Sandrine Couture, MDCM1*, Marc-Antoine Lepage, MD, MSc1*, Claire Godard-Sebillotte, MD, MPH, PhD2, Nadia Sourial, PhD3,4, Catherine Talbot-Hamon, MD, MSc (Epi)5, Richard Kremer, MD, PhD6, Ami Grunbaum, MDCM61Department of Medicine, McGill University Health Centre, Montréal, QC
2Department of Family Medicine, McGill University, Montréal, QC
3Département de médecine de famille et de médecine d’urgence, Université de Montréal, Montréal, QC
4Centre de recherche du Centre hospitalier de l’Université de Montréal, Montreal, QC
5Division of Geriatric Medicine, McGill University Health Centre, Montréal, QC
6Division of Medical Biochemistry, McGill University Health Centre, Montréal, QC
Older adults are more vulnerable to severe infection and mortality due to COVID-19. They have atypical presentations of the disease without respiratory symptoms, making early diagnosis clinically challenging. We aimed to compare the baseline characteristics, presentation, and disease course of older (≥70 yrs & ≥90 yrs) and younger (<70 yrs) patients hospitalized with COVID-19.
Retrospective review of 429 consecutive patients hospitalized at two tertiary care hospitals in Montreal, Canada, with PCR-confirmed COVID-19. Baseline characteristics, presentation, in-hospital complications, and outcomes were recorded. Desegregation by age was performed to compare older versus younger individuals. Additional subgroup analyses were performed amongst patients ≥70 stratifying by sex, living situation, and those presenting with geriatric syndromes compared to those without.
Patients ≥70 (n=260) presented less frequently with respiratory symptoms compared to patients <70 (n=169) (52% vs. 32%). 11% of patients ≥70 and 24% of patients ≥90 presented with a geriatric syndrome as their sole symptom compared to 3% of those <70. Older adults were more likely to develop disease complications (including delirium, acute kidney injury, and hypernatremia) and had higher in-hospital mortality (32% vs. 13%). Subgroup analyses revealed heightened vulnerability to complications in older men, those from long-term care, and those with at least one geriatric syndrome upon presentation.
Older adults presenting to hospital with COVID-19 often have no respiratory symptoms and can present with only a geriatric syndrome. New geriatric syndromes in older individuals should trigger evaluation for COVID-19 and consideration for early initiation of multidisciplinary care to prevent complications.
Key words: COVID-19, older adults, geriatric syndromes, outcomes, clinical research
Older adults are amongst the most vulnerable to complications and mortality from COVID-19.(1–3) During the first wave of the pandemic in Quebec, Canada, older adults aged 70 years and older accounted for 26.7% of confirmed COVID cases and for 63.6% of those hospitalized with the disease, while representing only 13.8% of the province’s population.(4) Furthermore, older adults aged 70 and above accounted for the majority (91.3%) of COVID-related deaths.(4)
There is growing evidence that older adults are more likely to have atypical presentations of COVID-19 with lack of fever, cough, or dyspnea.(5–7) Reports from Europe and the US suggest that COVID-19 may present as geriatric syndromes, including falls and delirium, in this population.(7–10) This is especially common in older adults from long-term care.(8,11,12) A recent Canadian study demonstrated that delirium was highly prevalent in older adults aged 65 and above with COVID-19 at the time of hospitalization and was associated with higher in-hospital mortality.(13) The nuances of the clinical presentation of older patients with COVID-19 have critical implications for early diagnosis, timely isolation, and infection control. An improved understanding of the disease course is crucial for enabling optimal care and prognostication in this high-risk population. Further Canadian data are required to fully characterize the impact of a non-respiratory presentation of COVID-19 in older adults on the disease course and outcomes.
The aims of this study are 1) to describe the clinical characteristics and outcomes of old persons (≥70) and older old persons (≥90) hospitalized with COVID-19 during the first wave in Montreal, Canada; and 2) to determine whether adults ≥70 presenting with at least one geriatric syndrome have different in-hospital course and mortality compared to those without.
We conducted a retrospective review of electronic medical records (EMR) of all patients aged 18 and above with laboratory-confirmed COVID-19 admitted between March 26th and July 16th, 2020 to two academic hospitals in Montreal, Canada. Both institutions provide tertiary and quaternary care to a large, diverse urban population. A confirmed case of COVID-19 was defined as a positive result of a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay from a nasal swab.
