The Impact of COVID-19 on Nurses

Dangerous Mutations: the Continuous Emergence of SARS-CoV-2 Variants

Mary C. Vrtis, Ph.D., MSN, RN, OCN, NEA-BC, FCN

Dangerous Mutations, the Continuous Emergence of SARS-CoV-2 Variants august 16, 2025 Download

Time to read:

56–85 minutes

Viral Reproduction

SARS-CoV-2, the virus that causes COVID-19, was the result of one or more mutation(s) in a critical location on a virus that likely mutated in a bat. The mutation in a single, invisible virus conferred the power to “jump species,” and infect human beings. The new virus was far more contagious from person-to-person than any previous type of Coronavirus the world had thus far seen.

Micro-organisms have one goal, and that is to reproduce to survive. These organisms do not have any conscious motivation to do us harm, but over millions of years they have developed amazing skills that allow them not only to survive, but to thrive in all kinds of hostile environments. When a virus or another type of microorganism enters the body and initiates infection an intact human immune system automatically fights back. See chapter Pathophysiology and Disease Process for more detail.

Viruses need a living host cell or “intermediary” animal or avian (bird) cell to survive through reproduction. An RNA virus is just a single strand of ribonucleic acids that provides instructions on how to use the host cellular functions and raw materials to build the proteins needed to create new viruses within. When it is successful, the virus ultimately causes the host cell to burst open and release viruses that prolong the host infection and/ or are shed and infect others. It is a competitive issue and the viral variants with the ability to reproduce better overshadow the prior variants and become dominant. See the chapter Pathophysiology and Disease Process for greater detail.

Figure 1 shows the SARS-CoV-2 variants of concern and the time period during which they were rising to dominance in the United States. Most of these variants have left immense human suffering in its wake. It is evident by looking retrospectively that each variant or subvariant that became dominant was better equipped to cause infection than the variant it ultimately replaced. As new dominant variants arose, older variants once in circulation eventually disappeared. These transitions did not happen in the same way in every part of any country at the same time. Often a variant that was better equipped to survive and thrive than its predecessors reached the dominant proportion faster in one geographical location than the next. Sometimes two variants of SARS-CoV-2 maintained roughly equal proportions for a time and then one became dominant and the other eventually disappeared. Typically, there is a lot of overlap.

The SARS-CoV-2 virus is highly adaptable, as evidenced by the number of pathological variants that have emerged since December 2019, see figure 1. This virus infects and reproduces quickly and efficiently, and “mistakes” in transcribing the information in the viral RNA happen often. Those transcription errors may be fatal for the virus, have no useful impact, or provide a better chance of launching a successful attack against a human (or other mammal) host. Mutation during replication is part of the evolutionary process (Rogozin, I. B., et al., 2024). Until the anti-COVID-19 vaccines were administered to enough people, the virus was clearly winning!

Rogozin, I. B., et al. (2024). Properties and mechanisms of deletions, insertions, and substitutions in the evolutionary history of SARS-CoV-2. International Journal of Molecular Sciences, 25, 3696. https://www.mdpi.com/1422-0067/25/7/3696

SARS-CoV-2 Variants and the Impact on Nurses and the U.S. Healthcare System: Looking Back so we can Move Forward

Why should we look back to learn more about SARS-CoV-2 variants that are no longer detectable? SARS-CoV-2 has taught us many painful lessons. We need to learn from them and assure the safety of our nation’s RNs, LPN’s, assistants, aides and other clinical team members who provide hands on care. The entire COVID-19 pandemic and all of the situations that could have been handled better can prepare nurses for the inevitable next mass infectious disease event – whether it happens due to this or another virus, bacteria, or fungus.

Each SARS-CoV-2 mutation of concern had an effect on the volume of patients, acuity-based staffing needs, death rates, and long-term consequences for those who recovered. The variants and subvariants of the SARS-CoV-2 virus discussed here have essentially disappeared because they were superseded by new mutant or recombinant variants that were better able to compete for human hosts. Though these particular variants no longer pose a problem, critically analyzing what has happened in the past provides an opportunity to plan for a better future. As the reader will see, each of the variants of concern that emerged were much more contagious than the earlier variants.

The Omicron subvariants currently circulating are less deadly than some of the earlier variants, especially in vaccinated people. Still, we need to be prepared to battle extremely contagious variants, and other types of infectious diseases that are even better able to cause great harm to humans than was the case in the past.

Nurses in leadership need to plan for a future where nurse safety is the number ONE priority when responding to mass infectious events. We CANNOT ever allow a situation where nurses and other healthcare providers race into an infectious disease outbreak or pandemic without the knowledge and equipment needed to keep everyone safe. Nurses and healthcare workers are not expendable.

Direct care nurses also need to understand how viruses, bacteria, and fungi take advantage of mutations that occur in transcription to survive. Nurses providing direct care are in the front-line position and if they understand what to look for, they may be able to see and report the warning signs that a new variant is emerging in real time.

Front line staff often recognize, for example, that patients seem to:

Be “sicker,” and need more direct nursing care.
Respond poorly to treatments that have been effective in the past.
Require longer lengths of stay.
Experience more severe complications than in the past.
Need more intensive care hours.
Die from the disease more frequently.

In reference to nosocomial infections, the question is whether there is a higher absentee rate in clinical and supportive staff, for example in housekeepers and/ or patient transporters.

Staff nurses need clear guidance on how to report patterns indicative of a possible mutation up the chain to someone who can act on the information. Healthcare organizations need infection control and prevention programs and processes for investigation and reporting to the local public health department. Early identification of an emerging issue can speed up local and worldwide intervention. Time matters.

When such information is passed on to infection control specialists, public health departments, and Centers for Disease Control and Prevention, then testing, genetic sequencing, and characterization of the variant can be implemented more quickly. With SARS-CoV-2, identification of variants with mutations that increased virulence, resistance to vaccines, effectiveness of medications used for treatment, and changes that resulted in high fail rates for some COVID-19 tests are sometimes not completed until after the variant has caused great harm. But now, the worldwide response to COVID-19 has streamlined the process and nurses have greater opportunity to play a very important role in outbreak containment. What we learned from the emergence of the SARS-CoV-2 variants that have already burned through the human population and have been extinguished provides excellent opportunities for learning how to be proactive with future outbreaks.

World-wide Collaboration

Classification of Variants and Subvariants

Due to the unprecedented number of people all over the globe who have suffered serious or critical illness, long term sequelae following infection, and the incredible number of deaths, scientists all over the world have been collaborating to find solutions. Rapid information sharing has had a positive impact on the ability to identify evolving concerns about the organism and efforts to find effective medications and treatments. One example of international cooperation is the efforts that have gone into genetic sequencing of subvariants of the SARS-CoV-2 virus that are obtained from patients throughout the world. A lot of countries are performing genetic sequence tests on a proportion of positive COVID-19 PCR tests currently obtained via nasal swabs. Because SARS-CoV-2 is an RNA (ribonucleic acid) virus the genetic sequence is a single strand of letters that refer to specific ribonucleic acids, not double strand DNA. The sequence is then entered into international databases and compared to other genomes already recorded.

Such efforts have resulted in rapid recognition and characterization of new variants. When a variant with substantial mutations is found and that version of SARS-CoV-2 begins infecting people in the community, the variant (or subvariant) gets an alpha-numeric designation based on its lineage, the micro-organism’s family tree. See subheading Viral Lineage below.

In the U.S., identified variants were categorized by the SARS-CoV-2 Interagency Group of the Department of Health and Human Services which brings together experts from the Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), Food and Drug Administration (FDA), Biomedical Advanced Research and Development Authority (BARDA), and the Department of Defense (DoD). As there are countless transitions going on in the U.S. government under the new administration in 2025, it is currently impossible to predict what the final mitigation plans will be for the next pandemic.

The categories for SARS-CoV-2 were:

Variants under monitoring (VUM).
Variants of interest (VOI).
Variants of concern (VOC).
Variants of high consequence (VOHC), CDC (2023 September 1).

The World Health Organization also categorizes variants based on what is happening worldwide. Although most variants that have reached the “variant of concern” level have spread across the globe quickly, the known variants were first identified in one location or in a few countries. At this point many countries are conducting genomic analysis on a proportion of positive PCR tests, and some are also using wastewater surveillance to determine the variants that are circulating in a community and then expelled through human waste, see figure 2. CDC (2025, retrieved February 16). National wastewater surveillance system. COVID-19 variants in wastewater. https://www.cdc.gov/nwss/rv/covid19-variants.html

Information about variants and how they are classified has been communicated to the public as well as medical care providers and the rest of the world by various organizations. The U.S. Centers for Disease Control and Prevention had been regularly publishing updates on variant proportions using the Nowcast estimates biweekly.

