COVID-19 Immunity

Updated May 25, 2024

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.”

9 JUL 2020: Nutrition, immunity and COVID-19 (BMJ Nutrition)

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 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: SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection (Nature)

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.”  

31 JUL 2021: Differences in the Concentration of Anti-SARS-CoV-2 IgG Antibodies Post-COVID-19 Recovery or Post-Vaccination (Cells)

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.

26 AUG 2021: Neutralization of SARS-CoV-2 variants by convalescent and BNT162b2 vaccinated serum (Nature Communications)

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” 

11 OCT 2021: Immunity to SARS-CoV-2 up to 15 months after infection (bioRxiv preprint)
“The data suggest that antiviral specific immunity especially memory B cells in COVID-19 convalescent patients is long-lasting, but some variants of concern, including the fast-spreading Delta variant, may at least partially escape the neutralizing activity of plasma antibodies.”

14 OCT 2021: COVID super-immunity: one of the pandemic’s great puzzles (Nature)

14 OCT 2021: Breakthrough SARS-CoV-2 infections in 620,000 U.S. Veterans, February 1, 2021 to August 13, 2021 (medRxiv preprint)

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)
“NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.”

15 OCT 2021: Mutation-induced changes in the receptor-binding interface of the SARS-CoV-2 Delta variant B.1.617.2 and implications for immune evasion (BBRC)
“Our study shows reduced binding of neutralizing antibodies and provides a possible mechanism for the immune evasion exhibited by the Delta variant.”

15 OCT 2021: Neutralizing antibody activity in convalescent sera from infection in humans with SARS-CoV-2 and variants of concern (Nature)
“In summary, using convalescent sera from individuals infected in wave 1, we showed that cross-neutralizing antibodies are detected up to 10 months POS in some individuals. Infection with B.1.1.7, B.1.351 or B.1.617.2 generates a cross-neutralizing antibody response that is effective against the parental virus but has reduced neutralization against divergent lineages.”

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”

25 OCT 2021: Effectiveness of Covid-19 Vaccination Against Risk of Symptomatic Infection, Hospitalization, and Death Up to 9 Months: A Swedish Total-Population Cohort Study (Lancet Preprint)
“Vaccine effectiveness of BNT162b2 against infection waned progressively from 92% (95% CI, 92-93, P<0·001) at day 15-30 to 47% (95% CI, 39-55, P<0·001) at day 121-180, and from day 211 and onwards no effectiveness could be detected (23%; 95% CI, -2-41, P=0·07”

29 OCT 2021: Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study (Infectious Diseases)
“The SAR in household contacts exposed to the delta variant was 25% (95% CI 18–33) for fully vaccinated individuals compared with 38% (24–53) in unvaccinated individuals. The median time between second vaccine dose and study recruitment in fully vaccinated contacts was longer for infected individuals (median 101 days [IQR 74–120]) than for uninfected individuals (64 days [32–97], p=0·001). SAR among household contacts exposed to fully vaccinated index cases was similar to household contacts exposed to unvaccinated index cases (25% [95% CI 15–35] for vaccinated vs 23% [15–31] for unvaccinated)”

29 OCT 2021: Anti-spike antibody response to natural SARS-CoV-2 infection in the general population (Nature)
“A latent class model classified 24% of participants as ‘non-responders’ not developing anti-spike antibodies, who were older, had higher SARS-CoV-2 cycle threshold values during infection (i.e. lower viral burden), and less frequently reported any symptoms. … The estimated anti-spike IgG half-life was 184 days, being longer in females and those of white ethnicity. We estimated antibody levels associated with protection against reinfection likely last 1.5-2 years on average, with levels associated with protection from severe infection present for several years.” 

1 NOV 2021: Association of Prior SARS-CoV-2 Infection With Risk of Breakthrough Infection Following mRNA Vaccination in Qatar (JAMA)
“Prior SARS-CoV-2 infection was associated with a statistically significantly lower risk for breakthrough infection among individuals receiving the BNT162b2 or mRNA-1273 vaccines in Qatar between December 21, 2020, and September 19, 2021.” 

