Lower than 10% of US adults have SARS-CoV-2 antibodies

A new study by researchers at Stanford University and Ascend Clinical Laboratory and published in the journal The Lancet in September 2020 reports the prevalence of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in a dialysis patient population in the US.

Advantages of the Sample

The researchers selected this population since these patients are tested every month to monitor their therapy and detect complications. This makes it easy to test for seropositivity to this virus without the need for another venepuncture since the dialysis port is in place. Moreover, these individuals typically have the risk factors that are considered to increase the risk of infection and severe COVID-19, including older age, non-white race, poverty, and diabetes, at a far higher frequency than in the rest of the US population. Thus, testing this population for seroprevalence using remainder plasma was considered a population-representative surveillance strategy that can be maintained longitudinally.

Study Characteristics

The researchers tested a randomly selected group of dialysis patients, aiming to arrive at an estimate of national exposure to SARS-CoV-2 in the period from the beginning of the pandemic to July 2020, by age, sex, region, and race.

The study included over 28,500 individuals, with the majority being tested in the first two weeks. The study also uses case testing data (nasal swab testing by a polymerase chain reaction, PCR), that can help to evaluate the correlation between seroprevalence and other measures of the pandemic such as the number of cases, deaths, percentage of positive tests, and community-based risk factors for seropositivity.

Less than Ten Percent Seropositivity

Overall, 8% of the tests were positive for antibodies. The highest seroprevalence was in the northeast, at ~27%, and the lowest in the south, at ~4%. There was no difference between males and females, but there was a slight drop in patients above 80 compared to those aged 45-64 years. The former were 20% less likely to be seropositive.

When classified by race, non-Hispanic Black patients were 2-3 times more likely to be seropositive, and non-Hispanic white patients the least.

Based on data from June 2020, the prevalence of PCR positive cases is estimated to be 826/100,000 US adults. In contrast, the current seroprevalence estimate is almost 9,000/100,000 population, indicating that only less than one in ten seropositive people are being picked up during the period of infection – despite the fact that the highest number of confirmed cases in the world is in the US at present.

On the other hand, a 9% seroprevalence indicates that most American adults are still free of the virus. This includes dialysis patients who have one of the highest risk levels for COVID-19-related mortality in the world.

Poor Correlation with Other Measures

The highest variation between estimates was in New York, at ~34%, but seven states had zero variation. The best correlation was with the measure of cumulative deaths per 100,000 population. People from more impoverished neighborhoods had twice the risk, while those from crowded areas had a tenfold risk. The mobility-restrictive measures implemented in March of this year reduced seroconversion rates by 60%, it was found.

Possible Limitations

The study presents robust data since the samples were collected on a routine basis, eliminating numerous sources of bias, unlike most other studies. On the other hand, the seroprevalence in the dialysis group may overestimate the community prevalence for several reasons.

One, this group contains a higher proportion of poorer and ethnic-minority individuals. Black Americans are known to have a fourfold risk of end-stage kidney disease compared to whites. Secondly, the patients might use shared transport to reach the center for hemodialysis, as well as being in the center for 10-12 hours each visit, both of which could promote higher transmission.

On the other hand, dialysis patients are less likely to be working and more likely to be confined to home, thus reducing transmission chances. And finally, seroconversion may be weaker in these patients, due to a weaker immune response, as seen in studies on hepatitis B immunization in this group, where only up to 75% of vaccinated individuals seroconverted vs 95% in the general population.

Another confounding factor is the possible absence of the most seriously ill SARS-CoV-2 patients in the dialysis group because of death or hospitalization with other indications, thus ensuring their exclusion from the dialysis group.

Implications

The estimated seroprevalence is in agreement with those from earlier studies, both in the US and in Geneva, Switzerland, and shows that less than a tenth of Americans has been exposed to the virus by July 2020. Thus, herd immunity is still a distant dream, despite the large outbreaks in the first part of the year, just as is seen with other extensive seroprevalence surveys in the similarly hard-hit UK and Spain.  

The study also highlights the disparities in healthcare among ethnic, racial, and socioeconomic groups, which have become further exaggerated with the current pandemic. The tenfold risk of seroprevalence among those living in high-density areas as in crowded cities, confined spaces, and large gatherings as in carnivals, shows the essential nature in the viral spread.

The somewhat lower odds of seropositivity among older people could be because they are more careful to keep a distance from other potentially infectious people, but it is not possible to rule out the chance that more older people might be hospitalized or have died of the infection, thus excluding them from the sample group in this study.

Given these factors, the study provides a model for community surveillance of the pandemic and highlights the feasibility and cost-effectiveness of using repeatedly collected routine collected samples from a group of individuals already undergoing monitoring to fully measure the true incidence of SARS-CoV-2 infection and complement more rapid and limited surveys. The accuracy of this estimate is shown by the lack of correlation between this and other currently used measures of prevalence, except for cumulative deaths, to some extent.

Such surveys can also help to evaluate the adequacy of testing, and the longitudinal follow-up may predict hospitalizations and ICU admissions, given the short 10-day gap, on average, between exposure and seroconversion. This helps with preparedness measures. They can also help assess how well preventive and therapeutic interventions work. And all of these benefits arrive at a little additional cost as remainder plasma is used, obviating the need for venepuncture with the requirements for staff, equipment and infrastructure, while including groups that are traditionally left out or under-represented.

The study includes, “Serial sampling of dialysis remainder plasma should be used to determine trends in disease prevalence and the effect of various strategies being implemented around the USA to reduce the burden of COVID-19 on the general population.”

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