# National French Survey of Coronavirus Disease (COVID-19) Symptoms in People Aged 70 and Over

Cédric Annweiler, Guillaume Sacco, Nathalie Salles, Jean-Pierre Aquino, Jennifer Gautier, Gilles Berrut, Olivier Guérin, Gaetan Gavazzi

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Cédric Annweiler, Guillaume Sacco, Nathalie Salles, Jean-Pierre Aquino, Jennifer Gautier, et al.  
National French Survey of Coronavirus Disease (COVID-19) Symptoms in People Aged 70 and Over.  
Clinical Infectious Diseases, 2021, 72 (3), pp.490-494. 10.1093/cid/ciaa792. hal-04582834

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# National French Survey of Coronavirus Disease (COVID-19) Symptoms in People Aged 70 and Over

Cédric Annweiler,<fnref n="1" />,²,³,✉ Guillaume Sacco,<fnref n="1" />,² Nathalie Salles,⁴ Jean-Pierre Aquino,⁵
Jennifer Gautier,<fnref n="1" /> Gilles Berrut,⁶ Olivier Guérin,⁷,⁸ and Gaetan Gavazzi,⁹ on behalf of
the SFGG COVID-19 study group

The objective of this national French survey was to determine the coronavirus disease 2019 (COVID-19) semiology in seniors (n = 353; mean, 84.7 ± 7.0 years). A total of 57.8% of patients exhibited ≤3 symptoms, including thermal dysregulation (83.6%), cough (58.9%), asthenia (52.7%), polypnea (39.9%), and gastrointestinal signs (24.4%). Patients ≥80 years exhibited falls (*P* = .002) and asthenia (*P* = .002). Patients with neurocognitive disorders exhibited delirium (*P* < .001) and altered consciousness (*P* = .001). Clinical peculiarities of COVID-19 were reported in seniors.
**Clinical Trials Registration.** NCT04343781.

**Keywords:** COVID-19; SARS-CoV-2; semiology; symptomatology; older adults.

Since December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is spreading worldwide from China, affecting millions of people. Although older adults do not appear more prone than younger ones to be infected, they are more at risk of developing severe and lethal forms of COVID-19 [1–3]. The core question is thus to properly discuss the diagnosis of COVID-19 in older patients. It is commonly admitted that the semiology of older adults differs from that encountered in younger ones. Changes in the clinical expression of the diseases and difficulties in interpreting the clinical signs in older patients could blur

the diagnosis process. If these peculiarities were also retrieved with COVID-19, it could be the cause of delayed diagnosis among older patients and be responsible for delayed care and isolation measures with subsequent higher risk of virus propagation. The objective of this national French survey was to describe and identify the symptoms most frequently encountered in people aged 70 years and older diagnosed with COVID-19.

## METHODS

This cross-sectional study was conducted by the French Society of Geriatrics and Gerontology. An online standardized questionnaire was sent by email to all Society members and widely communicated through the professional networks in geriatrics and infectious diseases. Physicians were asked to report, between March 22 and April 5, 2020, their last 10 patients aged ≥70 years with confirmed SARS-CoV-2 infection (as defined as a positive reverse transcriptase-polymerase chain reaction [RT-PCR] test result). Those who had treated fewer than 10 diagnosed patients were asked to submit a questionnaire for each of them. The study was conducted in accordance with the ethical standards set forth in the Helsinki Declaration (1983), was declared to the National Commission for Information Technology and civil Liberties (ar20-0031v1), and was registered on clinicaltrials.gov under number NCT04343781.

The following characteristics were collected for each patient: demographic (age, sex, place where living, place of care, most recent disability score according to the Iso-Resource Group)[4], and medical history (major neurocognitive disorders [MND], hypertension, diabetes mellitus, asthma or chronic obstructive pulmonary disease, cardiomyopathy, severe chronic renal failure defined as creatinine clearance <30 mL/min, solid or hematological cancer).

The following symptoms observed within the first 72 hours of SARS-CoV-2 infection (ie, 72 hours from suspicion, possibly before diagnostic confirmation by RT-PCR test) were collected for each patient using yes/no questions: general signs (sudden deterioration of general condition, temperature, blood pressure), respiratory signs (cough, polypnea), ear nose and throat signs (rhinorrhea, odynophagia, otalgia, conjunctivitis, dysgeusia or ageusia, anosmia), gastrointestinal signs (diarrhea, nausea, vomiting) and geriatric syndromes (falls, hypo- or overactive delirium, altered consciousness). Changes in complete blood count (leukopenia, lymphopenia, thrombocytopenia) were also collected, with details when available.

Qualitative variables were described using numbers and percentages, and quantitative variables using means and standard deviations. Comparisons between participants aged ≥80 years and <80 years, and between those with and without MND,

Received 18 April 2020; editorial decision 9 June 2020; accepted 11 June 2020; published online June 18, 2020.

Correspondence: C. Annweiler, Department of Geriatric Medicine, Angers University Hospital, F-49933 Angers, France (Cedric.Annweiler@chu-angers.fr).

**Clinical Infectious Diseases®** 2021;72(3):490–4

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. DOI: 10.1093/cid/ciaa792

<footnote n="1">¹Department of Geriatric Medicine and Memory Clinic, Research Center on Autonomy and Longevity, University Hospital, Angers, France, ²UPRES EA 4638, Université d'Angers, Angers, France, ³Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, the University of Western Ontario, London, Ontario, Canada, ⁴Department of Clinical Gerontology, University Hospital, Bordeaux, France, ⁵Délégation générale de la Société Française de Gériatrie et Gérontologie (SFGG), Paris, France, ⁶Pôle hospitalo-universitaire de gérontologie clinique, CHU de Nantes, France, ⁷Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Service de Médecine Gériatrique et Thérapeutique, Nice, France, ⁸Université Côte d'Azur, CNRS UMR 7284/INSERM U108, Institute for Research on Cancer and Aging Nice (IRCAN), Faculté de médecine, Nice, France, and ⁹Service Gériatrie Clinique, Centre Hospitalo-Universitaire Grenoble-Alpes, Saint-Martin-d'Hères, France</footnote>
# National French Survey of Coronavirus Disease (COVID-19) Symptoms in People Aged 70 and Over

Cédric Annweiler,<fnref n="1" />,²,³,✉ Guillaume Sacco,<fnref n="1" />,² Nathalie Salles,⁴ Jean-Pierre Aquino,⁵
Jennifer Gautier,<fnref n="1" /> Gilles Berrut,⁶ Olivier Guérin,⁷,⁸ and Gaetan Gavazzi,⁹ on behalf of
the SFGG COVID-19 study group

The objective of this national French survey was to determine the coronavirus disease 2019 (COVID-19) semiology in seniors (n = 353; mean, 84.7 ± 7.0 years). A total of 57.8% of patients exhibited ≤3 symptoms, including thermal dysregulation (83.6%), cough (58.9%), asthenia (52.7%), polypnea (39.9%), and gastrointestinal signs (24.4%). Patients ≥80 years exhibited falls (P = .002) and asthenia (P = .002). Patients with neurocognitive disorders exhibited delirium (P < .001) and altered consciousness (P = .001). Clinical peculiarities of COVID-19 were reported in seniors.
**Clinical Trials Registration.** NCT04343781.

**Keywords:** COVID-19; SARS-CoV-2; semiology; symptomatology; older adults.

Since December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is spreading worldwide from China, affecting millions of people. Although older adults do not appear more prone than younger ones to be infected, they are more at risk of developing severe and lethal forms of COVID-19 [1–3]. The core question is thus to properly discuss the diagnosis of COVID-19 in older patients. It is commonly admitted that the semiology of older adults differs from that encountered in younger ones. Changes in the clinical expression of the diseases and difficulties in interpreting the clinical signs in older patients could blur

the diagnosis process. If these peculiarities were also retrieved with COVID-19, it could be the cause of delayed diagnosis among older patients and be responsible for delayed care and isolation measures with subsequent higher risk of virus propagation. The objective of this national French survey was to describe and identify the symptoms most frequently encountered in people aged 70 years and older diagnosed with COVID-19.

## METHODS

This cross-sectional study was conducted by the French Society of Geriatrics and Gerontology. An online standardized questionnaire was sent by email to all Society members and widely communicated through the professional networks in geriatrics and infectious diseases. Physicians were asked to report, between March 22 and April 5, 2020, their last 10 patients aged ≥70 years with confirmed SARS-CoV-2 infection (as defined as a positive reverse transcriptase-polymerase chain reaction [RT-PCR] test result). Those who had treated fewer than 10 diagnosed patients were asked to submit a questionnaire for each of them. The study was conducted in accordance with the ethical standards set forth in the Helsinki Declaration (1983), was declared to the National Commission for Information Technology and civil Liberties (ar20-0031v1), and was registered on clinicaltrials.gov under number NCT04343781.

The following characteristics were collected for each patient: demographic (age, sex, place where living, place of care, most recent disability score according to the Iso-Resource Group)[4], and medical history (major neurocognitive disorders [MND], hypertension, diabetes mellitus, asthma or chronic obstructive pulmonary disease, cardiomyopathy, severe chronic renal failure defined as creatinine clearance <30 mL/min, solid or hematological cancer).

The following symptoms observed within the first 72 hours of SARS-CoV-2 infection (ie, 72 hours from suspicion, possibly before diagnostic confirmation by RT-PCR test) were collected for each patient using yes/no questions: general signs (sudden deterioration of general condition, temperature, blood pressure), respiratory signs (cough, polypnea), ear nose and throat signs (rhinorrhea, odynophagia, otalgia, conjunctivitis, dysgeusia or ageusia, anosmia), gastrointestinal signs (diarrhea, nausea, vomiting) and geriatric syndromes (falls, hypo- or overactive delirium, altered consciousness). Changes in complete blood count (leukopenia, lymphopenia, thrombocytopenia) were also collected, with details when available.

