Epidemiology and Clinical Presentation of COVID-19 in Older Adults

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains asymptomatic in 33% to 90% of older adults depending on their immune status from prior infection, vaccination, and circulating strain. Older adults symptomatic with SARS-CoV-2 often both present atypically, such as with a blunted fever response, and develop more severe disease. Early and late reports showed that older adults have increased severity of coronavirus disease 2019 (COVID-19) with higher case fatality rates and higher intensive care needs compared with younger adults. Infection and vaccine-induced antibody response and long-term effects of COVID-19 also differ in older adults.

Key points

• •The range of presentation with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, from asymptomatic infection to critical illness, changes with age. Older adults will more commonly have an atypical clinical presentation, nonspecific symptoms, and blunted fever response to SARS-CoV-2 infection.
• •Most coronavirus disease 2019 (COVID-19) hospitalization and mortality occur in older adults, with severity compounded by underlying illnesses.
• •Although vaccination significantly reduces the risk of severe COVID-19 and mortality in older adults, it may take 3 or more exposures for the spike protein as antigen to develop an antibody repertoire that can neutralize a broader range of variants.

Abbreviations.

SARS-CoV-2	Severe Acute Respiratory Syndrome Coronavirus 2
ICU	Intensive Care Unit
CDC	Centers for Disease Control and Prevention
WHO	World Health Organization
CLIA	Clinical Laboratory Improvement Amendments
PPE	Personal Protective Equipment
PASC	Post-Acute Sequelae of COVID
COPD	Chronic Obstructive Pulmonary Disease

Introduction

History/Background

Coronaviruses, enveloped positive-stranded RNA viruses, infect both people and animals. In December 2019, the World Health Organization (WHO) identified a new coronavirus, reported first in Wuhan, China, as a cause of pneumonia in several countries including Thailand and Japan.^{1 , 2} The International Committee on Virus Taxonomy named the new virus “severe acute respiratory syndrome coronavirus-2” (SARS-CoV-2).³ WHO designated the disease it caused “COVID-19” (coronavirus disease 2019).⁴ On January 21, 2020, the Centers for Disease Control and Prevention (CDC) reported the first confirmed travel-related case in the United States (US), in the state of Washington.⁵ On January 31, 2020, WHO issued a Global Health Emergency. This was followed by a US public emergency declaration on February 3, 2020.²

The similarity of SARS-CoV-2 coronavirus’ RNA sequence to that of coronaviruses found in bats led scientists to consider bats as the primary reservoir of SARS-like coronaviruses⁶ and the original source of the 2019 SARS-CoV-2 Wuhan strain.⁷ SARS-CoV-2 binds to the human cell angiotensin-converting enzyme 2 host receptor as a primary mechanism to gain entrance.⁸ SARS-CoV-2 continues to evolve over time, acquiring mutations that improve efficiency in infection and evasion of immunity in people. CDC’s data projection tool, Nowcast, identifies and tracks emerging variants and predicts more recent proportions of circulating variants to inform appropriate public health action plans (Fig. 1 ).⁹ The Omicron variant’s added capacity to evade humoral immunity gives it a replication advantage over prior variants that can improve infectiousness and fuel its spread.10, 11, 12

Fig. 1.

Regional proportions from specimens collected week of October 29, 2022 in CDC page with a model that estimates more recent proportions of circulating variants. (From CDC Data Tracker: Monitoring Variant Proportions.)

^aEnumerated lineages are US VOC and lineages circlulating above 1% nationally in at least one week period. ”other” represents the aggregation of lineages which are circulating <1% nationally during all weeks displayed.

^bBA 1,BA 3 and their sublineages (except BA 1.1 and its sublineages) are aggregated with B.1.1.529. Except BA.2.12.1, BA.2.75.BA.2.75.2 and their sublineages, BA.2 sublineages are aggregated with BA.2.Except BA.4.6,sublineages of BA.4 are aggregated to BA.4.Except BF.7,BA.5.2.6,BQ.1 and BQ.1.1,sublineages of BA.5 are ggregated to BA.5.For all the lineages listed in the above table, their sublineages are aggregated to the listed parental lineages respectively. Prevously, BA.5.2.6 were aggregated with BA.5. Lineages BA.2.75.2, BA.4.6,BF.5.2.6 and BQ.1.1 contain the spike substitution R346T.

Available from: https://covid.cdc.gov/covid-data-tracker/?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fcases-updates%2Fvariant-proportions.html#circulatingVariants, Accessed on October 29, 2022).

Conservatively, in the US, SARS-CoV-2 has killed more than 1 million of the more than 90 million people infected by September, 2022.¹³ Older adults suffered the greatest morbidity and mortality early in the COVID-19 pandemic.¹⁴ Although adults aged older than 65 years represent only about 16% of the US population, they account for 31% of reported cases, 45% of hospitalizations, 53% of intensive care unit (ICU) admissions, and 80% of COVID-19–associated deaths.¹⁵ CDC reports a considerably higher incidence of COVID-19 deaths per 100,000 population in those aged older than 65 years compared with younger individuals (Fig. 2 ).¹⁶ In the subset living in nursing homes (NHs), SARS-CoV-2 infected more than 1 million, 13% of whom subsequently died by August, 2022.¹⁷ This article will discuss epidemiology and different clinical presentations of COVID-19 in older adults.

