Clinical expressions, characteristics and treatments of confirmed COVID-19 in nursing home residents: a systematic review

Our review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement [18].

In our sample, we included all articles reporting primary quantitative studies relevant to the clinical expressions, characteristics and treatments of confirmed cases of COVID-19 among NH residents. Studies written in languages other than English, Norwegian, Danish, or Swedish were excluded.

In this systematic review we use the term “nursing home” as a label for the institutions in the articles included in our study. We acknowledge that different interpretations of the term “nursing home” in the different countries can be found, but in this systematic review the term is used for institutions run by health care professionals serving older adults who need 24-h health and care services. Sanford et al. (2015) offers a definition of NHs that states that NHs are facilities “that provides 24-h functional support and care for persons who require assistance with ADLs and who often have complex health needs and increased vulnerability” [19]. The institutions in the included articles in this systematic review are covered by this definition.

Two comprehensive searches for literature in different electronic databases were conducted using combined search terms related to “COVID-19” and “nursing home”. The first search for literature, conducted on 22 April 2021, probed the databases PubMed, CINAHL, and AgeLine, whereas the second, conducted on 5 July 2021, probed those three databases in addition to the EMBASE and PsycINFO databases. The search terms used in the second search differed somewhat for the various databases, as presented in the search log in Table 1. For both searches, medical subject headings (MeSH) and a combination of the search fields “Title”, “Abstract”, “Heading word” and “Key word” were used when available to ensure the best possible searches. We also re-examined our searches of the databases and searches of the reference lists of the articles for other eligible literature. In addition, a recommended study identified through manual literature searches was also assessed but excluded due to overlap of data with another study in this review.

In addition, 17 studies identified via other methods were assessed. The flow diagram for the searches for literature (the PRISMA 2020 flow diagram) and screening appears in Fig. 1. After 427 were excluded, 28 eligible articles were read in full. Of them, 9 were excluded for various reasons, as also shown in Fig. 1. The screening and selection of the studies were conducted individually by all researchers, and any disagreements were discussed until consensus was reached.

To assess quality of the included studies the Newcastle–Ottawa assessment scale (NOS) was used. The studies were assessed according to three perspectives: (1) selection of the population/study group, (2) comparability of the groups, and (3) assessment of outcome [20]. Quality scores were identified by assigning stars for the different categories, and all 19 included studies in this review achieved seven stars or more of nine possible stars according to NOS. Three researchers (AN, BL and AMMR) assessed the quality of the included studies.

A data extraction form was prepared that included study characteristics, including authors, year of publication, country, aim, study design/methods, number of participants, and outcomes. All researchers were involved in the process of data extraction.

Any disagreements in the quality assessment and data extraction phase were discussed by the researchers until a consensus was reached.

Characteristics of the included studies are presented in Table 2.

Due to the heterogeneity in the study designs, methods, and outcomes in the articles, we presented the findings in a narrative synthesis. Data were grouped according to symptoms, signs, comorbidity, laboratory findings, medical treatment, and mortality among NH residents confirmed to have COVID-19. For single symptoms and findings comparable across studies, a weighted mean (M_weighted, mean of proportions) and the range of proportions were calculated to account for the large variation in the number of participants in the studies.

The articles examined in our systematic review were approved by ethics committees at the hospitals, universities or institutes, and local health authorities and/or institutional review boards.

This systematic review did not require ethical approval from the institution or an ethics committee due to secondary data analysis of existing data.

Fifteen of the studies [21‐24, 27, 28, 30‐35, 37‐39] involved identification of signs and symptoms among NH residents confirmed to have COVID-19 as reported in Table 3. The most commonly identified symptoms and signs, reported as M_weighted and range, were fever (53.7%, 10.0%–86.0%), cough (56.5%, 19.6%–70.7%), hypoxia (32.3%, 3.0%–95.5%), delirium or confusion (31.2%, 3.0%–57.6%), dyspnoea, shortness of breath or respiratory distress (27.4%, 8.0%–61.0%), and/or abdominal pain, nausea, vomiting, and/or diarrhoea (24.1%, 6.0%–40.0%).

