccines and SARS-CoV-2 infection

In a recent study posted on medRxiv * Researchers in the United States, a preprint server, found a breakthrough case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the incidence of reinfection in unvaccinated and vaccinated individuals. Is being evaluated.

study: Time to reinfection and breakthrough SARS-CoV-2 infection in vaccines: a retrospective cohort study. Image Credit: PhotobyTawat / Shutterstock.com

Preface

To date, SARS-CoV-2, the virus responsible for coronavirus disease 2019 (COVID-19), has infected more than 411 million people and killed more than 5.81 million people worldwide. .. To control the spread and mortality caused by COVID-19, vaccines were developed at an unprecedented pace and administered worldwide. As of February 14, 2022, more than 10.19 billion COVID-19 vaccines have been distributed worldwide.

In particular, the messenger ribonucleic acid (mRNA) vaccine developed for SARS-CoV-2 has been very helpful in suppressing pandemics, reducing serious consequences and saving lives. According to the United States Centers for Disease Control and Prevention (CDC), the risk of infection, hospitalization, and mortality in unvaccinated individuals is significantly higher than in fully vaccinated individuals.

Despite the success of these vaccines, their Effectiveness SARS-CoV-2 delta variants have emerged in most parts of the world and have since become dominant and then restricted. To this end, reports of breakthrough infections, hospitalizations, and deaths in vaccinated individuals have increased.

Apart from vaccine-induced protection, unvaccinated individuals who recovered from COVID-19 experienced some immunity to reinfection.

Considering various spatiotemporal variables, this study examines the incidence of COVID-19 after vaccination in the western United States from December 12, 2020 to November 5, 2021. Here, researchers also studied reinfection rates among unvaccinated individuals to assess the protection provided by adaptive immunity.

About research

Researchers conducted a retrospective cohort study using electronic data from Providence-Cent. Joseph Health (PSJH) is a community medical system with hospitals and clinics across five states in the western United States, including Alaska, California, Montana, Oregon, and Washington. The mRNA vaccines included in this study were the Pfizer-BioNTechBNT162b2 and Modern RNA-1273 vaccines, as well as the adenoviral vector vaccine JNJ-78436735 (Janssen).

Vaccine-induced and infection-induced immunity was studied from individuals in five states. The two results evaluated in this study included breakthrough infections between vaccine-induced immune cohorts and reinfections between infection-induced immune cohorts. Both results were confirmed by the positive SARS-CoV-2 polymerase chain reaction (PCR) test results.

Investigation result

Of the total 2,627,914 patients eligible to be included in the vaccine-induced immune cohort, 51.4% received two doses of the BNT162b2 vaccine, 41.4% received two doses of mRNA-1273, and 7.2% received one dose of JNJ-78436735. It was administered. This cohort mainly included people between the ages of 18 and 44, the majority of whom were female, non-Hispanic / Latino, Caucasian / Caucasian, and Californian inhabitants.

Of the fully vaccinated ones, 0.36% were positive, most of them aged 18-44 years and were vaccinated in the first quarter of 2021. Probability of survival against breakthrough infections.

(A) Frequency of vaccine breakthrough infections (number per day) beginning 21 days after the last COVID-19 vaccine administration. (B) Normalized frequency of vaccine breakthrough infections (definition) starting 21 days after the last dose of COVID-19 vaccine. The normalized frequency distributions of the breakthrough cases of the mRNA-1273 and BNT162b2 vaccines are almost normally distributed on averages of 161.8 days and 152.8 days, respectively. That of the breakthrough case of the JNJ-78436735 vaccine averages 123. 6 days and is biased to the right. The line shows the average number of days to breakthrough for each vaccine.

The time distribution of these vaccines showed that two doses of mRNA-1273 were the most effective, whereas one dose of JNJ-78436735 was the least effective. The median time to breakthrough cases in the JNJ-7843735, BNT162b2, and mRNA-1273 vaccine populations was 130, 155, and 168 days, respectively.

Researchers also examined acquired immunity from previous SARS-CoV-2 infections by characterizing the reinfection rate in this cohort of unvaccinated people. Like the vaccinated cohorts, the majority of these individuals were females between the ages of 18 and 44 and were identified as non-Hispanic / Latin Caucasian / Caucasian.

Of the 64,424 unvaccinated cohorts, 0.88% were re-infected with SARS-CoV-2, 17.18% had not undergone another COVID-19 diagnostic test during the study period, and the remaining 81.5% had SARS. -I had not experienced a CoV-2 reinfection. During the research period.

One interesting observation was that the number of vaccinated comorbidities was significantly higher than that in the unvaccinated cohort of comorbidities. People with comorbidity may have been more likely to be vaccinated because comorbidity is considered a risk factor for severe COVID-19.

In summary, the incidence of reinfection was found to be higher in the infection-induced immune cohort at 0.9% than in the vaccine-induced cohort at 0.4%. This finding is smaller than that described in previous reports where the risk of SARS-CoV-2 infection was observed to be 6-fold higher in COVID-induced immunity compared to vaccine-induced immunity, but others. Several factors can affect these findings. Possible confounding factors include geolocation, vaccines, variants, demographics, and pandemic timeframes, all of which are re-inoculations for both vaccinated and unvaccinated individuals. It can affect the infection rate.

(A) Kaplan-Meier estimation of survival function of infection-induced immunity. Reinfection is defined by a positive COVID-19 PCR or NAAT test 90 days after the previous positive test. The range of the X-axis is extended to over 600 days, but only 350 days are displayed for controlled comparison with the vaccinated cohort (y-axis).[0,1]). (B) A more detailed enlarged view of A (y-axis)[0.98,1]) (C) Kaplan-Meier estimation of survival function limited to re-infected patients. Approximately 5% of re-infected patients had an infection interval of more than 350 days. (D) Normalized frequency of reinfection 9 months after initial infection.

Limitations

Current studies do not directly compare the protection provided by the vaccine with innate immunity because it is difficult to establish the recovery time required for infectious immunity. In addition, the current study was conducted over a defined period of time, which could lead people to experience breakthrough infections later, which would distort the data distribution.

The point of reinfection cannot be accurately determined as the actual reinfection and is not an unusually long-lasting initial infection. To this end, researchers chose a conservative threshold 90 days after the first positive test to determine cases of reinfection. In addition, they added that the data were limited due to the inconsistency in vaccine deployment among the three vaccines.

In summary, researchers are seeking further analysis, including alternative data sources, sequencing, titer levels, and other deep immunophenotypic data.

Conclusion

Current studies have shown demographic information, survival functions, and probability distributions for large samples of patients undergoing vaccination breakthrough infections or post-infection reinfections within the PSJH network.

The three BNT162b2, mRNA-1273, and JNJ-78436735 vaccines have all been found to significantly reduce the risk of breakthrough infections in the real world for 350 days.

Importantly, current studies reaffirm that the risks associated with COVID-19 are far greater than the slight benefits gained from previous infections.

*Important Notices

medRxiv Publish preliminary scientific reports that should not be considered definitive as they have not been peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.