Phase One: first upstroke of viral death curve.

Phase Two: Second upstroke of viral death curve; worse than the first one by at least 10 fold.

Phase Three: another spike after everyone figures the pandemic is over.

Stage One Release of Restrictions of Isolation

Stage Two Release of Restrictions of Isolation and protection

Stage Three Release of all Restrictions of Isolation, protection, distancing, etc.

2020 COVID19 Death curves; by shifting the curve, without a "cure" or the vaccine, the area under the curve must be satisfied; i.e. the integrated number of deaths remains the same.

1918 Conditions remain the same today for COVID19, pretty well the same recommendations.

Another representation of the death curve.

Compare the similarity to the 1918 Pandemic Flu death curve.

See the age related COVID19 mortality rate. The evidence for "reverse isolation" for anyone over 60 years of age, just because of age, and more so with additional pre-morbid conditions. (This has always been isolation is the person is healthy, or "reverse isolation " if the patient has pre-morbid conditions that predispose them to death by COVID19. Isolation is a medical term, quarantine is more of a legal term. For example, in Canada if someone breaks a legal quarantine, they are subject to up to a million dollar fine and prison time.)

July 15, 2020: Okay we are now at the point between Stage Two and Three "Reopening" from quarantines and isolations, with the use of PPE and social distancing in place, and Phase Two beginning as per the 1918 daily death rate curve. I note at this time that the above measures did work in New York and elsewhere to lower the death curve on Phase One. This prevented natural herd-immunity being achieved in Phase One, but only to flatten and prolong the curve out over time, there is yet to be a "cure" or a good vaccine distributed. Thus, we are following the scenario of the death curve of the 1918 flu Pandemic repeated here in 2020 COVID-19 Pandemic. See attached mark-up graph with my labels to show the various points mentioned above. Thank you and stay safe, Gary Ordog, MD.

July 26, 2020: The psychological impact of COVID-19 will never be fully realized. I don't think my grandparents ever fully recovered from 1918 (or the First World War). These are some of my own feelings on the subject:

1. Hypothesis: Clinical COVID-19 infections leave the patients with various degrees of brain trauma (physiologically speaking) from hypoxia, corticosteroid administration, sedative and narcotic administration, microemboli, microthrombosis, etc.

2. Hypothesis 2: Clinical and subclinical COVID-19 causes encephalitis with encephalopathy in many cases, with the resultant neurocognitive and psychological sequelae.

3. Those patients in critical condition often have residual ICU psychosis or at least psychological sequelae, if they recover. (e.g. the result of being sedated and paralyzed and tied down on a ventilator, for a prolonged period of time.

4. The rest of society that are otherwise not infected have isolation; with its resultant anxiety, depression, loneliness, etc.

5. World-wide economic shut-down leads to loss of income, leading to anxiety, depression, despair, etc.

6. World-wide travel shut-down leads to further isolation, depression, anxiety, etc.

7. There are probably only a few people in the world who are unaffected by the results of the COVID-19 Pandemic, in one way or another. The lasting effects on each individual will probably be life-long; as it was in my grandparents from 1918.

Stay safe and thank you for letting me speak. Gary Ordog, MD

Doctors' Guide Alert: COVID-19 AUGUST 7, 2020

COVID-19: Total cases rise by more than 53,000 in US

According to CDC's update on August 6, the case count of COVID-19 in the US stands at 4,802,491* cases, including 157,631* deaths, in 55 (50 states, District of Columbia, Puerto Rico, Guam, Northern Marianas, and US Virgin Islands) jurisdictions. This represents an additional 53,685 cases and 1,320 deaths compared to the update on the preceding day.This is a record high, higher than Phase One in the United States. We are definitely on the upslope of Phase Two of the 1918 death curve. Enforcement of the Public Health codes and recommendations couldn't hurt??

August 10, 2020: still on upstroke of Phase Two of the 1918 Death Curve; with around 55,000 new cases and over a thousand deaths per day in the US from COVID-19 (positive PCR for cases, and deaths.)

This is my hand-drawn graph comparing 1918 to COVID-19 Pandemics. The Phases are the upsurges in deaths. The "Troughs" between the Phases are due to "lock-down" but during the trough Stages 1 to 3 "reopens" occur. The re-openings, including protests and rioting, lead to increased exposure and then the next Phase. This was the course of 1918 Pandemic, but COVID-19 is playing out very similar. On August 14, 2020; we are currently on the upstroke of Phase Two of COVID-19.

Published in JAMA today. (Journal of the American Medical Association):

August 15, 2020 COVID-19 and 1918 Death Rate NYC Comments.

