list-of-evidence-showing-there-is-strong-immunity-from-natural-covid-19-infections

List of Evidence Showing There Is Strong Immunity from Natural COVID-19 Infections [Updated April 23, 2022]


Here is a running list of studies and anecdotal evidence showing that there is a robust, natural immune response to COVID-19, and that, once a person who’s had COVID-19 has recovered, they are overwhelmingly immune to the disease.


A letter from the Department of Health and Human Services stating that it has no record of an unvaccinated individual who has been infected with COVID-19, recovered, and then been infected again. (As confirmed by a positive PCR test.)

LINK TO FOIA LETTER FROM DEPARTMENT OF HEALTH AND HUMAN SERVICES


Guidance from the WHO as of May 10, 2021:

The NIH’s “Lasting Immunity” letter posted January 26, 2021:

Link to NIH webpage

1. Clinical Infectious Diseases (posted June 5, 2021)

TITLE: Necessity of COVID-19 vaccination in previously infected individuals

METHODS: Employees of the Cleveland Clinic Health System working in Ohio on Dec 16, 2020, the day COVID-19 vaccination was started, were included. Any subject who tested positive for SARS-CoV-2 at least 42 days earlier was considered previously infected. One was considered vaccinated 14 days after receipt of the second dose of a SARS-CoV-2 mRNA vaccine. The cumulative incidence of SARS-CoV-2 infection over the next five months, among previously infected subjects who received the vaccine, was compared with those of previously infected subjects who remained unvaccinated, previously uninfected subjects who received the vaccine, and previously uninfected subjects who remained unvaccinated.

CONCLUSION:  Among the 52238 included employees, 1359 (53%) of 2579 previously infected subjects remained unvaccinated, compared with 22777 (41%) of 49659 not previously infected. The cumulative incidence of SARS-CoV-2 infection remained almost zero among previously infected unvaccinated subjects, previously infected subjects who were vaccinated, and previously uninfected subjects who were vaccinated, compared with a steady increase in cumulative incidence among previously uninfected subjects who remained unvaccinated. Not one of the 1359 previously infected subjects who remained unvaccinated had a SARS-CoV-2 infection over the duration of the study. In a Cox proportional hazards regression model, after adjusting for the phase of the epidemic, vaccination was associated with a significantly lower risk of SARS-CoV-2 infection among those not previously infected (HR 0.031, 95% CI 0.015 to 0.061) but not among those previously infected (HR 0.313, 95% CI 0 to Infinity).

Individuals who have had SARS-CoV-2 infection are unlikely to benefit from COVID-19 vaccination, and vaccines can be safely prioritized to those who have not been infected before.

LINK TO STUDY


https://twitter.com/SenseReceptor/status/1402840303074119685

2. The Lancet (Published March 17, 2021)

TITLE: Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study

METHODS: In this population-level observational study, we collected individual-level data on patients who had been tested in Denmark in 2020 from the Danish Microbiology Database and analysed infection rates during the second surge of the COVID-19 epidemic, from Sept 1 to Dec 31, 2020, by comparison of infection rates between individuals with positive and negative PCR tests during the first surge (March to May, 2020). For the main analysis, we excluded people who tested positive for the first time between the two surges and those who died before the second surge. We did an alternative cohort analysis, in which we compared infection rates throughout the year between those with and without a previous confirmed infection at least 3 months earlier, irrespective of date. We also investigated whether differences were found by age group, sex, and time since infection in the alternative cohort analysis. We calculated rate ratios (RRs) adjusted for potential confounders and estimated protection against repeat infection as 1 – RR.

CONCLUSION: During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2·20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2·11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0·65% [95% CI 0·51–0·82]) tested positive again during the second surge compared with 16 819 (3·27% [3·22–3·32]) of 514 271 who tested negative during the first surge (adjusted RR 0·195 [95% CI 0·155–0·246]). Protection against repeat infection was 80·5% (95% CI 75·4–84·5). The alternative cohort analysis gave similar estimates (adjusted RR 0·212 [0·179–0·251], estimated protection 78·8% [74·9–82·1]). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47·1% (95% CI 24·7–62·8). We found no difference in estimated protection against repeat infection by sex (male 78·4% [72·1–83·2] vs female 79·1% [73·9–83·3]) or evidence of waning protection over time (3–6 months of follow-up 79·3% [74·4–83·3] vs ≥7 months of follow-up 77·7% [70·9–82·9]).