Fig. 2.

COVID-19 weekly deaths per 100,000 population by age group, United States between March 01, 2020, and October 22, 2022. (Adapted from cdc data tracker: Monitoring variant proportions.)

US: Includes data up to the week ending on October 22, 2022. Percentage of cases repoting age by date-99.91%.

US territories are included in case and death counts but not in opulation counts. Potential six-week delay in case reporting to CDC denoted by gray bars. Weekly data with five or less cases have been suppressed.

^aCase Earliest Date is the earliest of the clinical date (related to illness or specimen collection and chosen by a defined hierarchy) and the Data Received by CDC. The date for the current week extends through Saturday.

^bCase rates for south dakota during the week ending Aug 07,2021,and Texas during the week ending Jun 25,2022, are reflective of a data reporting artifafct.Surveillance data are providional, and as additional clinical data becomes available,the case rates over time are subject to change.

Available from: https://covid.cdc.gov/covid-data-tracker/?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fcases-updates%2Fvariant-proportions.html#circulatingVariants, Accessed October 22, 2022). Source: CDC COVID-19 Case line-level data, 2019 US census, HHS protect; visualization: Data analytics & visualization task force and CDC DEO situational awareness public health science team.

Definitions

Centers for Disease Control and Prevention and World Health Organization definitions of coronavirus disease 2019 stages

Acute coronavirus disease 2019

(Table 1 and below)^{18 , 19} Symptomatic SARS-CoV-2 infection with symptoms that last up to 4 weeks following illness onset.

Fig. 3.

Organ and systems which are affected by SARS-CoV-2 in the long term with symptoms and signs of COVID-19.^121,127,136, 137, 138, 139, 140, 141, 142, 143 (Figure was adapted from Designed by Freepik from www.freepik.com).

Table 1.

Definitions

Term	Definition
SARS-CoV-2	Severe acute respiratory syndrome coronavirus-2SARS-CoV-2 named by the International Committee on Virus Taxonomy is the virus that causes COVID-193
COVID-19	Coronavirus disease 2019 is an infectious disease, designated by WHO as COVID-19, which is caused by SARS-CoV-2, a coronavirus discovered in 20194
Asymptomatic infection	Infection while having no symptoms. Includes both presymptomatic individuals and individuals who will never develop symptoms
Presymptomatic infection	Infection before inevitable development of symptoms
Transmission144	Presymptomatic	An index has no symptoms during the exposure period of their closed contacts but later develops symptoms
	Asymptomatic	An index case never develops symptoms or signs of infection
	Postsymptomatic	An index case has no symptoms during the exposure period of their close contacts, but previously had symptoms
Criteria of suspected cases of SARS-CoV-2 infection101,145 When suspicious: new onset fever and/or respiratory symptoms (eg, sore throat, cough, nasal congestion, rhinorrhea, shortness of breath). Other common nonrespiratory symptoms: new changes in taste or smell, diarrhea, chills, anorexia, headache, and muscle pain	Clinical criteria Epidemiologic criteria	Acute onset of fever and cough OR Acute onset of any 3 or more of the following signs or symptoms: fever, cough, general weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, and anorexia Contact of a probable or confirmed case or linked to a COVID-19 cluster
	Illness	Severe acute respiratory illness
	Testing	No clinical signs or symptoms, nor meeting epidemiologic criteria, with a positive professional use or self-test SARS-CoV-2 antigen-RDT
Clinical criteria in the absence of a more likely diagnosis (CDC)146 (Organ systems and associated symptoms and signs by all ages and older adults are summarized in Fig. 3. As discussed later in this article, older adults may present differently.)	Acute onset or worsening of at least 2 symptoms or signs	Fever (measured or subjective), chills, rigors, myalgia, headache, sore throat, nausea or vomiting, diarrhea, fatigue, congestion, and runny nose
	OR
	Acute onset or worsening of at least one symptoms or sign	Cough; shortness of breath; difficulty breathing; olfactory disorder; taste disorder; confusion or change in mental status; persistent pain or pressure in the chest; pale, gray, or blue-colored skin, lips, or nail beds, depending on skin tone; inability to wake or stay awake
	OR
	Severe respiratory illness with at least	Clinical or radiographic evidence of pneumonia, or acute respiratory distress syndrome
Laboratory criteria (CDC)146,147 Laboratory evidence using methods approved or authorized by the US Food and Drug Administration (FDA) or designated authority	Confirmatory laboratory evidence	Detection of SARS-CoV-2 ribonucleic acid (RNA) in a postmortem respiratory swab or clinical specimen using a diagnostic molecular amplification test performed by a Clinical Laboratory Improvement Amendments (CLIA)-certified provider OR Detection of SARS-CoV-2 by genomic sequencing
	Presumptive laboratory evidence	Detection of SARS-CoV-2–specific antigen in a postmortem obtained respiratory swab or clinical specimen using a diagnostic test performed by a CLIA-certified provider
	Supportive laboratory evidence	Detection of antibody in serum, plasma, or whole blood specific to natural infection with SARS-CoV-2 (antibody to nucleocapsid protein) OR
		Detection of SARS-CoV-2–specific antigen by immunocytochemistry in an autopsy specimen OR
		Detection of SARS-CoV-2 RNA or specific antigen using a test performed without CLIA oversight
Epidemiologic linkage146	One or both of the following exposures in the prior 14 d (CDC)	Close contacta with a confirmed or probable case of COVID-19 disease OR
		Member of an exposed risk cohort as defined by public health authorities during an outbreak or high transmission
	Probable case (WHO)145	An individual who meets clinical criteria of suspected case and is a contact of a probable or confirmed case, or is linked to a COVID-19 cluster
	Confirmed case (WHO)145	An individual with a positive nucleic acid amplification test (NAAT), regardless of clinical criteria or epidemiologic criteria OR A person meeting clinical criteria and/or epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 antigen-RDT
	Symptomatic case (WHO)145	An individual who is infected with SARS-CoV-2 and has symptoms
Case classification (CDC)146	Suspect	Meets supportive laboratory evidence with no prior history of being a confirmed or probable case
	Probable	Meets clinical criteria and epidemiologic linkage with no confirmatory or presumptive laboratory evidence for SARS-CoV-2 OR
		Meets presumptive laboratory evidence OR
		Meets vital records criteria with no confirmatory laboratory evidence for SARS-CoV-2
	Confirmed	Meets confirmatory laboratory evidence
Testing	Positive test	A positive test indicates likelihood of present or past SARS-CoV-2 infection whether symptomatic or recovered
	Types of tests148, 149, 150, 151	Direct detection of SARS-CoV-2 RNA by NAATs or reverse-transcription polymerase chain reaction from the upper respiratory tract)
		Serologic tests detecting antibodies to the virus in the blood. Usually used to detect previous infection or response to vaccine
		Antigen tests detecting SARS-CoV-2 antigen with nasal swab or saliva sample
		Breathalyzer that uses gas chromatography-mass spectrometry to detect exhaled volatile organic compounds specific to SARS-CoV-2 infection
		Interferon-gamma release assay
Definition of COVID stages (CDC and WHO)18,19	Acute COVID-19	Symptoms of COVID-19, up to 4 wk following the onset of illness
	Long COVID or Post-COVID Conditions (PCC)	(See text for details) (Also called long-haul COVID, postacute COVID-19, postacute sequelae of SARS CoV-2 infection (PASC), long-term effects of COVID, chronic COVID)23