The following data were extracted from the EMR: baseline demographics, living situation, pre-existing medical conditions, home medications, and symptoms at presentation. The Charlson Comorbidity Index(14) was calculated to capture the degree and severity of comorbidities. We extracted laboratory and imaging findings at the time of admission, as well as complications, need for intensive care or ventilatory support, and discharge destination or in-hospital death until July 16th, 2020. Data were extracted independently by two of the investigators based on a standardized form. In case of disagreement between reviewers, assistance of a third reviewer was sought for resolution.
Patients <70 years old are classified as younger and those ≥70 as older. A subgroup of ≥90 year-olds is also presented, classified as the older old. The threshold of 70 years old was selected in order to align with Quebec-sourced epidemiological data from the first wave of the pandemic that found 70–79-year-olds to be the youngest cohort, representing a higher proportion of hospitalizations (21.0%) and deaths (18.0%) compared to next-youngest cohort (14.3% of hospitalizations, 6.2% of deaths for 60–69–year-olds).(4) The ≥90 subgroup is considered to explore our hypotheses in the extremely old.
We defined non-respiratory presentations as absence of cough, dyspnea, hemoptysis, sputum production, nasal congestion, and sore throat. In keeping with the American Geriatrics Society’s recommendations to define geriatric syndromes as common conditions in older adults having significant consequences for functioning and quality of life,(15) we considered falls, delirium, and functional decline as geriatric syndromes at presentation. Malnutrition, deconditioning, and pressure injury were also considered geriatric syndromes when assessing for in-hospital complications.
Continuous variables are presented as means and standard deviations (SD). Categorical variables are summarized as counts and percentages. Based on our findings, we performed three subgroup analyses within the ≥70 age group comparing complications and outcomes between men and women, between those coming from independent living situations (home and autonomous private residence) and those from long-term care facilities, and lastly between those presenting with a geriatric syndrome and those without. Descriptive statistics were performed with IBM SPSS Statistics for Mac v27.0 (SPSS Inc. Chicago, IL).
Institutional review board approval was obtained for data collection. All patient information was de-identified with respect to names and dates.
Four hundred and twenty-nine patients were hospitalized with PCR-confirmed COVID-19 between March 26th and July 16th, 2020. Sixty-one per cent were ≥70 years old. Adults ≥70 averaged 83 years old (SD 7.3) and adults <70 averaged 55 yrs (SD 11.7). Forty-nine per cent of patients ≥70 and 37% of patients <70 were women. Fifty-one patients (12%) were ≥90 years old.
TABLE 1 Population characteristics of patients <70, ≥70, and ≥90 admitted to hospital with COVID-19
Patients ≥70 had more pre-existing medical conditions at baseline than patients <70 (mean Charlson Comorbidity Index 6 vs. 2). These comorbidities included higher proportions of hypertension, coronary artery disease, heart failure, cerebrovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, major neurocognitive disorder, and active cancers. This was reflected by a greater number of home medications: 75% of patients ≥70 had polypharmacy (>5 medications) compared to 41% of patients <70. Amongst all patients ≥70, those ≥90 had more geriatric syndromes at baseline including history of falls and dementia.
Fifty-nine per cent of patients ≥70 originated from long-term care facilities and 32% were living at home in the community. Seventy-two per cent of patients ≥90 came from long-term care facilities.
Patients ≥70 had a lower proportion of respiratory symptoms of cough (27% vs. 47%) and dyspnea (33% vs. 48%) compared to their younger counterparts. Fifty-two per cent of patients ≥70 and 63% of patients ≥90 presented without any respiratory symptoms, compared to 32% of patients <70.
TABLE 2 Clinical presentation of patients <70, ≥70, and ≥90 admitted to hospital with COVID-19
Patients ≥70 had a higher proportion of delirium (29% vs. 7%), functional decline (14% vs. 1%), and falls (15% vs. 5%). Patients ≥90 had higher proportion of falls at presentation compared to the overall ≥70 group (31% vs. 15%). Eleven per cent of patients ≥70 and 24% of patients ≥90 presented with a geriatric syndrome as their sole symptom, compared to 3% of patients <70.
