BACKGROUND AND PURPOSE:

• Among the unvaccinated, previous SARS-CoV-2 infection may provide some immunity against subsequent infection
  • Persistence of antibodies beyond 6 months remains unknown
• Alejo et al. (JAMA, 2022) characterized natural immunity and long-term durability among unvaccinated individuals using anti–spike antibodies

METHODS:

• Cross-sectional study
• Participants
  • Healthy adults
  • Unvaccinated against COVID-19
• Exposures
  • COVID confirmed: Test-confirmed COVID-19 infection
  • COVID unconfirmed: Suspected COVID-19 but not tested
  • No COVID: No suspected COVID-19 | Never tested positive
• Study design
  • Participants recruited via social media
  • Participant-completed questionnaire: Demographics | COVID-19 status | Mask use
  • Participants placed into an exposure group using weighted random sampling (relative weights based on the estimated unvaccinated US population by age, race and ethnicity, and education)
  • Antibody testing: Invited to get tested over a month 
    • Qualitative detection of antibodies against the SARS-CoV-2 antinucleocapsid (N) protein | Positive cutoff index ≥1.0
    • Semiquantitative detection of antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD) | Positive cutoff ≥0.8 U/mL
• Primary outcome
  • Association between antibody titers and previous infection status

RESULTS:

• COVID confirmed: 295 | COVID unconfirmed: 275 | No COVID: 246
  • 1580 individuals invited to undergo serologic testing: 52% accepted (n=816)
  • Mean age 48.0 years | 52% women | 82% White
  • Reported routine mask use in public: 14%
• Among COVID confirmed participants
  • Median months passed since diagnosis: 8.7 (IQR, 1.9 to 12.9)
  • Tested positive for anti-RBD: 99%
  • Median anti-RBD level: 205 (IQR, 61 to 535) U/mL
  • There was no evidence of association between time after infection and antibody titer
    • 0.8% increase per month (95% CI, –2.4% to 4.2%); P=0.62
• Among COVID unconfirmed participants
  • Tested positive for anti-RBD: 55%
  • Median anti-RBD level: 131 (IQR, 35 to 402) U/mL
• Among no COVID participants
  • Tested positive for anti-RBD: 11%
  • Median anti-RBD level: 82 (IQR, 19 to 172) U/mL

CONCLUSION:

• Among those participants who received a positive COVID-19 test, 99% had anti-RBD antibodies with persistence up to 20 months
• Among those who thought that they had COVID-19, only approximately half of the cohort had detectable antibodies
• Whether these antibodies are associated with protection against future SARS-CoV-2 encounters is still unclear
• Authors acknowledge limitations including selection bias and the fact that antibody levels alone do not directly correlate with immunity
• The authors state

Although evidence of natural immunity in unvaccinated healthy US adults up to 20 months after confirmed COVID-19 infection is encouraging, it is unclear how these antibody levels correlate with protection against future SARS-CoV-2 infections, particularly with emerging variants

Learn More – Primary Sources:

Prevalence and Durability of SARS-CoV-2 Antibodies Among Unvaccinated US Adults by History of COVID-19

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