^aClose contact is generally defined as being within 6 feet for a cumulative period of at least 15 min during a 24-h period. However, this depends on several exposure and setting variables (eg, in the setting of an aerosol-generating procedure in a health-care setting without proper PPE, it may be “any period of time.”

Long COVID or postcoronavirus disease 2019 conditions

Some individuals infected with SARS-CoV-2 have persistent or new symptoms that last 2 to 3 months beyond their initial infection.20, 21, 22 More formally known as postacute sequelae of COVID-19 (PASC), it is also called long COVID, long-haul COVID, postacute COVID-19, long-term effects of COVID-19, and chronic COVID-19.²³

Epidemiology

Risk for Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Older Adults

Immunosenescence and immunity in older adults with coronavirus disease 2019

Immunosenescence refers to a multifactorial process with aging that results in immune dysfunction.24, 25, 26 Examples of consequences of immune senescence include alterations in inflammatory response, infection severity and recovery, and reduced vaccine response,²⁷ such as occurs with influenza and other causes of pneumonia.^{20 , 28 , 29} Moreover, immune memory from prior infections and vaccination wanes over time, with a consequent increasing susceptibility to reinfection. For example, prior betacoronavirus infection that causes the common cold could offer some protection against SARS-CoV-2 by providing naturally acquired cross-protective immunity. Immunosenescence contributes to reduced initial vaccine response with age and also the more rapid decay in antibody levels following vaccination.^{21 , 22 , 30} Poor or decreased capability to mount a cytokine response in the case of severe infection likely contributes to older adults’ proneness to atypical presentations of severe COVID-19 infection, and lesser or delayed symptoms and blunted fever response.^{31 , 32} Both cellular senescence, which leads to permanent cell growth arrest with aging, and decreased antibody response in older adults that occurs within immunosenescence, seem to play a significant role in SARS-CoV-2’s impact on the host–pathogen interaction.32, 33, 34 Natural killer (NK) cells, participants in innate immunity, serve as first-line defenders against viral infections in the human body.^{35 , 36} The phenotype and function of NK cells change and decay during aging by way of transformed surface molecules, which reduces their capacity to bind to virally infected cells.³⁵ SARS-CoV-2 also exhausts NK cell phenotypes. This may potentiate the severity of disease by allowing the virus to escape from the NK cells’ first-line cellular antiviral reactivity.37, 38, 39 Therefore, both aging and SARS-CoV-2 impair functioning of the antiviral cytotoxic NK cells in a way that can increase the severity of COVID-19 in older adults.³²

