Several recent studies show that not all who get a positive COVID-19 diagnosis by RT-PCR develop antibodies against the SARS-CoV-2 virus or seroconvert. An Israeli group showed that 5% of all their COVID-19 positive patients did not seroconvert (Oved K et al., EClinicalMedicine 29 (2020) The team of Wellinghausen et al. from Germany (J Clin Virol. 2020;130) showed that 85% of confirmed COVID-19 contacts failed to seroconvert. A New York group showed in their seroprevalence studies that 20% of participants who had positive PCR results did not develop antibodies against SARS-CoV-2. (Pathela P et al., J Infect Dis. 2021 Apr)
The team of Thiruvengadam R et al. from India found that whereas all those with severe COVID-19 developed antibodies, only 89.6% of those with moderate and 77% of those with asymptomatic disease did. (Am J Trop Med Hyg. 2021). In a CDC study Cavanaugh AM et al showed that in Kentucky between May – June 2021, reinfection was higher in those with prior COVID-19 but stayed unvaccinated compared to those who were vaccinated (MMWR 2021;70(32);1081-83). Thus we see that the development of protective antibodies after an infection is not always assured. The protection thought afforded by a prior positive PCR test might be illusory.
What Determines Who Seroconverts After Natural Infection?
Seroconversion after infection seems to hinge on the viral load that a person harbors in the nasopharynx. The higher the viral load, the greater the chances are that a person will seroconvert. Masiá M and her group from Spain showed that low viral load, quick clearance of the virus, and low levels of inflammatory markers predict non-seroconversion (Open Forum Infect Dis. 2021). Liu W and a team from the University of Pennsylvania studied 72 patients in Alabama. They found that younger patients and those with low viral loads in the nasopharynx often do not seroconvert (Emerg Infect Dis. 2021;27(9))
Are There Vaccinated Patients Who do Not Seroconvert?
Unlike those who get a natural infection, all those who get a COVID-19 vaccine seroconvert. However, the level of immune response differs. A UK group studied 46,000 participants who either received the Pfizer or AstraZeneca COVID-19 vaccine. They found out that the response depended on prior infection status, age, sex, vaccine type, and number of doses (Wei J et al. Nature Microbiology; 6:1140–1149 (2021)) They teased out four response groups to the vaccines:
- Previously infected group: anti-spike IgG levels started higher pre-vaccination (but below the threshold for positivity) and rapidly rose.
- High response group: IgG levels increased rapidly and to a higher level before plateauing.
- A medium response group: those in the group had mean antibody levels slightly below the high-response group but still above the positivity threshold.
- A low response group: those in this group had mean IgG levels below the positivity threshold throughout, peaking at ~10 ng /ml–1, and their response was delayed.
Anti-spike IgG Positivity by Time from 1st Immunization By Age Vaccine Type and Prior Covid-19 infection
The low response group formed about 6% of the cohort. Those in this group tended to be older than 60 years, male, were on immunosuppressants like corticosteroids, and had chronic diseases like rheumatoid arthritis, chronic liver disease, cancer, type 2 diabetes, obesity (BMI ≥ 30 kg per m squared), and COPD. What was also evident was that patients who had a prior infection and did receive a dose of a COVID-19 vaccine did develop the most potent immune response.
Main Take Home Points
Though one can get adequate immunity after a COVID-19 infection, the immune response is unpredictable since not all seroconvert. On the other hand, though about 6% of all who get a COVID-19 vaccine have a poor immune response, all those who get vaccinated seroconvert. The most potent immune response is seen in those who have had a prior infection. It follows that instead of depending on immunity from a prior infection that can be unpredictable, those with previous COVID-19 infections are best served by receiving at least one shot of a COVID-19 vaccine.
By Nana Dadzie Ghansah an anesthesiologist who practices in Lexington, Kentucky