Gary Ordog, MD, DABEM, DABMT | County of Los Angeles, Department of Health Services, (retired) Thank you for your interesting article. My writing here is precipitated by the fact that COVID-19 is not over yet. Yes, so far, COVID-19 appears to be following the death curve of 1918, and we in the Americas are on the upslope of Phase Two of Three, as happened in 1918. Even the Reopening Trough One of COVID-19 was similar to that of 1918, with protests and rioting. In 1918 Phase Two was worse than Phase One, we shall possibly witness similar figures in the next few months. With no valid cure as yet, we are dependent on the administration of a 'good' vaccine to put an end to this. Hopefully, it will be in time to prevent the Trough Two, followed by more public insurrection and finally, Phase Three. The 1918 flu had no cure or vaccine, but we now have the hope of a 'good' vaccine which should prevent the decimation that COVID-19 would have projected for the next two years. Thank you and stay safe until then. CONFLICT OF INTEREST: None Reported Research Letter Public Health August 13, 2020 Comparison of Estimated Excess Deaths in New York City During the COVID-19 and 1918 Influenza Pandemics Jeremy Samuel Faust, MD, MS; Zhenqiu Lin, PhD; Carlos del Rio, MD JAMA Netw Open. 2020;3(8):e2017527. doi:10.1001/jamanetworkopen.2020.17527 COVID-19 Resource Center Introduction During the 1918 H1N1 influenza pandemic, there were approximately 50 million influenza-related deaths worldwide, including 675 000 in the US. Few persons in the US have a frame of reference for the historic levels of excess mortality currently being observed during the coronavirus disease 2019 (COVID-19) pandemic.1 In this study, excess deaths in New York City during the peak of the 1918 H1N1 influenza pandemic were compared with those during the initial period of the COVID-19 outbreak.

Update August 20, 2020. COVID-19: Death toll passes 787,000 globally According to the European Centre for Disease Prevention and Control (ECDC), since 31 December 2019 and as of 20 August 2020, 22,431 929 cases of COVID-19 have been reported, including 787,773 deaths. Comments 300801007 replied on Thu, 08/20/2020 - 14:34 The death rate is still significant, evidence that the "flattening of the curve" will result in the same 'area' under the curve, at least until an effective vaccine is given. COVID-19 has not 'disappeared.' Stay safe, thank you, Gary Ordog MD. Reference: https://www.ecdc.europa.eu/en/geographical-distribution-2019-ncov-cases

USA deaths up to 1404 per day from COVID-19. See:

COVID-19 AUGUST 21, 2020

COVID-19: More than 46,000 new cases reported in US

According to CDC's update on August 20, the case count of COVID-19 in the US stands at 5,506,929* cases, including 172,416* deaths, in 55 (50 states, District of Columbia, Puerto Rico, Guam, Northern Marianas, and US Virgin Islands) jurisdictions. This represents an additional 46,500 cases and 1,404 deaths compared to the update on the preceding day.

NZ response to Phase Two:

Here is a case curve in the news today, showing an exponential increase during Phase Two starting now. The headlines:

Public health officials call for tighter restrictions, warn COVID-19 could spiral out of control (by CBC News). This confirms what I was talking about 8 months ago, and compare this curve with my previous death curve, they look almost identical.

They are still trying to "flatten the curve" in this graph, as well.

Please follow this articles. Hopefully it may fulfill your requirements.

NOVEMBER 13, 2020

COVID-19: More than 143,000 additional cases reported in US

According to CDC's update on November 12, the case count of COVID-19 in the US stands at 10,314,254* cases, including 241,069* deaths, in 55 (50 states, District of Columbia, Puerto Rico, Guam, Northern Marianas, and US Virgin Islands) jurisdictions. This represents an additional 143,408 cases and 1,479 deaths compared to the update on the preceding day. The record highs keep increasing!

Update November 18, 2020:

US surpasses 250,000 coronavirus deaths as virus mortality rate surges

Joe Murphy and Corky Siemaszko

The United States has recorded a quarter-million COVID-19 deaths, the latest NBC News numbers showed Wednesday, and the death rate has been accelerating in recent weeks as cases have been surging across the country.

Provided by TODAY

The 250,000th death was logged Wednesday morning, the data revealed.

In the last four weeks there has been a 42 percent increase in the number of fatalities, from a weekly average of 821 per day in early October to last week’s average of 1,167 fatalities per day, according to an NBC News analysis of the available data.

"White House task force warns of ‘aggressive, unrelenting spread’ of virus" White House task force warns of ‘aggressive, unrelenting spread’ of virus.

And, a year after the first COVID-19 infection was reported in China, people were dying in America at a pace not seen since mid-August, the analysis showed.

Meanwhile, the number of confirmed COVID-19 cases continued to climb rapidly and the pandemic showed no sign of slowing down as the holiday season loomed and two very promising vaccines were still months away from widespread distribution.

In addition to deaths, the U.S. leads the world with 11.4 million COVID-19 infections, the NBC News figures showed.

"Right now, we are in an absolutely dangerous situation that we have to take with the utmost seriousness," Brett Giroir, the Trump Administration's coronavirus testing czar, told MSBNC's Andrea Mitchell. "This is not crying wolf. This is the worst rate of rise in cases that we have seen in the pandemic in the United States. And, right now, there's no sign of flattening."

And with all 50 states plus Washington, D.C., the U.S. Virgin Islands and Guam reporting increases Wednesday in coronavirus cases over the past 14 days, according to the latest NBC News data, hospitals and the doctors and nurses contending with a deluge of sick patients were at the breaking point.

"We're approaching, I think, desperation," Dr. Julie Watson, Chief Medical Officer at Integris Health in Oklahoma, said on MSNBC. "I think we have to have our citizens helping us by wearing a mask and keeping their distance.”

Asked for her reaction to Oklahoma Gov. Kevin Stitt's continued refusal to impose a mask mandate, Watson said “It is baffling to me how this has become a political issue."