7 NOV 2021: The majority of SARS-CoV-2-specific antibodies in COVID-19 patients with obesity are autoimmune and not neutralizing (Nature Obesity)
“The results from this study show that the majority of COVID-19 patients with obesity make almost undiscernible amounts of neutralizing anti-SARS-CoV-2 antibodies, suggesting that obese individuals may be at a higher risk to respond poorly to SARS-CoV-2 infection. … All of our recruited participants with obesity, however, made autoimmune antibodies.”

8 NOV 2021: Protective immunity after recovery from SARS-CoV-2 infection (Lancet Infectious Disease)

9 NOV 2021: T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study (Lancet Microbe)
“Our study of 289 health-care workers builds on the findings of earlier reports describing a powerful boosting effect of previous SARS-CoV-2 infection on the antibody response to a single dose of vaccine”

10 NOV 2021: Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2 (Nature)
“We provide T-cell and innate transcript evidence for abortive, seronegative SARS-CoV-2 infection. Longitudinal samples from SN-HCW and an additional cohort, showed RTC (particularly polymerase)-specific T-cells were enriched before exposure, expanded in vivo, and preferentially accumulated in those in whom SARS-CoV-2 failed to establish infection, compared to those with overt infection. “

24 NOV 2021: Severity of SARS-CoV-2 Reinfections as Compared with Primary Infections (NEJM)
Reinfections had 90% lower odds of resulting in hospitalization or death than primary infections. Four reinfections were severe enough to lead to acute care hospitalization.” 

6 DEC 2021: The germinal centre B cell response to SARS-CoV-2 (Nature)

6 DEC 2021: Pre-existing humoral immunity to human common cold coronaviruses negatively impacts the protective SARS-CoV-2 antibody response (Cell Host & Microbe)
“These findings suggest that similar to influenza virus, prior exposure to coronaviruses with sufficient homology can hinder the immune response to a novel coronavirus.” 

6 DEC 2021: Evidence for increased SARS-CoV-2 susceptibility and COVID-19 severity related to pre-existing immunity to seasonal coronaviruses (Cell)
“specific pre-existing immunity to seasonal coronaviruses may increase susceptibility to SARS-CoV-2 and predispose individuals to an adverse COVID-19 outcome”

6 DEC 2021: Evidence for increased SARS-CoV-2 susceptibility and COVID-19 severity related to pre-existing immunity to seasonal coronaviruses (Cell)
“specific pre-existing immunity to seasonal coronaviruses may increase susceptibility to SARS-CoV-2 and predispose individuals to an adverse COVID-19 outcome”

8 DEC 2021: Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and monoclonal antibodies (medRxiv preprint)
“Neutralization performed with sera from double (no-booster) or triple BNT162b2-vaccinated (sampled 0.5 or 6 months after boosting) revealed an 11.4-, 37.0- and 24.5-fold reduction, respectively (Figure 1A). Sera from double mRNA1273-vaccinated (no-booster) and additionally BNT162b2-booster (sampled 0.5 or 6 months after booster vaccination) showed a 20- and 22.7-fold reduction in the neutralization capacity (Figure 1B). Poor neutralization against Delta and no efficacy against Omicron were observed using sera from heterologous ChAdOx1 and BNT162b2 vaccinated individuals (Figure 1C). Additionally, the BNT162b2- booster group showed a significant increase of NAb titers but a 27.1-fold reduction in neutralization against Omicron. (Figure 1C). Convalescent sera poorly neutralize VoCs, however in combination with vaccination provides superior protection. Neutralization of Omicron was 32.8-fold reduced using sera from double BNT162b2-vaccinated and infected individuals (Figure 1A). 

The currently used monoclonal antibodies imdevimab and casirivimab efficiently prevented Delta infection, however, possibly as a consequence of amino acid substitutions5 failed to neutralize Omicron (Figure 1D).” 

9 DEC 2021: Minimal cross-over between mutations associated with Omicron variant of SARS-CoV-2 and CD8+ T cell epitopes identified in COVID-19 convalescent individuals (bioRxiv preprint)
“These data suggest that virtually all individuals with existing anti-SARS-CoV-2 CD8+ T-cell responses should recognize the Omicron VOC, and that SARS-CoV-2 has not evolved extensive T-cell escape mutations at this time.”