As shown in figure 2, at the time of this writing, Omicron XEC was the predominant variant, but LPB.8.1 will likely replace XEC in the near future. At the time of this writing in February 2025, there were no variants of high consequence circulating in the United States. Figure 2 provides examples of how information on variants has been provided by the U.S. CDC. CDC (2025, retrieved February 16). Weighted and Nowcast estimates in United States for 2-week periods in 2/2/25-2/15/25.https://covid.cdc.gov/covid-data-tracker/#variant-proportions

Basic Concepts

Reproduction Number and Transmission

The letter R is used to represent the viral reproduction number and refers to the average number of people that a single infected person successfully transmits the disease to (Leung, 2021).

Note that the first infected individual will likely come into contact with several people who should be quarantined, but the disease is not transmitted to all contacts. R refers to the number of people symptomatically or asymptomatically infected. The first person in the chain of transmission is the “primary” contact. Secondary contacts are the people who come in contact with someone who was infected by the first person in the chain (Leung, 2021).

Leung, N. H. (2021). Transmissibility and transmission of respiratory viruses. Nature Reviews Microbiology, 19, 528-545. https://www.nature.com/articles/s41579-021-00535-6

The basic reproduction number, R naught, abbreviated as R₀, is calculated at the beginning of an epidemic, when the population is still highly susceptible. For COVID-19 calculations of R₀ have also been made as the populations of additional countries were newly infected or as new strains of concern have emerged worldwide (Leung, 2021). Calculations were made for the ancestral (original) strain of COVID-19 initially in China and then in other parts of the world as SARS-CoV-2 invaded more countries (GISAID, 2023a).

R₀ for SARS-CoV-2 was initially calculated to be 2.2 for the ancestral variant in China (Li, et al. 2020 January 29). As COVID-19 spread rapidly across China, Zhao, et al. (2021) estimated that R₀ was 2.75 outside the epicenter in a mid-size city approximately 900 km (560 miles) from Wuhan (Zhao, et al, 2021).

Li, Q., et al. (2020, January 29 online). Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. The New England Journal of Medicine, 382, 13, 1199-1207. DOI: 10.1056/NEJMoa2001316. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121484/pdf/NEJMoa2001316.pdf

Zhao, H., et al. (2021). Transmission dynamics of SARS-CoV-2 in a mid-size city of China. BMC Infectious Diseases, 21, 793. https://doi.org/10.1186/s12879-021-06522-9

Transmission rates for viruses change over time for several reasons. As a population becomes less susceptible to the infection, as more people become vaccinated, the rate will decrease. With some viruses the rate of transmission will drop if people develop at least temporary immunity after being infected.

Superspreader events increase the number of people infected at a single event – which drastically alters the transmission rate. In addition, some competing variants of the virus will decrease the ability of other variants to cause infection if the emerging variants are:

Capable of causing harm (more virulent), and/ or
Able to form a stronger bond between the spike protein and the ACE2 receptor on the human cell, and/ or
Better at evading the immune system, and/ or
Have a longer period during which they can cause infection or asymptomatic transmission.

Efforts to limit transmission by educating the population on basic prevention activities such as frequent hand hygiene, face masks, non-powered respirators, powered respirators, eye protection, and social distancing does reduce transmission rates if they are implemented by enough individuals within the population. Environmental controls are also useful.

R_t, the effective reproduction number, or number of people infected by one person, can be calculated at any time. The R_t in a particular area will change over time and is dependent on multiple external and virus-specific variables. When population immunity reaches a point where the R_t is less than 1, viruses (or variants) generally start to die out. When vaccination is able to prevent active infection, then the R_t measured at various time points will decrease as the number of people vaccinated increases. If another variant of a virus is more contagious than the circulating variant being measured, the R_t for the circulating variant will likely decrease.

When a reproductive number R is less than 1, it means that one infected person is on average infecting less than one additional person. The virus (or variant of a virus that mutates rapidly) is likely to start to die out. The larger the R number, the more people who will be infected by one person. When the R is larger than 1, then the epidemic or pandemic will continue to grow and infect more and more people. Zhao, H., et al. (2021). Transmission dynamics of SARS-CoV-2 in a mid-size city of China. BMC Infectious Diseases, 21, 793. https://doi.org/10.1186/s12879-021-06522-9

SARS-CoV-2 viruses are related to the original form of the virus that was first identified in China. This version of the virus may be called the ancestral, wild-type, or origin strain. Mutations were already evident in the earliest days of existence and found when China sequenced genomes of virus from the first patients who were infected.

As with a human nuclear family tree that goes back to the first known family ancestor, the Pango lineage system goes back generation by generation to the ancestral strain of the SARS-CoV-2 virus. Figure 3 shows the ancestry of the previously circulating Omicron KP.2 and KP.3 subvariants of Omicron JN.1. The JN.1 was a subvariant of Omicron BA.2.86 (also known as B.1.1.529.2) is a subvariant of B.1.1.529, the first identified Omicron and a subvariant of the ancestral or wild-type SARS-CoV-2 virus.

There have been countless SARS-CoV-2 variants that were not competitive and disappeared. Other mutations generate variants of concern as the changes in the genome bestowed a competitive advantage over earlier versions of the virus.

Mutations that result in variants of concern tend to be those that provide the emerging variant with a competitive advantage over other circulating variants that exist in a locale at any given time. Examples of advantages frequently seen with SARS-CoV-2 mutations include variants that:

Produce higher amounts of virus expelled by respiration, see figure 4.
Develop a stronger attachment to the host cell.
Evade the human immune system.
Become resistant to COVID-19 vaccines.
Induce severe and critical illness due to increased virulence.

Variants of concern that have emerged recently have had over 30 mutations that make the virus more transmissible and lethal. So far, those who are vaccinated have milder disease and are less likely to die than those who refused the vaccines. Centers for Disease Control and Prevention (2025). Benefits of getting vaccinated. https://www.cdc.gov/covid/vaccines/benefits.html

Case Fatality Rates versus Mortality Rates

Case fatality rates are calculated by dividing the number of infection related deaths by the number of confirmed cases of a disease to determine the percentage of patients that died. The formula is:

(number of deaths/ number of confirmed cases of COVID-19 infection) x 100.

The infection mortality rate (IFR) is another way to measure deaths, but an accurate total number of infections in the geographic location is needed to calculate it. With COVID-19 the recognized infections won’t be an accurate representation of total infections because asymptomatic patients cannot be measured unless everyone person is tested.

The formula for the IFR is:

Infection fatality ratio (%) = No. of deaths from infection/total no. of infected individuals X 100.2

World Health Organization. (2020 August). Estimating mortality from COVID-19. https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci-Brief-Mortality-2020.1

The mortality rate is measured by calculating the number of deaths as a percentage of the number of deaths per 100,000 people in the population.

The formulas can be modified as needed when the researcher limits study to a specific time frame and population. For example, a study conducted from date 1 to date 2, during which all working hospital staff were tested before starting their shifts.

The case fatality rate will always be an estimate of the actual rate with SARS-CoV-2 because asymptomatic people who actually have a COVID-19 infection cannot be identified without testing an entire population. So, unless every person in the location for the area in question is actually tested, the confirmed case numbers will be inaccurate. However, the case fatality rate does provide information that shows trends.

Estimates of Case Fatality Rates for Nine Countries While Variants of Concern were Dominant

We used data from the World Health Organization COVID-19 dashboard to graph a comparison of ten distinct SARS-CoV-2 variants and subvariants in nine different countries. The countries included (China, Germany, Italy, India, Iran, South Korea, Spain, UK, and US) were chosen because each had cases of COVID-19 early in the worldwide spread of the pandemic. Each of these variants and subvariants had specific characteristics that will be discussed below that resulted from mutations in the viral genome that provided a competitive advantage.

There were many other mutations that occurred, and some of those mutations gained dominance temporarily in a specific geographical area and then died out. The variants shown in the graph in figure 5 all were dominant worldwide for a period of time, and each was replaced by a subsequent variant with greater ability to infect many people. As shown, case fatality rates for the variants were comparable in all nine countries.

There is a marked decrease in fatality rates after the first vaccines were introduced in mid-December in the U.S. and the UK. Case fatality rates dropped most rapidly in countries with the largest proportion of vaccinated people. See Vaccinations below. There is also some innate immunity that results from a previous infection, however, reinfection with subsequent versions of COVID-19 are very common – as are multiple reinfections with the initial variant. As we’ll discuss below, most of the variants of concern that rose to dominance had mutations that conferred a degree of resistance to the existing vaccines.

Outcomes for SARS-CoV-2 Variants of Concern in the U.S.

In order to compare and contrast the overall impact of the SARS-CoV-2 variants of concern that affected the U.S., we compiled data from several sources for analysis. It was necessary to use some method to organize the information in a manner that facilitated comparison of variant characteristics and outcomes.