"The flu isn't political, heart disease is not political, kidney disease is not political, but somehow putting on a face covering to protect the person, you know, next to you or around you has somehow become political,” she said.

The grim numbers were piling up as President Donald Trump continued to balk at conceding the election to President-elect Joe Biden. As a result, the Democrat’s COVID-19 team has been trying to prepare to take over the responsibility of fighting the pandemic without access to information currently in the hands of the White House coronavirus task force led by Vice President Mike Pence.

“Our team cannot communicate with them,” Dr. David Kessler, a member of Biden’s advisory committee, said. “The sooner the Biden transition team can meet with officials working on these questions, the more seamlessly the transition will be the American people.”

And a lot of the information the Trump team is sitting on is dire.

In an internal report obtained Tuesday by NBC News, the White House coronavirus task force warned there is “now aggressive, unrelenting, expanding broad community spread across the country, reaching most counties, without evidence of improvement but rather, further deterioration.”

Pfizer says its vaccine is now 95 percent effective.

Also, the task force report warned that current efforts to stop the spread “are inadequate and must be increased to flatten the curve” and that the upcoming Thanksgiving holiday has the potential to “amplify transmission considerably.”

That message was undermined by Dr. Scott Atlas, one of Trump’s top pandemic advisers, who during interviews on Fox News this week appeared to encourage large Thanksgiving family gatherings and dismissed any talk about the rising number of deaths as fearmongering.

“Yes, there are people dying,” Atlas said Tuesday on the “Brian Kilmeade Show.” “But those deaths, the number of deaths, it’s not exploding like it did back in the spring.”

Atlas, a conservative ideologue who is a radiologist and not an expert on infectious diseases, has been accused of, among other things, peddling misinformation about herd immunity and making false claims about the effectiveness of masks at preventing the spread of Covid-19.

The federal Centers for Disease Control and Prevention and the world’s top public health experts say masks protect both the wearers and everybody else from infection.

NOVEMBER 27, 2020

COVID-19: US records more than 165,000 new cases

According to CDC's update on November 25^, the case count of COVID-19 in the US stands at 12,498,734* cases, including 259,005* deaths, in 55 (50 states, District of Columbia, Puerto Rico, Guam, Northern Marianas, and US Virgin Islands) jurisdictions. This represents an additional 165,282 cases and 1,989 deaths compared to the update on the preceding day. We are continuing to have in the USA historic numbers in this second or third spike. Only in retrospect in a few years from now will we be able to see the graph and whether this is still the upstroke of phase two, or an actual phase three. Gary Ordog, MD

November 29, 2020: We may have seen nothing yet. This Pandemic has barely started, with evidence that less than 10% in the US are seroconverted. Fortunately, mass vaccinations may take place soon with several effective vaccines. Otherwise true catastrophe.

1 Comment for this article.

November 29, 2020

SARS-CoV-2 Seroprevalence in the US comments.

Gary Ordog, MD, DABMT, DABEM | County of Los Angeles, Department of Health Services, Physician Specialist (ret.)

Thank you for the interesting study. Although your subject numbers seem large, I believe they represent less than one percent of the population, which makes the sample size small. Also, the method of using convenience blood, we really have no idea why these subjects were getting their blood drawn, but we do know it was not for the purpose of the study. That means that the small sample size may be skewed unknowingly and severely towards some unknown confounding variable, for example, perhaps most of them thought they had had COVID-19. So, the validity of drawing conclusions based upon these results is very low, and even trying to make valid conclusions about time trends is questionable because of the possibility of unknown changing confounding variables during that time. That said, I would like to comment on the implications of your study results, even though what I am concluding cannot be valid, just interesting. Most importantly, possibly only 10% of the population have been infected with SARS-CoV-2. That means that possibly, 90% of the population may be still prone to suffer from infection in the pandemic. Without a vaccination, the US could be facing a disaster. Fortunately, it looks like several vaccines are effective, and many more are in the works. If anything, it looks like your study shows that the vaccination program and its success is more important that ever. Thank you, and stay safe until then.

CONFLICT OF INTEREST: None Reported

Original Investigation

November 24, 2020

Estimated SARS-CoV-2 Seroprevalence in the US as of September 2020

Kristina L. Bajema, MD, MSc1; Ryan E. Wiegand, MS1; Kendra Cuffe, MPH1; et alSadhna V. Patel, MPH1; Ronaldo Iachan, PhD2; Travis Lim, DrPH1; Adam Lee, MS2; Davia Moyse, MA2; Fiona P. Havers, MD, MHS1; Lee Harding, MS2; Alicia M. Fry, MD, MPH1; Aron J. Hall, DVM, MSPH1; Kelly Martin, MPH2; Marjorie Biel, MPH2; Yangyang Deng, MS2; William A. Meyer III, PhD3; Mohit Mathur, MD, PhD4; Tonja Kyle, MS2; Adi V. Gundlapalli, MD, PhD1; Natalie J. Thornburg, PhD1; Lyle R. Petersen, MD, MPH1; Chris Edens, PhD1

Author Affiliations Article Information

JAMA Intern Med. Published online November 24, 2020. doi:10.1001/jamainternmed.2020.7976

COVID-19 Resource Center

editorial comment icon Editorial

Comment

Key Points

Question What proportion of persons across 52 US jurisdictions had detectable antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from July to September 2020?

