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A question of age
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Italy as of March 17, 2020 China as of February 11, 2020 No. of deaths Case-fatality No. of deaths Case-fatality (% of total) rate, %b (% of total) rate, %b
All 1625 (100) 7.2 1023 2.3
Age groups, y
0–9 0 0 0 0
10–19 0 0 1 (0.1) 0.2
20–29 0 0 7 (0.7) 0.2
30–39 4 (0.3) 0.3 18 (1.8) 0.2
40–49 10 (0.6) 0.4 38 (3.7) 0.4
50–59 43 (2.7) 1.0 130 (12.7) 1.3
60–69 139 (8.6) 3.5 309 (30.2) 3.6
70–79 578 (35.6) 12.8 312 (30.5) 8.0
≥80 850 (52.3) 20.2 208 (20.3) 14.8
Case-fatality rate by age group in Italy and Chinaa
a Data from China are from Chinese Centre for Disease Control and Prevention. Age was not available for 1 patient.b Case-fatality rate calculated as number of deaths/number of cases.
References: Onder G, Rezza G, Brusaferro S. Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy.JAMA. 2020 Mar 23. doi: 10.1001/jama.2020.4683.
Diseases N %Ischaemic heart disease 249 27.8Atrial fibrillation 213 23.7Heart failure 153 17.1Stroke 101 11.3Hypertension 655 73.0Diabetes 281 31.3Dementia 130 14.5Chronic obstructive pulmonary disease (COPD) 150 16.7Active cancer in the past 5 years 155 17.3Chronic liver disease 37 4.1Chronic renal failure 199 22.2
Number of comorbidities 0 comorbidities 15 2.1 1 comorbidity 151 21.3 2 comorbidities 184 25.9 3 comorbidities and over 360 50.7
The most commonly observed comorbidities in deceased COVID-19-positive patients
The dilemma of COVID-19, ageing and cardiovascular disease: insights from cardiovascular ageing science
Older patients with CVDLower ACE II levels
Higher angiotensin signalling
COVID-19SARS-CoV-2 binding to ACE II leads to reduced ACE II cell surface expression
Younger patients without CVDHigher ACE II levels
Lower angiotensin II signalling
Infected older patients with CVDCritically low ACE II levels
Exaggerated angiotensin II signalling
Infected younger patients without CVDModestly low ACE II levels
Modestly elevated angiotensin II signalling
Likely lower incidence of disease,but higher severity
Likely higher incidence of disease,but lower severity
References
AlGhatrif M, Cingolani O, Lakatta EG. The Dilemma of Coronavirus Disease 2019, Aging, and Cardiovascular Disease: Insights From Cardiovascular Aging Science. JAMA Cardiol. 2020 Apr 3. doi: 10.1001/jamacardio.2020.1329. http://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/statements/statement-older-people-are-at-highest-risk-from-covid-19,-but-all-must-act-to-prevent-community-spread (accessed April 2020)
Legend
ACE II: angiotensin II-converting enzyme
CVD: cardiovascular disease
SARS-CoV-2: severe acute respiratory syndrome coronavirus 2
Schematic of inflammatory profile before and after COVID-19 infection. Simplified schematic of the preinfection inflammatory profile among predisposed older individuals vs their younger counterparts.
