A surprising new study published on the preprint server medRxiv* in October 2020 reports a very high seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the city of Vera Cruz, Mexico. They are among the highest to be reported anywhere in the world.
Rising Wave in Latin America
Currently, Latin America is one epicenter of the COVID 19 pandemic, and Mexico is one of the most affected countries being the ninth-ranked country for cases (891,160) and mortality (88,924) as of October 26, 2020.
One way to estimate the load of infection is by assessing the seroprevalence at the population level. This would help to monitor its trend as well. However, the seroprevalence varies from country to country, among different populations, and during the pandemic phase.
Wide Screening Net
The current study focused on IgG seroprevalence against SARS-CoV-2, exploring its link with demographic features, a prior history of testing positive for the virus, and a history of symptoms deemed suspicious of COVID-19. These symptoms included having either fever, headache, or respiratory symptoms in the four weeks prior to testing, but without a confirmatory polymerase chain reaction (PCR) viral RNA test.
The researchers carried out serological testing in over 2,100 individuals between June 1 and July 31, 2020, all over 18 years of age, at two private diagnostic centers.
The youngest was 18, while the oldest was 98, with an average age of ~42 years. Just over half of these were asymptomatic. About a third had a history of suspicious symptoms, while ~14% reported a previous infection.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
High Seropositivity
Overall, the researchers found that almost a third (~30/%) of the tested individuals were seropositive. Over a fifth (~21%) were tested positive for IgG antibodies against the virus among the asymptomatic subjects. Among those with suspicious symptoms, almost a quarter had antibodies (~23%).
Among those with a history of the previous infection as confirmed by PCR, the seropositivity rate was ~74%.
Males were at a 17% increased risk compared to females for seropositivity. The only absolute risk factor was advancing age, which was correlated to a higher rate of seropositivity.
Implications
The researchers comment, "The number of infected subjects in our Mexican population is not encouraging and it should be interpreted with caution." The potential fall-out of this situation is two-fold.
On the one hand, a higher seroprevalence could move Mexico nearer to the goal of herd immunity. On the other hand, if immunity against SARS-CoV-19 is weak and transient, a higher caseload could merely mean that a more significant second wave could hit since the initial case number is so large.
Future Directions
The researchers point to the difficulty of measuring the population's actual seroprevalence at this time, especially with respect to the assays currently available. The accuracy of the test kits may change and with it, the estimated seroprevalence. The viral target chosen may cause varying efficiency of detection. The nucleocapsid antigen is thought to be the most sensitive target for those with low antibody responses.
Even in the current study, the call to participate may have been heeded by more symptomatic individuals and their family members relative to others, posing a potential selection bias. Again, if the exposed individual is tested too early, or the infected one too late, the test may be falsely negative since the antibody response takes time to rise to detectable levels and is thought to decline below detectable levels in at least some individuals, rapidly.
The threshold at which the test is declared positive also needs to be calibrated to the local population and the infection phase. Setting the threshold too high may miss the mild and convalescent, not to mention asymptomatic cases.
Earlier studies show considerable variation in the immune response between individuals, especially with mild or asymptomatic disease. One small preliminary study in Sweden showed that the proportion of people who showed T cell responses was always higher than that which tested seropositive by IgG testing.
Finally, the study took place in only one region and cannot offer a measure of the spread of the virus over Mexico's whole. Further longitudinal multicenter studies may help expand the relevance of the findings of this study.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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