Qualitative variables were described using numbers and percentages, and quantitative variables using means and standard deviations. Comparisons between participants aged ≥80 years and <80 years, and between those with and without MND,

Received 18 April 2020; editorial decision 9 June 2020; accepted 11 June 2020; published online June 18, 2020.

Correspondence: C. Annweiler, Department of Geriatric Medicine, Angers University Hospital, F-49933 Angers, France (Cedric.Annweiler@chu-angers.fr).

**Clinical Infectious Diseases®** 2021;72(3):490–4

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. DOI: 10.1093/cid/ciaa792

<footnote n="1">¹Department of Geriatric Medicine and Memory Clinic, Research Center on Autonomy and Longevity, University Hospital, Angers, France, ²UPRES EA 4638, Université d'Angers, Angers, France, ³Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, the University of Western Ontario, London, Ontario, Canada, ⁴Department of Clinical Gerontology, University Hospital, Bordeaux, France, ⁵Délégation générale de la Société Française de Gériatrie et Gérontologie (SFGG), Paris, France, ⁶Pôle hospitalo-universitaire de gérontologie clinique, CHU de Nantes, France, ⁷Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Service de Médecine Gériatrique et Thérapeutique, Nice, France, ⁸Université Côte d'Azur, CNRS UMR 7284/INSERM U108, Institute for Research on Cancer and Aging Nice (IRCAN), Faculté de médecine, Nice, France, and ⁹Service Gériatrie Clinique, Centre Hospitalo-Universitaire Grenoble-Alpes, Saint-Martin-d'Hères, France</footnote>
were performed using $\chi^2$ test for qualitative variables (or exact Fisher test where appropriate), and Student t test for quantitative variables (or Mann-Whitney U test where appropriate). Univariate logistic regressions were conducted to determine the association of each COVID-19 sign with age $\ge$80 years and history of MND. Finally, the profiles of COVID-19 patients were determined according to their symptoms, age, and history of MND using a multiple correspondence analysis. Two-sided P

values < .05 were considered significant. Analyses were performed with SAS (SAS Institute Inc.; v9.4) and R (R Core Team 2020; v3.6.3) using the FactoMineR and Factoshiny packages.

## RESULTS

Older patients' characteristics are presented in Table 1 (N = 353; mean $\pm$ SD, 84.7 $\pm$ 7.0 years; 54.7% women). Most patients

<table><caption>Table 1. Characteristics and Comparisons of Participants (N = 353) Separated According to Their Age and History of MNDs</caption><thead><tr><th rowspan="2"></th><th rowspan="2">Population of the Study (N = 353)</th><th colspan="3">Comparison of Patients &lt; and &gt; 80 y of Age</th><th colspan="3">Comparison of Patients With and Without MNDs</th></tr><tr><th>Age &lt; 80 y (n = 89)</th><th>Age $\ge$ 80 y (n = 264)</th><th>PValue<sup>a</sup></th><th>No MND (n = 219)</th><th>With MND (n = 134)</th><th>PValue<sup>a</sup></th></tr></thead><tbody><tr><td><strong>Sociodemographic data</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Male</td><td>160 (45.3)</td><td>47 (52.8)</td><td>113 (42.8)</td><td>.101</td><td>105 (48.0)</td><td>55 (41.0)</td><td>.206</td></tr><tr><td>Age (y), mean $\pm$ SD</td><td>84.7 $\pm$ 7.0</td><td>75.4 $\pm$ 2.9</td><td>87.8 $\pm$ 4.8</td><td></td><td>83.7 $\pm$ 7.2</td><td>86.3 $\pm$ 6.4</td><td><strong>&lt;.001</strong></td></tr><tr><td>Place where living</td><td></td><td></td><td></td><td>.0049</td><td></td><td></td><td></td></tr><tr><td>Community-dwelling</td><td>257 (72.8)</td><td>75 (84.3)</td><td>182 (68.9)</td><td></td><td>180 (82.2)</td><td>77 (57.5)</td><td><strong>&lt;.001</strong></td></tr><tr><td>Institution-dwelling</td><td>96 (27.2)</td><td>14 (15.7)</td><td>82 (31.1)</td><td></td><td>39 (17.8)</td><td>57 (42.5)</td><td></td></tr><tr><td>Place of care</td><td></td><td></td><td></td><td>.1845</td><td></td><td></td><td>.173</td></tr><tr><td>Hospital</td><td>324 (91.8)</td><td>79 (88.8)</td><td>245 (92.8)</td><td></td><td>204 (93.2)</td><td>120 (89.6)</td><td></td></tr><tr><td>Nursing home</td><td>23 (6.5)</td><td>8 (9.0)</td><td>15 (5.7)</td><td></td><td>11 (5.0)</td><td>12 (9.0)</td><td></td></tr><tr><td>Services residence</td><td>3 (0.9)</td><td>0 (0.0)</td><td>3 (1.1)</td><td></td><td>1 (0.5)</td><td>2 (1.5)</td><td></td></tr><tr><td>Personal residence</td><td>3 (0.9)</td><td>2 (2.3)</td><td>1 (0.4)</td><td></td><td>3 (1.4)</td><td>0 (0.0)</td><td></td></tr><tr><td>GIR<sup>b</sup></td><td></td><td></td><td></td><td><strong>&lt;.001</strong></td><td></td><td></td><td><strong>&lt;.001</strong></td></tr><tr><td>1</td><td>23 (7.1)</td><td>4 (5.0)</td><td>19 (7.7)</td><td></td><td>1 (0.5)</td><td>22 (17.3)</td><td></td></tr><tr><td>2</td><td>70 (21.5)</td><td>11 (13.8)</td><td>59 (24.0)</td><td></td><td>13 (6.5)</td><td>57 (44.9)</td><td></td></tr><tr><td>3</td><td>47 (14.4)</td><td>8 (10.0)</td><td>39 (15.9)</td><td></td><td>24 (12.1)</td><td>23 (18.1)</td><td></td></tr><tr><td>4</td><td>59 (18.1)</td><td>8 (10.0)</td><td>51 (20.7)</td><td></td><td>40 (20.1)</td><td>19 (15.0)</td><td></td></tr><tr><td>$\ge$ 5</td><td>127 (39.0)</td><td>49 (61.3)</td><td>78 (31.7)</td><td></td><td>121 (60.8)</td><td>6 (4.7)</td><td></td></tr><tr><td><strong>Medical history</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Major neurocognitive disorders</td><td>134 (38.0)</td><td>21 (23.6)</td><td>113 (42.8)</td><td><strong>.001</strong></td><td>0 (0.0)</td><td>134 (100.0)</td><td></td></tr><tr><td>Hypertension</td><td>234 (66.3)</td><td>50 (56.2)</td><td>184 (69.7)</td><td><strong>.012</strong></td><td>144 (65.8)</td><td>90 (67.2)</td><td>.786</td></tr><tr><td>Diabetes mellitus</td><td>80 (22.7)</td><td>23 (25.8)</td><td>57 (21.6)</td><td>.407</td><td>52 (23.7)</td><td>28 (20.9)</td><td>.535</td></tr><tr><td>Asthma or COPD</td><td>46 (13.0)</td><td>13 (14.6)</td><td>33 (12.5)</td><td>.610</td><td>32 (14.6)</td><td>14 (10.5)</td><td>.259</td></tr><tr><td>Cardiomyopathy</td><td>159 (45.0)</td><td>24 (27.0)</td><td>135 (51.1)</td><td><strong>&lt;.001</strong></td><td>92 (42.0)</td><td>67 (50.0)</td><td>.143</td></tr><tr><td>Severe chronic renal failure</td><td>38 (10.8)</td><td>5 (5.6)</td><td>33 (12.5)</td><td>.070</td><td>22 (10.1)</td><td>16 (11.9)</td><td>.577</td></tr><tr><td>Solid or hematological cancer</td><td>67 (19.0)</td><td>15 (16.9)</td><td>52 (19.7)</td><td>.554</td><td>45 (20.6)</td><td>22 (16.4)</td><td>.337</td></tr><tr><td><strong>General signs</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Sudden deterioration of general condition</td><td>186 (52.7)</td><td>34 (38.2)</td><td>152 (57.6)</td><td><strong>.002</strong></td><td>113 (51.6)</td><td>73 (54.5)</td><td>.599</td></tr><tr><td>Low blood pressure</td><td>51 (14.5)</td><td>8 (9.0)</td><td>43 (16.3)</td><td>.090</td><td>31 (14.2)</td><td>20 (14.9)</td><td>.842</td></tr><tr><td>Body temperature</td><td></td><td></td><td></td><td><strong>.011</strong></td><td></td><td></td><td><strong>.013</strong></td></tr><tr><td>No fever</td><td>58 (16.4)</td><td>14 (15.7)</td><td>44 (16.7)</td><td></td><td>36 (16.4)</td><td>22 (16.4)</td><td></td></tr><tr><td>Subfebrile temperature 37.5°–38°C</td><td>75 (21.3)</td><td>10 (11.2)</td><td>65 (24.6)</td><td></td><td>35 (16.0)</td><td>40 (29.9)</td><td></td></tr><tr><td>Hyperthermia $>$ 38°C</td><td>198 (56.1)</td><td>62 (69.7)</td><td>136 (51.5)</td><td></td><td>135 (61.6)</td><td>63 (47.0)</td><td></td></tr><tr><td>Alternation of hyperthermia and hypothermia</td><td>22 (6.2)</td><td>3 (3.4)</td><td>19 (7.2)</td><td></td><td>13 (5.9)</td><td>9 (6.7)</td><td></td></tr><tr><td><strong>Respiratory signs</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cough</td><td>208 (58.9)</td><td></td><td></td><td>.153</td><td></td><td></td><td><strong>&lt;.001</strong></td></tr><tr><td>Sputum</td><td>82 (23.2)</td><td>14 (15.7)</td><td>68 (25.8)</td><td></td><td>49 (22.4)</td><td>33 (24.6)</td><td></td></tr><tr><td>Dry</td><td>126 (35.7)</td><td>35 (39.3)</td><td>91 (34.5)</td><td></td><td>97 (44.3)</td><td>29 (21.6)</td><td></td></tr><tr><td>Polypnea</td><td>141 (39.9)</td><td></td><td></td><td>.165</td><td></td><td></td><td><strong>.014</strong></td></tr><tr><td>Between 23 and 29/min</td><td>94 (26.6)</td><td>17 (19.1)</td><td>77 (29.2)</td><td></td><td>58 (26.5)</td><td>36 (26.9)</td><td></td></tr><tr><td>$\ge$ 30/min</td><td>47 (13.3)</td><td>12 (13.5)</td><td>35 (13.3)</td><td></td><td>38 (17.4)</td><td>9 (6.7)</td><td></td></tr><tr><td><strong>ENT signs</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Rhinorrhea</td><td>32 (9.1)</td><td>9 (10.1)</td><td>23 (8.7)</td><td>.691</td><td>23 (10.5)</td><td>9 (6.7)</td><td>.229</td></tr></tbody></table>
were performed using $\chi^2$ test for qualitative variables (or exact Fisher test where appropriate), and Student t test for quantitative variables (or Mann-Whitney U test where appropriate). Univariate logistic regressions were conducted to determine the association of each COVID-19 sign with age $\ge$80 years and history of MND. Finally, the profiles of COVID-19 patients were determined according to their symptoms, age, and history of MND using a multiple correspondence analysis. Two-sided P