Methods

We used the following as “outcomes” for the period that each of the major variants became dominant over other circulating variants:

Patients with COVID-19 infections (cases) per day.
Hospitalizations for COVID-19 per day.
Deaths related to COVID-19 per day.
Published case fatality rates.
Healthcare workers and skilled nursing staff cases per day.
Healthcare workers and skilled nursing staff deaths per day.
Case fatality rates for healthcare workers and skilled nursing staff.

Healthcare and skilled nursing staff numbers were obtained from two separate U.S. databases. Despite extensive research we were not able to find any information that included healthcare personnel in all settings, nor were we able to find data specific to nurses. We were unable to locate information specific to nurses and other healthcare professionals in assisted living facilities, home health, in home personal care, dialysis centers, primary care providers or specialist physician offices, correctional facilities, and many other settings.

Skilled nursing facility staff deaths were obtained from the CDC, National Healthcare Safety Network (NHSN), Nursing Home COVID-19 data dashboard.

CDC (n.d.). National Healthcare Safety Network (NHSN), Nursing Home COVID-19 data dashboard. https://www.cdc.gov/nhsn/covid19/ltc-report-overview.html#anchor_1594393307.

We were also able to find some data on the generic occupational category “healthcare personnel,” but no information on the specific categories included.

Healthcare provider death data was archived and is now at Centers for Disease Control and Prevention (accessed 2024, July 9).

COVID-19 Deaths Among Healthcare Personnel, by week – ARCHIVED. The database was updated June 28, 2024, and there were “less than five” deaths recorded since June 2024. CDC (n.d.). COVID-19 Deaths Among Healthcare Personnel, by week – ARCHIVED.https://data.cdc.gov/Case-Surveillance/COVID-19-Deaths-Among-Healthcare-Personnel-by-week/xwa7-cukt/about_data.

References for table 1:

Johnson, A. G., et al. (2023, June 16). Comparison of COVID-19 mortality rates among adults age => 65 years who were unvaccinated and those who received a bivalent booster dose within the preceding 6 months – 20 U.S. jurisdictions, September 18, 22-April 1, 2023. Morbidity and Mortality Weekly, 72, 24, 667-669. https://www.cdc.gov/mmwr/volumes/72/wr/pdfs/mm7224a6-H.pdf
Secondary analysis: CDC (updated 2023, September 15). SARS CoV-2 Variant Proportions. https://data.cdc.gov/Laboratory-Surveillance/SARS-CoV-2-Variant-Proportions/jr58-6ysp/
Secondary analysis: CDC data tracker, cases, and deaths https://covid.cdc.gov/covid-data-tracker/
Secondary analysis: CDC (downloaded 2023, July 22). COVID-19 data tracker – cases and deaths among health care personnel.
https://covid.cdc.gov/covid-data-tracker/#health-care-personnel_healthcare-cases;
CDC, downloaded 2023 July 31. COVID-19 nursing home data – weekly death graph.
https://data.cms.gov/covid-19/covid-19-nursing-home-data). CDC data tracker, cases, and deaths https://covid.cdc.gov/covid-data-tracker/.
Tabatabai, M., et al. (2023). An analysis of COVID-19 mortality during the dominancy of Alpha, Delta, and Omicron. Journal of Primary Care, and Community Health, 14. https://pmc.ncbi.nlm.nih.gov/articles/PMC10125879/pdf/10.1177_21501319231170164.pdf
Technical Advisory Group (2021, June).
Liu, Y., & Rocklov, J. (2021, August).
Wang, C. (2023).
Auwaerter, P. G. (2022, July).

Due to the wide variation in number of days that any given variant of concern influenced outcomes, we used “cases per day,” “hospitalized per day,” and “deaths per day” to facilitate comparisons. To estimate the number of days a given variant was influential, we used the end of week date when the variant was at or greater than 10% of circulating variants in the U.S. using the information recorded on the “Weighted and Nowcast estimates in the United States for 2-week periods” published by the U.S. Centers for Disease Control and Prevention. To determine the start date and when it dropped near 10% as the end date of the period during which the outcomes were measured. There is overlap with dates, so these are approximate. When this information was not available, as was the case for the ancestral and Iota variants, we used information from published research to reconstruct the history as best we could, see table 1.

We also completed extensive literature searches and review in order to obtain variant specific information on characteristics, reproduction and transmission data, and documented case fatality rates. This research was not intended to be a comprehensive, quantitative study, but rather a starting point to help readers to understand how quickly things changed as new variants emerged and why the situation deteriorated so fast. Results are summarized in table 1.

SARS-CoV-2 Variants of Concern 2020 to 2021

The Ancestral Wild-type SARS-CoV-2 Variant

The first COVID-19 virus arrived without warning in the Wuhan province in China in December of 2019 and killed 1.9 million people by the end of the first year. In that SARS-CoV-2 was a brand new, novel virus, humans did not have any type of natural immunity to this highly contagious infection. By the time the pandemic related public health emergency was declared over on March 12, 2023, the virus had claimed the lives of 6.9 million citizens of the planet.

As of June 16, 2024, there have been more than 7,0515,600 deaths (data from: World Health Organization COVID-19 dashboard, https://ourworldindata.org/covid-cases) due to this invisible virus. We know that this recorded number is low, because to confirm a COVID-19 related death testing was required once it was available – and because this was a never seen before Coronavirus, tests were either not developed or not available in the huge numbers required in many countries for a year or more.

Secondary infections are those generated by the contacts of the primary infected person. At the beginning of this pandemic, this was a novel virus to which no human beings had any type of resistance, so people who came into close contact with someone infected were very likely to become infected (Leung, 2021). On average, the primary infected person transmitted the disease to 2 to 3 people, see figure 6, and each of those 2 to 3 people infected 2 to 3 more, and on and on. It is very easy to see why COVID-19 became a pandemic so fast.

The initial epidemiological contact tracing during the time of the ancestral, wild-type virus in China, researchers found 51% of the 198 people who tested positive and were ill with COVID-19, had not been in contact with the probable source location or anyone who was visibly ill (China CDC The 2019-nCoV Outbreak Joint Field Epidemiology Investigation Team, 2020, January 31). It was obvious in the early days that the primary contact person was often either pre-symptomatic (people who develop signs and symptoms of infection later) or totally asymptomatic (people who remain totally unchanged throughout the course of their infection and never show signs or symptoms of illness). This is one reason why stay-at-home orders and lockdowns did not work as well as expected.

China CDC The 2019-nCoV Outbreak Joint Field Epidemiology Investigation Team, 2020, January 31

The UK Scientific Advisory Group for Emergencies summarized what was known about characteristics of SARS-CoV-2 infections on February 11, 2020, as had been reported by China:

Case fatality rates (CFR) indicated that 2 to 3% of people with confirmed infection died.
Reproduction of the virus in the naïve population was at a transmission rate, R₀ of 2 to 3, that is on average one infected person infected 2 to 3 others.
Doubling rates were 4-5 days, this was the time it took for the cumulative number of patients with infections to double.
Incubation rates were 4 to 5 days (the range was 1 to 14 days), this was the time it took for symptoms to appear on average.
Duration of infectivity was 14 days with a peak at 2 to 6 days after symptoms started.

Children were known to contract COVID-19, but they were less likely to show symptoms (UK SAGE, 2020, February 11; UK SAGE, 2020, February 13).

Nurses and other healthcare workers were unable to utilize the type of personal protective equipment necessary to protect themselves and other patients due to the worldwide shortage. N95 and FFP-2 respirators and medical grade masks were being reused or not used at all in healthcare settings worldwide, especially in post-acute hospital care settings such as nursing care homes and in home care. See chapter A Global Shortage of Personal Protective Equipment for more detail. That situation combined with the virus’s ability to cause transmission from people with asymptomatic infection led to grave concerns about healthcare acquired (nosocomial) COVID-19 infections in clinical staff and patients who had been hospitalized for other reasons. See chapters Dying to Take Care of You: Nurses and Healthcare Workers Illness and Deaths, and The United Kingdom: Politics in the Pandemic for more information.

Case Fatality Rates/ Mortality Rates for the Ancestral Variant

The case fatality rate, initially ranged from 2.3% to 2.9% for the ancestral variant in China (China CDC, The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020, February 21; Li, Q., et al., 2020, January 29; Zhao, H., et al., 2021).

Infections and Deaths of Health Care Personnel January to October 31, 2020

The UK Scientific Advisory Group for Emergencies summarized what was known about characteristics of SARS-CoV-2 infections on February 11, 2020, as had been reported by China:

Case fatality rates (CFR) indicated that 2 to 3% of people with confirmed infection died.
Reproduction of the virus in the naïve population was at a transmission rate, R₀ of 2 to 3, that is on average one infected person infected 2 to 3 others.
Doubling rates were 4-5 days, this was the time it took for the cumulative number of patients with infections to double.
Incubation rates were 4 to 5 days (the range was 1 to 14 days), this was the time it took for symptoms to appear on average.
Duration of infectivity was 14 days with a peak at 2 to 6 days after symptoms started.