Eighty-five per cent of patients ≥70 developed complications during their hospitalization compared to 56% of patients <70. A higher proportion of acute kidney injury (AKI) (35% vs. 22%) and hypernatremia (32% vs. 17%) was observed in patients ≥70 compared to the <70 group. Patients ≥70 had higher proportion of delirium acquired in hospital (30% vs. 17%). The patients ≥90 had fewer venous thromboembolisms (0 vs. 17%) and bacterial pneumonia superinfections (6% vs. 17%) compared to the overall ≥70 group. Complication profiles were otherwise similar.
TABLE 3 Course in hospital and outcomes of patients <70, ≥70, and ≥90 admitted to hospital with COVID-19
Per institutional policy, goals of care were either based on previously available advanced directives or discussed with the patients and their family at the time of admission. Two hundred and sixty-two of 429 patients were eligible (143 or 85% of patients <70 and 119 or 46% of patients ≥70). Of these, 39 patients ≥70 were cared for in the ICU (33% of eligible and 15% of all adults ≥70), compared to 71 patients <70 (50% of eligible and 42% of all adults <70). One patient ≥90 was cared for in the ICU (10% of eligible, 2% if all patients ≥90).
Patients ≥70 had higher in-hospital all-cause mortality (32% vs 13%). Amongst this group, 49 patients who were not eligible for ICU care due to their established goals of care died (19%), compared to 35 patients (13%) who were eligible based on their goals of care.
Patients ≥90 had higher in-hospital mortality compared to the overall ≥70 group (43% vs. 32%).
Characteristics, complications, and outcomes of adults ≥70 presenting with at least one geriatric syndrome compared to those without are presented in Table 4. Of the adults ≥70 presenting with at least one geriatric syndrome, 73% were from long-term care residences compared to 48% of those without. Adults aged 70 or older presenting with a geriatric syndrome had a higher proportion of complications from their disease in hospital (93% vs. 77%) compared to those without, including new delirium (40% vs. 21%), AKI (45% vs. 28%), and hypernatremia (44% vs. 21%). Thirty-seven per cent of patients ≥70 presenting with a geriatric syndrome died compared to 28% of those who did not.
TABLE 4 Characteristics, complications, and outcomes of patients ≥70 admitted to hospital after presenting with at least one geriatric syndromea
Characteristics, complications, and outcomes of patients aged 70 and older according to their sex are presented in Table 5. Men had higher proportions of cardiac complications (17% vs. 9%) and bacterial pneumonia superinfection (24% vs. 9%) compared to women in this age group. When considering their goals of care, men ≥70 were more likely to be cared for in ICU (44% vs. 16%) and receive mechanical ventilation than women ≥70 (23% vs. 8%). In this age group, mortality was higher amongst men than women (35% vs. 29%).
TABLE 5 Characteristics, complications, and outcomes of older patients ≥70 hospitalized with COVID-19 according to sex
Characteristics, complications, and outcomes of adults ≥70 from independent living situations compared to those from long-term care are presented in Table 6. Patients from long-term care were more likely to present with delirium (39% vs. 15%) and to develop delirium in hospital (34% vs. 24%) compared to patients from independent living situations. Complication profiles and outcomes were otherwise similar.
TABLE 6 Characteristics, complications, and outcomes of older patients ≥70 hospitalized with COVID-19 according to living situation
We report the characteristics, presenting features, and in-hospital outcomes of 429 COVID-19–affected patients hospitalized in two academic hospitals in Montreal, Canada, with particular attention to those above age 70 having a geriatric syndrome at their presentation to hospital. Patients ≥70 differed from patients <70 in their presentations. Over 50% of adults ≥70 lacked any respiratory symptoms, presenting with geriatric syndromes like functional decline, fall, and delirium; these were the only symptoms in 12% of the ≥70 group. Adults ≥70 had more complications during hospitalization with higher proportions of new delirium, AKI, and hypernatremia. Patients ≥70 were more likely to die of their disease. These findings were exacerbated by increasing age, as patients ≥90 even more commonly had a geriatric syndrome as their sole presenting symptom and had higher mortality than the overall older group.