values < .05 were considered significant. Analyses were performed with SAS (SAS Institute Inc.; v9.4) and R (R Core Team 2020; v3.6.3) using the FactoMineR and Factoshiny packages.

## RESULTS

Older patients' characteristics are presented in Table 1 (N = 353; mean $\pm$ SD, 84.7 $\pm$ 7.0 years; 54.7% women). Most patients

<table><caption>Table 1. Characteristics and Comparisons of Participants (N = 353) Separated According to Their Age and History of MNDs</caption><thead><tr><th rowspan="2"></th><th rowspan="2">Population of the Study (N = 353)</th><th colspan="3">Comparison of Patients &lt; and &gt; 80 y of Age</th><th colspan="3">Comparison of Patients With and Without MNDs</th></tr><tr><th>Age &lt; 80 y (n = 89)</th><th>Age $\ge$ 80 y (n = 264)</th><th>PValue<sup>a</sup></th><th>No MND (n = 219)</th><th>With MND (n = 134)</th><th>PValue<sup>a</sup></th></tr></thead><tbody><tr><td colspan="8"><strong>Sociodemographic data</strong></td></tr><tr><td>Male</td><td>160 (45.3)</td><td>47 (52.8)</td><td>113 (42.8)</td><td>.101</td><td>105 (48.0)</td><td>55 (41.0)</td><td>.206</td></tr><tr><td>Age (y), mean $\pm$ SD</td><td>84.7 $\pm$ 7.0</td><td>75.4 $\pm$ 2.9</td><td>87.8 $\pm$ 4.8</td><td></td><td>83.7 $\pm$ 7.2</td><td>86.3 $\pm$ 6.4</td><td><strong>&lt;.001</strong></td></tr><tr><td>Place where living</td><td></td><td></td><td></td><td><strong>.0049</strong></td><td></td><td></td><td></td></tr><tr><td>Community-dwelling</td><td>257 (72.8)</td><td>75 (84.3)</td><td>182 (68.9)</td><td></td><td>180 (82.2)</td><td>77 (57.5)</td><td><strong>&lt;.001</strong></td></tr><tr><td>Institution-dwelling</td><td>96 (27.2)</td><td>14 (15.7)</td><td>82 (31.1)</td><td></td><td>39 (17.8)</td><td>57 (42.5)</td><td></td></tr><tr><td>Place of care</td><td></td><td></td><td></td><td>.1845</td><td></td><td></td><td>.173</td></tr><tr><td>Hospital</td><td>324 (91.8)</td><td>79 (88.8)</td><td>245 (92.8)</td><td></td><td>204 (93.2)</td><td>120 (89.6)</td><td></td></tr><tr><td>Nursing home</td><td>23 (6.5)</td><td>8 (9.0)</td><td>15 (5.7)</td><td></td><td>11 (5.0)</td><td>12 (9.0)</td><td></td></tr><tr><td>Services residence</td><td>3 (0.9)</td><td>0 (0.0)</td><td>3 (1.1)</td><td></td><td>1 (0.5)</td><td>2 (1.5)</td><td></td></tr><tr><td>Personal residence</td><td>3 (0.9)</td><td>2 (2.3)</td><td>1 (0.4)</td><td></td><td>3 (1.4)</td><td>0 (0.0)</td><td></td></tr><tr><td>GIR<sup>b</sup></td><td></td><td></td><td></td><td><strong>&lt;.001</strong></td><td></td><td></td><td><strong>&lt;.001</strong></td></tr><tr><td>1</td><td>23 (7.1)</td><td>4 (5.0)</td><td>19 (7.7)</td><td></td><td>1 (0.5)</td><td>22 (17.3)</td><td></td></tr><tr><td>2</td><td>70 (21.5)</td><td>11 (13.8)</td><td>59 (24.0)</td><td></td><td>13 (6.5)</td><td>57 (44.9)</td><td></td></tr><tr><td>3</td><td>47 (14.4)</td><td>8 (10.0)</td><td>39 (15.9)</td><td></td><td>24 (12.1)</td><td>23 (18.1)</td><td></td></tr><tr><td>4</td><td>59 (18.1)</td><td>8 (10.0)</td><td>51 (20.7)</td><td></td><td>40 (20.1)</td><td>19 (15.0)</td><td></td></tr><tr><td>$\ge$ 5</td><td>127 (39.0)</td><td>49 (61.3)</td><td>78 (31.7)</td><td></td><td>121 (60.8)</td><td>6 (4.7)</td><td></td></tr><tr><td colspan="8"><strong>Medical history</strong></td></tr><tr><td>Major neurocognitive disorders</td><td>134 (38.0)</td><td>21 (23.6)</td><td>113 (42.8)</td><td><strong>.001</strong></td><td>0 (0.0)</td><td>134 (100.0)</td><td></td></tr><tr><td>Hypertension</td><td>234 (66.3)</td><td>50 (56.2)</td><td>184 (69.7)</td><td><strong>.012</strong></td><td>144 (65.8)</td><td>90 (67.2)</td><td>.786</td></tr><tr><td>Diabetes mellitus</td><td>80 (22.7)</td><td>23 (25.8)</td><td>57 (21.6)</td><td>.407</td><td>52 (23.7)</td><td>28 (20.9)</td><td>.535</td></tr><tr><td>Asthma or COPD</td><td>46 (13.0)</td><td>13 (14.6)</td><td>33 (12.5)</td><td>.610</td><td>32 (14.6)</td><td>14 (10.5)</td><td>.259</td></tr><tr><td>Cardiomyopathy</td><td>159 (45.0)</td><td>24 (27.0)</td><td>135 (51.1)</td><td><strong>&lt;.001</strong></td><td>92 (42.0)</td><td>67 (50.0)</td><td>.143</td></tr><tr><td>Severe chronic renal failure</td><td>38 (10.8)</td><td>5 (5.6)</td><td>33 (12.5)</td><td>.070</td><td>22 (10.1)</td><td>16 (11.9)</td><td>.577</td></tr><tr><td>Solid or hematological cancer</td><td>67 (19.0)</td><td>15 (16.9)</td><td>52 (19.7)</td><td>.554</td><td>45 (20.6)</td><td>22 (16.4)</td><td>.337</td></tr><tr><td colspan="8"><strong>General signs</strong></td></tr><tr><td>Sudden deterioration of general condition</td><td>186 (52.7)</td><td>34 (38.2)</td><td>152 (57.6)</td><td><strong>.002</strong></td><td>113 (51.6)</td><td>73 (54.5)</td><td>.599</td></tr><tr><td>Low blood pressure</td><td>51 (14.5)</td><td>8 (9.0)</td><td>43 (16.3)</td><td>.090</td><td>31 (14.2)</td><td>20 (14.9)</td><td>.842</td></tr><tr><td>Body temperature</td><td></td><td></td><td></td><td><strong>.011</strong></td><td></td><td></td><td><strong>.013</strong></td></tr><tr><td>No fever</td><td>58 (16.4)</td><td>14 (15.7)</td><td>44 (16.7)</td><td></td><td>36 (16.4)</td><td>22 (16.4)</td><td></td></tr><tr><td>Subfebrile temperature 37.5°-38°C</td><td>75 (21.3)</td><td>10 (11.2)</td><td>65 (24.6)</td><td></td><td>35 (16.0)</td><td>40 (29.9)</td><td></td></tr><tr><td>Hyperthermia $> 38°C$</td><td>198 (56.1)</td><td>62 (69.7)</td><td>136 (51.5)</td><td></td><td>135 (61.6)</td><td>63 (47.0)</td><td></td></tr><tr><td>Alternation of hyperthermia and hypothermia</td><td>22 (6.2)</td><td>3 (3.4)</td><td>19 (7.2)</td><td></td><td>13 (5.9)</td><td>9 (6.7)</td><td></td></tr><tr><td colspan="8"><strong>Respiratory signs</strong></td></tr><tr><td>Cough</td><td>208 (58.9)</td><td></td><td></td><td>.153</td><td></td><td></td><td><strong>&lt;.001</strong></td></tr><tr><td>Sputum</td><td>82 (23.2)</td><td>14 (15.7)</td><td>68 (25.8)</td><td></td><td>49 (22.4)</td><td>33 (24.6)</td><td></td></tr><tr><td>Dry</td><td>126 (35.7)</td><td>35 (39.3)</td><td>91 (34.5)</td><td></td><td>97 (44.3)</td><td>29 (21.6)</td><td></td></tr><tr><td>Polypnea</td><td>141 (39.9)</td><td></td><td></td><td>.165</td><td></td><td></td><td><strong>.014</strong></td></tr><tr><td>Between 23 and 29/min</td><td>94 (26.6)</td><td>17 (19.1)</td><td>77 (29.2)</td><td></td><td>58 (26.5)</td><td>36 (26.9)</td><td></td></tr><tr><td>$\ge$ 30/min</td><td>47 (13.3)</td><td>12 (13.5)</td><td>35 (13.3)</td><td></td><td>38 (17.4)</td><td>9 (6.7)</td><td></td></tr><tr><td colspan="8"><strong>ENT signs</strong></td></tr><tr><td>Rhinorrhea</td><td>32 (9.1)</td><td>9 (10.1)</td><td>23 (8.7)</td><td>.691</td><td>23 (10.5)</td><td>9 (6.7)</td><td>.229</td></tr></tbody></table>
<table><caption>Table 1. Continued</caption><thead><tr><th rowspan="2"></th><th rowspan="2">Population of<br>the Study<br>(N = 353)</th><th colspan="3">Comparison of Patients &lt; and &gt;<br>80 y of Age</th><th colspan="3">Comparison of Patients With and Without<br>MNDs</th></tr><tr><th>Age &lt; 80 y<br>(n = 89)</th><th>Age ≥ 80 y<br>(n = 264)</th><th>P Value<sup>a</sup></th><th>No MND<br>(n = 219)</th><th>With MND<br>(n = 134)</th><th>P Value<sup>a</sup></th></tr></thead><tbody><tr><td>Odynophagia</td><td>9 (2.6)</td><td>2 (2.3)</td><td>7 (2.7)</td><td>1.000</td><td>7 (3.2)</td><td>2 (1.5)</td><td>.492</td></tr><tr><td>Otalgia</td><td>2 (0.6)</td><td>1 (1.1)</td><td>1 (0.4)</td><td>.441</td><td>2 (0.9)</td><td>0 (0)</td><td>.528</td></tr><tr><td>Conjunctivitis</td><td>3 (0.9)</td><td>1 (1.1)</td><td>2 (0.8)</td><td>1.000</td><td>1 (0.5)</td><td>2 (1.5)</td><td>.560</td></tr><tr><td>Dysgeusia—ageusia<sup>c</sup></td><td>25 (7.1)</td><td>8 (9.0)</td><td>17 (6.5)</td><td>.428</td><td>22 (10.1)</td><td>3 (2.3)</td><td><strong>.006</strong></td></tr><tr><td>Anosmia<sup>c</sup></td><td>7 (2.0)</td><td>0 (0)</td><td>7 (2.7)</td><td>.198</td><td>6 (2.8)</td><td>1 (0.8)</td><td>.260</td></tr><tr><td><strong>Gastrointestinal signs</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Diarrhea</td><td>77 (21.8)</td><td>23 (25.8)</td><td>54 (20.5)</td><td>.287</td><td>53 (24.2)</td><td>24 (17.9)</td><td>.165</td></tr><tr><td>Nausea—vomiting</td><td>22 (6.2)</td><td>3 (3.4)</td><td>19 (7.2)</td><td>.197</td><td>16 (7.3)</td><td>6 (4.5)</td><td>.286</td></tr><tr><td><strong>Geriatric syndromes</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Falls</td><td>66 (18.7)</td><td>7 (7.9)</td><td>59 (22.4)</td><td><strong>.002</strong></td><td>36 (16.4)</td><td>30 (22.4)</td><td>.164</td></tr><tr><td>Hypoactive delirium</td><td>62 (17.6)</td><td>14 (15.7)</td><td>48 (18.2)</td><td>.599</td><td>25 (11.4)</td><td>37 (27.6)</td><td><strong>&lt;.001</strong></td></tr><tr><td>Overactive delirium</td><td>32 (9.1)</td><td>5 (5.6)</td><td>27 (10.2)</td><td>.190</td><td>12 (5.5)</td><td>20 (14.9)</td><td><strong>.003</strong></td></tr><tr><td>Altered consciousness</td><td>37 (10.5)</td><td>6 (6.7)</td><td>31 (11.7)</td><td>.183</td><td>14 (6.4)</td><td>23 (17.2)</td><td><strong>.001</strong></td></tr><tr><td><strong>Biology</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Lymphopenia<sup>d</sup></td><td>247 (74.6)</td><td>66 (78.6)</td><td>181 (73.3)</td><td>.336</td><td>165 (79.3)</td><td>82 (66.7)</td><td><strong>.011</strong></td></tr><tr><td>Lymphocytes/mm<sup>3</sup> (n = 246), mean ± SD</td><td>725 ± 267</td><td>730 ± 285</td><td>723 ± 261</td><td>.856</td><td>692 ± 258</td><td>791 ± 275</td><td><strong>.016</strong></td></tr><tr><td>Leukopenia<sup>e</sup></td><td>9 (2.7)</td><td>2 (2.4)</td><td>7 (2.8)</td><td>1.000</td><td>5 (2.4)</td><td>4 (3.2)</td><td>.733</td></tr><tr><td>Leukocytes/mm<sup>3</sup> (n = 17), mean ± SD</td><td>2 394 ± 881</td><td>2613 ± 1174</td><td>2327 ± 818</td><td>.571</td><td>2261 ± 1091</td><td>2545 ± 603</td><td>.630</td></tr><tr><td>Thrombopenia<sup>f</sup></td><td>85 (25.4)</td><td>24 (28.6)</td><td>61 (24.3)</td><td>.436</td><td>58 (27.6)</td><td>27 (21.6)</td><td>.244</td></tr><tr><td>Thrombocytes/mm<sup>3</sup> (n = 84), mean ± SD</td><td>115 523 ± 29 085</td><td>113 708 ± 32 512</td><td>116 250 ± 27 860</td><td>.984</td><td>112 810 ± 31 743</td><td>121 577 ± 21 354</td><td>.355</td></tr></tbody></table>