Children were known to contract COVID-19, but they were less likely to show symptoms (UK SAGE, 2020, February 11; UK SAGE, 2020, February 13).

Case Fatality Rates/ Mortality Rates for the Ancestral Variant

Infections and Deaths of Health Care Personnel January to October 31, 2020

As shown in table 1, there was a high degree of risk to clinicians involved in providing medical care to patients infected with COVID-19 without adequate respiratory protection. During this period of time, the global shortage of N-95 respirators was profound, and nurse surveys showed that the majority of nurses were reusing one time use respirators for prolonged periods of time, wearing regular medical masks, reusing both types of personal protective equipment, or not using any type of respiratory protective gear. Chapter A Global Shortage of Personal Protective Equipment goes into detail on this topic.

During the 304 days while the ancestral wild-type variant was dominant over 297,805 U.S. healthcare providers were infected at a rate of 980 clinicians per day. More than 8,886,342 people in the U.S. infected and diagnosed during that period, and there were likely far more who were transmitting COVID-19 to others while asymptomatic. Registered nurses, licensed practical nurses, and nursing assistants provided most of the necessary direct, hands-on care. Most of these infections were occupation related and healthcare acquired, because of the:

Lack of appropriate protective equipment.
Spread of the virus spread exponentially throughout the world.
Failure to recognize that transmission was airborne (not just by droplet).
Need to provide care for extremely sick people without protection.
Scarcity of effective treatments.

Although nurses and healthcare professionals know how to prevent a respiratory virus from spreading, it was not possible to do so as would normally be the case due to the factors noted above. In addition, this was an unprecedented situation that was far more complicated than the pandemic influenza situations that reoccur so often.

From January 29, 2020, to October 31, 2020, it was documented that at least 2,251 U.S. healthcare providers died from COVID-19 infections at a rate of 7.4 per day. There are likely many more clinicians who died for whom occupation was not recorded as record keeping was not at 100% in heavily affected healthcare facilities or anywhere else. In fact, it was nearly six months into the pandemic on May 31, 2020, before skilled nursing facilities were required to report staff deaths. To date, we have not been able to locate any publicly accessible information on employee healthcare acquired COVID-19 related deaths on the Occupational Health and Safety Administration (OSHA) sites either.

During the declared public health emergency related to the pandemic, at least 5,927 healthcare providers died from these infections.

As shown in figure 7, the number of clinical staff deaths in healthcare facilities and skilled nursing homes was extremely high. The worldwide pandemic reached the U.S. with full force in March of 2020 and the highest number of staff deaths occurred during the first 12 months from March 2020 to March 2021.

For the U.S. there are no actual numbers to show how many nurses and other healthcare professionals developed an occupational, healthcare associated infection, how many required hospitalization, critical care, or died following a COVID-19 infection. There is no simple method to obtain such information available. Whereas clinical information that uses the alphanumeric ICD-10 codes for COVID-19 can be easily sorted, there are no such options to look at specific occupations.

The U.S. standard certificate of death does request “decedent’s usual occupation (indicate the type of work done during most of working life. Do not use retired,” (National Vital Statistics System, 2003), so the information should be on a patient’s death certificate – but it would not be easy to extract. It is extremely important that information on healthcare acquired infections be collected for analysis, and even more important to address nosocomial infections in healthcare providers in the future. It does not do much good to use full respiratory protection with patients only if one or more staff members are transmitting an infection to each other asymptomatically.

One example of such a situation was a study conducted by Shah, et al. (2020) in the UK. In one hospital in Scotland, 11.6% of 6,346 patients hospitalized for COVID-19 from March 1 to June 6, 2020, were healthcare workers. Infected workers passed the infection to 141 of their family members and also to each other and patients (Shah, et al., 2020).

New Mutations, New Variants

The Iota Variant B.1.526 and other variants, circulating November/ December 2020 to June 2021

The Iota variant (B.1.526) was first identified in New York City, New York in November of 2020 and then spread across the U.S. and to other countries through December 2020 to June 2021. During this same period the Alpha variant B.1.1.7 was spreading in competition with Iota. There were also a number of other variants circulating at the same time, including B.1.427/B.1.429 (Epsilon), P.1 (Gamma), B.1.525 (Eta), and B.1.351 (Beta). Testing was still very limited. It was not thought that Iota would produce severe disease (Thompson, C. N., et al., 2021). So, it is not known which variants were associated with the high number of cases, hospitalizations, and deaths during this period.

When larger numbers of whole genome sequencing samples were obtained it was evident that there were two B.1.526 variants with very different characteristics. Iota B.1.526 did not cause severe disease, but B.1.526 E484K, had a mutation in the E484K gene that affected the receptor binding domain that is involved with viral entry into the host cell and attachment to the ACE2 receptor. Variant B.1.526 accounted for 3% of variants circulating January 1, 2021, but increased to 34% by mid-February and then stayed at 35 to 45%. B.1.526 E484K was also increasing, as was Alpha B.1.1.7. On April 5, 2021, the distribution of circulating variants was B.1.526 at 16% (Iota), B.1.526 E484K was at 25% (Iota with mutation), and B.1.1.7 (Alpha) had reached 36% of (Thompson, C. N., et al., 2021).

Preliminary studies suggested that the E484K mutation may be associated with resistance to vaccines and also to the monoclonal antibody treatments that had been very effective with the wild-type ancestral variant (Annavajhala, et al., 2021; Thompson, et al., 2021). Like other variants that came before and after, B.1.526 is no longer detectable (European Centre for Disease Prevention and Control, 2024). However, the E484K specific gene mutation seen in Iota has also been found in other, later variants. See chapter Pathophysiology and Disease Process for more detailed information. The Alpha virus was also circulating In New York In December 2020, and eventually won the competition. Remnants of Iota were still circulating in Hawaii and possibly other states as late as July 2021 (Hawaii DOH, 2021).

The U.S. from October 31, 2020, to February 27, 2021

There was a marked escalation in the number of people infected with COVID-19, hospitalized, and who died in the U.S. from approximately October 31, 2020, to February 27, 2021. On October 28, 2020, the total, cumulative COVID-19 case count was 8,863,342. During this 120-day period, over 20 million (20,065,957) NEW cases of COVID-19 were identified in the U.S., at a rate of approximately 168,622 cases per day. In that 119-day period, 1.5 million (1,448,438) people needed to be hospitalized, 7.2% of those who contracted the disease, at a rate of 12,172 NEW patients per day. During that same 119-day period, 304,026 people died from the infection, at a rate of 2,555 per day.

Healthcare Worker Deaths October 31, 2020, to February 27, 2021

NO ONE WAS PREPARED FOR SUDDEN SURGES as more virulent variants emerged and literally changed everything that affected practicing nurses and other healthcare workers.

During this same time period, 273,159 healthcare workers and nursing home staff became ill with COVID-19 infections at a rate of 2,295/ day. Another 1,122 healthcare providers died at a rate of 9.4 per day (secondary analysis: CDC, updated 2023, September 15. SARS CoV-2 Variant Proportions. https://data.cdc.gov/Laboratory-Surveillance/SARS-CoV-2-Variant-Proportions/jr58-6ysp/; CDC COVID-19 data tracker – cases and deaths among health care workers, https://covid.cdc.gov/covid-data-tracker/#health-care-personnel_healthcare-cases; CDC, COVID-19 data tracker; COVID-19 nursing home data – weekly death graph. https://data.cms.gov/covid-19/covid-19-nursing-home-data; CDC data tracker, cases, and deaths https://covid.cdc.gov/covid-data-tracker/). See chapter Dying to Take Care of You: Nurse and Healthcare Provider COVID-19 Infections and Deaths for more details.

It is unclear what happened to cause these dramatic changes in cases and outcomes. There were many SARS-CoV-2 genetic sequences uploaded to the https://GISAID.org database by scientists worldwide. Were the increases due to the Iota variants alone? Were Iota B.1.526 and Iota E484K circulating together? Was the Alpha circulating earlier? Was there another subvariant of the wild-type SARS-CoV-2 involved? Were there superspreader events in some states that skewed the data? We will probably never know.

Zeller, et al. (2021) showed that there were hotspots in Louisiana, California, Washington state, New York, and Texas in early 2020. Seven different subvariants had been found in the U.S., including B.1, B.1.427 and B.1.429 (Epsilon), B.1.526 (Iota), and B.1.595 and B.1.596.

