Variants Raise Risk of Novel Coronavirus Resurgence

Army veteran Howard Horton prepares to get his COVID vaccine from another Army veteran, VA nurse Michael Clark, RN, in Houston. Photo from Michael E. DeBakey VAMC Facebook page

ATLANTA — Two approved vaccines and a drop in cases and hospitalizations in late January provided a spot of light after a year of grim news on the COVID-19 front. The war is far from won, however. New, more contagious variants of SARS-CoV-2 raise the risk of a surge in cases and higher numbers of associated deaths this spring.

At the same time, analyses of cases over the past year reveal a troubling and previously unrecognized mortality risk in individuals thought to have recovered from COVID-19.

The new developments raise the peril for veterans, who tend to be in higher risk groups as a function of their age and comorbidities. Servicemembers, too, are more likely to contract strains with greater communicability as a result of their frequently close quarters and high degree of interaction.

Emerging strains with clusters of mutations that increase transmissibility have spread rapidly around the globe. The U.K. variant, B.1.1.7, has appeared in 70 countries and more than 28 states. The naitonal Centers for Disease Control and Prevention warned in mid-January that B.1.1.7 was expected to be the dominant strain in the United States. by March, and its increased infectivity could lead to an even bigger surge than the country experienced in December and January.

At least 32 countries had reported the presence of the South African strain, B.1.351, and two states had identified cases of community transmission by late January. The Brazilian variant, P.1, had been found in least six countries as well as Minnesota, while the Danish variant, L452, accounted for more than one-quarter of cases in Los Angeles and had been identified in more than a dozen states at presstime. One homegrown variant that rose from 10% of cases in Columbus, OH, to more than 60% in two weeks had also been detected in six other states.

“These variants seem to spread more easily and quickly than other variants, which may lead to more cases of COVID-19. An increase in the number of cases will put more strain on health care resources, lead to more hospitalizations, and potentially more deaths,” the CDC warned.

As if that isn’t enough cause for alarm, recent research indicating that the U.K. variant might be 30% to 40% more deadly and that the South African strain could limit the effectiveness of antibody cocktails and plasma treatments compounded concern among U.S. public health officials. Likewise, analyses suggested that the Brazilian variant might evade detection by antibodies in individuals who have already had COVID-19, enabling reinfection.

So far, the vaccines already authorized in the U.S. and those nearing approval appeared to provide some protection against the new strains, even though recently released data showed significantly less efficacy against the South African variant than the common and U.K. strains. While “severe disease was still handled reasonably well by the vaccines, it is a wake-up call to all of us that we will continue to see the evolution of mutants,” said Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases.

Rehospitalization and Death

As the new variants raised the prospect of more patients with COVID-19 being admitted to hospitals in coming months, researchers at the VA Ann Arbor, MI, Health System and the University of Michigan identified significant dangers for those being discharged. Results of their study were published in the January issue of JAMA.1

They found that veterans previously hospitalized with COVID-19 had a 40% to 60% higher risk of death or readmission within 10 days of discharge than matched groups of patients with other types of pneumonia or heart failure treated at the same 132 VA hospitals. Just under 14% of discharged COVID-19 patients landed back in the hospital or died within the first week and a half.

“By comparing COVID-19 patients’ long-term outcomes with those of other seriously ill patients, we see a pattern of even greater-than-usual risk right in the first one to two weeks, which can be a risky period for anyone,” said the study’s first author John Donnelly, PhD, MSPH, an epidemiologist at Michigan Medicine, the University of Michigan’s academic medical center.

Diagnoses among those readmitted included COVID-19 for 30.2%, sepsis for 8.5%, pneumonia 3.1%, and heart failure 3.1%. During their rehospitalization, 22.6% required intensive care, 7.1% needed mechanical ventilation, and 7.9% received vasopressors.