Aging also impairs T cell receptor (TCR) diversity, an essential mechanism that facilitates the immune system’s ability to detect foreign antigens. TCR diversity, driven by thymic stimulation of T cells in the first decades of life, persists with the homeostatic proliferation of naïve T cells.⁴⁰

Progressive regression in thymic size and senescence of certain T cell clones results in a declining output of new naïve T cells and reduces TCR diversity.⁴¹ COVID-19 patients have significantly less TCR diversity compared with healthy controls, a feature compounding the reduced diversity resulting from aging. Thus, the COVID-19 pathophysiology seen in older adults seems to relate to the impairment in TCR diversity.^{42 , 43}

Aging lymphocytes have lower capacity of proliferation in defense against viral infections, and higher proportions of B and T lymphocytes become apoptotic with aging.⁴⁴ Adults aged 65 years or older have impaired coordination of SARS-CoV-2 antigen-specific immune responses, and aging and poor COVID-19 outcomes are associated with paucity of naïve T cells.⁴⁵

Vaccination in older adults with coronavirus disease 2019

Four manufacturers produce COVID-19 vaccines for the US. For the initial vaccination series, available vaccines include 2 mRNA vaccines, BNT162b2 (Pfizer-BioNTech, Michigan, USA) and mRNA-1273 (Moderna, Massachusetts, USA), an adjuvant recombinant protein vaccine, NVX-CoV2373 (Novavax, Maryland, USA), and an adenoviral vector vaccine, Ad26.COV2 (Janssen/Johnson & Johnson, Indiana, USA).46, 47, 48, 49, 50 The mRNA vaccines also have been used to boost the initial series until September, 2022, when the booster doses were replaced by bivalent mRNA vaccines that include code for both the ancestral strain used in the original series and the then circulating Omicron BA.4 and BA.5 strains. For individuals unvaccinated against COVID-19, infection provides only fleeting or partial protection from recurrent infection and disease.⁵¹ Older individuals vaccinated with BNT162b2 mRNA vaccine without prior SARS-CoV-2 infection (infection naïve) have significantly lower antibody levels than infection naïve younger adults. Unsurprisingly, the negative correlation between age and antibody levels after vaccination with SARS-CoV-2 vaccination also occurs with other vaccines.^{22 , 30} This lower antibody response in older adults likely signifies less absolute and less durable protection from infection, with shorter intervals of protective titers and increased likelihood of breakthrough infection.³⁰ Antibody decline occurs from 2 weeks to 6 months after administration of the initial pair of BNT162b2 mRNA vaccine in NH residents. NH residents experienced a more than 81% drop of antispike, receptor-binding domain (RBD), and neutralizing antibody level regardless of prior COVID-19 infection status during these 6 months (Fig. 4 and Fig. 5 ).^{21 , 30} Although antibody levels may wane, booster doses seem to improve clinical protection in NH residents.⁵² Future boosting strategies, particularly for older adults, need to address the relative drop in antibody levels and other measures of immunity following vaccination to their relevance for clinical protection, especially in the context of their relevance to the evolving virus.

Fig. 4.

Humoral immune assessment of BNT162b2 messenger RNA (mRNA) vaccine vaccination in NH residents. Postvaccination anti-spike, anti-receptor-binding domain (RBD) and serum neutralization titers are shown.Control: vaccinated younger healthcare workers or unvaccinated SARS-CoV-2-convalescent individuals. The dotted lines: median preimmunization value in the SARS-CoV-2-naive subjects. Abbreviations: AU, antibody unit; NH, nursing home; pNT50, pseudovirus neutralization titer.³⁰

Fig. 5.

Antibody levels two weeks and six months after BNT162b2 mRNA vaccination in healthcare workers (HCWs) and NH residents with and without SARS-CoV-2 infection prior to vaccination. Abbreviations: AU, arbitrary unit; BAU, binding arbitrary unit; NH, nursing home; pNT50, pseudovirus neutralization; RBD, receptor-binding domain.²¹

(Designed by Freepik).

Aging (affecting clearing of virus)

Mucociliary clearance, a first line of defense against lower respiratory tract infections, functions by sweeping mucus, particles, and microorganisms up and out of the lungs. Both aging and SARS-CoV-2 impair mucociliary clearance and affect older adults’ ability to clear the virus.53, 54, 55 This reduced clearance of microorganisms can also increase the risk of coinfection with age. In Hong Kong, the risk of hospitalization with dual infection increases with age, where less than 35% of hospitalizations with dual infection occur in the group of individuals aged younger than 65 years, and 65% occurs in older adults who represent only 19% of the overall population.^{56 , 57} SARS-CoV-2 infection introduces the possibility of dual infections and thereby worse outcomes.⁵⁸ As older adults experience worse outcomes overall with SARS-CoV-2 infection, the association of coinfection with COVID-19 severity may have an amplified risk in older adults.