Among the studies that did not identify any symptoms in COVID-19-positive NH residents at the time of testing, the M_weighted was 50.1% (3.0%–56.4%). For the studies that identified an asymptomatic course during the follow-up period, the M_weighted was 23.5% (4.0%–37.1%).

Two studies, Bielza et al. and De Spiegeleer et al. [24, 26] revealed that some NH residents displayed a severe course of COVID-19; 253 of 341 (74.2%) and 37 of 154 (24%) of the NH residents, respectively. Although De Spiegeleer et al. did not define the symptoms of severe courses of COVID-19 in their study, Bielza et al. defined such courses as involving a temperature exceeding 38 °C, systolic blood pressure less than 100 mm Hg, a heart rate exceeding 100 beats per minute, basal oxygen saturation of less than 90%, respiratory rate exceeding 30 per minute, and an altered level of consciousness.

Comorbid conditions in NH residents, as shown in Table 3, were identified in 16 studies [21‐30, 32‐35, 38, 39]. In the studies of Graham et al. and Sacco et al., comorbidities were not divided according to whether the patients were positive or negative for COVID-19; thus, their data were omitted from our study. The remaining 14 studies identified comorbid conditions in NH residents confirmed to have COVID-19. The most frequent comorbidities reported and expressed as M_weighted and range were hypertension (78.6%, 25.3%–91.3%), dementia or cognitive impairment (55.3%, 46.0%–100.0%), cardiovascular disease (52.0%, 8.2%–84.7%), diabetes (38.7%, 13.4%–50.5%), renal disease (27.1%, 8.8%–42.0%), and pulmonary disease (26.0%, 7.3%–38.0%).

Laboratory findings for NH residents with confirmed COVID-19 are reported in three of the articles [22, 23, 32] as described in Table 3.

Atalla et al. found elevated C-reactive protein levels (CRP ≥ 5 mg/L) in four of 10 (40%) NH residents or whom laboratory tests were performed [22]. By comparison, Poloni et al. found that 50 of 57 (87.7%) NH residents had an elevated CRP (reference range 2.9–76.2 nmol/L) with an overall median of 152.4 nmol/L. In their study, CRP was higher in the deceased group (367.6 nmol/L) than in the living group (88.6 nmol/L) [32].

Atalla et al. detected a low lymphocyte count (< 0.8 k/μL) in three of 75 (4%) NH residents, whereas Poloni et al. found that 51 of 57 (89.5%) NH residents had low lymphocyte counts with a median count of 1.3 × 10⁹/L [22, 32].

Both Atalla et al. and Beiting et al. assessed low and high white blood cell (WBC) counts. Atalla et al. found a low WBC count (< 4 k/μL) in 13 of 81 (16%) NH residents, whereas Beiting et al. found that 61 of 155 (39.4%) NH residents displayed a low WBC count (< 4.8 1000/mm³). In the two studies, high WBC counts (> 10 k/μL and > 10.8 1000/mm³, respectively) were found in seven of 87 (8%) and in 13 of 155 (8.4%) NH residents, respectively [22, 23].

Regarding elevated D-dimer levels (> 0.51 μg/mL), Atalla et al. found such levels in 54 of 90 (60.0%) NH residents tested, and 47 of the 90 (52%) had low haemoglobin (Hb < 12 g/dL) [22]. In Beiting et al.’s study, 46 of 155 (29.7%) NH residents had acute kidney injury indicated by elevated creatinine levels (> 0.03 mg/dL or 1.5 × baseline), and 38 of the 155 (24.5%) exhibited hypernatremia (Na > 145 mEq/L) [23].

Those two research groups also reported abnormal chest X-ray results in their studies [22, 23]. In Atalla et al.’s study, the most common findings were interstitial densities (8/27 residents, 29.6%), unilateral base infiltrates (7/27, 29.6%), patchy unilateral densities (5/27, 18.5%), and patchy bilateral densities (4/27, 14.8%) [22].