The authors of the study suggested that Mardi Gras parades in New Orleans on February 5, 2020, were likely superspreader events given the rapid spread of infections and the lack of genetic diversity in Louisiana shortly thereafter. During February and March 9, 2020, In New Orleans variants B.1 and B.1.595 were the dominant circulating variants and in Shreveport, Louisiana, B.1 and B.1.596 were dominant (Zeller, et al., 2021). All seven subvariants listed are no longer detectable.

The Alpha B.1.1.7 SARS-CoV-2 Variant, February 27 to July 3, 2021

COVID-19 became a leading cause of death in the U.S. during the Alpha period. On October 3, 2020, COVID-19 infections accounted for 7.1% of all deaths in the U.S., and by January 9, 2021, 30% of all U.S. deaths were due to COVID-19. Secondary analysis: CDC (downloaded 2023, March 10) CDC, 2023). COVID-19 data tracker – U.S. data table for total cases. https://covid.cdc.gov/covid-data-tracker/#datatracker-home; CDC (downloaded 2023, July 10). COVID-19 data tracker – U.S. data table for cumulative death trends, United States. https://covid.cdc.gov/covid-data-tracker/#datatracker-home).

Alpha was first identified in England on September 20, 2020, and it was apparent early on that it would be a serious threat. Davies, et al. (2021) found that there were 17 mutations from the ancestral genome. Mutations were identified that affected the ability of the virus to enter the cells and attach to the ACE2 receptors, transmit to and infect more people, escape the immune system especially in immunosuppressed people, and it had a deletion that caused specific commercial PCR tests to fail. The reproduction rate (R) was estimated to be 45 to 82% higher than all the other known variants in early 2021 (Davies, et al., 2021).

The Alpha variant spread very quickly and caused high mortality worldwide. Tabatabai, et al. (2023) used data from the CDC COVID-19 case surveillance public use data, and information from death certificates to estimate a U.S. case fatality rate of 5.35% for the Alpha variant. Patients were excluded unless the COVID-19 was lab confirmed. Deaths without a COVID-19 cause documented on the death certificate were excluded from the analysis. Deaths during that period were attributed to Alpha as it accounted for the highest proportion of circulating variants, but the specific lab analysis for cases was not available to most researchers due to extremely limited testing (Tabatabai, et al., 2023).

The case fatality rate for Alpha reported above was consistent with findings of studies from other countries. Cetin, et al. (2021) reported that the arrival of the Alpha variant in Turkey increased the COVID-19 case fatality rate from a baseline of 0.84% for those who were not infected with the Alpha variant in that country to 5.3% for those with a confirmed Alpha infection. For patients over 70, the fatality rate was 13.6% for the other circulating variants, but for patients 70 and older with a confirmed Alpha variant infection, 31.5% of patients died (Cetin, et al., 2021).

The Alpha variant was isolated in the U.S. in November 2020 and was in competition with other variants for dominance until the end of February 2021. We used the time period from when it reached a 10% proportion of circulating variants to when it dropped to 10% as the time during which it influenced outcomes, February 27, 2021, to July 3, 2021, see table 1.

For the week ending February 27, 2021, Alpha accounted for 11.4% of circulating variants and it was projected to reach 72.4% by May 8, 2021, with a range from 52.8 to 82.5% for the ten U.S. Health and Human Services regions (Prabasaj, P., et al., 2021).

By mid-April of 2021 up to 66% of U.S. COVID-19 infections were caused by the lethal Alpha variant (Tabatabai, et al., 2023). Alpha was a very toxic virus, highly transmissible, and it was estimated to have an R₀ of 4.5 to 5.5 (Technical Advisory Group, 2021 June). Transmission was 43 to 90% greater than the circulating variants that existed at that time (Davies, et al., 2021), see figure 8. As noted above R₀ for the ancestral Wild-type variant was 2.2 to 2.75%. As it was much more contagious, Alpha had a competitive advantage over circulating variants at the time.

This variant had approximately 17 mutations that provided a competitive advantage over earlier SARS-CoV-2 variants of concern. Alpha, also known as B.1.1.7, was transmitted easily from person to person. Monoclonal antibodies that had become a mainstream treatment for ancestral SARS-CoV-2 did not work as well for this variant. Alpha produced a higher viral load than did previous variants, which meant that it was more contagious. Other mutations made it easier for the virus to attach to and enter human cells (Davies, et al., 2021). A specific deletion mutation caused one of the main PCR tests to fail to identify the virus, and that caused false negative results in patients who were infected – patients who then thought there was no need to isolate or quarantine (Davies, et al., 2021; Galloway, et al., 2021). During this 126-day period of Alpha dominance, 5.9 million (5,859,544) people in the U.S. developed a COVID-19 infection at a rate of 46,504 patients per day. More than 547,631 (9.3%) who were infected required hospitalization, increasing the number of people sick enough to need in-hospital monitoring by 4,346 per day. In the U.S. alone, over 66,573 people lost their lives during this 126-day period at a rate of 528 per day, see table 1.

Nurse and Other Healthcare Worker Deaths during Alpha

There were 341,567 new cases of healthcare workers/ nursing home staff infected with COVID-19 during the Alpha dominant time, with 2,711. Fortunately, there were only 220 healthcare personnel deaths (1.7 per day) recorded during this time (secondary analysis: CDC, downloaded 2023, July 22. COVID-19 data tracker – cases and deaths among health care personnel. https://covid.cdc.gov/covid-data-tracker/#health-care-personnel_healthcare-cases; CDC, downloaded 2023 July 31. COVID-19 nursing home data – weekly death graph. https://data.cms.gov/covid-19/covid-19-nursing-home-data).

The number of healthcare worker deaths began to drop as the vaccine rollout began in mid-December. Supplies were limited so healthcare and essential workers were prioritized. Increasing numbers of healthcare providers were vaccinated with the first and in some cases second dose of Moderna or Pfizer vaccines. The Alpha variant did demonstrate immune evasion and was able to cause infection in vaccinated people, but the course of the infection was less severe. So, large numbers of nursing and other healthcare workers who were vaccinated got sick, but few died.

Mitigation Strategies February 2021 to January 2022

During this time period risk was mitigated by the segment of the population that followed public health advice by social distancing, wearing masks as indicated, regularly performing hand hygiene and surface disinfection, and self-isolating to protect others when sick. Pre-travel requirements for testing, mask mandates on public transportation, and remote work options also helped reduce transmission.

Rising vaccination rates, fueled by armies of volunteers who helped to administer the vaccines had a major impact on reducing risk of life-threatening effects of the infection. Starting early in January 2021, COVID-19 vaccines were administered in the U.S. at an initial rate of approximately one million per day (Galloway, et al., 2021).

The Delta B.1.617.2 Variant, June 5, 2021, to January 1, 2022

Delta was another deadly variant that emerged in India and reached the U.S. in May of 2021. Mild disease was often characterized by runny nose, headache, gastrointestinal concerns, and fever, but cough and loss of smell were not as common as with previous variants. Hearing loss did result in some people. Severe and life-threatening disease related to Delta often involved impaired coagulation with thromboembolisms that caused serious gastrointestinal issues, and gangrene of tissues and vital organs (Hagen, 2021).

We used the time period from June 5, 2021, to January 1, 2022, for outcome analysis. Delta was ultimately replaced by the even more highly contagious Omicron SARS-COV-2 variant during December 2021 to January of 2022.

The very first Delta variant B.1.617 was identified in October of 2020 in Maharashtra, India. Subvariants B.1.617.1 and B.1.617.2 were found in December of 2020 in India, and B.1.617.3 emerged in India in February of 2021. B.1.617 and subvariants accounted for over 60% of circulating variants in India from January to April of 2021 (Thye, et al., 2021). Approximately 10 to 15% of people infected were under the age of 20 years old. A number of mutations in the S or Spike proteins provided competitive advantages in the ability of SARS-CoV-2 B.1.617 and subvariants to attach to the host cell, transmit from person to person, and resist the existing vaccines (Thye, et al., 2021).

On January 18, 2021, Delta accounted for 10.54% of circulating variants, and the proportion increased slowly until the end of March 2021 when it was the variant found in 18.35% of genetically sequenced tests from India (WHO COVID-19 dashboard, https://ourworldindata.org/explorers/coronavirus-data-explorer).

Shortly thereafter, the Delta variant gained a foothold and spread within India and to the rest of the world. On April 12, 2021, Delta had risen to 52.29%, and by May 10^th to 91.37%. Cases of Delta in the UK reached 17.87% on May 10. By June 7, 2021, Delta was the variant identified in 98.01% of cases in India, 83.8% in the UK, 14.12% in the U.S., 11.04% in Italy, 9.19% in Spain, and 7.07% in Germany (secondary analysis WHO COVID-19 dashboard. https://ourworldindata.org).

