COVID-19 Immunity

Updated October 20, 2021

21 MAY 2014: T cell-mediated immune response to respiratory coronaviruses (Springer)
“SARS-CoV-specific memory T cells persist in SARS-recovered patients for up to 6 years post-infection.”

22 DEC 2020: Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence (Science Immunology)
“SARS-CoV-2-specific Bmem cell numbers are stable over time, we propose that these Bmem may represent a more robust marker of long-lived humoral immune responses than serum antibodies. Therefore, cellular measurements of the immune response could be more reliable markers for maintenance of immunity following natural infection or vaccination.”

6 JAN 2021: Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection (Science)
“our data show immune memory in at least three immunological compartments was measurable in ~95% of subjects 5 to 8 months PSO, indicating that durable immunity against secondary COVID-19 disease is a possibility in most individuals.”

7 JAN 2021: Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19 (Cell)
“mild COVID-19 elicits memory lymphocytes that persist and display functional hallmarks of antiviral immunity.” 

18 JAN 2021: Evolution of antibody immunity to SARS-CoV-2 (Nature)
“the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response.”

5 FEB 2021: Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection (Science)
“immune memory in three immunological compartments remained measurable in greater than 90% of subjects for more than 5 months after infection. Despite the heterogeneity of immune responses, these results show that durable immunity against secondary COVID-19 disease is a possibility for most individuals.”

5 MAR 2021: Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection (Nature Immunology)
“our data are reassuring that functional SARS-CoV-2-specific T cell responses are retained at 6 months following infection.”

10 MAR 2021: Antibody Responses in Seropositive Persons after a Single Dose of SARS-CoV-2 mRNA Vaccine (NEJM Correspondence) 
“We found that a single dose of mRNA vaccine elicited rapid immune responses in seropositive participants, with postvaccination antibody titers that were similar to or exceeded titers found in seronegative participants who received two vaccinations.” 

15 MAR 2021: Reinfection Rates Among Patients Who Previously Tested Positive for Coronavirus Disease 2019: A Retrospective Cohort Study (Clinical Infectious Diseases)
“Prior infection in patients with COVID-19 was highly protective against reinfection and symptomatic disease. This protection increased over time, suggesting that viral shedding or ongoing immune response may persist beyond 90 days and may not represent true reinfection.”

26 MAR 2021: B-Cell Memory Responses to Variant Viral Antigens (Viruses)

1 APR 2021: Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2 (NatureMedicine)
“we observed that spike-specific IgG antibody levels and ACE2 antibody binding inhibition responses elicited by a single vaccine dose in individuals with prior SARS-CoV-2 infection (n = 35) were similar to those seen after two doses of vaccine in individuals without prior infection (n = 228)”

9 APR 2021: SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN) (Lancet)
“This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals.”

15 APR 2021: Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals after mRNA vaccination (Science Immunology)
“Two shots of the mRNA vaccines were needed to induce peak antibody and memory B cell responses against SARS-CoV-2 in naïve patients, whereas only one shot induced peak responses in convalescent patients.” 

19 APR 2021: COVID-19 Testing and Possible Reinfections (Epic Health Research Network)
“0.4% of patients who previously tested positive for COVID were possibly reinfected.”

23 APR 2021: Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes (Science)
“we expect the greatest selection for escape where immunity is strongest. …partially immune individuals (permitting intermediate levels of selection and transmission) could maximize levels of escape”

24 APR 2021: Protection of previous SARS-CoV-2 infection is similar to that of BNT162b2 vaccine protection: A three-month nationwide experience from Israel (medRxiv preprint)
“Vaccination was highly effective with overall estimated efficacy for documented infection of 92·8%; hospitalization 94·2%; severe illness 94·4%; and death 93·7%. Similarly, the overall estimated level of protection from prior SARS-CoV-2 infection for documented infection is 94·8%; hospitalization 94·1%; and severe illness 96·4%. Our results question the need to vaccinate previously-infected individuals.”

25 APR 2021: Reinfection With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Patients Undergoing Serial Laboratory Testing (Clinical Infectious Disease)
“Reinfection was identified in 0.7% during follow-up of 9119 patients with SARS-CoV-2 infection.”

27 APR 2021: SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy (Lancet)
“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.”