The medical and pharmacological treatments of the NH residents confirmed to have COVID-19 are described in Table 3. The treatments were administered for COVID-19 and did not include treatment given on a regular basis for other conditions. Six studies presented data on medical and pharmacological treatments [22‐24, 35‐37]. The treatments were used to improve outcomes, as part of palliative care, or as end-of-life treatment. Treatments included inhalers, antibiotics, anticoagulation, oxygen supplementation, parenteral or enteral fluids or nutrition, hydroxychloroquine, and medication based on the NH resident’s needs (such as pro re nata prescriptions). In the studies of Beiting et al. and Bielza et al., treatment with antibiotics were described. This treatment was prescribed for 21.5% and 58.4% of the NH residents, respectively [23, 24]. Oxygen supplementation was described in the studies of Atalla et al., Beiting et al., and Shi et al. In these studies, 44.1%, 27.3%, and 39.7% of the NH residents in the studies received supplemental oxygen [22, 23, 35]. Two of the studies by Atalla et al. and Bielza et al. described treatment with the anticoagulation agent, Enoxaparin. In the study of Atalla et al. 47.7% received this treatment, and in the study of Bielza 75.1% [22, 24]. Posology was not stated.

Transfers to hospital were reported in six of the included studies, and the rate of hospital transfers varied from 6.9% to 50% for residents with confirmed COVID-19 [21, 23, 24, 31, 37, 39]. Strang et al. reported that nursing home residents who were transferred to hospital were generally younger (83.3 years versus 86.7 years; p < 0.00001) and more often male (p < 0.0001) [37]. The study of Tobolowsky et al. showed that relative risk (RR) of hospitalisation was higher among COVID-19- positive NH residents with underlying hepatic disease (RR 1.6, 95% confidence interval [CI] 1.1–2.2) or obesity (RR 1.5, 95% CI 1.1–2.1) and for those treated with continuous positive airway pressure (RR 1.6, 95% CI 1.2–2.1) [39].

Mortality in NH residents with confirmed COVID-19 was reported in 17 of the studies as shown in Table 3 [21‐25, 27‐35, 37‐39]. The reported mortality rates ranged from 15.7% to 100.0% while the observation periods varied from three weeks to eight months. Cognitive impairment or dementia, hypoxia or change in oxygen status, old age (≥ 84 years), and male gender were associated with higher mortality in 10 studies [22, 24, 25, 27, 30, 32, 33, 36, 37, 39]. Overall, 11,008 NH residents confirmed to have COVID-19 were included in the 17 studies reporting mortality, and 4427 (40.2%) of them died during the observation period of the studies.

Regarding symptoms and signs of COVID-19, approximately half of the NH residents in the studies had fever and cough while one-third had hypoxia. Those findings align with the findings of other studies reporting these signs and symptoms in both NH residents and older adult patients in hospitals [12, 17, 40, 41]. Several of the NH residents with confirmed COVID-19 had no symptoms at the time of testing but developed one or more symptoms compatible with COVID-19 during the course of the disease. Our findings also show that an asymptomatic course during the follow-up period may occur. It should not be overlooked that those who were defined as asymptomatic may have had symptoms weeks before testing, but is it likely that some of the NH residents underwent an asymptomatic course. Thus, although NH residents with COVID-19 may present with typical symptoms and signs such as fever, cough, and dyspnoea, these symptoms may also be absent in this population. COVID-19’s capacity to present without symptoms or follow an asymptomatic course has also been described for the general population [2]. A systematic review and meta-analysis estimated that 42.8% of the general population confirmed to have COVID-19 had no symptoms at the time of testing, and 35.1% remained asymptomatic during the follow-up period. This study also revealed that younger people and children had a higher percentage of asymptomatic courses than older adults. People with no comorbidities also had a higher percentage of asymptomatic courses than for those with comorbidities [42]. Due to advanced age and frailty, the basal body temperature decreases, and, for that reason, it has been suggested that fever in NH residents should be defined as a single oral temperature exceeding 37.8 °C (> 100 °F), repeated oral temperatures exceeding 37.2 °C (> 99 °F), or those exceeding 1.1 °C (> 2 °F) over the basal temperature [15, 16].