Hearing and visual changes with age

Sensory changes with age can indirectly affect SARS-CoV-2 infection risk. For example, presbycusis may lead individuals to shout or lower their masks to facilitate communication for those with the most hearing impairment, increasing the risk for more efficient virus aerosolization and thereby transmission.59, 60, 61 Potential and frequent SARS-CoV-2 transmission can also occur via ocular droplet deposition, a feature that remains considerably underestimated as a mode of transmission.⁶² However, because visual impairment also occurs more commonly with advanced age, the consequent increased use of eyeglasses⁶³ could offer a modicum of protection against SARS-CoV-2 inoculation.^{64 , 65}

Multiple Morbidities (Affecting Immune Competence, Clearance of Virus)

COVID-19 severity, defined as hospitalization due to COVID-19, intensive care unit admission, need for intubation/mechanical ventilation, and COVID-19–related mortality, depends in part, on underlying conditions and morbidities. Severe COVID-19 occurs more often with the following risk factors that we also see more commonly in older adults66, 67, 68, 69, 70:

• •Cancer
• •Cerebrovascular diseases
• •Chronic kidney disease
• •Chronic lung diseases (including COPD, interstitial lung diseases, bronchiectasis, pulmonary embolism, and pulmonary hypertension)
• •Chronic liver diseases (including cirrhosis, alcoholic hepatitis, alcoholic liver disease, and nonalcoholic fatty liver disease)
• •Type-2 diabetes mellitus
• •Disabilities
• •Congestive heart failure, coronary artery disease, and other cardiomyopathies
• •Dementia
• •Obesity (body mass index [BMI] ≥30 kg/m²)
• •Physical inactivity
• •Smoking history
• •Use of immunosuppressive medications including steroids

Underlying morbidities in older adults have added significance, given the synergies of aging and morbidities on COVID-19 severity. The February 28 and March 18, 2020, long-term care facility SARS-CoV-2 outbreaks in Washington State offer an example of this. The hospitalization rate of 55% and fatality rate of 34% occurred in a group with a median age of 83 years (n = 101) and with 94% having an underlying chronic condition.⁷¹ State and territorial jurisdiction cases reported through July 21, 2022, show a 330-times higher rate of death in individuals aged older than 85 years, compared with individuals aged 18 to 29 years.⁶⁸ Even vaccination does not entirely overcome the more severe age-associated outcomes in late life. Risk for a severe COVID-19 outcome after primary vaccination was higher in individuals aged older than 65 years and in individuals with at least one underlying condition.⁷²

Exposure and Transmissibility

Older adults in long-term care settings endure common and uncommon respiratory disease outbreaks.73, 74, 75 SARS-CoV-2 spreads by direct contact and respiratory droplets or secretions. Transmission occurs through fomites from contaminated hands or by contact with contaminated surfaces before self-inoculation, such as through touching the eyes, nose, or mouth.⁷⁶ Frequent and close contact between health-care staff and nursing residents with functional impairments increase the risk of COVID-19 transmission.77, 78, 79 Some patients with cognitive impairment cannot maintain social distance or use personal protective devices, affecting their risk for getting infected or infecting others once infected, thus increasing the transmission risk in the long-term care setting. Cognitive impairment and delirium can complicate proper use of personal protective equipment (PPE), and thereby could result in higher rates of transmission.⁸⁰ The long-term care workforce has many challenges that can leave it unprepared to manage infectious outbreaks, from adequate PPE resources to high turnover that affects the ability to keep staff trained, increased use of per diem staff, and the risk of unexpected vectors of infection.81, 82, 83, 84, 85, 86, 87 Frail older adults with functional impairment, particularly those in long-term care settings, are at significantly higher risk of SARS-CoV-2 infection, such as when they receive close, hands-on care from asymptomatic health-care workers who could unwittingly inoculate them.^{77 , 88}

Data from 44,672 confirmed cases of COVID-19 during the first COVID-19 transmission surge in China showed that an initial overall case-fatality rate of 2.3% increased to 8.0% among older adults aged 70 to 79 years, and 14.8% for those aged 80 years and older.⁸⁹ Older individuals not only experience higher fatality rates but also seem more likely to spread infection.⁹⁰ The higher old-age dependency ratio (the number of individuals aged older than 64 years relative to the number of working-age individuals [15–64 year old]), suggests a higher level of transmission among the older population. This conceivably could influence both the severity and longevity of COVID-19 symptoms in older adults. Those with sustained increased risk of close contact transmission (higher inoculum) may have asymmetrically greater risk for infection and more severe outcomes. This risk could occur especially in situations where individuals live in close quarters or share bedrooms, bathrooms, and dining areas.⁹¹

Reinfection and Breakthrough Infection in Older Adults

Reinfection with SARS-CoV-2 that causes COVID-19 occurs when a SARS-CoV-2–infected individual recovers, and later becomes reinfected.⁹² Breakthrough infection, or vaccine breakthrough infection, occurs after an individual is vaccinated against SARS-CoV-2 and nevertheless becomes infected and symptomatic with SARS-CoV-2.⁹³ Before the Omicron variant wave of infections, risk for reinfection was less. Apparently, the level of added protection reduced the risk of reinfection for pre-Omicron variants by around 80%, lasting 6 to 9 months.^{94 , 95} However, the reduced reinfection risk did not pertain to infection with Omicron, a feature attributed to Omicron’s immune evasion characteristics.10, 11, 12

