publication date: Mar. 20, 2020
Sifting through fatality data and projections on COVID-19:
People with cancer, other comorbidities face highest risk
By Matthew Bin Han Ong
This story is part of The Cancer Letter’s ongoing coverage of COVID-19’s impact on oncology. A full list of our coverage, as well as the latest meeting cancellations, is available here.
Early data from China and Italy confirm that cancer patients are at higher risk for developing severe adverse events and dying after testing positive for the novel coronavirus.
In Italy, cancer patients account for about 20% of deaths stemming from the novel coronavirus. The preliminary analysis of 355 deaths—out of a sample total of 2003 deaths—was conducted by the Istituto Superiore di Sanità, the Italian National Institute of Health.
In the study sample, nearly half of the patients who died had three or more existing comorbid conditions. The analysis, which includes data reported through March 17, is published here.
The preliminary data are relevant to the U.S., because many Americans have comorbid conditions, said Otis Brawley, the Bloomberg Distinguished Professor of Oncology and Epidemiology at Johns Hopkins University.
“The proportion of the U.S. population with comorbid conditions is quite high, especially when we start talking about people over the age of 50,” Brawley said to The Cancer Letter. “When you consider obesity as a comorbid condition, we’re talking 35-40% of the American population of adults.”
Adverse events, case-fatality rates for cancer patients
Using data from China, a study published Feb. 24 in JAMA found that the case-fatality rate for patients with cancer was 5.6% in a sample of 1,023 deaths among 44,672 confirmed cases.
The data are derived from a total of 72,314 case records and updated through Feb. 11, according to study authors Zunyou Wu and Jennifer McGoogan at the Chinese Center for Disease Control and Prevention in Beijing.
“The overall case-fatality rate (CFR) was 2.3% (1,023 deaths among 44,672 confirmed cases),” the authors wrote. “No deaths occurred in the group aged 9 years and younger, but cases in those aged 70 to 79 years had an 8.0% CFR and cases in those aged 80 years and older had a 14.8% CFR. No deaths were reported among mild and severe cases.
“The CFR was 49% among critical cases. CFR was elevated among those with preexisting comorbid conditions—10.5% for cardiovascular disease, 7.3% for diabetes, 6.3% for chronic respiratory disease, 6.0% for hypertension, and 5.6% for cancer.
“Among the 44,672 cases, a total of 1,716 were health workers (3.8%), 1,080 of whom were in Wuhan (63%). Overall, 14.8% of confirmed cases among health workers were classified as severe or critical and 5 deaths were observed.”
In a study published March 1 in The Lancet Oncology, cancer patients are more likely to be admitted to the intensive care unit and require invasive ventilation, or die, compared with patients without cancer.
The study was conducted by researchers at the China State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, within The First Affiliated Hospital of Guangzhou Medical University.
Using a data cutoff date of Jan. 31, the authors identified 1,590 cases of COVID-19 with sufficient records of previous disease history from 575 hospitals in 31 provincial administrative regions in China.
“Eighteen (1%; 95% CI 0·61–1·65) of 1,590 COVID-19 cases had a history of cancer, which seems to be higher than the incidence of cancer in the overall Chinese population (285·83 [0·29%] per 100,000 people, according to 2015 cancer epidemiology statistics),” the authors wrote.
“Patients with cancer were observed to have a higher risk of severe events (a composite endpoint defined as the percentage of patients being admitted to the intensive care unit requiring invasive ventilation, or death) compared with patients without cancer (seven [39%] of 18 patients vs 124 [8%] of 1,572 patients; Fisher’s exact p=0·0003).”
Patients who underwent chemotherapy or surgery in the past month had a numerically higher risk—75%, three of four patients—of clinically severe events than patients who did not receive chemotherapy or surgery, 43% six of 14 patients.
“These odds were further confirmed by logistic regression (odds ratio [OR] 5·34, 95% CI 1·80–16·18; p=0·0026) after adjusting for other risk factors, including age, smoking history, and other comorbidities,” the authors wrote. “Cancer history represented the highest risk for severe events. Among patients with cancer, older age was the only risk factor for severe events (OR 1·43, 95% CI 0·97–2·12; p=0·072).”
COVID-19 appears to cause T cell counts to be reduced significantly, especially among elderly patients and in patients requiring intensive care, according to another study by researchers in China.
The researchers retrospectively reviewed the counts of total T cells, CD4+, CD8+ T cell subsets, and serum cytokine concentration from inpatient data of 522 patients with laboratory-confirmed COVID-19. The patients were admitted into two hospitals in Wuhan from December 2019 to January 2020.
“T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted,” the authors concluded.
“There has been an emerging interest in cytokine release syndrome (CRS) because of #COVID19,” NCI Director Ned Sharpless tweeted March 15. “CRS is well-described in patients with certain cancers as a direct complication or as a side effect to certain types of therapies, such as CAR T-cell therapy.”
Overall case-fatality risk estimates
While it may be too early to establish statistically meaningful COVID-19 overall mortality rates—age-adjusted or not—for the U.S. population, epidemiologists and infectious disease experts are modeling for fatalities in the U.S. based on data from other countries, and also making active comparisons as the outbreak grows.
Using preliminary data, the Centers for Disease Control and Prevention concluded in a March 16 report that its findings are similar to data from China, which indicated that over 80% of deaths occurred among persons aged 60 years or older.
“Since February 12, 4,226 COVID-19 cases were reported in the United States; 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths occurred among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years,” CDC authors wrote in the March 16 Morbidity and Mortality Weekly Report.
These preliminary data also demonstrate that severe illness leading to hospitalization, including ICU admission and death, can occur in adults of any age with COVID-19. About 40% of patients who were hospitalized were below 55 years of age.