The Dilemma of Coronavirus Disease 2019, Aging,and Cardiovascular DiseaseInsights From Cardiovascular Aging Science
As we brace for the imminent impact of the coronavi-rus disease 2019 (COVID-19) pandemic, we are facedwith a controversy on how to best minimize the risk oflethal disease among the most vulnerable of us. Prelimi-nary epidemiological data show an uneven-handed im-pact on the population, with an exponential increase indisease severity and mortality in those beyond the sixthdecade of life with cardiovascular disease (CVD) and dia-betes. Given that angiotensin-converting enzyme 2(ACE2), an enzyme coopted by severe acute respira-tory syndrome coronavirus 2 (SARS-CoV-2) to enter epi-thelial cells, is upregulated in patients with CVD and dia-betes treated with angiotensin-converting enzymeinhibitors (ACEIs) and angiotensin receptor blockers(ARBs), it was proposed that this increase in ACE2 ex-pression underpins the greater COVID-19 severity in thispopulation. This has created substantial controversy re-garding the approach to patients taking ACEIs/ARBs inpreparation for the pandemic, with some advocating fordiscontinuing these medications while expert opinionsrecommended against discontinuation, given the lack ofstrong evidence.1
To begin to unravel this complex dilemma, we mustconsider the role of ACE2 not only in COVID-19 patho-genesis but also as a component of renin-angiotensinsystem (RAS) signaling throughout the body. First, onemust recognize the scarcity of data on the topic, par-ticularly in humans. Nonetheless, the urgency of the situ-ation makes it imperative to use inductive reasoning toguide our next steps toward protecting our patients. Itis well established now that while ACE2 is targeted bySARS-CoV-2 to gain entrance into cells, it plays a majoranti-inflammatory role in RAS signaling by convertingangiotensin II, the quintessential perpetrator ofinflammation,2 to angiotensin 1-7, which carries anti-inflammatory properties.3
What has been missing in discussions of the afore-mentioned dilemma is the age-associated decline inACE2 expression, as observed in the lungs of rats,4 whichis in line with a constellation of major proinflammatorychanges perpetrated by an age-associated increase inRAS signaling throughout the body.5 Exaggerated formsof this proinflammatory profile are also salient patho-physiologic features of hypertension and diabetes, whichare highly prevalent at older ages.5 The upregulation ofACE2 in individuals with diabetes and hypertensiontreated with ACEIs/ARBs is, in a way, restorative of physi-ological function. Hence, these observations raise an ap-parent paradox: given ACE2 itself is the gateway of SARS-CoV-2 entry into cells, how can the reduction in ACE2levels in older persons and those with CVD predisposefor greater COVID-19 severity?
Thisapparentparadoxbecomesclear ifwedistinguishthe role of ACE2 as a gateway for SARS-CoV-2 facilitatingthe infection from its pivotal anti-inflammatory functionin RAS signaling that is compromised in individuals withCOVID-19, contributing to its severity (Figure).3 Indeed,data on the severe acute respiratory syndrome epidemicof 2003 demonstrates this divergence in factors predis-posing to disease occurrence and its severity; in the formerepidemic, although younger individuals in their thirdand fourth decades of life accounted for most of thoseinfected,6 theseyoungerpatientshadlowerdiseasesever-ity and risk of mortality compared with older people withpreexisting conditions.
Similarly, in the COVID-19 pandemic, it is plausiblethat greater expression of ACE2 leads to higher predis-position to incur the disease; preliminary epidemio-logic data from South Korea, where the most population-wide testing has taken place, show that most cases areamong younger adults7 who are expected to have higherlevels of ACE2.4 However, when it comes to COVID-19severity, reduction in ACE2 levels with aging and CVD andits associated upregulation of angiotensin II proinflam-matory pathway8 likely predispose older individuals withcardiovascular comorbidities to severe forms of COVID-19, as has been observed in Italy.7 This predisposition isexploited with SARS-CoV-2 binding to ACE2 itself, fur-ther reducing ACE2 cell surface expression, upregulat-ing angiotensin II signaling in the lungs, and yielding acute
Figure. Schematic of Inflammatory Profile Before and AfterCoronavirus Disease 2019 (COVID-19) Infection
Older patients with CVDLower ACE2 levelsHigher angiotensin signaling
Younger patients without CVDHigher ACE2 levelsLower angiotensin IIsignaling
COVID-19SARS-CoV-2 binding to ACE2 leads to reduced ACE2 cell surface expression
Infected older patients with CVD
Critically low ACE2 levelsExaggerated angiotensin II signaling
Likely lower incidence of disease, but higher severity
Infected younger patients without CVD
Modestly low ACE2 levelsModestly elevated angiotensin II signaling
Likely higher incidence ofdisease, but lower severity
Simplified schematic of the preinfection inflammatory profileamong predisposed older individuals vs their youngercounterparts. ACE2 indicates angiotensin-converting enzyme 2;CVD, cardiovascular disease; SARS-CoV-2, severe acuterespiratory syndrome coronavirus 2.
VIEWPOINT
Majd AlGhatrif, MD,MALaboratory ofCardiovascular Science,National Institute onAging, NationalInstitutes of Health,Baltimore, Maryland;and Divisions ofCardiology andHospital Medicine,Department ofMedicine, JohnsHopkins School ofMedicine, Baltimore,Maryland.
Oscar Cingolani, MDDivision of Cardiology,Department ofMedicine, JohnsHopkins School ofMedicine, Baltimore,Maryland.
Edward G. Lakatta,MDLaboratory ofCardiovascular Science,National Institute onAging, NationalInstitutes of Health,Baltimore, Maryland.