LINK TO STUDY

3. The Lancet (Published April 27, 2021)

TITLE: SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy

METHODS: “All SARS-CoV-2 antibody-positive persons from April 16 to December 31, 2020 with a PCR-positive swab ≥14 days after the first-positive antibody test were investigated for evidence of reinfection. Viral genome sequencing was conducted for paired viral specimens to confirm reinfection. Incidence of reinfection was compared to incidence of infection in the complement cohort of those who were antibody-negative.”

CONCLUSION: “Among 43,044 antibody-positive persons who were followed for a median of 16.3 weeks (range: 0–34.6), 314 individuals (0.7%) had at least one PCR positive swab ≥14 days after the first-positive antibody test. Of these individuals, 129 (41.1%) had supporting epidemiological evidence for reinfection.”

“Reinfection is rare in the young and international population of Qatar. Natural infection appears to elicit strong protection against reinfection with an efficacy ~95% for at least seven months.”

LINK TO STUDY

4. Journal of Cell Biology (Published July 14, 2021)

TITLE: Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells

METHODS: “We initiated two prospective COVID-19 patient cohorts in Seattle and Atlanta during the first surge of the pandemic to investigate long-term immunity to SARS-CoV-2. Among 254 COVID-19 patients enrolled and frequently sampled, we identify binding and neutralizing antibodies to SARS-CoV-2 as well as antigen-specific B and T cells elicited early after infection, define their specificities, quantify the extent of antibody boosting of cross-reactive responses to other coronaviruses, and further characterize the decay rate and durability of these immune parameters over 250 days. We employ highly standardized or validated assays that are also being used to evaluate immunity in recent and ongoing clinical vaccine trials….”

CONCLUSION: “Establishing immune memory is essential in the defense against SARS-CoV-2 infection. To end the COVID-19 pandemic, it is critical to know how long immunity against SARS-CoV-2 will persist after infection and whether it will be sufficient to prevent new infections and severe disease in years to come. Identifying, in-depth, the adaptive immune components leading to recovery and modeling the trends of each response was enabled by the longitudinal sampling of a large number of COVID-19 patients. Here, we show that most convalescent COVID-19 patients mount durable antibodies, B cells, and T cells specific for SARS-CoV-2 up to 250 days, and the kinetics of these responses provide an early indication for a favorable course ahead to achieve long-lived immunity. Because the cohort will be followed for 2–3 more years, we can build on these results to define the progression to long-lived immunity against this novel human coronavirus, which can guide rational responses when future outbreaks occur.”

LINK TO STUDY


5. Medical Archive (Posted August 25, 2021)

TITLE: Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections

METHODS: We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naïve individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel.

CONCLUSION: This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.

LINK TO STUDY

6. Medical Archive (posted August 29, 2021)

TITLE: A Systematic Review of the Protective Effect of Prior SARS-CoV-2 Infection on Repeat Infection

METHODS: For this systematic review, we searched scientific publications on PubMed and, the pre-print server, MedRxiv through August 18, 2021. Eligible studies were retrieved on August 18, 2021. We used the following search term on PubMed: (((“Cohort Studies”[Majr]) AND (“COVID-19”[Mesh] OR “SARS-CoV-2”[Mesh])) OR “Reinfection”[Majr]) OR “Reinfection”[Mesh]. We used the following search term on MedRxiv: “Cohort Studies” AND “COVID-19” OR “SARS-CoV-2” AND “Reinfection”. The search terms were broad to encompass all possibilities for applicable studies. There were no restrictions on the date of publication. Studies that did not describe cohorts with estimates of the risk of SARS-CoV-2 reinfection among those with previous infection were excluded. Studies that included vaccinated participants were either excluded or limited to sub-groups of non-vaccinated individuals. To identify relevant studies with appropriate control groups, we developed the following criteria for studies to be included in the systematic analysis: (1) baseline polymerase chain reaction (PCR) testing, (2) a negative comparison group, (3) longitudinal follow-up, (4) a cohort of human participants, i.e., not a case report or case series, and (5) outcome determined by PCR. The review was conducted following PRISMA guidelines. We assessed for selection, information, and analysis bias, per PRISMA guidelines.

