Antibody map shows how Covid-19 spread through the United States this spring

After a dramatic winter, and long summer, it seems the Covid-19 has penetrated every corner and cul-de-sac in America. But scientists aren't so sure, based on an in-depth new survey.

Most people in the US have still not been exposed to the virus, according to a survey published Friday in The Lancet.

Based on a survey of 28,503 people who were receiving dialysis treatment, the study reports that 8 percent of people tested positive for coronavirus antibodies. Based on that sample, the authors estimate that 9.3 percent of the US population at large has coronavirus antibodies.

The study was funded by Ascend Clinical Laboratories, a lab that receives samples from dialysis labs. The research was conducted by a team out of Stanford University.

Dialysis patients may not be a perfect representation of the US population – they are often older and less likely to go outside in public. But Wafaa El-Sadr, the director of the Global Health Initiative at the Columbia Mailman School of Public Health, comments that these estimates still provide a useful overview. El-Sadr was not involved with the research.

"[Seroprevalence, or the level of a pathogen in a population,] data thus far in the US have always had their limitations," El-Sadr tells Inverse. "They made a good effort...so that it could be as representative as possible."

Thomas McDade is the director of Northwestern’ Laboratory for Human Biology Research and was also not involved with the study.

"We have to be careful about drawing conclusions beyond the population of dialysis patients," he tells Inverse.

However, we can still learn something from this data, McDade observes. For instance, the things that might predict exposure to the virus, like where someone lives or demographic trends, reveal where the virus has spread and to whom.

The states with the highest percentages of Covid-19 antibodies – The team collected data from dialysis at 1,300 clinics nationwide. Those patients were tested for antibodies in July.

Because it can take two to three weeks for enough antibodies to show up on a test, the survey offers a snapshot of how many people may have had antibodies in June.

That means this study is a snapshot of the period before the virus resurged this summer, but after it devastated the Northeast and hotspots like Louisiana in March and April. That pattern is reflected in the antibody data, which differed a lot depending on the region:

• 27.6 percent of the study population in the Northeast had antibodies.
• 7.4 percent of the study population in the Midwest had antibodies.
• 5.1 percent of the study population in the South had antibodies.
• 4.2 percent of the study population in the West had antibodies.

"At that time, the Northeast has been hit the hardest with by Covid-19," El-Sadr says. "It's not surprising that there would be a higher seroprevalence noted in those individuals, compared to [people in] other regions in the country."

McDade notes that the regional differences were expected, based on the patchwork way that the US states created Covid-19 policies and the population density by region.

"I think the reality is that there is a lot of regional variation in seroprevalence, based on population density and the timing of policies," he says.

Who has antibodies? – Black or Hispanic people were 3.9 times more likely to have coronavirus antibodies than white people, according to the study.

An accompanying commentary written by scientists at Imperial College London points out that racial disparities in Covid-19 exposure fit with trends reported in England, representing an "alarming discrepancy" that "demands urgent attention."

The costs are high – The Covid tracking project reports that Black people in the United States are dying from Covid-19 at 2.4 times the rate of white people.

The study also showed that people living in places with a population density of greater than 8,607 people per square mile had higher chances of having antibodies. The connection "does make intuitive sense," says El-Sadr, but there are other explanations from previous antibody studies that add nuance.

The divide between rich and poor — In New York City, for instance, Manhattan has the most people per square mile of all the boroughs. However, it has the lowest percentage of people with antibodies. That's because while there are more people per square mile in Manhattan, there are fewer people sharing a single household (Covid-19 spreads easily within a household), says El-Sadr.

"You'll find that then the boroughs like Queens and Brooklyn that have higher household densities are the ones that have been more severely affected," she says.

That means that rather focusing on a city's density it may pay to look more closely at how many people are sharing a single home, which in any populous city, is a key indicator of income or wealth.

Thinking beyond herd immunity – Serology surveys are typically used as markers of exposure, not immunity. Scientists are still unsure how immunity to Covid-19 works or how long it lasts. This 9.3 percent number still suggests is that herd immunity through natural infection is out of reach anyway, placing additional import on developing a vaccine and rolling it out nationwide.

"It's extremely unlikely, if not impossible, that we're going to reach herd immunity through natural infection," El-Sadr says.

Even if we were close, and immunity guaranteed to be long-lasting (we still don't know), the cost of letting the virus run rampant was severe. High seroprevalence was most tightly tied to one measure all: deaths from the coronavirus per 100,000 people.

As El-Sadr explains, this places the additional onus on the country not to just develop a vaccine that is safe and effective but roll it out across the entire country – especially groups who are running a higher risk of death.

"I think the message to me is that, for vaccines, is we're going to have to really have plans in place, she says.

"We'd have to have a very broad-based national strategy as to how we're going to get it out there to all the people who need it because, looking at a map, it looks like we have to cover the whole country."

Abstract:

Methods: For this cross-sectional study, in partnership with a central laboratory that receives samples from approximately 1300 dialysis facilities across the USA, we tested the remainder plasma of 28503 randomly selected adult patients receiving dialysis in July, 2020, using a spike protein receptor binding domain total antibody chemiluminescence assay (100% sensitivity, 99·8% specificity). We extracted data on age, sex, race and ethnicity, and residence and facility ZIP codes from the anonymized electronic health records, linking patient-level residence data with cumulative and daily cases and deaths per 100 000 population and with nasal swab test positivity rates. We standardized prevalence estimates according to the overall US dialysis and adult population, and present estimates for four pre-specified strata (age, sex, region, and race and ethnicity).

Findings: The sampled population had similar age, sex, and race and ethnicity distribution to the US dialysis population, with a higher proportion of older people, men, and people living in majority Black and Hispanic neighborhoods than in the US adult population. Seroprevalence of SARS-CoV-2 was 8·0% (95% CI 7·7–8·4) in the sample, 8·3% (8·0–8·6) when standardized to the US dialysis population, and 9·3% (8·8–9·9) when standardized to the US adult population. When standardized to the US dialysis population, seroprevalence ranged from 3·5% (3·1–3·9) in the west to 27·2% (25·9–28·5) in the northeast. Comparing seroprevalence and case counts per 100000 population, we found that 9·2% (8·7–9·8) of seropositive patients were diagnosed. When compared with other measures of SARS-CoV-2 spread, seroprevalence correlated best with deaths per 100 000 population (Spearman’s ρ=0·77). Residents of non-Hispanic Black and Hispanic neighborhoods experienced higher odds of seropositivity (odds ratio 3·9 [95% CI 3·4–4·6] and 2·3 [1·9–2·6], respectively) compared with residents of predominantly nonHispanic white neighborhoods. Residents of neighborhoods in the highest population density quintile experienced increased odds of seropositivity (10·3 [8·7–12·2]) compared with residents of the lowest density quintile. County mobility restrictions that reduced workplace visits by at least 5% in early March, 2020, were associated with lower odds of seropositivity in July, 2020 (0·4 [0·3–0·5]) when compared with a reduction of less than 5%.

Interpretation: During the first wave of the COVID-19 pandemic, fewer than 10% of the US adult population formed antibodies against SARS-CoV-2, and fewer than 10% of those with antibodies were diagnosed. Public health efforts to limit SARS-CoV-2 spread need to especially target racial and ethnic minority and densely populated communities.