Clinical deterioration remained a significant risk for at least two months after the index hospitalization. Among veterans with COVID-19, 9.1% died in the first 60 days after leaving the hospital. Nearly one in five required readmission to a VA hospital in that period. While high, the 60-day rates compared favorably to the rates of readmission and death for matched patients initially hospitalized with non-COVID-19 pneumonia or heart failure, at 31.7% and 37.0%, respectively. The mortality rate during the initial hospitalization was far higher among veterans with COVID-19 at 18.5% than among those with pneumonia, 2.2%, or heart disease, 1.7%.

The researchers compared outcomes for 2,179 veterans hospitalized with COVID-19 to those for 2,156 with pneumonia and 4,269 with heart failure. All patients were admitted between March 1 and June 1, 2020, and discharged between March 1 and July 1, 2020. About 95% of the patients were male and half were Black. On average, COVID-19 patients remained in the hospital 12.6 days during the initial hospitalization and 10.5 days when readmitted.

“[T]his is yet more evidence that COVID-19 is not ‘one and done,’” said co-author Theodore Iwashyna, MD, PhD, of the VA Ann Arbor Health System. “For many patients, COVID-19 seems to set off cascades of problems that are every bit as serious as those we see in other diseases. But too little of our healthcare response — and too little research — is designed to help these patients as they continue for days, weeks, even months to recover from COVID-19.”

Another study by University of Michigan researchers confirmed the results in a study of 1,250 COVID-19 patients admitted to 38 hospitals in Michigan last spring and summer which was published in the Annals of Internal Medicine. Nearly one-quarter of patients died during their hospitalization. Of the survivors, 7% died and 15% required rehospitalization in the first two months after discharge.2

At 60 days post-hospitalization, 39% reported they had been unable to resume their regular activities, 12% couldn’t care for themselves, 23% continued to suffer shortness of breath when climbing stairs, and one-third had continuing symptoms of COVID-19. In addition, 40% of those who had been working when they fell ill had not been able to resume their employment and 26% of those who had returned to work required reduced or hours or reduced duties because of lingering health issues.

A pre-print study conducted at the University of Leicester in the UK found, meanwhile, that the risk of rehospitalization and death continued for more than four months. With a mean follow-up of 140 days after discharge, 29.4% of 47,780 hospitalized COVID-19 patients were readmitted and 12.3% died. Those rates were 3.5 times and 7.7 times higher than seen in matched controls.

The impact on health extended well beyond death and readmission. “Individuals discharged from hospital following COVID-19 face elevated rates of multi-organ dysfunction compared with background levels, and the increase in risk is neither confined to the elderly nor uniform across ethnicities,” the authors of the British study said.3

The British researchers also found a significantly higher incidence of new diagnoses of diabetes, major cardiovascular events, kidney disease, and acute liver disease in patients following COVID-19 hospitalization compared to matched controls. While the absolute risk of post-discharge adverse events was greatest in individuals age 70 and above, the relative ratio of adverse events was higher in individuals younger than 70 years of age when comparing patients with COVID-19 to those hospitalized for other reasons.

The rapidly accumulating evidence of COVID-19’s significant long-term impact on health calls for reconsideration of care practices for patients following hospitalization, said Donnelly. “Now, the question is what to do about it. How can we design better discharge plans for these patients? How can we tailor our communication and post-hospital care to their needs? And how can we help their caregivers prepare and cope?”


  1. Donnelly JP, Wang XQ, Iwashyna TJ, Prescott HC. Readmission and Death After Initial Hospital Discharge Among Patients With COVID-19 in a Large Multihospital System. JAMA. 2021;325(3):304–306. doi:10.1001/jama.2020.21465
  2. Chopra V, Flanders SA, O’Malley M, Malani AN, Prescott HC. Sixty-Day Outcomes Among Patients Hospitalized With COVID-19. Ann Intern Med. 2020 Nov 11:M20-5661. doi: 10.7326/M20-5661. Epub ahead of print. PMID: 33175566; PMCID: PMC7707210.
  3. Ayoubkhani D, Khunti K, Nafilyan V, Maddox T, Humberstone B, Diamond I, Banerjee A. Epidemiology of post-COVID syndrome following hospitalisation with coronavirus: a retrospective cohort study. medRxiv. 2021 January 15. doi: 10.1101/2021.01.15.21249885