10 DEC 2021: Infant T cells are developmentally adapted for robust lung immune responses through enhanced T cell receptor signaling (Science Immunology)

11 DEC 2021: Efficient mucosal antibody response to SARS-CoV-2 vaccination is induced in previously infected individuals (medRxiv preprint)
“Our results suggest that the level of mucosal SIgA responses induced by mRNA vaccination depend on pre-existing immunity. Indeed, vaccination induced only a weak mucosal SIgA response in individuals without pre-existing mucosal antibody responses to SARS-CoV-2 while SIgA induction after vaccination was efficient in COVID-19 survivors. … Of note, among participants in the longitudinal observational PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2) study, breakthrough infection cases after vaccination have so far only been identified in individuals without SARS-CoV-2 infection prior to vaccination, and not in individuals with SARS-CoV-2 infection prior to vaccination (personal communication, data not yet published).” 

11 DEC 2021: SARS-CoV-2 B.1.1.529 variant (Omicron) evades neutralization by sera from vaccinated and convalescent individuals (medRxiv preprint)

11 DEC 2021: Reduced neutralisation of SARS-COV-2 Omicron-B.1.1.529 variant by post-immunisation serum (medRxiv preprint)

15 DEC 2021: Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2 (bioRxiv preprint)
“We found B.1.1.529 to be markedly resistant to neutralization by serum not only from convalescent patients, but also from individuals vaccinated with one of the four widely used COVID-19 vaccines. Even serum from persons vaccinated and boosted with mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies to all known epitope clusters on the spike protein, we noted that the activity of 18 of the 19 antibodies tested were either abolished or impaired”

15 DEC 2021: Universal Coronavirus Vaccines — An Urgent Need (NEJM)
“These sobering facts suggest that SARS-CoV-2 is unlikely to be eliminated, let alone eradicated; it will probably continue to circulate indefinitely in periodic outbreaks and endemics. Meanwhile, an unknown number of animal coronaviruses, of unknown transmissibility and lethality, may well emerge in the foreseeable future. We must therefore greatly accelerate our efforts in coronavirus vaccinology.

The limitations of SARS-CoV-2 vaccines suggest that they will ultimately need to be replaced by second-generation vaccines that induce more broadly protective and more durable immunity.”

15 DEC 2021: Risk of hospitalization and mortality after breakthrough SARS-CoV-2 infection by vaccine type and previous SARS-CoV-2 infection utilizing medical claims data (medRxiv preprint)

15 DEC 2021: Considerable escape of SARS-CoV-2 variant Omicron to antibody neutralization (bioRxiv preprint)
“Omicron was totally or partially resistant to neutralization by all mAbs tested. Sera from Pfizer or AstraZeneca vaccine recipients, sampled 5 months after complete vaccination, barely inhibited Omicron. Sera from COVID-19 convalescent patients collected 6 or 12 months post symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 5 to 31 fold lower against Omicron than against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and to a large extent vaccine-elicited antibodies.”

16 DEC 2021: Antibody Response and Variant Cross-Neutralization After SARS-CoV-2 Breakthrough Infection (JAMA Research Letter)
“Results of this study showed substantial boosting of humoral immunity after breakthrough infection, despite predominantly mild disease. Boosting was most notable for IgA, possibly due to the differences in route of exposure between vaccination and natural infection. In addition, breakthrough sera demonstrated improved variant cross-neutralization”

17 DEC 2021: Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers (Cell)

21 DEC 2021: Large-scale genomic study reveals robust activation of the immune system following advanced Inner Engineering meditation retreat (Biological Sciences)
“Strikingly, 220 genes directly associated with immune response, including 68 genes related to interferon signaling, were up-regulated, with no significant expression changes in the inflammatory genes.”

22 DEC 2021: Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection (Nature Immunology)
Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.”

22 DEC 2021: Local and systemic responses to SARS-CoV-2 infection in children and adults (Nature)
“We postulate that higher paediatric innate interferon-responses restrict viral replication and disease progression.”
Press Release:

22 DEC 2021: SARS-CoV-2 spike-specific memory B cells express higher levels of T-bet and FcRL5 after non-severe COVID-19 as compared to severe disease (PLOS ONE)
“Collectively, our results highlight subtle differences in the B cells response after non-severe and severe COVID-19 and suggest that the memory B cell response elicited during non-severe COVID-19 may be of higher quality than the response after severe disease.”