Data presented as n (%) where applicable. P < .05 indicated in bold.

(57.8%) exhibited ≤3 symptoms, and 15% had 0–1 symptom during the first 72 hours of the infection. The most frequent symptoms were thermal dysregulation (83.6%), cough (58.9%), and sudden deterioration of general condition (52.7%). Polypnea was found in 39.9% including n = 47 with severe polypnea ≥ 30 cycles/min, and gastrointestinal signs in 24.4% including n = 77 with diarrhea. Biologically, 76.4% of the population had lymphopenia, with 725 ± 267 lymphocytes per mm³ on average.

Comparison of those < 80 and > 80 years of age showed that falls (22.4% vs 7.9%, P = .002; odds ratio [OR] = 3.37; 95% confidence interval [95% CI], 1.48–7.69) and sudden deterioration of general condition (57.6% vs 38.2%, P = .002; OR = 2.20; 95% CI, 1.34–3.59) were more frequently after 80 years of age, whereas fever was less frequent (51.5% vs 69.7%, P = .011; OR = 0.46; 95% CI, .28–.77).

Comparison between patients with and without MND showed that those with MND exhibited more often hypoactive (27.6% vs 11.4%, P < .001; OR = 2.96; 95% CI, 1.69–5.20) and overactive delirium (14.9% vs 5.5%, P = .003; OR = 3.03; 95% CI, 1.43–6.42) and altered consciousness (17.2% vs 6.4%,

P = .001; OR = 3.03; 95% CI, 1.50–6.13), and less often hyperthermia (47.0% vs 61.6%, P = .013; OR = 0.55; 95% CI, .36–.85), cough (46.3% vs 66.7%, P < .001; OR = 0.35; 95% CI, .21–.57), and dysgeusia-ageusia (2.3% vs 10.1%, P = .006; OR = 0.21; 95% CI, .06–.70).

Finally, the multiple correspondence analysis results distinguished between 2 profiles of older patients. The first profile matched with patients younger than age 80 years without MND, who exhibited more frequent hyperthermia and cough during the first 72 hours of the infection, but no fall, altered consciousness, or hypoactive delirium. In contrast, the second profile matched with patients aged 80 years and older with MND; the latter exhibiting more frequently no specific symptoms, and most often an absence of hyperthermia, polypnea, cough, and dysgeusia-ageusia.

## DISCUSSION

This national French survey shows that older adults with COVID-19 exhibit a pauci-symptomatic clinical picture with less than 3 signs during the first 72 hours of the infection, generally combining general and respiratory signs (eg,

<footnote><sup>a</sup>Comparisons based on $\chi^2$ test or exact Fisher test for qualitative variables, and Student t test or Mann-Whitney U test for quantitative variables, as appropriate.</footnote>