Findings In this repeated, cross-sectional study of 177 919 residual clinical specimens, the estimated percentage of persons in a jurisdiction with detectable SARS-CoV-2 antibodies ranged from fewer than 1% to 23%. Over 4 sampling periods in 42 of 49 jurisdictions with calculated estimates, fewer than 10% of people had detectable SARS-CoV-2 antibodies.

Meaning While SARS-CoV-2 antibody prevalence estimates varied widely across jurisdictions, most people in the US did not have evidence of previous SARS-CoV-2 infection.

Abstract

Importance Case-based surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimates the true prevalence of infections. Large-scale seroprevalence surveys can better estimate infection across many geographic regions.

Objective To estimate the prevalence of persons with SARS-CoV-2 antibodies using residual sera from commercial laboratories across the US and assess changes over time.

Design, Setting, and Participants This repeated, cross-sectional study conducted across all 50 states, the District of Columbia, and Puerto Rico used a convenience sample of residual serum specimens provided by persons of all ages that were originally submitted for routine screening or clinical management from 2 private clinical commercial laboratories. Samples were obtained during 4 collection periods: July 27 to August 13, August 10 to August 27, August 24 to September 10, and September 7 to September 24, 2020.

Exposures Infection with SARS-CoV-2.

Main Outcomes and Measures The proportion of persons previously infected with SARS-CoV-2 as measured by the presence of antibodies to SARS-CoV-2 by 1 of 3 chemiluminescent immunoassays. Iterative poststratification was used to adjust seroprevalence estimates to the demographic profile and urbanicity of each jurisdiction. Seroprevalence was estimated by jurisdiction, sex, age group (0-17, 18-49, 50-64, and ≥65 years), and metropolitan/nonmetropolitan status.

Results Of 177 919 serum samples tested, 103 771 (58.3%) were from women, 26 716 (15.0%) from persons 17 years or younger, 47 513 (26.7%) from persons 65 years or older, and 26 290 (14.8%) from individuals living in nonmetropolitan areas. Jurisdiction-level seroprevalence over 4 collection periods ranged from less than 1% to 23%. In 42 of 49 jurisdictions with sufficient samples to estimate seroprevalence across all periods, fewer than 10% of people had detectable SARS-CoV-2 antibodies. Seroprevalence estimates varied between sexes, across age groups, and between metropolitan/nonmetropolitan areas. Changes from period 1 to 4 were less than 7 percentage points in all jurisdictions and varied across sites.

Conclusions and Relevance This cross-sectional study found that as of September 2020, most persons in the US did not have serologic evidence of previous SARS-CoV-2 infection, although prevalence varied widely by jurisdiction. Biweekly nationwide testing of commercial clinical laboratory sera can play an important role in helping track the spread of SARS-CoV-2 in the US.

Introduction

The first severe acute respiratory syndrome 2 (SARS-CoV-2) infection in the US was identified in January 2020,1 followed soon after by reports of community transmission.2-5 The US remains severely affected by the coronavirus disease 2019 (COVID-19) pandemic, with more than 9 million cases and 230 000 deaths reported through November 1, 2020.6 With limited testing availability and mild and asymptomatic infections contributing to underascertainment of SARS-CoV-2 infections through passive case reporting,7-9 seroprevalence surveys are important for refining estimates of infection and transmission.10

Most seroprevalence surveys conducted in the US thus far have been limited to specific geographic areas,11,12 focused on unique high-risk populations,13,14 or not designed for repeated sampling over time.15 Testing of commercial clinical laboratory residual sera has offered a practical, scalable approach to estimate in a more general population the prevalence of persons who develop SARS-CoV-2 antibodies over repeated time intervals.10,16

In a nationwide expansion of commercial clinical laboratory serologic testing, we aim to understand how seroprevalence varied across different geographic regions, sexes, age groups, and periods. In this biweekly, repeated cross-sectional study, we tested for SARS-CoV-2 antibodies using sera from persons across the 50 US states, the District of Columbia, and Puerto Rico who sought clinical care. Initial findings from the first testing period were released on the US Centers for Disease Control and Prevention (CDC) website (COVID Data Tracker).17 In this article, we present seroprevalence estimates from specimens collected over 4 periods from July to September 2020.

Methods

Study Design

Residual patient sera from specimens collected for routine screening (eg, cholesterol, thyroid) or clinical management by 2 commercial laboratories (laboratory A and laboratory B) across 50 US states, Washington DC, and Puerto Rico between July 27 and September 24, 2020, were analyzed. Approximately every 2 weeks, we selected a convenience sample of residual sera from the pool of all available, deduplicated specimens to target equal sample numbers in 4 age groups (0-17 years, 18-49 years, 50-64 years, and ≥65 years) in each jurisdiction. Because laboratory A completed biweekly sampling 3 days after laboratory B for each period, the total number of days included in each period across all jurisdictions was slightly more than 2 weeks. To reduce selection bias, the laboratories reviewed tests that were ordered on the same day as the specimen identified in the convenience sample and excluded the specimen if any requests for SARS-CoV-2 antibody testing were noted.