CONCLUSION: We identified 1,392 reports. Of those, 10 studies were eligible for our systematic review. The weighted average risk reduction against reinfection was 90.4% with a standard deviation of 7.7%. Protection against SARS-CoV-2 reinfection was observed for up to 10 months. Studies had potential information, selection, and analysis biases.

The protective effect of prior SARS-CoV-2 infection on re-infection is high and similar to the protective effect of vaccination. More research is needed to characterize the duration of protection and the impact of different SARS-CoV-2 variants.

LINK TO STUDY


7. Medical Archive (Posted November 16, 2021)

TITLE: Continued Effectiveness of COVID-19 Vaccination among Urban Healthcare Workers during Delta Variant Predominance

METHODS: We followed a population of urban Massachusetts HCWs (45% non-White) subject to epidemiologic surveillance. We accounted for covariates such as demographics and community background infection incidence, as well as information bias regarding COVID-19 diagnosis and vaccination status.

CONCLUSION: During the study period (December 16, 2020 to September 30, 2021), 4615 HCWs contributed to a total of 1,152,486 person-days at risk (excluding 309 HCWs with prior infection) and had a COVID-19 incidence rate of 5.2/10,000 (114 infections out of 219,842 person-days) for unvaccinated person-days and 0.6/10,000 (49 infections out of 830,084 person-days) for fully vaccinated person-days, resulting in an adjusted VE of 82.3% (95% CI: 75.1–87.4%). For the secondary analysis limited to the period of delta variant predominance in Massachusetts (i.e., July 1 to September 30, 2021), we observed an adjusted VE of 76.5% (95% CI: 40.9–90.6%). Independently, we found no re-infection among those with prior COVID-19, contributing to 74,557 re-infection-free person-days, adding to the evidence base for the robustness of naturally acquired immunity.

LINK TO STUDY


LINK TO CORRESPONDENCE IN THE NEW ENGLAND JOURNAL OF MEDICINE


8. Medical Archive (Posted August 25, 2021)

TITLE: Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections

METHODS: “We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naïve individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel.”

CONCLUSION: This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.”

LINK TO STUDY


9. Viruses (Published April 13, 2022)

TITLE: Incidence and Risk Factors of COVID-19 Vaccine Breakthrough Infections: A Prospective Cohort Study in Belgium

METHODS: “We used data from the LINK-VACC project: a prospective, real-time cohort with national-level coverage in Belgium. The population of interest comprised all individuals aged 18 years and above, living in Belgium, who had been fully vaccinated with a primary vaccination scheme for at least 14 days with a COVID-19 vaccine approved by the European Medicine Agency, between 1 February 2021 and 5 December 2021. We chose a 14-day interval to allow time for an immune response to develop. Two mRNA vaccines (BNT162b2: 2 doses of 30 µg/dose and mRNA-1273: 2 doses of 100 µg/dose) and two viral vector vaccines (ChAdOx1: 2 doses of >2.5 × 108 infectious units and Ad26.COV2.S: 1 dose of >8.92 log10 infectious units) were used.”

CONCLUSION: “Based on data of over eight million fully vaccinated adults, we observed an incidence of breakthrough infections of 11.2 per 100 person years, with 4.6% of all included persons testing positive during a mean follow up of 150 days. Factors associated with an increased risk of a breakthrough infection were younger age, female sex, non-healthcare workers, vaccination with adenoviral-vector-based vaccines, a higher background virus level and being tested frequently for COVID-19. Having had a prior COVID-19 infection before vaccination and having received a booster vaccine were associated with a lower risk of a breakthrough infection. Among those with a breakthrough infection, having had a prior COVID-19 infection also lowered the odds of experiencing symptoms.”

“Having had a prior COVID-19 infection before vaccination reduced the risk of a breakthrough infection and possibly, inherently, also the risk of more severe outcomes. These results added to the growing evidence that naturally acquired immunity together with vaccine-induced immunity (hybrid immunity) has an additional protective effect, compared to only one of the two. Among persons with breakthrough infections, those who had a prior COVID-19 infection were less likely to have symptoms than COVID-19 naïve persons, and this was the case for almost every type of symptom. We are, to the best of our knowledge, the first to demonstrate that hybrid immunity reduces the risk of nearly all types of COVID-19-related symptoms, both mild and severe.”