23 DEC 2021: Evolution of enhanced innate immune evasion by SARS-CoV-2 (Nature)
“We found that Alpha has dramatically increased subgenomic RNA and protein levels of N, Orf9b and Orf6, all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein required for RNA sensing adaptor MAVS activation. … We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful Alpha transmission, and may increase in vivo replication and duration of infection”
Press Release:

24 DEC 2021: COVID-19 Vaccination and Breakthrough Infections in Patients with Cancer (Annals of Oncology)
“Patients with cancer who develop breakthrough COVID-19 following full vaccination remain susceptible to severe outcomes.”

27 DEC 2021: Omicron infection enhances neutralizing immunity against the Delta variant (pre-published manuscript)
We enrolled both previously vaccinated and unvaccinated individuals who were infected with SARS-CoV-2 in the Omicron infection wave in South Africa soon after symptom onset. We then measured their ability to neutralize both Omicron and Delta virus at enrollment versus a median of 14 days after enrollment. Neutralization of Omicron increased 14-fold over this time, showing a developing antibody response to the variant. Importantly, there was an enhancement of Delta virus neutralization, which increased 4.4-fold.”

28 DEC 2021: SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron (medRxiv preprint)
”We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations.”

29 DEC 2021: Immunogenicity of heterologous BNT162b2 booster in fully vaccinated individuals with CoronaVac against SARS-CoV-2 variants Delta and Omicron: the Dominican Republic Experience (medRxiv preprint)
“Notably, none of the 2x CoronaVac recipients had detectable neutralizing antibody against SARS-CoV-2 Omicron variant.” 

1 JAN 2022: Effectiveness of COVID-19 vaccines against Omicron or Delta infection (medRxiv preprint)
“receipt of 2 doses of COVID-19 vaccines was not protective against Omicron. Vaccine effectiveness against Omicron was 37% (95%CI, 19-50%) ≥7 days after receiving an mRNA vaccine for the third dose.”

6 JAN 2022: Protection afforded by prior infection against SARS-CoV-2 reinfection with the Omicron variant (medRxiv preprint)
“Protection afforded by prior infection in preventing symptomatic reinfection with Alpha, Beta, or Delta is robust, at about 90%. While such protection against reinfection with Omicron is lower, it is still considerable at nearly 60%. Prior-infection protection against hospitalization or death at reinfection appears robust, regardless of variant.”

“previous vaccination does not appear to be protective against several previously documented outcomes of COVID-19 such as long-COVID features, arrhythmia, joint pain, type 2 diabetes, liver disease, sleep disorders, and mood and anxiety disorders.”

12 JAN 2022: Neutralization of ancestral SARS-CoV-2 and variants Alpha, Beta, Gamma, Delta, Zeta and Omicron by mRNA vaccination and infection-derived immunity through homologous and heterologous variants (medRxiv preprint)

14 JAN 2022: SARS-CoV-2 Reinfections: Overview of Efficacy and Duration of Natural and Hybrid Immunity (SSRN)
“Observational studies indicate that natural immunity may offer equal or greater protection against SARS-CoV-2 infections compared to individuals receiving two doses of an mRNA vaccine, but data are not fully consistent. The combination of a previous SARS-CoV-2 infection and a respective vaccination, termed hybrid immunity, seems to confer the greatest protection against SARS-CoV-2 infections, but several knowledge gaps remain regarding this issue. Natural immunity should be considered for public health policy regarding SARS-CoV-2.”

18 JAN 2022: Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity (Science Translational Med)
MedXpress Press Release
“Wang said the immunological factors the researchers have identified—a sluggish neutralizing-antibody response, deficient fucose levels on antibody-attached sugar chains, and hyperabundant receptors for fucose-deficient antibodies—were each, on their own, modestly predictive of COVID-19 severity. But taken together, they allowed the scientists to guess the disease’s course with an accuracy of about 80%.”

19 JAN 2022: SARS-CoV-2 infections in children: understanding diverse outcomes (Cell Immunity)

19 JAN 2022: COVID-19 Cases and Hospitalizations by COVID-19 Vaccination Status and Previous COVID-19 Diagnosis — California and New York, May–November 2021 (CDC Early Release)
“During May–November 2021, case and hospitalization rates were highest among persons who were unvaccinated without a previous diagnosis. Before Delta became the predominant variant in June, case rates were higher among persons who survived a previous infection than persons who were vaccinated alone. By early October, persons who survived a previous infection had lower case rates than persons who were vaccinated alone.”