<footnote><sup>b</sup>27 missing data.</footnote>

<footnote><sup>c</sup>2 missing data.</footnote>

<footnote><sup>d</sup>22 missing data.</footnote>

<footnote><sup>e</sup>20 missing data.</footnote>

<footnote><sup>f</sup>18 missing data.</footnote>

<footnote>Abbreviations: COPD, chronic obstructive pulmonary disease; ENT, ear nose and throat; GIR, Iso-Resource Group; MND, major neurocognitive disorders; SD, standard deviation.</footnote>
<table><caption>Table 1. Continued</caption><thead><tr><th rowspan="2"></th><th rowspan="2">Population of<br>the Study<br>(N = 353)</th><th colspan="3">Comparison of Patients &lt; and &gt;<br>80 y of Age</th><th colspan="3">Comparison of Patients With and Without<br>MNDs</th></tr><tr><th>Age &lt; 80 y<br>(n = 89)</th><th>Age ≥ 80 y<br>(n = 264)</th><th>P Value<sup>a</sup></th><th>No MND<br>(n = 219)</th><th>With MND<br>(n = 134)</th><th>P Value<sup>a</sup></th></tr></thead><tbody><tr><td>Odynophagia</td><td>9 (2.6)</td><td>2 (2.3)</td><td>7 (2.7)</td><td>1.000</td><td>7 (3.2)</td><td>2 (1.5)</td><td>.492</td></tr><tr><td>Otalgia</td><td>2 (0.6)</td><td>1 (1.1)</td><td>1 (0.4)</td><td>.441</td><td>2 (0.9)</td><td>0 (0)</td><td>.528</td></tr><tr><td>Conjunctivitis</td><td>3 (0.9)</td><td>1 (1.1)</td><td>2 (0.8)</td><td>1.000</td><td>1 (0.5)</td><td>2 (1.5)</td><td>.560</td></tr><tr><td>Dysgeusia—ageusia<sup>c</sup></td><td>25 (7.1)</td><td>8 (9.0)</td><td>17 (6.5)</td><td>.428</td><td>22 (10.1)</td><td>3 (2.3)</td><td><strong>.006</strong></td></tr><tr><td>Anosmia<sup>c</sup></td><td>7 (2.0)</td><td>0 (0)</td><td>7 (2.7)</td><td>.198</td><td>6 (2.8)</td><td>1 (0.8)</td><td>.260</td></tr><tr><td><strong>Gastrointestinal signs</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Diarrhea</td><td>77 (21.8)</td><td>23 (25.8)</td><td>54 (20.5)</td><td>.287</td><td>53 (24.2)</td><td>24 (17.9)</td><td>.165</td></tr><tr><td>Nausea—vomiting</td><td>22 (6.2)</td><td>3 (3.4)</td><td>19 (7.2)</td><td>.197</td><td>16 (7.3)</td><td>6 (4.5)</td><td>.286</td></tr><tr><td><strong>Geriatric syndromes</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Falls</td><td>66 (18.7)</td><td>7 (7.9)</td><td>59 (22.4)</td><td><strong>.002</strong></td><td>36 (16.4)</td><td>30 (22.4)</td><td>.164</td></tr><tr><td>Hypoactive delirium</td><td>62 (17.6)</td><td>14 (15.7)</td><td>48 (18.2)</td><td>.599</td><td>25 (11.4)</td><td>37 (27.6)</td><td><strong>&lt;.001</strong></td></tr><tr><td>Overactive delirium</td><td>32 (9.1)</td><td>5 (5.6)</td><td>27 (10.2)</td><td>.190</td><td>12 (5.5)</td><td>20 (14.9)</td><td><strong>.003</strong></td></tr><tr><td>Altered consciousness</td><td>37 (10.5)</td><td>6 (6.7)</td><td>31 (11.7)</td><td>.183</td><td>14 (6.4)</td><td>23 (17.2)</td><td><strong>.001</strong></td></tr><tr><td><strong>Biology</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Lymphopenia<sup>d</sup></td><td>247 (74.6)</td><td>66 (78.6)</td><td>181 (73.3)</td><td>.336</td><td>165 (79.3)</td><td>82 (66.7)</td><td><strong>.011</strong></td></tr><tr><td>Lymphocytes/mm<sup>3</sup> (n = 246), mean ± SD</td><td>725 ± 267</td><td>730 ± 285</td><td>723 ± 261</td><td>.856</td><td>692 ± 258</td><td>791 ± 275</td><td><strong>.016</strong></td></tr><tr><td>Leukopenia<sup>e</sup></td><td>9 (2.7)</td><td>2 (2.4)</td><td>7 (2.8)</td><td>1.000</td><td>5 (2.4)</td><td>4 (3.2)</td><td>.733</td></tr><tr><td>Leukocytes/mm<sup>3</sup> (n = 17), mean ± SD</td><td>2 394 ± 881</td><td>2613 ± 1174</td><td>2327 ± 818</td><td>.571</td><td>2261 ± 1091</td><td>2545 ± 603</td><td>.630</td></tr><tr><td>Thrombopenia<sup>f</sup></td><td>85 (25.4)</td><td>24 (28.6)</td><td>61 (24.3)</td><td>.436</td><td>58 (27.6)</td><td>27 (21.6)</td><td>.244</td></tr><tr><td>Thrombocytes/mm<sup>3</sup> (n = 84), mean ± SD</td><td>115 523 ± 29 085</td><td>113 708 ± 32 512</td><td>116 250 ± 27 860</td><td>.984</td><td>112 810 ± 31 743</td><td>121 577 ± 21 354</td><td>.355</td></tr></tbody></table>

Data presented as n (%) where applicable. P < .05 indicated in bold.

Abbreviations: COPD, chronic obstructive pulmonary disease; ENT, ear nose and throat; GIR, Iso-Resource Group; MND, major neurocognitive disorders; SD, standard deviation.

(57.8%) exhibited ≤3 symptoms, and 15% had 0–1 symptom during the first 72 hours of the infection. The most frequent symptoms were thermal dysregulation (83.6%), cough (58.9%), and sudden deterioration of general condition (52.7%). Polypnea was found in 39.9% including n = 47 with severe polypnea ≥ 30 cycles/min, and gastrointestinal signs in 24.4% including n = 77 with diarrhea. Biologically, 76.4% of the population had lymphopenia, with 725 ± 267 lymphocytes per mm³ on average.

Comparison of those < 80 and > 80 years of age showed that falls (22.4% vs 7.9%, P = .002; odds ratio [OR] = 3.37; 95% confidence interval [95% CI], 1.48–7.69) and sudden deterioration of general condition (57.6% vs 38.2%, P = .002; OR = 2.20; 95% CI, 1.34–3.59) were more frequently after 80 years of age, whereas fever was less frequent (51.5% vs 69.7%, P = .011; OR = 0.46; 95% CI, .28–.77).

Comparison between patients with and without MND showed that those with MND exhibited more often hypoactive (27.6% vs 11.4%, P < .001; OR = 2.96; 95% CI, 1.69–5.20) and overactive delirium (14.9% vs 5.5%, P = .003; OR = 3.03; 95% CI, 1.43–6.42) and altered consciousness (17.2% vs 6.4%,

P = .001; OR = 3.03; 95% CI, 1.50–6.13), and less often hyperthermia (47.0% vs 61.6%, P = .013; OR = 0.55; 95% CI, .36–.85), cough (46.3% vs 66.7%, P < .001; OR = 0.35; 95% CI, .21–.57), and dysgeusia-ageusia (2.3% vs 10.1%, P = .006; OR = 0.21; 95% CI, .06–.70).

Finally, the multiple correspondence analysis results distinguished between 2 profiles of older patients. The first profile matched with patients younger than age 80 years without MND, who exhibited more frequent hyperthermia and cough during the first 72 hours of the infection, but no fall, altered consciousness, or hypoactive delirium. In contrast, the second profile matched with patients aged 80 years and older with MND; the latter exhibiting more frequently no specific symptoms, and most often an absence of hyperthermia, polypnea, cough, and dysgeusia-ageusia.

DISCUSSION

This national French survey shows that older adults with COVID-19 exhibit a pauci-symptomatic clinical picture with less than 3 signs during the first 72 hours of the infection, generally combining general and respiratory signs (eg,

<footnote><sup>a</sup>Comparisons based on $\chi^2$ test or exact Fisher test for qualitative variables, and Student t test or Mann-Whitney U test for quantitative variables, as appropriate.</footnote>

<footnote><sup>b</sup>27 missing data.</footnote>

<footnote><sup>c</sup>2 missing data.</footnote>

<footnote><sup>d</sup>22 missing data.</footnote>

<footnote><sup>e</sup>20 missing data.</footnote>

<footnote><sup>f</sup>18 missing data.</footnote>
hyperthermia and cough) with peculiarities that should alert the clinician (eg, sudden deterioration of general condition, diarrhea, lymphopenia, geriatric syndromes including falls and delirium). Various clinical profiles were highlighted across older adults, especially among the oldest-old ≥80 years and those with chronic diseases such as MND.

Our survey provides the first description of the COVID-19 signs in older, and even oldest-old, adults with comorbidities [1-3]. Compared with previous meta-analyses in younger adults [5-7], we found that older adults with COVID-19 often exhibit thermal dysregulation, which, however, results less often in hyperthermia (56% here vs 82% [5] to 91% [6] in younger adults) and more often in subfebrile temperatures or alterations of hyperthermia and hypothermia (not described thus far to our knowledge). The prevalence of cough was similar (59% here vs 61% [5] to 72% [7] in younger adults). In contrast, the sudden deterioration of general condition, mostly illustrated by marked asthenia, was particularly frequent in older adults (53% here vs 36% [5] to 51% [6] in younger adults). Also, older adults exhibited more often dyspnea (40% here vs 26% [5] to 30% [6] in younger adults) and gastrointestinal signs (24.4% here with mostly diarrhea [21.8%] vs 10% in younger adults [5, 8]). This should encourage clinicians to integrate the gastrointestinal signs into the diagnostic reasoning for SARS-CoV-2 infection in older adults. Older adults had less often anosmia (2% here vs 86% in younger adults [9]) and dysgeusia-ageusia (7% here vs 89% in younger adults [9]). The latter prevalence should be cautiously interpreted however because of olfactory and gustatory dysfunctions with advancing age [10]. Finally, we found a higher proportion of lymphopenia in older adults compared with the general population (75% here vs 55% [3]). Lymphopenia was more significant than that usually observed in the normal aging population (750/mm³ vs 1432/mm³ in the literature [11]), and may explain part of the excess mortality observed in older adults with COVID-19 [1].

Our study has a number of limitations. This is an observational cross-sectional study conducted on a panel of French older patients who may be not representative of the general older population. The 64 physicians who responded to the survey, however, came from all French regions. A reporting bias cannot be ruled out because the accuracy and completeness of the data were entirely reliant upon physicians' declarations, although the questionnaire was designed to limit variability in readers' interpretations by asking only factual data. Also, in the absence of mass screening policy in France, only patients for whom a biological test had been carried out because of suspected infection, for clinical reasons for example, could be included, which may have overestimated the prevalence of some signs. The lack of control group prevented to determine the average number of symptoms met in non-COVID-19 French older adults. Similarly, no data were available on the use of concomitant drugs, for example

of antibiotics, which could partially explain increases in gastrointestinal signs. Finally, only patients diagnosed with RT-PCR test were included, although the sensitivity of this test presents a relatively high risk of false negatives (sensitivity of 72%) [12], which may have excluded a number of patients with COVID-19.