Laboratory A collected specimens from 7 jurisdictions (Arizona, Indiana, Maryland, Pennsylvania, New Jersey, New York, and Virginia), and laboratory B, which was involved in an earlier CDC-led seroprevalence survey,10 provided residual sera from the remaining 45 jurisdictions. Each performed chemiluminescent immunoassay testing for SARS-CoV-2 antibodies and provided CDC with deidentified information on patient age, sex, state, and specimen collection date. The zip code of residence and ordering clinician zip code were also collected. For both laboratories, most specimens were collected in the outpatient setting, although individual-level data on the source of specimens were not available. Information on patient race/ethnicity and symptoms was also not available.

This activity was reviewed by CDC and determined to be consistent with non–human participant research activity.18 Informed consent was waived, as data were deidentified. Reporting of this study followed the Strengthening the Reporting of Observational Studies in Epidemiology statement.19

Laboratory Methods

Each laboratory processed and transported specimens according to standard procedures. Most specimens did not require −4 °F storage, and none more than a single thaw cycle. Laboratory A tested all specimens at a central facility using the Roche Elecsys Anti-SARS-CoV-2 pan-immunoglobulin immunoassay that targets the nucleocapsid protein and has a sensitivity of 100% (95% CI, 88.3%-100.0%) and specificity of 99.8% (95% CI, 99.7%-99.9%). Specimens were considered reactive at a cutoff index of 1.0 or greater without serum dilution.20 Laboratory B performed testing at 19 regional facilities on samples from 45 jurisdictions using the Abbott ARCHITECT SARS-CoV-2 IgG immunoassay targeting the nucleocapsid protein or Ortho-Clinical Diagnostics VITROS SARS-CoV-2 IgG immunoassay targeting the spike protein. Specimens tested by ARCHITECT were considered reactive at a cutoff index of 1.4 or greater, whereas specimens tested by VITROS were considered reactive at a cutoff index of 1.0 or greater. Using these definitions of reactivity, ARCHITECT had a sensitivity of 100.0% (95% CI, 95.8%-100.0%) and specificity 99.6% (95% CI, 99.0%-99.9%); VITROS had a sensitivity of 90.0% (95% CI, 76.9%-96.0%) and specificity of 100.0% (95% CI, 99.1%-100.0%).20 An internal comparative study demonstrated 98.5% qualitative result concordance between the ARCHITECT and VITROS platforms.21 For all assays, sensitivity was determined in symptomatic persons with real-time reverse transcriptase polymerase chain reaction–confirmed SARS-CoV-2 infection. All assays were granted Emergency Use Authorization by the US Food and Drug Administration and used according to the Instructions for Use provided by the manufacturers.20,22

Statistical Analysis

Power analyses set a target of 980 samples (245 per age group) to be tested per jurisdiction within each 2-week period. Assuming a baseline seroprevalence of 3%,10 this sample size was determined to allow for 70% power to detect a 2% increase in seroprevalence.

For each testing period, we calculated overall seroprevalence estimates by jurisdiction, as well as site-specific age group, sex, and metropolitan status according to 2013 Rural-Urban Continuum Codes (RUCC) classification23 for states with sufficient samples to support precise subgroup estimates. We used patient residential zip code data (or the ordering clinician’s zip code if the patient’s zip code was missing) to determine county of residence and assigned metropolitan status based on RUCC codes 1 to 3 and nonmetropolitan status RUCC codes 4 to 9. To produce seroprevalence estimates, the samples in each jurisdiction were weighted to the population using iterative poststratification or raking.24 Full details on the weighting procedures are included in the eMethods in the Supplement. Briefly, seroprevalence was calculated as the number of reactive specimens divided by the number of specimens tested. Raking was performed across age, sex, and metropolitan status dimensions to create weights that were adjusted to 2018 American Community Survey 5-year population totals for sex, each age category, and metropolitan status.25 For the raking process to converge, probabilistic imputation was performed for patients with missing data on sex, age category, or metropolitan status.

Confidence intervals were calculated using bootstrap resampling.26 For each bootstrap resample, false-positive and false-negative rates were generated from a binomial distribution using results from the assay performance specifications.20 These rates were applied to the bootstrap resample, raked as described earlier in the article, and the seroprevalence was estimated. The process was repeated 500 times and 95% CIs were calculated from 2.5th and 97.5th quantiles of the bootstrap distribution. We report the final adjusted seroprevalence estimate as the mean of the bootstrap distribution. Estimates based on fewer than 75 specimens were not reported because of potential instability.

Finally, seroprevalence estimates were used to predict the total number of SARS-CoV-2 infections in each jurisdiction by applying the estimated seroprevalence to each site’s population.25 To determine the ratio of estimated to reported infections, we assumed that most persons develop detectable antibodies by 7 to 14 days following infection.27 We then divided the estimates of total infections per testing period by cumulative reported case counts28 as of 14 days before the median collection date for each jurisdiction. SAS Software, version 9.4 (SAS Institute), and R, version 3.6.3 (R Core Team), were used for data management and analyses.