21 JAN 2022: Decreased memory B cell frequencies in COVID-19 delta variant vaccine breakthrough infection (EMBO Molecular Medicine)
Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor-binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant.”

24 JAN 2022: Evaluation of disease severity during SARS-COV-2 reinfection, January 2020 to April 2021, England: an observational study (Journal of Infection)
“Prior SARS-CoV-2 infection was associated with lower odds of dying, and both prior infection and immunisation showed a protective effect against severe disease in selected populations. Older age, sex and underlying comorbidities appeared as principal risk factors for illness severity at reinfection.”

25 JAN 2022: Vaccination before or after SARS-CoV-2 infection leads to robust humoral response and antibodies that effectively neutralize variants (Science Immunology)
“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.”

26 JAN 2022: COVID-19 and the Common Cold—Preexisting Coronavirus Antibodies May Hinder SARS-CoV-2 Immunity (JAMA)
“As increased SARS-CoV-2 antibodies after infection correlated with greater disease, these findings raise the possibility that pre-existing betacoronavirus IgG and IgA negatively impact the immune response to SARS-CoV-2, which results in greater duration of antigen and therefore more SARS-CoV-2 antibodies.” … “Prior immunity to a related, yet distinct, coronavirus could hinder immunity to a new coronavirus”

3 FEB 2022: Prevalence and Durability of SARS-CoV-2 Antibodies Among Unvaccinated US Adults by History of COVID-19 (JAMA)
In this cross-sectional study of unvaccinated US adults, antibodies were detected in 99% of individuals who reported a positive COVID-19 test result, in 55% who believed they had COVID-19 but were never tested, and in 11% who believed they had never had COVID-19 infection. Anti-RBD levels were observed after a positive COVID-19 test result up to 20 months, extending previous 6-month durability data.”

7 FEB 2022: The presence of serum anti-SARS-CoV-2 IgA appears to protect primary health care workers from COVID-19 (European Journal of Immunology)

9 FEB 2022: Protection against the Omicron Variant from Previous SARS-CoV-2 Infection (NEJM)
“protection against reinfection with the omicron variant was lower [than previous variants] (approximately 60%) but still considerable. In addition, the protection of previous infection against hospitalization or death caused by reinfection appeared to be robust, regardless of variant.”

10 MAR 2022: Omicron BA.2 specifically evades broad sarbecovirus neutralizing antibodies (bioRxiv preprint)
“we show that BA.2 causes strong neutralization resistance, comparable to BA.1, in vaccinated individuals’ plasma. However, BA.2 displays more severe antibody evasion in BA.1 convalescents, and most prominently, in vaccinated SARS convalescents’ plasma, suggesting a substantial antigenicity difference between BA.2 and BA.1 we showed that BA.2 exhibits distinct antigenicity compared to BA.1 and provided a comprehensive profile of SARS-CoV-2 antibody escaping mutations.”

12 FEB 2022: Ground Truths on Prior Covid: How failure of the United States to acknowledge the evidence has unnecessarily fueled divisiveness and a war against mandates (Eric Topol Substack)

17 MAR 2022: Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants (Cell)
“Following either Delta or Omicron breakthrough infection, limited variant-specific cross-neutralizing immunity was observed. These results suggest that Omicron breakthrough infections are less immunogenic than Delta, thus providing reduced protection against reinfection or infection from future variants.”

17 MAR 2022: Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination (Cell)
“We find that prior vaccination with Wuhan-Hu-1-like antigens followed by infection with Alpha or Delta variants gives rise to plasma antibody responses with apparent Wuhan-Hu-1-specific imprinting manifesting as relatively decreased responses to the variant virus epitopes, compared with unvaccinated patients infected with those variant viruses. …“The extent to which vaccine boosting or infection with different variants will effectively elicit antibody responses to new epitopes or rather increase responses to the epitopes of antigens encountered previously, as in the “original antigenic sin” phenomenon described for influenza virus infection and vaccination (Arevalo et al., 2020; Zhang et al., 2019), will be an important topic of ongoing study.”