24 MAY 2021: SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans (Nature)
“our results indicate that mild infection with SARS-CoV-2 induces robust antigen-specific, long-lived humoral immune memory in humans.”
Press Release.

24 MAY 2021: Gandhi: 7 Reasons Why We Should Not Need Boosters for COVID-19 (Leaps)

25 MAY 2021: SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients (Science Immunology)
“this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.”

25 MAY 2021: Variants of concern are overrepresented among post-vaccination breakthrough infections of SARS-CoV-2 in Washington State (medRxiv preprint)
“In this study, SARS-CoV-2 variants of concern were found to be overrepresented in vaccine breakthrough cases when compared to cases circulating in the general population of Washington State over the same time interval.”

3 JUN 2021: SARS-CoV-2 specific memory B-cells from individuals with diverse disease severities recognize SARS-CoV-2 variants of concern (medRxiv preprint)

9 JUN 2021: Associations of Vaccination and of Prior Infection With Positive PCR Test Results for SARS-CoV-2 in Airline Passengers Arriving in Qatar (JAMA Research Letter)
“The relative risk for PCR positivity was 0.22 (95% CI, 0.17-0.28) for vaccinated individuals and 0.26 (95% CI, 0.21-0.34) for individuals with prior infection compared with no record of vaccination or prior infection” 

14 JUN 2021: Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection (Nature)
“The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants.”

19 JUN 2021: Necessity of COVID-19 vaccination in previously infected individuals (medRxiv preprint)
“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.”

25 JUN 2021: Hybrid Immunity (Science)

30 JUN 2021: SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells (Nature Communications)
“we demonstrated that SARS-CoV-2-specific memory T cell responses were maintained in COVID-19 convalescent patients 10 months post-infection regardless of the disease severity. Notably, we found that SARS-CoV-2-specific TSCM cells were successfully developed, indicating that SARS-CoV-2-specific T cell memory may be long-lasting in COVID-19 convalescent patients.”

1 JUL 2021: Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2 infection(medRxiv preprint)
“In summary, we provide evidence of abortive seronegative SARS-CoV-2 infection with expansion of cross-reactive RTC-specific T cells, highlighting these highly conserved proteins as targets for future vaccines against endemic and emerging Coronaviridae.”

1 Jul 2021: SARS-CoV-2 Antibody Response in Persons with Past Natural Infection (NEJM Correspondence)
“These findings provide evidence that after the administration of a single dose of vaccine, the humoral response against SARS-CoV-2 in persons with a history of SARS-CoV-2 infection is greater than the response in previously uninfected participants who have received a second dose.”

7 JUL 2021: Long-Term Persistence of SARS-CoV-2 Neutralizing Antibody Responses After Infection and Estimates of the Duration of Protection (SSRN)
“We conclude that there will be relatively long-lived protection from re-infection following symptomatic COVID-19 disease.”

8 JUL 2021: The effect of methotrexate and targeted immunosuppression on humoral and cellular immune responses to the COVID-19 vaccine BNT162b2: a cohort study (Lancet Rheumatology)
“Functional humoral immunity to a single dose of BNT162b2 is impaired by methotrexate but not by targeted biologics, whereas cellular responses are preserved.” 

14 JUL 2021: Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells (Cell Reports Medicine)
“these results suggest that broad and effective immunity may persist long-term in recovered COVID-19 patients.”
Press Release

22 JUL 2021: Typically asymptomatic but with robust antibody formation: Children’s unique humoral immune response to SARS-CoV-2 (medRxiv preprint)
“The long-term humoral immune response to SARS-CoV-2 infection in children is robust and may provide long-term protection even after asymptomatic infection.”

29 JUL 2021: mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status (bioRxiv preprint)
“These results provide reassurance that vaccine-elicited T cells respond robustly to emerging viral variants, confirm that convalescents may not need a second vaccine dose, and suggest that vaccinated convalescents may have more persistent nasopharynx-homing SARS-CoV-2-specific T cells compared to their infection-naïve counterparts.”

30 JUL 2021: Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains (Scientific Reports)
“when a relaxation of non-pharmaceutical interventions happened at a time when most individuals of the population have already been vaccinated the probability of emergence of a resistant strain was greatly increased.”  