Delta had approximately 10 mutations. The viral load was higher than with previously circulating variants, and it attached more firmly to the ACE receptor on the human cell, making it easier to enter the cell and reproduce itself. This variant was also better equipped to evade the human immune response. The mutations that resulted in Delta increased the rate of transmission approximately 40 to 60% higher than with Alpha and by almost 100% compared to the ancestral wild-type virus. It had higher viral loads, up to 1,000 times higher than the amount of virus shed with other variants (CDC, 2021 August 6; Hagen, 2021). In England, the reproduction number for Delta was estimated to be 40 to 80% higher than was the case for Alpha (Technical Advisory Group, 2021).

Tabatabai, et al. (2023), the same team of researchers that estimated a U.S. case fatality rate of 5.35% for the Alpha variant recorded a rate of 7.5% while Delta was the predominant variant from May 20, 2021, to November 30, 2021. For this study, individuals were included if COVID-19 was confirmed by a lab, and if a COVID-19 cause of death was on the death certificate. (Tabatabai, et al., 2023).

Advanced age affected the Delta case fatality rate. In South Africa, 2.6% of those infected of all ages died, but the case fatality rate was 11.71% for those at or over the age of 60. In Italy, 12.8% of those aged 70 to 79 died, and mortality for individuals over 80 was 20.2%. A similar pattern was seen in China with an 8.0% case fatality rate for those people who were 70 to 79 and mortality increased to 14.8% for infected individuals over the age of 80. Vaccination status and comorbidities also contributed to higher mortality (Liu, et al., 2023).

Johnson, et al. (2022) found that the average weekly incidence of deaths in the U.S. during the period when Delta was dominant was 11.4 for unvaccinated persons and 0.7 per 100,000 population for those who were fully vaccinated (Johnson, et al., 2022). Overall, infection with Delta caused more severe disease in the unvaccinated than was the case with prior variants. Post vaccination breakthrough infections were not uncommon with Delta due to the immune evasion properties conferred by mutations, but the viral load decreased more quickly in those who were vaccinated (CDC, 2021, August 6).

The reproduction rate (R₀), the number of people on average that would be infected by one sick individual, was estimated at 3.2 to 8 with a mean of 5.08 (Liu & Rocklov, 2021). Case fatality was estimated to be quite high at 7.5 to 8.5% (Liu, et al., 2023; Tabatabai, et al, 2023; Wang, 2023), see figure 10.

One grave concern was that the Delta variant was resistant to the existing vaccinations. Post-vaccination breakthrough infections were common. As with Alpha, severity of illness was lessened for those who had received vaccinations (Aleem, et al., 2023; Thye, 2021).

Individuals who were vaccinated with the two doses, as recommended while this variant was dominant, were up to two times less likely to be hospitalized and also less likely to die (Hagen, 2021). In August 2022, the U.S. Centers for Disease Control and Prevention reported that when compared to people who had received the recommended two vaccinations individuals who were not vaccinated were more likely to die when infected. The risk of death increased with age and was:

3 times higher for the unvaccinated aged 18 to 29.
5 times higher for unvaccinated 30- to 49-year-olds.
6 times higher if unvaccinated at 50 to 64 years old.
9 times more likely for unvaccinated people aged 65 to 79.

For those age 80 or higher, the risk of death was four times higher (CDC, 2023 August 29).

Figure 11 shows that there were two waves of deaths in India and also in the United States. An estimated 2.8 million COVID-19 deaths occurred worldwide with 322,631 in India during Delta’s reign (secondary analysis WHO COVID-19 dashboard. https://ourworldindata.org).

In the U.S., early cases of the Delta variant were identified at the beginning of May 2021, but Alpha was still the most prevalent circulating variant. While Delta gained dominance in the U.S. from mid-June 2021, Alpha was waning (secondary analysis: CDC (updated 2023, September 15). SARS CoV-2 Variant Proportions. https://data.cdc.gov/Laboratory-Surveillance/SARS-CoV-2-Variant-Proportions/jr58-6ysp/).

In the U.S., the Delta B.1.617.2 subvariant began to rise to dominance in May of 2021. On May 1, 2021, the Delta variant accounted for 1% of variants circulating in the U.S., and by June 26, 2021, the proportion of U.S. variants that were B.1.617.2 was at 50%. Delta continued to be the highest proportion variant through to December 2021, until it was replaced by the first Omicron variant in December of 2021 (Lambrou, et al., 2022).

Concerns regarding how highly contagious the Delta variant was, with increased viral loads and high transmission rates prompted the U.S. Centers for Disease Control and Prevention to change the messaging. On July 27, 2021, the CDC updated guidance that was intended to:

Present the concerns about increased risk of contagion and that even vaccinated people could transmit the Delta virus.
Educate on the importance of up-to-date vaccinations to prevent severe disease, hospitalization and deaths.
Instruct Americans to wear masks indoors in public places to reduce the risk of contagion (CDC, 2021 August 6).

In the U.S. from June 5, 2021, to January 1, 2022, while the Delta variant remained above 10% of all circulating SARS-CoV-2 variants, a period of 210 days, over 20 million (20,379,776) NEW cases of COVID-19 infections were recorded in the U.S. (secondary analysis CDC data tracker, cases, and deaths, more than 20,379,776 Americans were infected at an average rate of 97,047 per day, more than twice the number of infections that Alpha produced. With 1.5 million hospitalizations at an average rate of 7,141 per day, U.S. hospitals in areas with high volume outbreaks were overwhelmed. At least 244,544 people in the U.S. died due to the infection at a rate of approximately 1,165 per day (secondary analysis WHO COVID-19 dashboard. https://ourworldindata.org). See table 1. Several factors mitigated the severity of this variant in the U.S., decreasing the case fatality rates. Once the vaccines became available in December of 2020, healthcare workers and first responders were prioritized. Public health education was still ignored by a large segment of the U.S. population who still believed that the pandemic was a hoax. But more people were listening to the advice of experts.

Nurse and Other Healthcare Worker Deaths During Delta

We used data from the CDC COVID-19 tracker for healthcare personnel and nursing home staff to calculate rates. As noted previously, healthcare personnel cases and deaths were maintained separately from skilled nursing home staff data. It was necessary to combine this data for more accurate totals.

A total of 253,880 nurses and other healthcare providers were infected, at the rate of 1,209 per day, during the Delta period. There were five healthcare/ nursing home staff deaths. The overall case fatality rate of 0.24% during this time period, see table 1. (Secondary analysis: CDC, downloaded 2023, July 22. COVID-19 data tracker – cases and deaths among health care personnel. https://covid.cdc.gov/covid-data-tracker/#health-care-personnel_healthcare-cases; CDC, downloaded 2023 July 31. COVID-19 nursing home data – weekly death graph. https://data.cms.gov/covid-19/covid-19-nursing-home-data).

Omicron Variants, Multiple Variants of Concern, December 2021

Omicron B.1.1.527 and BA.1, December 28, 2021, to April 2, 2022

Omicron arrived in the U.S. with variant B1.1.527, also known as BA.1 near the end of November 2021, and they remained over 10% of circulating variants from December 18, 2021, to April 2, 2022, approximately 105 days, as shown in figure 9. Within the 105 days of circulation 30,675,560 new cases of COVID-19 infections were recorded. This translated to 292,148 new cases per day due to the first Omicron variant. Countries that had managed to keep a relatively flat slope of the curve lost control and cases of Omicron infection skyrocketed worldwide.

B.1.1.527/ BA.1 had at least 30 mutations that provided competitive advantages over other circulating variants. Omicron was far more contagious and better able to bind to the ACE receptors on the outside of the human cell. The firm bond helped the virus to enter the cell and take over the cellular processes needed to reproduce itself. Monoclonal antibody medications were no longer effective with Omicron variants (Aleem, et al., 2023; Galloway, et al., 2021). More than 30 Omicron variants and subvariants had been identified (Ma, et al., 2023). The original vaccines were not as effective at preventing infection but did reduce severity and risk of death. The bivalent Omicron booster vaccination received emergency use authorization in January 2022 (Wong, E., et al., 2023). Asymptomatic and pre-symptomatic viral shedding continue to be of concern with the Omicron variants because most people do not realize they are infected until (if) symptoms appear. For those who developed symptoms, they were contagious for at least 2 days before symptoms and for at least 2 to 6 days after. For those who never developed symptoms viral shedding still occurred and they were contagious (Auwaerter, 2022 July 12). Table 1 shows Omicron variants of concern that have gained dominance and then have been replaced.

Reproduction Number and Transmission

With the emergence of the Omicron B.1.1.529/BA.1 a single sick individual could infect from 5.5 to 24 other people. The average basic reproduction number was 9.5). Given the ability to transmit from one person to another so easily, Omicron was responsible for widespread disease. One factor that increased R₀ was the ability to avoid the human immune system, especially in unvaccinated people. Unfortunately, this variant was also able to evade the existing vaccines and infect fully vaccinated people as well. However, as with other variants, vaccinated people were far less likely to die (Liu & Rocklov, 2021; Tabatabai, et al., 2023).