“Among 508 (12%) patients known to have been hospitalized, 9% were aged ≥85 years, 26% were aged 65–84 years, 17% were aged 55–64 years, 18% were 45–54 years, and 20% were aged 20–44 years,” CDC researchers wrote. “Less than 1% of hospitalizations were among persons aged ≤19 years. The percentage of persons hospitalized increased with age, from 2%–3% among persons aged ≤9 years, to ≥31% among adults aged ≥85 years.
“This first preliminary description of outcomes among patients with COVID-19 in the United States indicates that fatality was highest in persons aged ≥85, ranging from 10% to 27%, followed by 3% to 11% among persons aged 65–84 years, 1% to 3% among persons aged 55-64 years, <1% among persons aged 20–54 years, and no fatalities among persons aged ≤19 years.”
In other studies published with CDC, calculations show that the risk for death in Wuhan reached as high as 12%, with about 1% in other mildly affected areas in China.
“The elevated death risk estimates are probably associated with a breakdown of the healthcare system, indicating that enhanced public health interventions, including social distancing and movement restrictions, should be implemented to bring the COVID-19 epidemic under control,” researchers from Georgia State University and Kyoto University wrote in a paper published in CDC’s Emerging Infectious Diseases journal.
According to calculations using a lag time for fatality, broader estimates by a team of researchers from the University of Otago in New Zealand show that the adjusted case-fatality risk is likely to be around 0.9%.
“We estimated the case-fatality risk for 2019 novel coronavirus disease cases in China (3.5%); China, excluding Hubei Province (0.8%); 82 countries, territories, and areas (4.2%); and on a cruise ship (0.6%),” the authors wrote in a research letter published in CDC’s EID. Lower estimates might be closest to the true value, but a broad range of 0.25%–3.0% probably should be considered.
“The aCFR of 0.9% for China, excluding Hubei Province, might be most accurate. Nevertheless, given the residual uncertainties, health sector decision-makers and disease modelers probably should consider a broad range of 0.25%–3.0% for COVID-19 case-fatality risk estimates. The higher values could be more appropriate in resource poor settings where the quality of hospital and intensive care might be constrained.
“Higher values might also be appropriate in high-income countries with limited surge capacity in hospital services because elevated case-fatality risks could be seen at the peak of local epidemics,” the authors wrote. “Because COVID-19 is expected to further spread globally, ongoing work using country-specific cohorts will be needed to more robustly clarify the case-fatality risk of this new disease.”
Total fatality estimates for the U.S.
Early models from CDC show that between 160 million and 214 million people in the U.S.—50% to 65% of the total population—could be infected over the course of the epidemic, according to a projection that encompasses four scenarios.
According to the CDC models, as many as 200,000 to 1.7 million people could die.
“The worst-case scenario is either you do nothing or your mitigation and containments don’t succeed,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said March 15 on ABC News. “So, although that’s possible, it is unlikely if we do the kinds of things that we are essentially outlining right now.
“You block infections from coming in, and then within is when you have containment and mitigation,” Fauci said. “And that’s the reason why the kinds of things we’re doing that may seem like an overreaction will keep us away from that worst-case scenario.”
If 50% of the U.S. population is infected, CDC’s projections are likely to come true, even within the lower range of case-fatality risks—between 0.1% to 1%.
In an op-ed published March 10 for the Council on Foreign Relations, former CDC Tom Frieden wrote:
Source: Council on Foreign Relations
“The president asked me, ‘We’re not going to see a million deaths in this country, are we, doctor?’
“I replied, with more certainty than I felt, ‘No, Mr. President, we won’t.’ If asked the same question today about the novel coronavirus, I would have to reply, ‘I hope not, but that’s a possibility.’”
At this writing, there are 14,250 confirmed cases in the U.S. and 205 deaths. About two-thirds of the cases have been diagnosed in four states: 5,711 in New York, 1,376 in Washington state, 1,030 in California, and 742 in New Jersey.
A study published in Science estimated that, for every confirmed case, there are most likely five to 10 people with undiagnosed infections.
“We use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with SARS-CoV2, including the fraction of undocumented infections and their contagiousness,” the authors wrote. “We estimate 86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions. “
Milder cases, although on average about half as infectious as confirmed ones, are responsible for nearly 80% of new cases.
“Per person, the transmission rate of undocumented infections was 55% of documented infections ([46%–62%]), yet, due to their greater numbers, undocumented infections were the infection source for 79% of documented cases,” the authors wrote. “These findings explain the rapid geographic spread of SARS-CoV2 and indicate containment of this virus will be particularly challenging.”
Experts predict that U.S. hospitals could be be overrun with COVID-19 cases as early as March 23.
“Last night, I was on with state and local officials around the U.S. well into the night,” Andy Slavitt, a former acting administrator of the Centers for Medicare and Medicaid Services, tweeted March 14. “By March 23, many of our largest cities and hospitals are on course to be overrun with cases.”
There are only about 925,000 staffed hospital beds in the U.S., according to 2020 survey results published by the American Hospital Association.
“Every report describes [the situation in Italy] as a tsunami,” Slavitt tweeted. “And if it happens like a tsunami, in major cities we will have tenths of thousands more cases than we have beds, and we will have one ventilator for every eight people who need one.
“The U.S. and every country that hasn’t taken better preventive measures like South Korea and Japan is directly on course [to have a trajectory like Italy], lagging two weeks behind,” Slavitt tweeted. “The only way to prevent [a situation like] Italy, given our lack of testing, is to socially isolate. Congress even allocates money for people to stay home. That rarely happens. But we blew our chance at containment.
“Hospitals must get rid of elective procedures, expand negative pressure rooms, move ventilator capacity to hot spots, and seek additional where possible, create isolation negative pressure rooms, get tests for every front line worker, get masks, and other supplies.”