Connecting COVID-19 antibody responses to disease protection, one data set at a time

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Reports that most if not all COVID-19 survivors have antiviral antibodies are beginning to set benchmarks for immunity, but understanding how much protection different levels and types of antibodies provide will be critical for determining how well COVID-19 vaccines work.

The idea that exposure to a virus triggers production of antibodies that protect individuals from infectious disease is among the oldest principles in immunology. But because researchers’ understanding of SARS-CoV-2’s interaction with the human immune system is in its infancy, how this principle plays out for COVID-19 is still under investigation.

Recent studies from Chongqing Medical University and Icahn School of Medicine at Mount Sinai suggest anti-SARS-CoV-2 IgG antibodies are produced by the vast majority of recovered patients. As more human serological data comes online, the key question will be what antibody levels and specificities are associated with what types of protection.

That includes understanding how high antibody titers must be to prevent infection, or even reduce disease severity.

How antibody titers affect COVID-19 outcomes is one of the questions addressed by an FDA-sponsored centralized trial of convalescent plasma, which began enrolling patients last month (see “Bringing Access to Convalescent Plasma”).

Other critical questions include what SARS-CoV-2 antigens induce neutralizing antibodies that prevent viral entry into cells, and what types of antibodies trigger antibody-dependent enhancement (ADE) of SARS-CoV-2 infection (see Ensure COVID-19 Vaccines Don’t Make Infections Worse”).

Answers to these questions will inform interpretation of the first tranche of clinical trial data for COVID-19 vaccines, which typically use antibody titers as early readouts of efficacy. Preliminary data from the first clinical COVID-19 vaccines are due starting this month (see “End of the Beginning for COVID-19 Vaccines”).

Better understanding of what antibody levels and types are linked to COVID-19 protection will also identify which serological tests provide the best indication of who is safe to go back to work (see “Good Test Hunting”).

Anti up

Mounting evidence suggests people who overcome both mild and severe COVID-19 overwhelmingly produce IgG antibodies against SARS-CoV-2.

The Chongqing team surveyed 285 COVID-19 patients, 39 of whom had severe or critical disease, and detected IgG antibodies against the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins within 19 days of symptom onset in all of the participants. They also found 94.1% of the patients had generated IgM against the virus by 20-22 days after symptom onset.

In a separate cohort, COVID-19 antibodies were detected in 61/63 (96.8%) patients by the time of hospital discharge. Results were reported April 29 in Nature Medicine.

In a medRxiv preprint posted May 6, Mt. Sinai researchers similarly found anti-spike IgG in 621/624 (99.5%) individuals who had recovered from mild disease and had previously tested positive for COVID-19 by PCR.

Additionally, by making a titer of 1:80 the threshold for defining samples as positive for COVID-19 antibodies, the Mt. Sinai study supported FDA’s recommended antibody levels for convalescent plasma donation. The agency’s guidance states that neutralizing antibody titers of 1:80 may be acceptable but recommends a titer of at least 1:160.

Both studies measured the total amounts of IgG or IgM produced, rather than restricting detection to neutralizing antibodies.

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