10 AUG 2021: Transmission of SARS-CoV-2 Delta Variant Among Vaccinated Healthcare Workers, Vietnam (SSRN)
“Viral loads peaked at around 2-3 days before and after the development of clinical symptoms with prolonged PCR positivity of up to 33 days (median: 21 days). Viral loads were 251 times higher than those in cases infected with old SARS-CoV-2 strains detected in Vietnam between March and April 2020.” …”suggestive of ongoing transmission between the vaccinated people.” … “presymptomatic and/or asymptomatic transmission had occurred between the vaccinated members of staff” 

15 AUG 2021: Neutralization of VOCs including Delta one year post COVID-19 or vaccine (medRxiv preprint)
“Our results demonstrate initial reductions but thereafter stable SARS-CoV-2 IgG levels over 12 months following mild SARS-CoV-2 infection. … We furthermore show that these antibodies display neutralizing abilities against the B.1.1.7 (Alpha) and B.1.617.2 (Delta) strains similar to those against the wild-type strain, and that this capacity is maintained over time, implying a robust immunity also against these now globally spreading strains.” 

24 AUG 2021 Shedding of Infectious SARS-CoV-2 Despite Vaccination (medRxiv preprint)
“Low Ct values were detected in vaccinated people regardless of symptoms at the time of testing (Figure 1C). Ct values <25 were detected in 7 of 24 unvaccinated (29%; CI: 13-51%) and 9 of 11 fully vaccinated asymptomatic individuals (82%; CI: 48-97%), and 158 of 232 unvaccinated (68%, CI: 62-74%) and 156 of 225 fully vaccinated (69%; CI: 63-75%) symptomatic individuals”

25 AUG 2021: Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections (medRxiv preprint)
“SARS-CoV-2-naïve vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naïve vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected.” article.

29 AUG 2021: A Systematic Review of the Protective Effect of Prior SARS-CoV-2 Infection on Repeat Infection (medRxiv preprint) 
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.” 

30 AUG 2021: Anti- SARS-CoV-2 Receptor Binding Domain Antibody Evolution after mRNA Vaccination (bioRxiv preprint)
“While individual memory antibodies selected over time by natural infection have greater potency and breadth than antibodies elicited by vaccination, the overall neutralizing potency of plasma is greater following vaccination. These results suggest that boosting vaccinated individuals with currently available mRNA vaccines will increase plasma neutralizing activity but may not produce antibodies with breadth equivalent to those obtained by vaccinating convalescent individuals.”
Press Release

2 SEP 2021: Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations (JAMA)
83.3% for combined infection- and vaccine-induced antibodies in May 2021

7 SEP 2021: Hospitalisation among vaccine breakthrough COVID-19 infections (Lancet Infectious Disease) 
“Pre-existing comorbidities in the 14 patients with severe or critical illness included overweight (body–mass index >25 kg/m2; n=9), cardiovascular disease (n=12), lung disease (n=7), malignancy (n=4), type 2 diabetes (n=7), and use of an immunosuppressive agent (n=4). 13 of 14 patients had received BNT162b2.” 

20 SEP 2021: High genetic barrier to SARS-CoV-2 polyclonal neutralizing antibody escape (Nature)
“we show that 20 naturally occurring mutations in SARS-CoV-2 spike are sufficient to generate pseudotypes with near-complete resistance to the polyclonal neutralizing antibodies generated by convalescents or mRNA vaccine recipients. Strikingly, however, plasma from individuals who had been infected and subsequently received mRNA vaccination, neutralized pseudotypes bearing this highly resistant SARS-CoV-2 polymutant spike, or diverse sarbecovirus spike proteins. Thus, optimally elicited human polyclonal antibodies against SARS-CoV-2 should be resilient to substantial future SARS-CoV-2 variation and may confer protection against potential future sarbecovirus pandemics.”

21 SEP 2021: Equivalency of Protection from Natural Immunity in COVID-19 Recovered Versus Fully Vaccinated Persons: A Systematic Review and Pooled Analysis (medRxiv preprint)

21 SEP 2021: Outbreak of SARS-CoV-2 B.1.617.2 (Delta) Variant Infections Among Incarcerated Persons in a Federal Prison — Texas (MMWR early release)
“During a COVID-19 outbreak involving the Delta variant in a highly vaccinated incarcerated population, transmission rates were high, even among vaccinated persons. Although attack rates, hospitalizations, and deaths were higher among unvac- cinated than among vaccinated persons, duration of positive serial test results was similar for both groups. Infectious virus was cultured from vaccinated and unvaccinated infected persons.” 