The high proportion of non-respiratory COVID-19 presentations in our study is concordant with reports from France and the United Kingdom where delirium and falls were common reasons for hospitalizations in patients above age 80 with COVID-19.(7–9,16,17)
Geriatric syndromes appear especially prominent in long-term care residents as 73% of our patients with a geriatric syndrome at presentation were from long-term care. Similarly, delirium was a more common presenting feature amongst those residing in long-term care compared to those in independent living situations. This was shown in a single-centre cohort study in the United Kingdom where 18.8% of patients from nursing homes had atypical symptoms, as well as in a point-prevalence survey in United States nursing homes where 8% of COVID-19–positive patients had atypical symptoms, defined in both studies as absence of fever, cough, and dyspnea.(8,11)
Adults ≥70 in our study, especially those presenting with a geriatric syndrome, had higher proportions of AKI and hypernatremia in-hospital compared to younger patients. An analysis of the international HOPE-COVID-19 registry demonstrated more frequent dysnatremias in patients in this age group and increased mortality in patients with both hyponatremia and hypernatremia.(18) A French study of 821 patients hospitalized to geriatric wards with COVID-19 further observed AKI as a frequent complication, which was significantly more frequent in older adults who died.(19) The occurrence of these complications suggests a vulnerability of older adults hospitalized with COVID-19 and especially of those presenting with a geriatric syndrome to dehydration. Dehydration in older persons can have severe consequences. If left untreated, mortality can exceed 50%.(20,21) Furthermore, it is a common precipitating factor for geriatric syndromes, including delirium and falls.(22,23) In our study, adults ≥70 who had a geriatric syndrome at presentation were also more prone to develop a new delirium in hospital compared to those without.
Our findings are consistent with previous studies that have demonstrated an association between older age and mortality.(3,6,24) However, our study may underestimate complications and mortality in the older population as some patients were discharged to community inpatient centres to offload acute care beds during the first wave of the pandemic in Montreal. We suspect multiple patients may have died in the community. Amongst our subgroup analyses, our study suggests a trend for higher mortality in older adults presenting with a geriatric syndrome. This was previously demonstrated in American and Italian studies of the association between delirium and death in COVID-19 patients.(10,25)
Amongst our subgroup analyses, our study further demonstrated a different pattern of disease between older men and women, with older men exhibiting more complications and lethal disease. Men had higher proportion of cardiovascular complications and bacterial pneumonia superinfection in hospital. Additionally, men had higher frequency of intensive care admission, intubation and mechanical ventilation, and death. The association between male sex and severity of disease, as well as mortality, was demonstrated in reports of patients of all-ages hospitalized cases from China, Europe, and the United States.(26–29) A French study specifically conducted amongst older adults hospitalized on geriatric wards with COVID-19 demonstrated the probability of in-hospital mortality was increased with male sex.(19) The sexual dysmorphism in COVID-19 follows previous data demonstrating men and women have different immune responses to viral infections.(30,31)
Our study has limitations. First, it only considers older adults hospitalized with COVID-19. It is therefore not representative of all COVID-19 infections amongst older adults. Second, we only included patients from two hospitals within the Montreal area. However, we included all admitted patients, providing a comprehensive portrait of the most affected geographic area during the first wave of COVID-19 in Quebec. Moreover, the retrospective nature of the study required reliance on review of medical records for data extraction. Certain information was missing from baseline assessment, or may be less reliable due to being based on other physicians’ interpretation of findings or on patients’ recall of events (some of whom presented with delirium). We only assessed patients’ in-hospital course, limiting our assessment of long-term repercussions of disease. If a patient’s goals of care were geared towards comfort, imaging and laboratory examinations were limited. Lastly, comparisons in our study are descriptive and are intended to be regarded as hypothesis-generating for further studies.
This one of the first studies reporting the disease course of a Canadian cohort of older patients hospitalized with COVID-19 from presentation to in-hospital outcomes. The data emphasize the importance of non-respiratory presentations, especially of geriatric syndromes, as presenting features of COVID-19 in older adults. Our findings further demonstrate the heightened vulnerability of older adults presenting with a geriatric syndrome to complications, more so the extremes of age, men, and those from long-term care, emphasizing the need for early well-coordinated multidisciplinary care for these populations. We hope that the descriptive comparisons presented here will foster further discussion and exploration of new hypotheses.
Beware of non-respiratory presentations of COVID-19 in older persons. An older person developing a new geriatric syndrome in the context of the COVID-19 pandemic should prompt early isolation and testing.