Omicron B.1.1.529/ BA.1.1 caused 180,760 deaths with a case fatality rate of 0.59%. Tabatabai, et al. (2023) reported a case fatality rate for Omicron B.1.1.529/ BA.1 of 9.0%, see figure 12. As noted above, this team of researchers analyzed data from the CDC COVID-19 case surveillance public use data, for Omicron from December 1, 2021, to March 2022. The authors state that the publication did not cover Omicron BA subvariants. Patient cases were limited to those with lab confirmation of COVID-19 infection and a COVID-19 diagnosis on the death certificate (Tabatabai, et al., 2023). The much higher rates reported by these researchers was likely due to differences in dates used, and more restrictive criteria in that they required a COVID-19 diagnosis on the death certificate and a lab confirmed diagnosis.

We estimated that a total of 1,091,707 people required hospitalization during the 105-day wave when Omicron B.1.1.527/ BA.1 was over 10% of variants circulating, from December 18, 2021, to April 2, 2022. Of those infected, 3.6% required hospitalization, at a rate of 10,397 admissions per day. The sheer volume of patients requiring hospital care placed a back-breaking burden on the nurses and then entire U.S. healthcare system, see table 1.

Nurses and other health care providers were still getting sick with a total of 368,127 infected with SARS-CoV-2 at a rate of 3,505 per day. The case fatality was low at 0.1% with 420 staff deaths, or 2.9/ day (Secondary analysis: CDC, downloaded 2023, July 22. COVID-19 data tracker – cases and deaths among health care personnel. https://covid.cdc.gov/covid-data-tracker/#health-care-personnel_healthcare-cases; CDC, downloaded 2023 July 31. COVID-19 nursing home data – weekly death graph. https://data.cms.gov/covid-19/covid-19-nursing-home-data).

Omicron BA.5 June 4, 2022, to December 31, 2022

By January 22, 2022, 99.2% of variants of concern were Omicron subvariants (Lambrou, et al., 2022). The second major wave for Omicron began when variant BA.5 reached 10% of the circulating variants in the U.S. June 4, 2022, and then dropped to 10% December 31, 2022. The mutations in BA.5 resulted in a reproduction rate, R₀ of 18.5. With transmission rates this high, each infected person – symptomatic or asymptomatic was capable of creating superspreader events. Figure 13 illustrates the average number of primary infections caused by one infected person. Each of the 18 people infected in the first round were capable of infecting 18 more people, and so on (Auwaerter, 2022 July 12).

During this 210-day period during which Omicron BA.5 emerged as dominant, another 81,029 people died at a rate of 386 per day, case fatality 0.49%. Hospitalizations continued to be high at 4,816 per day for a total of 1,011,434 patients. Whereas Omicron B.1.1.528/ BA.1.1 had the lowest hospitalization rate at 3.6%, the percentage hospitalized while BA.5 rose and fell from dominance was at 6.0%. Healthcare providers continued to become infected with the rate increased to 4,953 per day with over 1 million (1,040,056) getting infected. An estimated 616 health care personnel died of COVID-19 infection at a rate of 2.9 per day. The staff case fatality rate was 0.13%, see table 1.

Mitigation Strategies: Vaccinations and Omicron

Bivalent booster vaccines that targeted ancestral and Omicron variants were introduced in 2022 (Abbasi, 2023). “Fully vaccinated” at that time included a booster injection that was designed to include Omicron. In the U.S. the updated version based on currently circulating variants was approved at the end of September 2023 and the terminology has changed from “fully vaccinated” to “vaccinated.”

COVID-19 now is an annual vaccine. Getting vaccinated is VERY important! Results from three studies conducted during periods when three different Omicron variants were predominant are as follows:

Omicron BA.5, September 18 to November 5, 2022 (n=1,717) – the mortality rate for those with the bivalent booster was 0.8% compared to 13.5% for unvaccinated persons.
Omicron BQ.1/ BQ1.1, November 6, 2022, to January 21, 2023 (n=4,537) – mortality was 1.6 to 1.8% for individuals who had the bivalent booster and 18.8% for the unvaccinated.
Omicron XBB.1.5, January 22 to April 1, 2023 (n=1907) – mortality rates for those vaccinated with the bivalent vaccine were 0.9 to 1.0% compared to 7.3% for unvaccinated people (Johnson, A. G., et al., 2023).

Omicron XBB.1.5, December 24, 2022, to August 5, 2023

Omicron XBB.1.5 rose to dominance during a 223-day period stretching from December of 2022 to August of 2023. Like the other mutations that came before, this variant rose to dominance quickly and then became essentially obsolete. The U.S. has stopped reporting the number of cases of COVID-19, so it was not possible to calculate case fatality rates for XBB from available data.

During this time period, there were 505,894 people hospitalized at a rate of 3,243 per day. People were still dying at a rate of 255 per day for a total of 39,715. Most of those deaths could have been avoided with vaccination, as noted above, 7.3% of unvaccinated people died, whereas only 1.0% of those who received the vaccine lost their lives. Another 329 healthcare professionals died as a result of COVID-19 infections at a rate of 2.1 per day and with a case fatality rate of 0.3%, see table 1.

Omicron Mutations

EG.5 was first detected in February of 2023, and the World Health Organization started monitoring it in July of 2023. Omicron EG.5 (Eris) was first identified in the U.S. in late May 2023 accounted for 29.4% of all circulating variants. This variant is a descendant of XBB.1.9.2 and has characteristics that allow it to escape the immune system, and it had a growth advantage over other variants, such as XBB.1.16 and XBB.1.5. EG.5 had a lower risk for severe disease than some of the other variants and did not increase hospitalization rates. (World Health Organization, 2023, August 9. EG.5 initial risk evaluation. https://www.who.int/docs/default-source/coronaviruse/09082023eg.5_ire_final.pdf?sfvrsn=2aa2daee_3)

EG.5 never exceeded approximately 25% when HV.1 started to increase and reached 29% and was then JN.1 emerged around November 2023 and it successfully competed with all other variants circulating. JN.1 reached 93% of all circulating variants the week of February 3, 2024, and was essentially gone and forgotten by June 8, 2024. KP.2 initially appeared to have a future, but it is now losing ground to Omicron KP.3 – which accounted for approximately 33% of circulating variants of COVID-19 in late June of 2024 (CDC., accessed 2024, June. National and regional variant proportions. https://covid.cdc.gov/covid-data-tracker/#variant-proportions).

As shown on figure 14, Omicron variants are constantly mutating, and one variant replaces all others within the race for dominance in a relatively short period of time. It is important to remain attentive to what is happening on this front. At the time of this writing, an easy way to stay on top of emerging variants is to periodically go to the CDC variant proportion page https://covid.cdc.gov/covid-data-tracker/#variant-proportions. See figure 13. These graphs provide a quick visualization of the changing variant environment. If an emerging variant is more transmissible and extremely virulent, patient acuity and staffing needs are likely to increase dramatically.

Vaccinations

The first COVID-19 vaccine administered outside of a clinical trial on was given on December 14, 2020, and by December 24, 2020, over 1 million doses of COVID-19 vaccines were administered to U.S. healthcare workers and older adults living in long term care facilities. A total of 2.8 million received the vaccine by December 31, 2020 (CDC, 2023, March 15). Figure 15 shows how the percentage of people who were up to date on vaccines improved by 2023. However, there were still many people who did not see the need.

SARS-CoV2, and its countless variants, have not disappeared, but the threat of serious disease has been lessened due to the availability of vaccines. The first doses of COVID-19 vaccines became available in some countries, including the U.S. in December of 2020, a full year after the SARS-CoV-2 virus was discovered, but in some developing countries, the vaccine was not available until July of 2021 (World Health Organization Coronavirus (COVID-19) dashboard, vaccination data https://covid19.who.int/who-data/vaccination-data.csv). Limited supplies in each country required that the vaccine be provided to those who were at highest risk for several months, so priority was given to first responders and healthcare providers. Over 13,474,185,140 doses of COVID-19 vaccines were administered worldwide as of July 9, 2023 (WHO Coronavirus (COVID-19) dashboard (https://covid19.who.int/). As of May 10, 2023, the last date rates were reported, the U.S. has administered at least 676,728,782 vaccine doses, see figure 15 (CDC data tracker, https://covid.cdc.gov/covid-data-tracker/#rates-by-vaccine-status).