LINK TO STUDY


10. Cureus (Published October 28, 2021)

TITLE: Equivalency of Protection From Natural Immunity in COVID-19 Recovered Versus Fully Vaccinated Persons: A Systematic Review and Pooled Analysis

METHODS: “We performed a qualitative and inclusive systematic review guided by the principles outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines published in 2020. We used PubMed as our primary database for published and peer-reviewed articles and MedRxIV for pre-published studies. We also included publically available briefings or communications available on the FDA and CDC websites, given their central position in the dynamics of the pandemic. These briefings included significant data on subgroups that were not presented in the academic literature. The search period was defined as December 1, 2020, to August 31, 2021. This period was selected to include vaccination efficacy trials that occurred before the large-scale administration of vaccinations.”

CONCLUSION: “Despite the massive investigational attention on SARS-CoV-2 infection, COVID illnesses and vaccine efficacy, our systematic review identified only a relatively few outcome studies that investigated the comparative benefit of vaccination in COVID-recovered individuals. Two relevant but separate questions need to be considered. First, does previous infection protect individuals to the same degree as what we currently consider “full vaccination” in COVID-naïve individuals? Second, is there an incremental benefit of vaccination to previously infected individuals?… In summary, our analysis demonstrates that natural immunity in the COVID-recovered performs better than full-vaccination alone in COVID-naïve persons. However, there is a small absolute benefit to vaccination in COVID-recovered persons.”

LINK TO STUDY


11. Medical Archive (Posted January 23, 2022)

TITLE: Risk of COVID-19 Reinfection and Vaccine Breakthrough Infection, Madera County, California, 2021

ABSTRACT/METHODS:

“The hazard ratio (HR) for death (from all causes) after COVID-19 infection vs. vaccination was 11.7 (95% CI 5.91-23.1, p<0.05). The HR for testing positive for COVID-19 >14 days after initial COVID-19 infection or after completing primary COVID-19 vaccination was 1.98 (95% CI 1.53-2.58 p<0.001). As the majority of positive COVID-19 tests in the post COVID-19 cohort occurred within 90 days of the initial infection, and as these early positives may not represent a new infection, we also compared rates of testing COVID-19 positive 90 days after initial infection or vaccination. After removing these early positive ≥ COVID-19 tests that occurred between days 14-90, the HR ratio for testing COVID-19 positive is now lower for the post COVID-19 cohort compared with the vaccinated cohort. The risk for having a positive COVID-19 test occurring 90 days after an initial COVID-19 infection or after vaccination was 0.54 (95% CI 0.33-0.87, p<0.05) for the post COVID-19 group vs Vaccinated group.”

“COVID-19 testing results (negative and positive, including antigen tests, molecular testing and COVID-19 antibody tests) must be reported to the California Reportable Disease Exchange system (CalREDIE). Commercial, public health and most clinical laboratories report results electronically directly to CalREDIE.
Rapid antigen testing may be reported by manual entry through internet or app-based access. The
extent to which home self-testing results are reported is not known. All reported COVID-19 test results with demographic information in CalREDIE for residents of Madera County, California were accessed.
COVID-19 Immunization data for California are reported to a statewide database SNOWFLAKE. Death
data for Madera County are reported directly to the Department of Public Health Vital Statistics
department.

“Persons were identified and all duplicates were removed by grouping results based on a unique DOB,
gender and first three initials of their first and last names. For each person the following information
was determined: their first and last COVID-19 positive test dates, their first COVID-19 negative test date,
their vaccination status and administration dates, whether they completed the primary vaccine series,
and their date of death if deceased (all cause mortality). Vaccine recipients who had no COVID-19 test
data were also included in this dataset.”

CONCLUSION/DISCUSSION: In this analysis, the risk of death after testing positive for COVID-19 was, as expected, significantly higher than for the vaccinated and unvaccinated cohorts. For subjects that survived their initial COVID-19 infection, the risk of testing positive for COVID-19 positive again was higher in the first 14-90 days for the post COVID-19 cohort compared with the vaccinated cohort. However, the hazard ratio for retesting COVID-19 positive between 90-300 days after the initial COVID-19 infection or after completing vaccination, for the post COVID-19 cohort was significantly lower than for the vaccinated cohort (HR 0.54, 95% CI 0.44-0.87, p<0.05). The unvaccinated cohort had, as expected, the highest risk of COVID-19 infection during this 300-day time period.”

LINK TO STUDY


Journal: CDC’s Morbidity and Mortality Weekly Report (MMWR)

LINK TO CDC’S MMWR REPORT

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