In conclusion, this national French survey revealed that the clinical picture of older adults with COVID-19 includes both general and respiratory signs like in younger adults (eg, hyperthermia and cough), but also more peculiar features such as marked asthenia, diarrhea, lymphopenia, and geriatric syndromes. We also reported various clinical profiles across older adults, notably in those aged 80 years and older and those with a history of MND who appeared particularly pauci- or asymptomatic during the first 72 hours of the infection. These findings should be integrated into the clinical reasoning in geriatric medicine and encourage the systematization of diagnostic tests for SARS-CoV-2 infection in older adults.

### Notes

**Author contributions.** C. A. has full access to all of the data in the study, takes responsibility for the data, the analyses, and interpretation, and has the right to publish any and all data, separate and apart from the attitudes of the sponsors. All authors have read and approved the manuscript. Study concept and design: C. A., G. S., N. S., G. B., O. G., and G. G. Acquisition of data: C. A., G. S., N. S., J. P. A., J. G., G. B., O. G., and G. G. Analysis and interpretation of data: C. A., G. S., and J. G. Drafting of the manuscript: C. A., G. S., and J. G. Critical revision of the manuscript for important intellectual content: N. S., J. P. A., G. B., O. G., and G. G. Statistical expertise: J. G. Administrative, technical, or material support: C. A. Study supervision: C. A.

**Acknowledgments.** The authors thank all participants and services for their cooperation; Melinda Beaudenon, MS, and Romain Simon, MS, from the Research Center on Autonomy and Longevity, University Hospital of Angers, France; Caroline Pastorelli, from the French Society of Geriatrics and Gerontology (SFGG); and the COVID-19 study group of the SFGG. SFGG COVID-19 study group: Didier Albert, Cédric Annweiler, Gaëlle Annweiler, Jean-Pierre-Aquino, Marine Asfar, Adeline Bannier, Jean Barré, Axel Bernard, Gilles Berrut, Mohand Chérif Bessai, Yves Beucher, Maëlle Beunardeau, Isabelle Biajoux, Clémence Boully, Anne-Sophie Boureau, Antoine Brangier, Thomas Brunet, Hélène Campana Briault, Edouard Chaussade, Adrien Cohen, Julian Cornaglia, Axelle Courau, Nicolas Crochette, Sylvie Dardalhon, Guillaume Duval, Marine de La Chapelle, Séverine Deledicq, Mathilde Devaux, Gael Durel, Élise Fiaux, Thibaut Fraisse, Xavier Galimard, Jennifer Gautier, Gaetan Gavazzi, Béatrice Gonzalez, Olivier Guérin, Aline Gury, Valérie Haguenauer-Bariteau, Julie Hamrit, Céline Hervo, Béatrice Lacave, Maxime Le Floch, Gwenaël Le Moal, Pierre-Marie Liais, Matthieu Lilamand, Jocelyne Loison, Paul Loubet, Karin Maley, Hélène Mangeard, Géraldine Martin-Gaujard, Marc Mennecart, Hélène Meytadier, Jean-Marc Michel, Nathalie Michel-Laaengh, Elena Paillaud, Mathieu Priner, Emeline Proye, Guillaume Sacco, Nathalie Salle, Denis Soriano, Maturin Tabue Teguo, Julien Vernaudon, François Weill, and Julien Zirnhelt. Permission has been obtained from all persons named in this section. No participant objected to the use of anonymized clinical and biological data for research purposes.

**Disclaimer.** Patient level data are freely available from the corresponding author at Cedric.Annweiler@chu-angers.fr. There is no personal identification risk within this anonymized raw data, which is available after notification and authorization of the competent authorities.

**Potential conflicts of interest.** The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
hyperthermia and cough) with peculiarities that should alert the clinician (eg, sudden deterioration of general condition, diarrhea, lymphopenia, geriatric syndromes including falls and delirium). Various clinical profiles were highlighted across older adults, especially among the oldest-old ≥80 years and those with chronic diseases such as MND.

Our survey provides the first description of the COVID-19 signs in older, and even oldest-old, adults with comorbidities [1-3]. Compared with previous meta-analyses in younger adults [5-7], we found that older adults with COVID-19 often exhibit thermal dysregulation, which, however, results less often in hyperthermia (56% here vs 82% [5] to 91% [6] in younger adults) and more often in subfebrile temperatures or alterations of hyperthermia and hypothermia (not described thus far to our knowledge). The prevalence of cough was similar (59% here vs 61% [5] to 72% [7] in younger adults). In contrast, the sudden deterioration of general condition, mostly illustrated by marked asthenia, was particularly frequent in older adults (53% here vs 36% [5] to 51% [6] in younger adults). Also, older adults exhibited more often dyspnea (40% here vs 26% [5] to 30% [6] in younger adults) and gastrointestinal signs (24.4% here with mostly diarrhea [21.8%] vs 10% in younger adults [5, 8]). This should encourage clinicians to integrate the gastrointestinal signs into the diagnostic reasoning for SARS-CoV-2 infection in older adults. Older adults had less often anosmia (2% here vs 86% in younger adults [9]) and dysgeusia-ageusia (7% here vs 89% in younger adults [9]). The latter prevalence should be cautiously interpreted however because of olfactory and gustatory dysfunctions with advancing age [10]. Finally, we found a higher proportion of lymphopenia in older adults compared with the general population (75% here vs 55% [3]). Lymphopenia was more significant than that usually observed in the normal aging population (750/mm³ vs 1432/mm³ in the literature [11]), and may explain part of the excess mortality observed in older adults with COVID-19 [1].

Our study has a number of limitations. This is an observational cross-sectional study conducted on a panel of French older patients who may be not representative of the general older population. The 64 physicians who responded to the survey, however, came from all French regions. A reporting bias cannot be ruled out because the accuracy and completeness of the data were entirely reliant upon physicians' declarations, although the questionnaire was designed to limit variability in readers' interpretations by asking only factual data. Also, in the absence of mass screening policy in France, only patients for whom a biological test had been carried out because of suspected infection, for clinical reasons for example, could be included, which may have overestimated the prevalence of some signs. The lack of control group prevented to determine the average number of symptoms met in non-COVID-19 French older adults. Similarly, no data were available on the use of concomitant drugs, for example

of antibiotics, which could partially explain increases in gastrointestinal signs. Finally, only patients diagnosed with RT-PCR test were included, although the sensitivity of this test presents a relatively high risk of false negatives (sensitivity of 72%) [12], which may have excluded a number of patients with COVID-19.

In conclusion, this national French survey revealed that the clinical picture of older adults with COVID-19 includes both general and respiratory signs like in younger adults (eg, hyperthermia and cough), but also more peculiar features such as marked asthenia, diarrhea, lymphopenia, and geriatric syndromes. We also reported various clinical profiles across older adults, notably in those aged 80 years and older and those with a history of MND who appeared particularly paucï- or asymptomatic during the first 72 hours of the infection. These findings should be integrated into the clinical reasoning in geriatric medicine and encourage the systematization of diagnostic tests for SARS-CoV-2 infection in older adults.

## Notes

**Author contributions.** C. A. has full access to all of the data in the study, takes responsibility for the data, the analyses, and interpretation, and has the right to publish any and all data, separate and apart from the attitudes of the sponsors. All authors have read and approved the manuscript. Study concept and design: C. A., G. S., N. S., G. B., O. G., and G. G. Acquisition of data: C. A., G. S., N. S., J. P. A., J. G., G. B., O. G., and G. G. Analysis and interpretation of data: C. A., G. S., and J. G. Drafting of the manuscript: C. A., G. S., and J. G. Critical revision of the manuscript for important intellectual content: N. S., J. P. A., G. B., O. G., and G. G. Statistical expertise: J. G. Administrative, technical, or material support: C. A. Study supervision: C. A.

**Acknowledgments.** The authors thank all participants and services for their cooperation; Melinda Beaudenon, MS, and Romain Simon, MS, from the Research Center on Autonomy and Longevity, University Hospital of Angers, France; Caroline Pastorelli, from the French Society of Geriatrics and Gerontology (SFGG); and the COVID-19 study group of the SFGG. SFGG COVID-19 study group: Didier Albert, Cédric Annweiler, Gaëlle Annweiler, Jean-Pierre-Aquino, Marine Asfar, Adeline Bannier, Jean Barré, Axel Bernard, Gilles Berrut, Mohand Chérif Bessai, Yves Beucher, Maëlle Beunardeau, Isabelle Biajoux, Clémence Boully, Anne-Sophie Boureau, Antoine Brangier, Thomas Brunet, Hélène Campana Briault, Edouard Chaussade, Adrien Cohen, Julian Cornaglia, Axelle Courau, Nicolas Crochette, Sylvie Dardalhon, Guillaume Duval, Marine de La Chapelle, Séverine Deledicq, Mathilde Devaux, Gael Durel, Élise Fiaux, Thibaut Fraisse, Xavier Galimard, Jennifer Gautier, Gaetan Gavazzi, Béatrice Gonzalez, Olivier Guérin, Aline Gury, Valérie Haguenauer-Bariteau, Julie Hamrit, Céline Hervo, Béatrice Lacave, Maxime Le Floch, Gwenaël Le Moal, Pierre-Marie Liais, Matthieu Lilamand, Jocelyne Loison, Paul Loubet, Karin Maley, Hélène Mangeard, Géraldine Martin-Gaujard, Marc Mennecart, Hélène Meytadier, Jean-Marc Michel, Nathalie Michel-Laaengh, Elena Paillaud, Mathieu Priner, Emeline Proye, Guillaume Sacco, Nathalie Salle, Denis Soriano, Maturin Tabue Teguo, Julien Vernaudon, François Weill, and Julien Zirnhelt. Permission has been obtained from all persons named in this section. No participant objected to the use of anonymized clinical and biological data for research purposes.