A geriatric syndrome at presentation to hospital in a COVID-19–positive patient should trigger proactive measures to prevent and treat delirium and dehydration.
We have read and understood the Canadian Geriatrics Journal’s policy on conflicts of interest disclosure and declare no conflict of interest for this paper.
This work was supported by the Canadian Institutes for Health Research grants MOP-142287 and PJT-162158(RK).
1 Fu L, Wang B, Yuan T, et al. Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: a systematic review and meta-analysis. J Infect. 2020;80(6):656–65. Epub 2020/04/14. doi: 10.1016/j.jinf.2020.03.041.
2 Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020;323(18):1775–76. doi: 10.1001/jama.2020.4683.
3 Imam Z, Odish F, Gill I, et al. Older age and comorbidity are independent mortality predictors in a large cohort of 1305 COVID-19 patients in Michigan, United States. J Intern Med. 2020;288(4):469–76. Epub 2020/06/05. doi: 10.1111/joim.13119.
4 Institut national d’excellence en santé et en services sociaux (INESSS). Première vague de la pandémie de COVID-19 au Québec: regard sur les facteurs associés aux hospitalisations et aux décès 2020 [Décembre 2020]. Available from: https://www.inesss.qc.ca/fileadmin/doc/INESSS/COVID-19/COVID-19_INESSS_EP_Portrait_cohorte_COVID.pdf
5 Leung C. Risk factors for predicting mortality in elderly patients with COVID-19: a review of clinical data in China. Mech Ageing Dev. 2020;188:111255. Epub 2020/05/01. doi: 10.1016/j.mad.2020.111255.
6 Brill SE, Jarvis HC, Ozcan E, et al. COVID-19: a retrospective cohort study with focus on the over-80s and hospital-onset disease. BMC Med. 2020;18(1):194. Epub 2020/06/27. doi: 10.1186/s12916-020-01665-z.
7 Annweiler C, Sacco G, Salles N, et al. National French survey of coronavirus disease (COVID-19) symptoms in people aged 70 and over. Clin Infect Dis. 2020;72(3):490–94. doi: 10.1093/cid/ciaa792.
8 Rawle MJ, Bertfield DL, Brill SE. Atypical presentations of COVID-19 in care home residents presenting to secondary care: a UK single centre study. Aging Med. 2020;3(4):237–44. Epub 2021/01/05. doi: 10.1002/agm2.12126.
9 Vrillon A, Hourregue C, Azuar J, et al. COVID-19 in older adults: a series of 76 patients aged 85 years and older with COVID-19. J Am Geriatr Soc. 2020;68(12):2735–43. Epub 2020/10/13. doi: 10.1111/jgs.16894.
10 Kennedy M, Helfand BKI, Gou RY, et al. Delirium in older patients with COVID-19 presenting to the emergency department. JAMA Netwk Open. 2020;3(11):e2029540. Epub 2020/11/20. doi: 10.1001/jamanetworkopen.2020.29540.
11 Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. New Eng J Med. 2020;382(22):2081–90. Epub 2020/04/25. doi: 10.1056/NEJMoa2008457.
12 Janus SIM, Schepel AAM, Zuidema SU, de Haas EC. How typical is the spectrum of COVID-19 in nursing home residents? J Am Med Dir Assoc. 2021;22(3):511–13. Epub 2021/01/28. doi: 10.1016/j.jamda.2020.12.028.
13 Forget MF, Del Degan S, Leblanc J, et al. Delirium and inflammation in older adults hospitalized for COVID-19: a cohort study. Clin Interv Aging. 2021;16:1223–30. Epub 2021/07/09. doi: 10.2147/cia.S315405.
14 Frenkel WJ, Jongerius EJ, Mandjes-van Uitert MJ, van Munster BC, de Rooij SE. Validation of the Charlson Comorbidity Index in acutely hospitalized elderly adults: a prospective cohort study. J Am Geriatr Soc. 2014;62(2):342–46. Epub 2014/02/14. doi: 10.1111/jgs.12635.
15 Inouye SK, Studenski S, Tinetti ME, Kuchel GA. Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc. 2007;55(5):780–91. Epub 2007/05/12. doi: 10.1111/j.1532-5415.2007.01156.x.