Clinical Characteristics of Coronavirus Disease 2019 in Older Adults

Multimorbidity, frailty, and immunosenescence combine to increase the vulnerability to COVID-19 with advanced age.⁹⁶ SARS-CoV-2 infection often remains asymptomatic, a likelihood that changes with underlying immunity from infection, such as acquired from infection with its betacoronavirus cousins and vaccination.97, 98, 99, 100

When SARS-CoV-2 infection produces symptoms, that is, COVID-19, they may include any combination of fever, cough, fatigue, shortness of breath, myalgia, anorexia, sore throat, headache, chills, and loss of taste and smell sensation¹⁰¹ (Fig. 5). During the early surge of COVID-19, shortness of breath occurred more frequently among adults aged older than 60 years (12%), compared with younger adults (3%).¹⁰² A research collaboration of 86 emergency departments (EDs) in 27 US states used the RECOVER Network registry for a multicenter cohort study. Older adults in this study had more atypical presentations: neurologic symptoms, especially confusion and altered mental status, and more malaise and dyspnea compared with younger individuals.⁹⁶ Additionally, clinicians may miss shortness of breath in older adults when it presents as functional decline with impaired mobility or frequent falls, rather than a more obvious respiratory symptom that occurs with SARS-CoV-2 infection.¹⁰³

Changes with advanced age can blunt fever response, dyspnea, and cough with COVID-19.^{96 , 104} A study of Veterans living in 134 community living centers (CLCs) operated by the Veterans Administration evaluated temperatures through the course of SARS-CoV-2 infection. One-fourth of them did not have meaningful temperature elevations over baseline. Moreover, the temperature for 75% of these NH residents with SARS-CoV-2 infection never exceeded 38°C at any time during the 2 weeks before and after their maximum temperature (Fig. 6 ).¹⁰⁴ Thus, in older adults, particularly those in NH settings where SARS-CoV-2 may be circulating, using a lower temperature threshold to 37.2°C will alert staff to consider early testing and will improve sensitivity for screening by temperature for SARS-CoV-2 infection.¹⁰⁵ A second elevated reading improves specificity for infection. CDC suggests that isolation and further evaluation for COVID-19 should be triggered by more than 2 temperatures greater than 37.2°C, especially with the presence of atypical symptoms of worsening malaise, new dizziness, or diarrhea¹⁰⁶ but temperature elevation alone should be enough to trigger isolation and further evaluation for COVID-19 if there is an index of suspicion from known contact.

Fig. 6.

Temperature trends according to maximum temperature. This compares daily temperatures relative to the maximum temperature. The shaded area denotes the 95% confidence intervals, and T0 refers the testing date for SARS-CoV-2.

(Adapted from Rudolph, J.L., et al., Temperature in Nursing Home Residents Systematically Tested for SARS-CoV-2. J Am Med Dir Assoc, 2020. 21(7): p. 895–899.e1; with permission).

As noted above, older adults can remain asymptomatic with SARS-CoV-2 infection or develop symptoms more slowly. At a long-term care skilled facility in King County, Washington, 56% of residents with SARS-CoV-2 infection had no symptoms at the time of testing, whereas 77% were presymptomatic at time of testing. Screening by fever and symptom-based criteria would have missed half of these cases.¹⁰⁷

Coronavirus disease 2019 complications

COVID-19 can lead to many complications. In a retrospective cohort study, individuals aged 65 years and older who were continuously enrolled in a Medicare Advantage plan with prescription drug coverage from January, 2019, to the date of SARS-CoV-2 diagnosis had higher the risk of complications that include respiratory failure, fatigue, hypertension, memory problems, kidney injury, mental health problems, hypercoagulopathy, and cardiac rhythm problems, compared with matched comparison groups without COVID-19.¹⁰⁸ A nationwide study from Sweden reported higher incidence of deep vein thrombosis and pulmonary embolism in older adults with highest rate of pulmonary embolism in the age group 50 to 70 years. The increase in incidence rate ratio with age specific to deep vein thrombosis during 1 to 90 days after SARS-CoV-2 infection was greatest for the first compared with the second and third pandemic waves in Sweden.¹⁰⁹

Severity of coronavirus disease 2019

National Institute of Health (NIH) guidelines define individuals with severe COVID-19 as having “.SpO2 <94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (Pao ₂/Fio ₂) <300 mm Hg, a respiratory rate >30 breaths/min, or lung infiltrates >50%.” NIH defines individuals with critical COVID-19 as having “.respiratory failure, septic shock, and/or multiple organ dysfunction.” Underlying morbidity modulates the risk for severe COVID-19 in older adults such as cardiopulmonary disease, diabetes, cancer, obesity, or chronic kidney disease.⁶⁷ Although COVID-19 vaccination reduces the risk of severe illness, vaccine immunogenicity and efficacy to BNT162b2 mRNA declines with advanced age leaving some people vulnerable to a breakthrough infection that can result in severe illness.^{21 , 110}