Results

During 4 collection periods between July 27 and September 24, 2020, we tested 177 919 residual sera specimens from all 50 states, Washington DC, and Puerto Rico (Table). Of all specimens, 103 771 (58.3%) were from women, 26 716 (15.0%) were from persons 17 years or younger, and 47 513 (26.7%) were from persons 65 years or older. The Abbott ARCHITECT and Ortho-Clinical Diagnostics VITROS assays were the most commonly used assays, accounting for 84 815 (47.7%) and 65 258 tests (36.7%), respectively. The remaining 27 846 specimens (15.7%) were tested using the Roche Elecsys assay. Specimens were collected from 2496 of 3141 US counties (79.5%) (eFigure 1 in the Supplement), and 26 290 specimens (14.8%) were from persons residing in nonmetropolitan areas (Table).

Seroprevalence estimates were calculated by jurisdiction over the 4 collection periods (Figure 1 and eTables 3-6 in the Supplement). Seroprevalence ranged from 0.0% (95% bootstrap CI, 0.0%-4.4%) in South Dakota in period 2 to 23.3% (95% bootstrap CI, 20.1%-26.3%) in New York in period 1. In jurisdictions with enough tested samples to calculate an estimate, which included 46 of 49 sites (93.3%) in period 1, 46 of 51 sites (90.2%) in period 2, 48 of 50 sites (96.0%) in period 3, and 46 of 52 sites (88.5%) in period 4, fewer than 10% of specimens had detectable SARS-CoV-2 antibodies.

SARS-CoV-2 prevalence estimates were also calculated by jurisdiction stratified by sex, age group, and metropolitan status during each collection period (Figure 2, Figure 3, and Figure 4 and eTables 3-6 in the Supplement). Overall seroprevalence estimates varied by jurisdiction and period. There were no consistent differences between men and women across all jurisdictions, although in certain states (eg, Iowa, Louisiana, and Mississippi), seroprevalence was higher in women, while in others (eg, Maryland and Pennsylvania) seroprevalence was often higher in men. Seroprevalence in persons 65 years or older was generally lower than in adults age 18 to 49 years. Fewer samples were available for children and adolescents age 0 to 17 years, and among the 26 jurisdictions for which we could estimate seroprevalence across all periods, estimates varied relative to adult age groups. In the 23 jurisdictions with sufficient samples to calculate estimates by metropolitan status, seroprevalence in certain jurisdictions (eg, Iowa, Pennsylvania, and Tennessee) was higher in metropolitan counties, while in others (eg, Alabama and Mississippi) seroprevalence was higher in nonmetropolitan counties.

In 49 jurisdictions with sufficient samples to estimate seroprevalence across all periods, changes from period 1 to 4 varied across sites (Figure 1). The largest absolute percentage point decreases occurred in New York (6.3%) and North Dakota (6.1%), while large increases occurred in Georgia (6.2%) and Minnesota (4.5%). Ratios comparing estimated to reported SARS-CoV-2 infections during periods 1 and 4 ranged from less than 1 in Alaska for both periods to 12.5 in Pennsylvania during period 1 (eTables 1 and 2 in the Supplement).

Discussion

In a US nationwide survey of SARS-CoV-2 seroprevalence, we tested more than 177 000 residual specimens submitted for non–SARS-CoV-2 testing during 4 periods from July to September 2020 and found that in nearly all jurisdictions, fewer than 10% of people in the US had evidence of previous SARS-CoV-2 infection using currently available commercial IgG assays. Seroprevalence varied across regions and between metropolitan/nonmetropolitan areas, with estimates as high as 23% in the Northeast and 13% in the South, while estimates in the Midwest and West were less than 10%. Seroprevalence was often lowest in older age groups. Changes in seroprevalence over 2 months were generally modest and differed across jurisdictions.

We expanded a previous CDC-led seroprevalence survey from 10 to 52 represented jurisdictions,10 broadening the geographic scope and representativeness of SARS-CoV-2 serosurveillance in the US. Early surveys in California and New York focused on distinct community transmission hot spots.11,12,15 Others concentrated on high-risk populations, such as health care workers13,29 and adult patients receiving dialysis,14 in addition to other unique groups like blood donors.30 By testing for SARS-CoV-2 antibodies in persons of all ages who are receiving outpatient and inpatient clinical care, we may be better able to estimate seroprevalence in the general US population. Furthermore, our study includes 15% of samples tested from persons living in nonmetropolitan areas, which matches the distribution of US residents23 and achieves wider geographic representation than previous nationwide studies.14 We also present state-level estimates, whereas other studies were more optimally designed to calculate regional-level estimates.30

Our findings add to a growing body of work examining population-level SARS-CoV-2 exposure, as well as differences in transmission across regions. We found that most people in the US did not have evidence of previous SARS-CoV-2 infection. This is consistent with other large-scale seroprevalence surveys conducted in the US,10,14,30 as well as population-based surveys in the United Kingdom,31 Spain,32 and Geneva33 that were conducted over periods with substantial SARS-CoV-2 community transmission. Similar to other US surveys, we found the overall prevalence of SARS-CoV-2 to be highest in the Northeast,10,14,30 likely reflecting the high incidence of SARS-CoV-2 transmission in New York City (New York) and surrounding regions during the spring and summer of 2020.34 While several studies reported higher seroprevalence in more densely populated metropolitan areas,14,31,32 our findings were more mixed and reflect the heterogeneity of SARS-CoV-2 transmission across the US.