Emerging Variants Can Change Everything

Much has been learned about how fast the situation worldwide became disastrous when new and more toxic variants emerged, resulting in increased death and disability. With mitigation strategies such as vaccinations, at home testing, self-isolation, and widespread, voluntary application of public health measures, the situation has been improving. The Omicron variants are extremely contagious and capable of infecting vaccinated and unvaccinated people, but they have relatively low case fatality rates. Those who are vaccinated tend to have less severe disease and are significantly less likely to die from the infection than those who refuse vaccination.

The U.S. CDC, World Health Organization, and most countries are closely monitoring variant proportions, so as to plan for manufacture, distribution, and administration of up-to-date vaccines based on ever changing variant characteristics. With a virus that mutates as often as SARS-CoV-2 does, this is a continuous challenge. There are currently 32 circulating variants and subvariants, of Omicron being monitored, https://covid.cdc.gov/covid-data-tracker/#variant-proportions. As described above, genetic sequencing is continuous, so that new variants of concern can be identified quickly. We urge nurse leaders who also serve as Infection Preventionist (IP) professionals to pay attention to emerging variants and their characteristics. Emerging COVID-19 mutations will continue to impact acute as well as post-acute patient care needs in the future as has been the case in the past, especially if the variants become more capable of resisting the effects of vaccine-induced immunity. Waiting until the data was available retrospectively has not worked out very well. We need to proactively have real time systems place in our practice settings so we can immediately implement effective strategies to protect staff from illness, disability, and death.

Front Line Staff Nurses are an Invaluable Resource

Nurses providing direct care to sick patients are very likely to notice changes in the clinical picture that herald the onset of a new variant. Mechanisms for rapid transmission of nurse observations to those who need to know and have the ability to investigate further are very important. For example, a 24/7 internal method for bedside nurses to communicate concerns to the organization’s infection preventionist, the infection control team, or the nurse responsible for tracking infections may need to be developed. Communication between healthcare organizations and public health professionals in a timely manner is very important. Someone on every nursing team in every type of practice setting needs to be responsible for initiating an investigation and taking the appropriate actions.

Why? Just imagine what could have happened if the clinicians in that one hospital in China had not reported that small cluster of patients with an acute respiratory infection to the local public health office. No doubt that the COVID-19 pandemic would have been far more devastating than was the case.

Knowledge-based, comprehensive nursing assessment skills save lives. Understanding how to prevent infections saves lives. Timely implementation of transmission-based precautions to prevent cross-patient transmission saves lives.

When a nurse sees early signs and symptoms of infection from COVID-19 or any other type of infection, the nurse needs to be free to act immediately. No matter what the practice setting is, waiting to obtain an order from the primary care provider/ attending physician before implementing transmission-based precautions can be deadly. Registered nurses have the knowledge needed to isolate and quarantine infected patients, and themselves, if necessary, until all the facts are in, or the recommended quarantine period is over.

If a nurse puts a patient on transmission-based precautions and it turns out they do not have the suspected infection, harm is unlikely. However, the actual harm that results from failure to contain a highly transmissible infection is clear in COVID-19 cases and deaths. Policies and evidence-based procedures need to provide clear guidance for quarantine, testing protocols, and personal protective equipment necessary to protect staff from possible infection.

Regardless of the type of outbreak organism under discussion (virus, bacteria, or fungus), the astute, well-informed staff nurse will likely see patterns before anyone else does. A nurse’s eyes, ears, and nose can detect a potential disaster before it happens. Be alert for sudden increases in patients admitted to the workplace who have evidence of infection, similar symptoms, more severe symptoms than expected for a given infection, a higher rate of death, or anything else that appears to be different. Clusters of infection from a given neighborhood, referral source, or a specific unit in a facility provide important epidemiological data for an investigation. These kinds of changes may well signal the emergence of a variant that could be even more dangerous than the circulating versions of an organism. Whatever the setting, school, critical care, infection prevention, prison, home care, skilled nursing facility, assisted living, etc., use of the nursing process to assess and analyze the situation is an extremely important intervention. Reporting up the chain of command within the organization and to the Infection Prevention Practitioner or person filling this role needs to be easy and uncomplicated. Communication between public health departments and agencies/ facilities will need to continue to be collaborative forever.

COVID-19: The Public Health Emergency Has Ended; COVID-19 Will be With Us for Many Years to Come

The United Nations World Health Organization announced that the COVID-19 public health emergency ended May 5, 2023 (WHO, 2023, May 5). The U.S. Centers for Disease Control and Prevention ended the public health emergency on May 11, 2023 (CDC, 2023, September 12). Do NOT get comfortable or complacent. The “public health emergency” may be declared over, but the virus that caused the disaster is alive and well and continuously mutating. SARS-CoV2 continues to cause morbidity and mortality worldwide.

The World Health Organization COVID-19 situation report dated August 3, 2023, indicated that in the 28 days ending July 30, 2023, there were over 1 million new cases of COVID-19 and 3,100 deaths worldwide. It will continue to be very important for global citizens to be vaccinated at the recommended frequency with vaccines updated for the predominant variants indefinitely to keep this virus in check!

Summary

SARS-CoV-2 spread rapidly throughout the U.S. with the numbers increasing dramatically starting in March of 2020. Vaccines were not available until December of 2020, but distribution took time. Cases and deaths rose quickly during the 12 months from March 2020 to February 27, 2021. During this time, 537,743 people died. Testing and genetic sequencing increased over time but was still not widely available. The ancestral wild-type SARS-CoV-2 and several other variants, including Iota, Alpha, Epsilon, Gamma, Eta, and Beta were circulating during this period.

The SARS-CoV-2 virus mutated frequently and many of the mutations produced genetic changes that were beneficial to the virus. Four years of natural selection of beneficial mutations sequentially generated new variants that were better able to survive and thrive by developing resistance to vaccines and monoclonal antibodies.

It is an inexcusable fact that so many nurses and healthcare clinicians lost their lives or their quality of life to this virus because pandemic planners did not anticipate what actually happened. It is absolutely imperative that failure to protect the front line staff will never, ever happen again.

The ancestral wild type and subsequent variants of concern that emerged in any one country expanded worldwide very quickly. Case fatality rates were highest during the first pre-vaccine period and as healthcare systems and individual clinicians worldwide adjusted to the expanding pandemic. Over time each new variant transmitted person to person more easily than the previous variant of concern and asymptomatic transmission remains a concern.

Medical and scientific mitigation strategies include:

Monitoring emerging variants worldwide.
Upgrading the vaccines for emerging variants.
Understanding of viral characteristics and genetics.
Recognition that we are one worldwide human population.

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The Impact of COVID-19 on Nurses

Dangerous Mutations: the Continuous Emergence of SARS-CoV-2 Variants

Mary C. Vrtis, Ph.D., MSN, RN, OCN, NEA-BC, FCN

Viral Reproduction

SARS-CoV-2 Variants and the Impact on Nurses and the U.S. Healthcare System: Looking Back so we can Move Forward

World-wide Collaboration

Classification of Variants and Subvariants

Basic Concepts

Reproduction Number and Transmission

Case Fatality Rates versus Mortality Rates

Estimates of Case Fatality Rates for Nine Countries While Variants of Concern were Dominant

Outcomes for SARS-CoV-2 Variants of Concern in the U.S.

Methods

SARS-CoV-2 Variants of Concern 2020 to 2021

The Ancestral Wild-type SARS-CoV-2 Variant

Case Fatality Rates/ Mortality Rates for the Ancestral Variant

Infections and Deaths of Health Care Personnel January to October 31, 2020

Case Fatality Rates/ Mortality Rates for the Ancestral Variant

Infections and Deaths of Health Care Personnel January to October 31, 2020

New Mutations, New Variants

The Iota Variant B.1.526 and other variants, circulating November/ December 2020 to June 2021

The U.S. from October 31, 2020, to February 27, 2021

Healthcare Worker Deaths October 31, 2020, to February 27, 2021

The Alpha B.1.1.7 SARS-CoV-2 Variant, February 27 to July 3, 2021

Nurse and Other Healthcare Worker Deaths during Alpha

Mitigation Strategies February 2021 to January 2022

The Delta B.1.617.2 Variant, June 5, 2021, to January 1, 2022

Nurse and Other Healthcare Worker Deaths During Delta

Omicron Variants, Multiple Variants of Concern, December 2021

Omicron B.1.1.527 and BA.1, December 28, 2021, to April 2, 2022

Reproduction Number and Transmission

Omicron BA.5 June 4, 2022, to December 31, 2022

Mitigation Strategies: Vaccinations and Omicron

Omicron XBB.1.5, December 24, 2022, to August 5, 2023

Omicron Mutations

Vaccinations

Emerging Variants Can Change Everything

Front Line Staff Nurses are an Invaluable Resource

COVID-19: The Public Health Emergency Has Ended; COVID-19 Will be With Us for Many Years to Come

Summary

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