Coronavirus disease 2019 in older adults: risk stratification, risk factors, and prevention

Initial Chinese, United Kingdom (UK), and US COVID-19 cohorts show that among all the risk factors, age dominates as the most important determinant of severity.^{15 , 89 , 111} Individuals aged 70 to 79 years and older than 80 years had hospitalization and case fatality rates at least 4-fold that among the entire Chinese cohort.⁸⁹ Among adults aged older than 80 years in a UK cohort, the risk of mortality was 20-fold that among adults aged 50 to 59 years.¹¹¹ In the US cohort, individuals aged older than 65 years accounted for 80% of total deaths.¹⁵ In older adults, comorbidity burden also contributes to the risk for severe COVID-19. Individuals with both advanced age and a high comorbidity burden commonly experience severe COVID-19. Individuals with one reported underlying condition have a 6-fold higher hospitalization rate and 12-fold higher mortality rate than those with no underlying conditions (45.4% vs 7.6% and 19.5% vs 1.6%, respectively).¹¹²

Primary prevention offers the best approach to counter introduction and spread of COVID-19 and has proven especially effective in the long-term care setting. In NHs, implementation of basic and fundamental prevention methods begins with setting policy, education, and adherence to and monitoring of best practices. Best practices address vaccination, surveillance, and other policies. Staff should seek to maximize and track resident and staff vaccination rates while keeping vaccines up-to-date. Routine symptom screening can directly trigger testing for SARS-CoV-2 or other infections. When a test result identifies a SARS-CoV-2 infection, it should trigger contact tracing if not broader testing of other residents on the ward or in the facility. Staff also should model and promote appropriate use of masks and restrict visitors according to prevailing CDC or local health department guidelines. As a sole strategy to determine who to isolate or mask, symptom-screening alone will fail to prevent the transmission of SARS-CoV-2 in NHs because symptom screening alone will fail to detect 40% or more of SARS-CoV-2 infections.^{113 , 114} These findings remind us that more than 50% of NH residents infected with SARS-CoV-2 were asymptomatic or presymptomatic at time of testing. Moreover, given that some have nondiagnostic tests followed by a diagnostic test day,¹¹⁵ which means neither symptoms nor testing fully discriminate those infected with SARS-CoV-2 infection from those who are not at a given moment. Considered together, these point to a very important contributory factor of the transmission of SARS-CoV-2 in this population, that is, the failure to recognize the limitations to our approach to surveillance, and consequent premature relaxation of policies that limit transmission.

Successful masking strategies in NH residents and health-care professionals can critically limit the opportunity for SARS-CoV-2 transmission. N-95 respirators offer better protection for care activities with NH residents than surgical masks. However, masking, along with distancing and hand washing, reducing time in shared air spaces (reduced ventilation), high efficiency air filtration, and other strategies collectively can reduce the likelihood of transmission.¹¹⁴ However, NH residents can be infected with low inoculum viral load and may stay asymptomatic despite of all those precautions.⁹¹

Atypical clinical presentation of coronavirus disease 2019 in older adults

Older adults with COVID-19 present to the ED with more atypical symptoms. Health-care providers should consider COVID-19 in differential diagnosis in the ED and/or NH settings when faced with older adults with nonspecific symptoms such as falls, confusion, delirium, and worsening of functional impairment, especially when SARS-CoV-2 is known to be circulating in the community.^{96 , 103 , 116} Gastrointestinal symptoms are less commonly reported in older adults compared with younger adults, and older adults more commonly present to the ED with neurologic symptoms including altered mental status and confusion. Older adults presenting to the ED more often have abnormal laboratory findings, including elevated troponin and leukocyte levels, compared with younger individuals presenting to the ED.⁹⁶ Radiological differences are also noted between younger and older individuals with COVID-19; older adults with COVID-19 also more often have extensive lung involvement, and subpleural line and pleural thickening,¹¹⁷ with one study showing that in older adults with COVID-19, pleural effusion can be used as a distinctive prognostic marker.¹¹⁸ In NHs and other settings with older adults, awareness of these atypical findings and clinical presentations can help identify additional indications for early screening and other preventive measurements to support infection control efforts and improve patient outcomes.¹¹⁶

Long COVID or postacute sequelae of coronavirus disease 2019 older adults

The risk for Long COVID, formally called PASC, in older adults differs depending on the data sources. Reportedly, 1 in 4 older adults experience at least one potential PASC condition compared with 1 in 5 younger adults.¹¹⁹ However, new data from the US Household Pulse Survey performed by the National Center for Health Statistics indicate older adults less often reported PASC conditions than younger adults, with approximately 3 times as many adults aged 50 to 59 years having Long COVID relative to individuals aged older than 80 years.¹²⁰ In data on Veterans living in CLCs where daily symptom surveillance and trigger and sweep testing protocols are in place to optimally detect COVID, data suggests that around 1 in 5 of these older Veterans has one or more new PASC symptoms more than 2 months from their initial diagnosis.¹²¹ This rate exceeds that of the observational study and underlines the limitations in surveying older adults for PASC, where a variety of reasons can lead to their nonparticipation and undercounting, from issues that relate to privacy, illness, ability to respond through technology or telephone.¹²⁰ As such, the relative risk for PASC with age remains uncertain. A recent study suggests that nearly 55% of patients have at least 1 post-COVID sequelae 2 years after SARS-CoV-2 infection.¹²² Another study suggests that risk for this outcome increases with each additional infection. Those with Long COVID symptoms at 2 years scored lower on quality-of-life metrics had worse exercise capacity, more mental health abnormalities, and increased health-care use after discharge, compared with survivors without Long COVID symptoms.122, 123, 124, 125