Similar to numerous other surveys, we found SARS-CoV-2 seroprevalence to be lower in older adults compared with younger adults across nearly all jurisdictions.14,30-33 With endemic coronaviruses, seroprevalence typically increases through childhood into early adulthood,27 and a few studies of SARS-CoV-2 have shown seroprevalence to be lower in children and adolescents younger than 18 years compared with young adults.30,32,33 Seroprevalence among children and adolescents in our survey was more varied compared with adults and was likely affected by differences in exposure risk across the regions sampled.

The changes in overall seroprevalence over 4 collection periods that spanned 2 months were modest. The 6.1–percentage point reduction in North Dakota was affected by low sample sizes, particularly in nonmetropolitan counties, and is likely not a reflection of true population changes. The few population-level seroprevalence surveys with repeated measurements are generally consistent with small changes over time.16,30,33 While the estimates in our study cannot be directly compared with results from an earlier commercial clinical laboratory seroprevalence survey10,16 because of differences in the geographic distribution of the 2 study populations, participating laboratories, and SARS-CoV-2 serology tests used in each study, we observed similar patterns of declining seroprevalence in New York and increasing seroprevalence in Minnesota. The ability to conduct repeated commercial clinical laboratory residual sera testing over an extended period will be valuable to assist in the tracking of the jurisdiction-level spread of SARS-CoV-2.

Another potential application of repeated serological surveillance is the calculation of the ratio of estimated to reported SARS-CoV-2 infections. We observed a wide range of ratios across jurisdictions that may be affected by multiple factors, including differences in care-seeking behavior. Therefore, we caution against comparing these ratios across jurisdictions. Instead, monitoring relative changes over time within a jurisdiction may provide a complementary measure of testing capacity and other metrics of public health interest.

Although cross-sectional seroprevalence studies often indicate a higher burden of infection than reported cases alone,10 they may still underestimate the total number of prior infections. For one, persons with asymptomatic or mild infection may mount a less robust immune response than persons with more severe disease.35-38 Further, declines in SARS-CoV-2 antibodies following infection have been observed.35-39 The kinetics of waning antibodies also appear to differ by type of assay, viral target, and severity of infection35,40 We do not yet understand the association of these factors with estimating seroprevalence in the population or interpreting changes in seroprevalence over time.

More research is also needed to fully understand how the presence or absence of SARS-CoV-2 antibodies affects continued susceptibility to the virus and potential immunity in terms of severity of illness once exposed, subsequent recovery, and future reinfection. Large-scale seroprevalence surveys have relied on qualitative immunoassays10,14,30 which can be implemented at scale. However, these are not sufficient to estimate correlates of protection against SARS-CoV-2.41,42 Furthermore, other elements of innate or cellular immunity may confer protection to SARS-CoV-2 despite the absence of measurable antibodies.43 The dynamics of waning antibodies and persistence of B-cell and T-cell memory44-46 may lead to further underestimation of immunity over time when using qualitative immunoassays. Assays to detect other factors associated with the immune response, such as quantitative antibody levels and neutralizing antibodies for SARS-CoV-2, are resource intensive and not yet widely available.22

Limitations

This cross-sectional study has several important limitations. Persons who have blood taken for routine screening or clinical care may not represent the general US population. They can differ with regard to their underlying health, access to care, care-seeking behavior, exposure risk, or adherence to prevention measures, including use of masks and social distancing.47 While we excluded specimens collected for SARS-CoV-2 antibody testing, we could not exclude persons seeking care for COVID-19–related symptoms. The overall direction of bias resulting from these factors is unclear; for example, even if persons with acute SARS-CoV-2 infection were included, they may have presented for care during the window before antibodies could be detected.27

The study was not designed to produce a nationwide estimate of seroprevalence, nor does it necessarily represent the demographic or geographic distribution of residents within each jurisdiction. The concordance between the ARCHITECT and VITROS platforms was excellent but did not include comparison with the Roche assay, which further limits the ability to compare estimates across jurisdictions. Information on patient race/ethnicity or important social determinants of health that affect COVID-19 outcomes14,48-50 was not available, limiting our ability to further refine our weights and adjustments.

The geographic catchment of samples was determined by the distribution of the commercial clinical laboratory testing sites in each jurisdiction, which are often concentrated in urban areas. We also used convenience sampling in selecting from the pool of available commercial specimens, a method which is subject to potential biases. Despite the large size of the study, we did not reach our target sample numbers in all age groups or jurisdictions. We were therefore unable to estimate seroprevalence in Hawaii, South Dakota, and Wyoming for all periods or in the 0- to 17-year age group for many jurisdictions. Low sample numbers in nonmetropolitan counties also limited reliable metropolitan/nonmetropolitan subgroup estimates in several jurisdictions. Finally, specimens were tested using 1 of 3 immunoassays, each with slightly different performance characteristics. The specificity of all 3 assays was 99.6% or greater, while there was a broader range of sensitivity. Although we adjusted for assay performance specifications, including uncertainty based on validation testing, assay sensitivity among symptomatic persons with reverse-transcriptase polymerase chain reaction–confirmed SARS-CoV-2 infection as described in the manufacturer Instructions for Use is expected to be higher than in our study population, in which persons experiencing previous infection may have had milder disease or had blood drawn for antibody testing at differing times since infection.