16 Gan JM, Kho J, Akhunbay-Fudge M, et al. Atypical presentation of COVID-19 in hospitalised older adults. Ir J Med Sci. 2021;190(2):469–74. Epub 2020/09/23. doi: 10.1007/s11845-020-02372-7.
17 Zazzara MB, Penfold RS, Roberts AL, et al. Probable delirium is a presenting symptom of COVID-19 in frail, older adults: a cohort study of 322 hospitalised and 535 community-based older adults. Age Ageing. 2021;50(1):40–48. Epub 2020/09/29. doi: 10.1093/ageing/afaa223.
18 Ruiz-Sánchez JG, Núñez-Gil IJ, Cuesta M, et al. Prognostic impact of hyponatremia and hypernatremia in COVID-19 pneumonia. A HOPE-COVID-19 (Health Outcome Predictive Evaluation for COVID-19) registry analysis. Front Endocrinol. 2020;11:599255. Epub 2020/12/18. doi: 10.3389/fendo.2020.599255.
19 Zerah L, Baudouin É, Pépin M, et al. Clinical characteristics and outcomes of 821 older patients with SARS-Cov-2 infection admitted to acute care geriatric wards. J Gerontol A. 2021;76(3):e4–e12. Epub 2020/08/28. doi: 10.1093/gerona/glaa210.
20 Mahowald JM, Himmelstein DU. Hypernatremia in the elderly: relation to infection and mortality. J Am Geriatr Soc. 1981;29(4):177–80. Epub 1981/04/01. doi: 10.1111/j.1532-5415.1981.tb01761.x.
21 Weinberg AD, Minaker KL, Coble YD, et al. Dehydration: evaluation and management in older adults. JAMA. 1995;274(19):1552–56. Epub 1995/11/15. doi: 10.1001/jama.274.19.1552.
22 Hamrick I, Norton D, Birstler J, Chen G, Cruz L, Hanrahan L. Association between dehydration and falls. Mayo Clin Proc: Innov Qual Outcomes. 2020;4(3):259–65. Epub 2020/06/17. doi: 10.1016/j.mayocpiqo.2020.01.003.
23 Oh ES, Fong TG, Hshieh TT, Inouye SK. Delirium in older persons: advances in diagnosis and treatment. JAMA. 2017;318(12):1161–74. Epub 2017/10/04. doi: 10.1001/jama.2017.12067.
24 Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–62. Epub 2020/03/15. doi: 10.1016/S0140-6736(20)30566-3.
25 Garcez FB, Aliberti MJR, Poco PCE, et al. Delirium and adverse outcomes in hospitalized patients with COVID-19. J Am Geriatr Soc. 2020;68(11):2440–46. Epub 2020/08/25. doi: 10.1111/jgs.16803.
26 Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574–81. doi: 10.1001/jama.2020.5394.
27 Gebhard C, Regitz-Zagrosek V, Neuhauser HK, Morgan R, Klein SL. Impact of sex and gender on COVID-19 outcomes in Europe. Biol Sex Differ. 2020;11(1):29. Epub 2020/05/27. doi: 10.1186/s13293-020-00304-9.
28 Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. New Eng J Med. 2020;382(18):1708–20. Epub 2020/02/29. doi: 10.1056/NEJMoa2002032.
29 Harrison SL, Fazio-Eynullayeva E, Lane DA, Underhill P, Lip GYH. Comorbidities associated with mortality in 31,461 adults with COVID-19 in the United States: a federated electronic medical record analysis. PLoS Med. 2020;17(9):e1003321. Epub 2020/09/11. doi: 10.1371/journal.pmed.1003321.
30 Klein SL. The effects of hormones on sex differences in infection: from genes to behavior. Neurosci Biobehav Rev. 2000;24(6):627–38. Epub 2000/08/15. doi: 10.1016/s0149-7634(00)00027-0.
31 Ghosh S, Klein RS. sex drives dimorphic immune responses to viral infections. J Immunol. 2017;198(5):1782–90. Epub 2017/02/23. doi: 10.4049/jimmunol.1601166.
*Sandrine Couture & Marc-Antoine Lepage contributed equally to the authorship of this manuscript. ( Return to Text )
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Canadian Geriatrics Journal, Vol. 25, No. 3, September 2022