29 SEP 2021: No Significant Difference in Viral Load Between Vaccinated and Unvaccinated, Asymptomatic and Symptomatic Groups Infected with SARS-CoV-2 Delta Variant (medRxiv preprint) 
“A substantial proportion of asymptomatic, fully vaccinated individuals in our study had low Ct-values, indicative of high viral loads. Given that low Ct-values are indicative of high levels of virus, culture positivity, and increased transmission, our detection of low Ct-values in asymptomatic, fully vaccinated individuals is consistent with the potential for transmission from breakthrough infections prior to any emergence of symptoms.”

30 SEP 2021: Nosocomial outbreak caused by the SARS-CoV-2 Delta variant in a highly vaccinated population, Israel (EuroSurv)
“The attack rate among exposed individuals reached 23.3% in patients and 10.3% in staff, with 96.2% vaccination rate among exposed individuals. Moreover, several transmissions probably occurred between two individuals both wearing surgical masks, and in one instance using full PPE, including N-95 mask, face shield, gown and gloves.”

5 OCT 2021: One-year sustained cellular and humoral immunities of COVID-19 convalescents (Clinical Infectious Diseases)
“SARS-CoV-2-specific cellular and humoral immunities are durable at least until one year after disease onset.”

7 OCT 2021: SARS-CoV-2 infection generates tissue-localized immunological memory in humans (Science)
“we report from examination of SARS-CoV-2 seropositive organ donors (ages 10 – 74) that CD4+ T, CD8+ T, and B cell memory generated in response to infection is present in bone marrow, spleen, lung, and multiple lymph nodes (LNs) for up to 6 months post-infection. Lungs and lung-associated LNs were the most prevalent sites for SARS-CoV-2-specific memory T and B cells, with significant correlations between circulating and tissue-resident memory T and B cells in all sites.” 

8 OCT 2021: Predominance of antibody-resistant SARS-CoV-2 variants in vaccine breakthrough cases from the San Francisco Bay Area, California (medRxiv preprint)
“our results suggest that vaccine breakthrough infecions are overrepresnted by circulating antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may potentially transmit COVID-19 as efficiently as unvaccinated infections, regardless of the infecting lineage”

11 OCT 2021: Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity (Nature)
“While both groups retained neutralization capacity against all variants, plasma from previously infected vaccinated individuals displayed overall better neutralization capacity when compared to plasma from uninfected individuals that also received two vaccine doses” 

14 OCT 2021: mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (Science)
“All SARS-CoV-2 recovered individuals in our study had a robust population of antigen-specific memory B cells at pre-vaccination baseline, and these pre-existing memory B cells were significantly boosted by the first vaccine dose with little change after the second vaccine dose”

15 OCT 2021: Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine (Cell)
“The most significant observation of this study is that boosting after a longer interval leads to maintained immunogenicity.” 

21 OCT 2021: Coronavirus (COVID-19) Infection Survey, characteristics of people testing positive for COVID-19, UK (gov)
“The estimated number of reinfections in the UK between July 2020 and September 2021, is low overall (11.8 per 100,000 participant days at risk), and reinfections more likely to cause serious illness are even lower (5.5 per 100,000 participant days at risk”

Immunosuppression & Variants of Concern

5 FEB 2021: SARS-CoV-2 evolution during treatment of chronic infection (Nature)
“These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.”

5 MAY 2021: Researchers Tie Severe Immunosuppression to Chronic COVID-19 and Virus Variants (JAMA)

26 AUG 2021: The continuous evolution of SARS-CoV-2 in South Africa: a new lineage with rapid accumulation of mutations of concern and global detection (medRxiv preprint)
“Like several other VOCs, C.1.2 has accumulated a number of substitutions beyond what would be expected from the background SARS-CoV-2 evolutionary rate. This suggests the likelihood that these mutations arose during a period of accelerated evolution in a single individual with prolonged viral infection through virus-host co-evolution.” 

14 OCT 2021: mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (Science)