Other atypical signs or symptoms indicating infection in NH residents could be a change in mental or cognitive state such as delirium or confusion [15, 43]. Our systematic review revealed that among the studies reporting delirium or confusion, an average of 31.2% (M_weighted) of the NH residents was affected by the condition as a component of COVID-19, which is also described by Hashan et al. [17]. NH residents have a higher risk of developing delirium due to their higher rates of dementia, multimorbidity, frailty and older age than other populations [43]. Delirium is characterised by the acute appearance of symptoms, such as confusion, disorientation, delusions, hallucinations, agitation, hyperactivity, or hypoactivity [43, 44]. The condition can also have serious negative consequences, including the development or worsening of dementia in addition to an increased risk of hospitalisation and mortality. NH residents often have more frequent worsening patterns of delirium than patients in hospital, and the hypoactive form of delirium may be especially severe for people with dementia [43]. It is therefore imperative to highlight that delirium can be a presentation of COVID-19 among NH residents due to the severe negative consequences of this condition.

In our systematic review, changes in oxygen status were associated with higher mortality and thus represent a sign that is important to recognise among NH residents. Among patients admitted to hospital due to COVID-19, both dyspnoea and low oxygen saturation were associated with mortality [45]. The high mortality rate presented in this systematic review must be interpreted with caution. However, a report on mortality among nursing home residents based on 22 countries shows a similar result with an average of 41% [13]. Based on our results, it is not possible to determine any differences in the impact caused by COVID-19 on short- or long-term mortality.

Identifying the symptoms of COVID-19 in NH residents is important for early diagnosis and proper treatment before the condition worsens in addition to reducing the risk of the further transmission of SARS-CoV-2. In the case of suspected infection, having a liberal testing system to confirm or rule out COVID-19 can help to prevent the undetected spread of the virus. Due to the high percentage of asymptomatic patients, relying solely on symptom-based screening is insufficient for reliably identifying COVID-19. The presence of symptoms, such as fever and cough, should prompt further testing [46]. Future research should also investigate how the assessment of symptoms and the clinical evaluation of COVID-19 in NH residents are performed by NH staff.

The results of abnormal laboratory findings reported in the articles indicate elevated CRP and D-dimer levels, lymphopenia, leukopenia, and acute kidney injury among NH residents confirmed to have COVID-19. However, given the scarcity of studies that have reported such findings, it remains difficult to draw conclusions about the frequency of those findings and the significance of the test results. A meta-analysis among older adult patients with COVID-19 has shown that lymphopenia and leukopenia may be common in that population and that acute kidney injury is a common complication [41]. Another meta-analysis has shown that acute kidney injury and elevated CRP and/or D-dimer levels may be clinically relevant to mortality among patients with COVID-19 who are admitted to hospital [45]. Even though these findings may not be directly transferable to the NH resident population, who may differ in age and disease burden from patients admitted to hospital, it is important to note these results, since our systematic review indicate similar laboratory responses. The abnormal X-ray results considered in our systematic review were also too few to be generalisable; however, other studies have shown that pulmonary infiltrates among older adults with COVID-19 admitted to hospital may be common [40, 41, 47].