Conclusions

In this US nationwide seroprevalence cross-sectional study, we found that as of September 2020, most persons in the US did not have detectable SARS-CoV-2 antibodies, and seroprevalence estimates varied widely by jurisdiction. Continued biweekly testing of sera collected by commercial laboratories will allow for assessment of the changing epidemiology of SARS-CoV-2 in the US in the coming months. Our results reinforce the need for continued public health preventive measures, including the use of face masks and social distancing, to limit the spread of SARS-CoV-2 in the US.

Article Information

Accepted for Publication: November 6, 2020.

Published Online: November 24, 2020. doi:10.1001/jamainternmed.2020.7976

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Bajema KL et al. JAMA Internal Medicine.

Corresponding Author: Kristina L. Bajema, MD, MSc, US Centers for Disease Control and Prevention (CDC), 1600 Clifton Rd NE, Mailstop H24-6, Atlanta, GA 30329 ([email protected]).

Author Contributions: Drs Bajema and Edens had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Bajema, Iachan, Havers, Harding, Fry, Hall, Gundlapalli, Thornburg, Petersen, Edens.

Acquisition, analysis, or interpretation of data: Bajema, Wiegand, Cuffe, Patel, Iachan, Lim, Lee, Moyse, Harding, Kelly, Biel, Deng, Meyer, Mathur, Kyle, Gundlapalli, Thornburg, Petersen, Edens.

Drafting of the manuscript: Bajema, Wiegand, Cuffe, Patel, Iachan, Harding, Edens.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Bajema, Wiegand, Iachan, Lim, Lee, Harding, Kelly, Biel, Deng, Edens.

Obtained funding: Bajema, Cuffe, Havers, Fry, Hall, Gundlapalli, Petersen, Edens.

Administrative, technical, or material support: Bajema, Wiegand, Cuffe, Patel, Moyse, Havers, Fry, Hall, Meyer, Mathur, Kyle, Gundlapalli, Thornburg, Petersen, Edens.

Supervision: Iachan, Havers, Fry, Hall, Mathur, Meyer, Thornburg, Edens.

Conflict of Interest Disclosures: ICF, Inc, Quest Diagnostics, and BioReference Laboratories were awarded federal contracts from CDC for the execution of this project. No other disclosures were reported.

Funding/Support: This work was supported by CDC (Atlanta, Georgia).

Role of the Funder/Sponsor: CDC had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The findings and conclusions in the article are those of the authors and do not necessarily represent the official position of CDC.

Additional Contributions: We thank Gabriele Richardson, PhD, CDC, for mapping support as well as other members of CDC for administrative and technical support: Teresa Kinley, MS, Melissa Carter, PhD, Lauren Peel, JD, Adrean Mabry, BS, Saraine Ross, BA, Jasmine Chaitram, MPH, Alex Hoffmaster, PhD, Subbian Panayampalli, PhD, William Duck, MS, Eduardo Azziz-Baumgartner, MD, Adam MacNeil, PhD. We thank Quest and BioReference for testing specimens. From Quest: Brian Jaffa, MS, Caterina Powell, BS, Rebecca Parsons, BS, Brian Young, AA, Carol Bledsoe, Nicki Sylvester, MBA, Bonnie Bouck, AA, Georgia Schoemaker, BS, Stephanie Buchler, Larry Hirsch, BS, Narshimlu Ramdas, BTech, Neelima Donur, MS, Jeff Crawford, BS. From BioReference: James Weisberger, MD, Dan McNichol, MBA, Ada Gazzillo, BS, Nick Cetani, MS, Cesar Abril, MBA, Angela Canada, BS, Amal Abadeer, BA, and Pamela Depuy. These individuals were not compensated directly by CDC for their participation in this specific study.

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1 Comment for this article

November 29, 2020

SARS-CoV-2 Seroprevalence in the US comments.

Gary Ordog, MD, DABMT, DABEM | County of Los Angeles, Department of Health Services, Physician Specialist (ret.)

Thank you for the interesting study. Although your subject numbers seem large, I believe they represent less than one percent of the population, which makes the sample size small. Also, the method of using convenience blood, we really have no idea why these subjects were getting their blood drawn, but we do know it was not for the purpose of the study. That means that the small sample size may be skewed unknowingly and severely towards some unknown confounding variable, for example, perhaps most of them thought they had had COVID-19. So, the validity of drawing conclusions based upon these results is very low, and even trying to make valid conclusions about time trends is questionable because of the possibility of unknown changing confounding variables during that time. That said, I would like to comment on the implications of your study results, even though what I am concluding cannot be valid, just interesting. Most importantly, possibly only 10% of the population have been infected with SARS-CoV-2. That means that possibly, 90% of the population may be still prone to suffer from infection in the pandemic. Without a vaccination, the US could be facing a disaster. Fortunately, it looks like several vaccines are effective, and many more are in the works. If anything, it looks like your study shows that the vaccination program and its success is more important that ever. Thank you, and stay safe until then.

CONFLICT OF INTEREST: None Reported

DECEMBER 7, 2020

COVID-19: Close to 207,000 new cases reported in US

According to CDC's update on December 6, the case count of COVID-19 in the US stands at 14,462,527* cases, including 280,135* deaths, in 55 (50 states, District of Columbia, Puerto Rico, Guam, Northern Marianas, and US Virgin Islands) jurisdictions. The CDC noted that this represents an increase of 206,992 cases and 2,310 deaths compared to the update on the preceding day. 

Yes record highs!