A universally acceptable definition will need to wait until we know more about the symptoms, cause, and risk factors of PASC.¹²⁶ Some of the physical and mental symptoms of PASC include fatigue, muscle weakness, shortness of breath, chest pain, cough, anxiety, depression, posttraumatic stress disorder, poor memory, sleep disturbances, and concentration deficiency.^{127 , 128} Depression, insomnia, dyspnea, myalgias, anxiety, cognitive impairment, and fatigue are the most common PASC symptoms, in descending order among older Veterans living in CLCs.¹²¹ Risk factors for developing PASC include increased age, number of acute phase symptoms (>5), BMI, and female sex.¹²⁹ Notably, severity of illness in the initial infection has not correlated with the risk of developing PASC, although initial reports of PASC after hospitalization seem to indicate greater susceptibility to outcomes of PASC for hospitalized patients. Evidence linking the development of PASC to elevated inflammatory markers such as red cell distribution width, erythrocyte sedimentation rate, and C-reactive protein remains inconclusive.¹³⁰

PASC in older adults compared with those aged younger than 65 years, as extracted from the CERNER electronic health record database, more often includes renal failure, thromboembolic events, cerebrovascular disease, type 2 diabetes, muscle disorders, neurologic conditions, and mental health conditions (including mood disorders, anxiety, other mental conditions, and substance-related disorders).¹¹⁹ Persistent impaired cognitive functions in older adults have been reported for up to 1 year after acute COVID-19.¹³¹

Future directions

• •COVID-19 vaccine frequency and acceptance to optimize immunologic response and clinical effectiveness need further studies that emphasize outcomes in older adults.
• •The refinement of definitions for PASC, its epidemiology, impact, and approaches to management will evolve as new data become available.
• •We need to better understand what drives the severity of SARS-CoV-2 infection in older adults, especially because it relates to frailty, immune senescence, and inflammation.

Clinics care points

• •Older adults with COVID-19 have higher hospitalization and case fatality rates than younger adults.¹³²
• •SARS-CoV-2 infection remains asymptomatic from 33% to 90% of older adults, depending on underlying immune status from prior infection, vaccination, and circulating strain.¹³³
• •The high frequency of asymptomatic SARS-CoV-2 infection makes symptom-based testing ineffective as a sole means for early outbreak detection of SARS-CoV-2 in NH populations.¹¹³
• •Fever response is blunted in older adults with COVID-19; setting a lower threshold for triggering SARS-CoV-2 testing in older adults in NH settings improves sensitivity and can alert staff to consider the need to test for SARS-CoV-2 days earlier.^{104 , 105}
• •Older adults with underlying morbidities disproportionately suffer the most severe COVID-19 outcomes.^{134 , 135}
• •Health-care providers should consider adding COVID-19 to the differential diagnosis of clinical presentations such as falls, confusion, delirium, and worsening of functional impairment. This should drive SARS-CoV-2 testing, treatment, and measures to reduce spread (eg, distancing, masking, isolation).¹¹⁶
• •Older adults more often experience any of a broad range of sequelae of respiratory failure, fatigue, hypertension, memory problems, kidney injury, mental health problems, hypercoagulopathy, cardiac dysrhythmias, deep vein thrombosis, pulmonary embolism, and bleeding after COVID-19.^{108 , 109}
• •In older adults, vaccination reduces SARS-CoV-2 incident infection and subsequent severity,^{134 , 135} effects bolstered by booster vaccines.⁵²
• •N-95 respirators provide superior protection to other masks and can protect users from getting infection when caring for or visiting those infected with SARS-CoV-2.¹¹⁴ In conjunction with social distancing, minimizing time in rooms with infected individuals, frequent hand washing, and proper use of other PPE, individuals can avoid becoming infected. Absent N-95 respirator availability, other masks still can offer some protection. The use of masks should follow the greater standard of personal preference of health department guidelines.

Disclosure

Y. Abul: Received support from the Veterans Affairs Office of Academic Affiliations during the preparation of this article. C. Leeder: None to declare. S. Gravenstein (SG): SG reports potential conflicts with vaccine manufacturers Sanofi, Seqirus, Pfizer, related to grants, consulting, and speaking engagements. S G also consults with other pharmaceutical companies such as Langevoron, Genentec, Janssen, Novavax, Moderna, and Merck and has grants with Sunovion, and Essity.