In general, frequently reported diagnoses among NH residents are hypertension, cardiovascular disease, dementia, diabetes, and chronic obstructive pulmonary disorder, and studies also show that NH residents usually display three or more underlying health conditions [7, 9]. In our systematic review, we found that a high proportion of NH residents confirmed to have COVID-19 had hypertension, and more than half had dementia or cognitive impairment and cardiovascular disease. Based on our findings, we cannot confirm whether a higher incidence of multimorbidity among COVID-19 positive NH residents than those NH residents without COVID-19 exist. Dementia or cognitive impairment was associated with a higher risk of mortality, and studies show that people with dementia have a higher risk of getting COVID-19 and that their rate of mortality due to COVID-19 is greater than for people without dementia [48, 49]. NH residents are usually multimorbid adults who are at least 80 years old, and both multimorbidity and old age lead to an increase in the risk of a severe course of COVID-19 and mortality [7, 8, 10, 11] as do hypertension and cardiovascular disease, especially among NH residents [6, 12]. In the literature analysed in our systematic review, the specific description of severe courses of COVID-19 is not frequently outlined. Bielza et al. [24] described severe courses as involving a temperature exceeding 38 °C, systolic blood pressure less than 100 mm Hg, a heart rate exceeding 100 beats per minute, basal oxygen saturation of less than 90%, a respiratory rate exceeding 30 per minute, and an altered level of consciousness. Although residents with those signs were cared for in their NHs [24], it remains debated whether NH residents should be transferred to hospital or treated in their respective NHs for COVID-19. Few of the included studies reported transfers to hospital for NH residents with confirmed COVID-19, and the findings in our systematic review are too scarce to conclude anything about risk factors for hospitalisation for this population. However, most guidelines stipulate that NH residents should receive treatment and care in their NHs when possible [50]. In general, NHs have faced tremendous challenges in recruiting enough staff who are sufficiently qualified, a trend dating back to before the pandemic. The first wave of the pandemic greatly exacerbated those problems as several members of staff had to be absent due to restrictions. Added to that, some managers had to work from their own homes, there were quarantine requirements, physicians were absent and only available via telephone or video, and more staff were needed to meet the residents’ needs for more comprehensive care [51]. Hospitals generally have more resources and larger staffs of physicians, nurses, and other relevant staff members in addition to access to on-site services, such as laboratory- and X-ray departments [14]. Those differences between hospitals and NHs are relevant when deciding whether to transfer an NH resident to a hospital or not. From another point-of-view, NHs are both the homes and health institutions for their residents. When the pandemic broke out, it was exceptionally demanding for NH employees to manage the intensified care needs of their residents brought about by COVID-19 [51]. Determining whether a NH resident should be admitted to hospital may also be partly based on the resident’s preferences in relation to treatment. The benefits and risks of transferring NH residents to hospital should also be considered. After all, the right to adequate healthcare is a human right regardless of age, functional state, or place of residence [50, 52].

The medical and pharmacological treatments of NH residents confirmed to have COVID-19 identified in our systematic review were used to improve outcomes, as part of palliative care, or as end-of-life treatment. The treatments described were administered early on during the pandemic, and hydroxychloroquine was used in some severe cases of COVID-19. It turned out, however, that hydroxychloroquine did not provide any benefits for patients with COVID-19. In December 2020, it was strongly advised not to use the drug [53]. NH residents who displayed a severe course and/or who were near the end of life received oxygen therapy, parenteral or enteral fluids, and pro re nata prescriptions of palliative drugs. Despite those findings and to our knowledge studies that have described the medical and pharmacological treatment received by NH residents confirmed to have COVID-19 are scarce. Medical and pharmacological treatment require the close follow-up of patients; however, the staffing situation in NHs has continued to be strained [51, 52]. It is therefore possible that not all NHs provide equal opportunities for medical and pharmacological treatment, especially not treatment for the consequences of COVID-19. In the future, researchers should therefore focus on how NH staff offer treatment, care, and nursing to NH residents with severe courses of COVID-19.

In this review we rigorously followed both the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement and a systematic qualitative assessment system of the included studies, the Newcastle–Ottawa assessment scale (NOS). We conducted thorough literature searches using relevant databases (PubMed, CINAHL, AgeLine, Embase and PsycINFO), but the risk of missing studies cannot be ignored. The included studies were conducted exclusively in Europe or North America, possibly due to the geographical spread of the pandemic in which it first broke out and the exclusion of studies not published in English. In addition, the studies varied in sample size, length of follow-up period, and acquisition of data. Given such heterogeneity in study designs, methods, and outcomes, it proved impossible to perform a meta-analysis along with our systematic review. Our findings must therefore be interpreted with caution based on these limitations. Nevertheless, our review has allowed us to summarise important clinical findings about COVID-19 pertaining to this vulnerable population of NH residents.