**Disclaimer.** Patient level data are freely available from the corresponding author at Cedric.Annweiler@chu-angers.fr. There is no personal identification risk within this anonymized raw data, which is available after notification and authorization of the competent authorities.

**Potential conflicts of interest.** The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
## References

1. Sacco G, Brière O, Asfar M, Guérin O, Berrut G, Annweiler C. Symptoms of COVID-19 among older adults: systematic review of biomedical literature. Geriatr Psychol Neuropsychiatr Vieil **2020**, 18:135–40. doi:10.1684/pnv.2020.0863

2. Wang L, He W, Yu X, et al. Coronavirus disease 2019 in elderly patients: characteristics and prognostic factors based on 4-week follow-up. J Infect **2020**, 80: 639–45.

3. Chen T, Dai Z, Mo P, et al. Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study. J Gerontol A Biol Sci Med Sci **2020**, glaa089 Available from: https://doi.org/10.1093/gerona/glaa089

4. Aguilova L, Sauzéon H, Balland É, Consel C, N'Kaoua B. [AGGIR scale: a contribution to specifying the needs of disabled elders]. Rev Neurol (Paris) **2014**, 170:216–21.

5. Borges do Nascimento IJ, Cacic N, Abdulazeem HM, et al. Novel coronavirus infection (COVID-19) in humans: a scoping review and meta-analysis. J Clin Med **2020**, 9: 941.

6. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis, **2020**, 94: 91–95.

7. Sun P, Qie S, Liu Z, Ren J, Li K, Xi J. Clinical characteristics of hospitalized patients with SARS-CoV-2 infection: a single arm meta-analysis. J Med Virol **2020**, 92:612–7. Available from: https://doi.org/10.1002/jmv.25735.

8. Jin X, Lian J-S, Hu J-H, et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut **2020**, 69: 1002–9.

9. Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome? Rhinology **2020**, 58:299–301.

10. Zhang C, Wang X. Initiation of the age-related decline of odor identification in humans: a meta-analysis. Ageing Res Rev **2017**, 40:45–50.

11. Bender BS, Nagel JE, Adler WH, Andres R. Absolute peripheral blood lymphocyte count and subsequent mortality of elderly men. J Am Geriatr Soc **1986**, 34: 649–54.

12. Yang Y, Yang M, Shen C, et al. Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections. medRxiv **2020**: 2020.02.11.20021493. Available at: https://doi.org/10.1101/2020.02.11.20021493.
## References

1. Sacco G, Brière O, Asfar M, Guérin O, Berrut G, Annweiler C. Symptoms of COVID-19 among older adults: systematic review of biomedical literature. Geriatr Psychol Neuropsychiatr Vieil **2020**, 18:135–40. doi:10.1684/pnv.2020.0863

2. Wang L, He W, Yu X, et al. Coronavirus disease 2019 in elderly patients: characteristics and prognostic factors based on 4-week follow-up. J Infect **2020**, 80: 639–45.

3. Chen T, Dai Z, Mo P, et al. Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study. J Gerontol A Biol Sci Med Sci **2020**, glaa089 Available from: https://doi.org/10.1093/gerona/glaa089

4. Aguilova L, Sauzéon H, Balland É, Consel C, N'Kaoua B. [AGGIR scale: a contribution to specifying the needs of disabled elders]. Rev Neurol (Paris) **2014**, 170:216–21.

5. Borges do Nascimento IJ, Cacic N, Abdulazeem HM, et al. Novel coronavirus infection (COVID-19) in humans: a scoping review and meta-analysis. J Clin Med **2020**, 9: 941.

6. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis, **2020**, 94: 91–95.

7. Sun P, Qie S, Liu Z, Ren J, Li K, Xi J. Clinical characteristics of hospitalized patients with SARS-CoV-2 infection: a single arm meta-analysis. J Med Virol **2020**, 92:612–7. Available from: https://doi.org/10.1002/jmv.25735.

8. Jin X, Lian J-S, Hu J-H, et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut **2020**, 69: 1002–9.

9. Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome? Rhinology **2020**, 58:299–301.

10. Zhang C, Wang X. Initiation of the age-related decline of odor identification in humans: a meta-analysis. Ageing Res Rev **2017**, 40:45–50.

11. Bender BS, Nagel JE, Adler WH, Andres R. Absolute peripheral blood lymphocyte count and subsequent mortality of elderly men. J Am Geriatr Soc **1986**, 34: 649–54.

12. Yang Y, Yang M, Shen C, et al. Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections. medRxiv **2020**: 2020.02.11.20021493. Available at: https://doi.org/10.1101/2020.02.11.20021493.
# EVIDENCE SUPPORTS THE HIGH BARRIER TO RESISTANCE OF DOVATO UP TO 5 YEARS¹⁻³

## CONFIDENCE IN DOVATO ACROSS TREATMENT SETTINGS⁴⁻⁹

Treatment-naïve resistance rates, with up to

3 years of evidence⁵⁻⁷

0% (n=1/885)*,⁴

REAL-WORLD EVIDENCE

0.1% (n=1/953)*,¹,¹,¹,⁵,⁷

RANDOMISED CONTROLLED TRIALS

Treatment-experienced resistance rates, with up to

5 years of evidence¹⁻³

0.03%

(n=10/35,888)*,⁴

REAL-WORLD EVIDENCE

0%

(n=0/615)¹,⁸,⁸,⁹

RANDOMISED CONTROLLED TRIALS

## >300,000 PEOPLE LIVING WITH HIV HAVE BEEN TREATED WITH DOVATO GLOBALLY¹⁰

DOVATO is supported by a wealth of evidence, with the outcomes of >40,000 people living with HIV captured within clinical trials and real-world evidence, including those with:⁴⁻⁹,¹¹,¹²

<figure><img src="image_1.png" /></figure>

NO PRIOR TREATMENT EXPERIENCE¹³

<figure><img src="image_2.png" /></figure>

NO BASELINE RESISTANCE TESTING¹³

<figure><img src="image_3.png" /></figure>

HIGH BASELINE VIRAL LOAD (>100,000 copies/mL and even >1M copies/mL)⁶,¹³

<figure><img src="image_4.png" /></figure>

LOW CD4 + COUNT (≤200 cells/mm³)¹³

■ Patients from phase III RCTs
■ Patients from unique real-world cohorts

<figure><img src="image_5.png" /></figure>

## IS IT TIME TO RECONSIDER THE VALUE OF THE 2ND NRTI?

LEARN MORE

<figure><img src="image_6.png" /></figure>

DOVATO is indicated for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults and adolescents above 12 years of age weighing at least 40 kg, with no known or suspected resistance to the integrase inhibitor class, or lamivudine.¹³

Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/ or search for MHRA Yellowcard in the Google Play or Apple App store. Adverse events should also be reported to GSK on 0800 221441

## REFERENCES

1. Maggiolo F et al. BMC Infect Dis 2022; 22(1): 782.
2. Taramasso L et al. AIDS Patient Care STDS 2021; 35(9): 342–353.

3. Cicullo A et al. JAIDS 2021; 88(3): 234–237.

4. ViiV Healthcare. Data on File. REF-223795. 2024.

5. Cahn P et al. AIDS 2022; 36(1): 39–48.

6. Rolle C et al. Open Forum Infect Dis 2023; 10(3): ofad101.

7. Cordova E et al. Poster presented at 12th IAS Conference on HIV Science. 23–26 July 2023. Brisbane, Australia. TUPEB02.

8. De Wit S et al. Slides presented at HIV Glasgow. 23–26 October 2022. Virtual and Glasgow, UK. M041.

9. Llibre J et al. Clin Infect Dis 2023; 76(4): 720–729.

10. ViiV Healthcare. Data on File. REF-220949. 2024.

11. Rolle C et al. Poster presented IDWeek. 11–15 October 2023. Virtual and Boston, USA. 1603.

12. Slim J et al. Abstract presented IDWeek. 11–15 October 2023. Virtual and Boston, USA. 1593.

13. DOVATO. Summary of Product Characteristics. June 2023.

## PRESCRIBING INFORMATION

Dovato Prescribing Information

Legal Notices

Privacy Policy

Contact Us

ViiV Healthcare, 980 Great West Road, Brentford, Middlesex, London, UK.

ViiV trademarks are owned by or licensed to the ViiV Healthcare group of companies.

Non-ViiV trademarks are owned by or licensed to their respective owners or licensors.

©2024 ViiV Healthcare group of companies or its licensor. All rights reserved.

Intended for healthcare professionals only.

## ABBREVIATIONS

**3TC**, lamivudine; **CD4**, cluster of differentiation 4; **DTG**, dolutegravir; **FDA**, United States Food and Drug Administration; **FTC**, emtricitabine; **HIV**, human immunodeficiency virus; **ITT-E**, intention-to-treat exposed; **NRTI**, nucleoside/nucleotide reverse transcriptase inhibitor; **RCT**, randomised controlled trial; **RNA**, ribonucleic acid; **TAF**, tenofovir alafenamide fumarate; **TDF**, tenofovir disoproxil fumarate; **XTC**, emtricitabine.

## FOOTNOTES

*Data extracted from a systematic literature review of DTG+3TC real-world evidence. Overlap between cohorts cannot be fully excluded.