23 MAR 2022: Burden of PCR-Confirmed SARS-CoV-2 Reinfection in the U.S. Veterans Administration, March 2020 – January 2022 (medRxiv preprint)
We identified 308,051 initial cases of SARS-CoV-2 infection diagnosed in VHA between March 2020 and January 2022; 58,456 (19.0%) were associated with VHA hospitalizations. A second PCR-positive test occurred in 9,203 patients in VA at least 90-days after their first positive test in VHA; 1,562 (17.0%) were associated with VHA hospitalizations. An additional 189 cases were identified as PCR-positive a third time at least 90-days after their second PCR-positive infection in VHA; 49 (25.9%) were associated with VHA hospitalizations.” 

3 APR 2022: High rate of BA.1, BA.1.1 and BA.2 infection in triple vaccinated (medRxiv preprint)

25 APR 2022: Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection (Nature Mucosal Immunity)
“Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 variants had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2–4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups.”

1 MAY 2022: Evidence for Aerosol Transfer of SARS-CoV2-specific Humoral Immunity (preprint)
“aerosol transfer of antibodies between immune and non-immune hosts”

15 JUN 2022: Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections (NEJM)
“The analysis showed, as expected, that full mRNA vaccination plus a booster dose, atop natural immunity due to infection by an earlier variant, was associated with the strongest protection from Omicron infection. However, vaccine immunity against new infection appeared to wane rapidly, whereas people with a prior-variant infection were moderately protected from Omicron with little decline in protection even a year after their prior infection.”
Press Release:

17 JUN 2022: BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection (Nature)
“our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.”

13 JUL 2022: Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope (Cell)
“In summary, we demonstrate that SARS-CoV-2 can readily alter its Spike protein via a single amino acid substitution so that it is not recognized by CD8 T cells targeting the most prevalent epitope in Spike restricted by the most common HLA-I across the population. While it is not possible to directly attribute the emergence and propagation of the Spike P272L SARS-CoV-2 variant in parts of the world where HLA A∗02:01 is frequently expressed to CD8 T cell-mediated selection pressure, specific focusing of immune protection on a single protein (e.g. SARS-CoV-2 Spike favored by all currently approved vaccines [Krammer, 2020]) is likely to enhance any tendency for escape at predominant T cell epitopes like YLQPRTFLL.”
“…it has been suggested that strong antibody responses but weak CD8 T cell responses could contribute to acute COVID-19 pathogenesis and severity”

30 NOV 2022: Defective antifungal immunity in patients with COVID-19 (Frontiers in Immunology)
“Specific dysregulation of the immune system through functional exhaustion of Natural killer (NK) cells and T cells has been observed in COVID-19 through the expression of the exhaustion markers NK-G2A and PD-1. Reduced fungicidal activity of neutrophils from COVID-19 patients indicates that immune dysfunction/imbalance are important risk factors for invasive fungal disease (IFD). The COVID-19 pandemic has significantly increased the at-risk population for IFD.”

21 DEC 2022: The onset of de novo autoantibodies in healthcare workers after mRNA based anti-SARS-CoV-2 vaccines (Autoimmunity)
“…Since it is known that hyperstimulation of the immune system could lead to autoimmunity, these preliminary results seem to further sustain the idea that the hyperstimulation of the immune system might lead to an autoinflammatory mechanism and eventually to autoimmune disorders.” 

22 DEC 2022: Skewed fate and hematopoiesis of CD34+ HSPCs in umbilical cord blood amid the COVID-19 pandemic (iScience)
“These results indicate that SARS-CoV-2 infection and COVID-19 vaccination impair the functionalities and survivability of HSPCs in the UCB, which would make unprecedented concerns on the future of HSPC-based therapies.”

1 FEB 2023: Reports of Guillain-Barré Syndrome After COVID-19 Vaccination in the United States (JAMA Infectious Disease)
“This study found disproportionate reporting and imbalances after Ad26.COV2.S vaccination, suggesting that Ad26.COV2.S vaccination was associated with increased risk for GBS. No associations between mRNA COVID-19 vaccines and risk of GBS were observed.”

20 APR 2023: Immune Imprinting and Implications for COVID-19 (Vaccines)

17 MAY 2023: IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein (Vaccines)
“emerging evidence suggests that the reported increase in IgG4 levels detected after repeated vaccination with the mRNA vaccines may not be a protective mechanism; rather, it constitutes an immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. Increased IgG4 synthesis due to repeated mRNA vaccination with high antigen concentrations may also cause autoimmune diseases, and promote cancer growth and autoimmune myocarditis in susceptible individuals.”