**The reported rate reflects the sum-total of resistance cases calculated from GEMINI I and II (n=1/716, through 144 weeks), STAT (n=0/131, through 52 weeks), and D2ARLING (n=0/106, through 24 weeks).⁵⁻⁷

†GEMINI I and II are two identical 148-week, phase III, randomised, double-blind, multicentre, parallel-group, non-inferiority, controlled clinical trials testing the efficacy of DTG/3TC in treatment-naïve patients. Participants with screening HIV-1 RNA ≤500,000 copies/mL were randomised 1:1 to once-daily DTG/3TC (n=716, pooled) or DTG + TDF/FTC (n=717, pooled). The primary endpoint of each GEMINI study was the proportion of participants with plasma HIV-1 RNA <50 copies/mL at Week 48 (ITT-E population, snapshot algorithm).¹³

‡STAT is a phase IIIb, open-label, 48-week, single-arm pilot study evaluating the feasibility, efficacy, and safety of DTG/3TC in 131 newly diagnosed HIV-1 infected adults as a first line regimen. The primary endpoint was the proportion of participants with plasma HIV-1 RNA <50 copies/mL at Week 24.⁶

§2ARLING is a randomised, open-label, phase IV study designed to assess the efficacy and safety of DTG/3TC in treatment-naïve people with HIV with no available baseline HIV-1 resistance testing. Participants were randomised in a 1:1 ratio to receive DTG/3TC (n=106) or DTG + TDF/XTC (n=108). The primary endpoint was the proportion of participants with plasma HIV-1 RNA <50 copies/mL at Week 48.⁷ Results at week 24 of the study.

|| The reported rate reflects the sum-total of resistance cases calculated from TANGO (n=0/369, through 196 weeks) and SALSA (n=0/246, through 48 weeks).⁸,⁹

¶TANGO is a randomised, open-label, trial testing the efficacy of DOVATO in virologically suppressed patients. Participants were randomised in a 1:1 ratio to receive DOVATO (n=369) or continue with TAF-containing regimens (n=372) for up to 200 weeks. At Week 148, 298 of those on TAF-based regimens switched to DOVATO. The primary efficacy endpoint was the proportion of subjects with plasma HIV-1 RNA ≥50 copies/mL (virologic non-response) as per the FDA Snapshot category at Week 48 (adjusted for randomisation stratification factor).⁸,¹³

#SALSA is a phase III, randomised, open-label, non-inferiority clinical trial evaluating the efficacy and safety of switching to DTG/3TC compared with continuing current antiretroviral regimens in virologically suppressed adults with HIV. Eligible participants were randomised 1:1 to switch to once-daily DTG/3TC (n=246) or continue current antiretroviral regimens (n=247). The primary endpoint was the proportion of subjects with plasma HIV-1 RNA ≥50 copies/mL at Week 48 (ITT-E population, snapshot algorithm).⁹
# EVIDENCE SUPPORTS THE HIGH BARRIER TO RESISTANCE OF DOVATO UP TO 5 YEARS¹⁻³

## CONFIDENCE IN DOVATO ACROSS TREATMENT SETTINGS⁴⁻⁹

Treatment-naïve resistance rates, with up to

3 years of evidence⁵⁻⁷

0% (n=1/885)*,⁴

REAL-WORLD EVIDENCE

0.1% (n=1/953)*,¹,¹,¹,⁸,⁵⁻⁷

RANDOMISED CONTROLLED TRIALS

Treatment-experienced resistance rates, with up to

5 years of evidence¹⁻³

0.03%

(n=10/35,888)*,⁴

REAL-WORLD EVIDENCE

0%

(n=0/615)¹,⁸,⁸,⁹

RANDOMISED CONTROLLED TRIALS

## >300,000 PEOPLE LIVING WITH HIV HAVE BEEN TREATED WITH DOVATO GLOBALLY¹⁰

DOVATO is supported by a wealth of evidence, with the outcomes of >40,000 people living with HIV captured within clinical trials and real-world evidence, including those with:⁴⁻⁹,¹¹,¹²

<figure><img src="image_2.png" /></figure>

NO PRIOR TREATMENT EXPERIENCE¹³

<figure><img src="image_3.png" /></figure>

NO BASELINE RESISTANCE TESTING¹³

<figure><img src="image_4.png" /></figure>

HIGH BASELINE VIRAL LOAD (>100,000 copies/mL and even >1M copies/mL)⁶,¹³

<figure><img src="image_5.png" /></figure>

LOW CD4 + COUNT (≤200 cells/mm³)¹³

■ Patients from phase III RCTs
■ Patients from unique real-world cohorts

<figure><img src="image_6.png" /></figure>

## IS IT TIME TO RECONSIDER THE VALUE OF THE 2ND NRTI?

LEARN MORE

<figure><img src="image_7.png" /></figure>

DOVATO is indicated for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults and adolescents above 12 years of age weighing at least 40 kg, with no known or suspected resistance to the integrase inhibitor class, or lamivudine.¹³

Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/ or search for MHRA Yellowcard in the Google Play or Apple App store. Adverse events should also be reported to GSK on 0800 221441

### REFERENCES

1. Maggiolo F et al. BMC Infect Dis 2022; 22(1): 782.
2. Taramasso L et al. AIDS Patient Care STDS 2021; 35(9): 342–353.
3. Ciccullo A et al. JAIDS 2021; 88(3): 234–237.
4. ViiV Healthcare. Data on File. REF-223795. 2024.
5. Cahn P et al. AIDS 2022; 36(1): 39–48.
6. Rolle C et al. Open Forum Infect Dis 2023; 10(3): ofad101.
7. Cordova E et al. Poster presented at 12th IAS Conference on HIV Science. 23–26 July 2023. Brisbane, Australia. TUPEB02.
8. De Wit S et al. Slides presented at HIV Glasgow. 23–26 October 2022. Virtual and Glasgow, UK. M041.
9. Llibre J et al. Clin Infect Dis 2023; 76(4): 720–729.
10. ViiV Healthcare. Data on File. REF-220949. 2024.
11. Rolle C et al. Poster presented IDWeek. 11–15 October 2023. Virtual and Boston, USA. 1603.
12. Slim J et al. Abstract presented IDWeek. 11–15 October 2023. Virtual and Boston, USA. 1593.
13. DOVATO. Summary of Product Characteristics. June 2023.

### PRESCRIBING INFORMATION

Dovato Prescribing Information

Legal Notices

Privacy Policy

Contact Us

ViiV Healthcare, 980 Great West Road, Brentford, Middlesex, London, UK.

ViiV trademarks are owned by or licensed to the ViiV Healthcare group of companies.

Non-ViiV trademarks are owned by or licensed to their respective owners or licensors.

©2024 ViiV Healthcare group of companies or its licensor. All rights reserved.

Intended for healthcare professionals only.

### ABBREVIATIONS

**3TC**, lamivudine; **CD4**, cluster of differentiation 4; **DTG**, dolutegravir; **FDA**, United States Food and Drug Administration; **FTC**, emtricitabine; **HIV**, human immunodeficiency virus; **ITT-E**, intention-to-treat exposed; **NRTI**, nucleoside/nucleotide reverse transcriptase inhibitor; **RCT**, randomised controlled trial; **RNA**, ribonucleic acid; **TAF**, tenofovir alafenamide fumarate; **TDF**, tenofovir disoproxil fumarate; **XTC**, emtricitabine.

### FOOTNOTES

*Data extracted from a systematic literature review of DTG+3TC real-world evidence. Overlap between cohorts cannot be fully excluded.

**The reported rate reflects the sum-total of resistance cases calculated from GEMINI I and II (n=1/716, through 144 weeks), STAT (n=0/131, through 52 weeks), and D2ARLING (n=0/106, through 24 weeks).⁵⁻⁷

†GEMINI I and II are two identical 148-week, phase III, randomised, double-blind, multicentre, parallel-group, non-inferiority, controlled clinical trials testing the efficacy of DTG/3TC in treatment-naïve patients. Participants with screening HIV-1 RNA ≤500,000 copies/mL were randomised 1:1 to once-daily DTG/3TC (n=716, pooled) or DTG + TDF/FTC (n=717, pooled). The primary endpoint of each GEMINI study was the proportion of participants with plasma HIV-1 RNA <50 copies/mL at Week 48 (ITT-E population, snapshot algorithm).¹³

‡STAT is a phase IIIb, open-label, 48-week, single-arm pilot study evaluating the feasibility, efficacy, and safety of DTG/3TC in 131 newly diagnosed HIV-1 infected adults as a first line regimen. The primary endpoint was the proportion of participants with plasma HIV-1 RNA <50 copies/mL at Week 24.⁶

SD2ARLING is a randomised, open-label, phase IV study designed to assess the efficacy and safety of DTG/3TC in treatment-naïve people with HIV with no available baseline HIV-1 resistance testing. Participants were randomised in a 1:1 ratio to receive DTG/3TC (n=106) or DTG + TDF/XTC (n=108). The primary endpoint was the proportion of participants with plasma HIV-1 RNA <50 copies/mL at Week 48.⁷ Results at week 24 of the study.

|| The reported rate reflects the sum-total of resistance cases calculated from TANGO (n=0/369, through 196 weeks) and SALSA (n=0/246, through 48 weeks).⁸,⁹

¶TANGO is a randomised, open-label, trial testing the efficacy of DOVATO in virologically suppressed patients. Participants were randomised in a 1:1 ratio to receive DOVATO (n=369) or continue with TAF-containing regimens (n=372) for up to 200 weeks. At Week 148, 298 of those on TAF-based regimens switched to DOVATO. The primary efficacy endpoint was the proportion of subjects with plasma HIV-1 RNA ≥50 copies/mL (virologic non-response) as per the FDA Snapshot category at Week 48 (adjusted for randomisation stratification factor).⁸,¹³

#SALSA is a phase III, randomised, open-label, non-inferiority clinical trial evaluating the efficacy and safety of switching to DTG/3TC compared with continuing current antiretroviral regimens in virologically suppressed adults with HIV. Eligible participants were randomised 1:1 to switch to once-daily DTG/3TC (n=246) or continue current antiretroviral regimens (n=247). The primary endpoint was the proportion of subjects with plasma HIV-1 RNA ≥50 copies/mL at Week 48 (ITT-E population, snapshot algorithm).⁹