Viewpoint
CorrespondingAuthor: Majd AlGhatrif,MD, MA, Laboratory ofCardiovascular Science,National Institute onAging, NationalInstitutes of Health,251 Bayview Blvd,Baltimore, MD 21043([email protected]).
Opinion
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lung injury.3 Hence, compared with young individuals, older per-sons with CVD who already have reduced ACE2 levels will be ex-pected to be more predisposed to exaggerated inflammation withfurther reduction in ACE2 expression in the context of COVID-19,manifesting with greater disease severity.
In summary, older individuals, especially those with hyperten-sion and diabetes, have reduced ACE2 expression and upregula-tion of angiotensin II proinflammatory signaling; the increase in ACE2levels with ACEI/ARB treatment is more likely to be corrective tothese changes. We hypothesize that with superimposed COVID-19
disease, SARS-CoV-2 binding to ACE2 acutely exaggerates this pro-inflammatory background, predisposing these subpopulations togreater COVID-19 disease severity and mortality (Figure). Thishypothesis is in line with the evidence of a protective role of angio-tensin II antagonism against sepsis-associated acute lung injury9,10
and supports continuing therapy with ACEIs/ARBs and, more so,urgently calls for expanding ongoing trials treating patients with se-vere COVID-19 with RAS interventions to examine the role of theseinterventions in preventing lethal lung complications of COVID-19as cases surge around the world.
ARTICLE INFORMATION
Published Online: April 3, 2020.doi:10.1001/jamacardio.2020.1329
Conflict of Interest Disclosures: None reported.
REFERENCES
1. Bozkurt B, Kovacs R, Harrington B.HFSA/ACC/AHA statement addresses concerns re:using RAAS antagonists in COVID-19. AccessedMarch 22, 2020. https://professional.heart.org/professional/ScienceNews/UCM_505836_HFSAACCAHA-statement-addresses-concerns-re-using-RAAS-antagonists-in-COVID-19.jsp?utm_campaign=sciencenews19-20&utm_source=science-news&utm_medium=email&utm_content=phd03-17-20
2. Lakatta EG, Levy D. Arterial and cardiac aging:major shareholders in cardiovascular diseaseenterprises: part II: the aging heart in health: links
to heart disease. Circulation. 2003;107(2):346-354.doi:10.1161/01.CIR.0000048893.62841.F7
3. Kuba K, Imai Y, Rao S, et al. A crucial role ofangiotensin converting enzyme 2 (ACE2) in SARScoronavirus-induced lung injury. Nat Med. 2005;11(8):875-879. doi:10.1038/nm1267
4. Xie X, Chen J, Wang X, Zhang F, Liu Y. Age- andgender-related difference of ACE2 expression in ratlung. Life Sci. 2006;78(19):2166-2171. Publishedcorrection appears in Life Sci. 2006;79(26):2499.doi:10.1016/j.lfs.2005.09.038
5. Lakatta EG. The reality of getting old. Nat RevCardiol. 2018;15(9):499-500. doi:10.1038/s41569-018-0068-y
6. Liang W, Zhu Z, Guo J, et al; Beijing Joint SARSExpert Group. Severe acute respiratory syndrome,Beijing, 2003. Emerg Infect Dis. 2004;10(1):25-31.doi:10.3201/eid1001.030553
7. Backhaus A. Coronavirus: why it’s so deadly inItaly. Accessed March 22, 2020. https://medium.
com/@andreasbackhausab/coronavirus-why-its-so-deadly-in-italy-c4200a15a7bf
8. Rodrigues Prestes TR, Rocha NP, Miranda AS,Teixeira AL, Simoes-E-Silva AC. Theanti-inflammatory potential of ACE2/angiotensin-(1-7)/Mas receptor axis: evidence from basic andclinical research. Curr Drug Targets. 2017;18(11):1301-1313. doi:10.2174/1389450117666160727142401
9. Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acutelung failure. Nature. 2005;436(7047):112-116. doi:10.1038/nature03712
10. Wang D, Chai XQ, Magnussen CG, et al.Renin-angiotensin-system, a potentialpharmacological candidate, in acute respiratorydistress syndrome during mechanical ventilation.Pulm Pharmacol Ther. 2019;58:101833. doi:10.1016/j.pupt.2019.101833
Opinion Viewpoint
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Case-Fatality Rate and Characteristics of Patients Dying inRelation to COVID-19 in Italy
Only 3 cases of coronavirus disease 2019 (COVID-19)were identified in Italy in the first half of February 2020and all involved people who had recently traveled toChina. On February 20, 2020, a severe case of pneu-monia due to SARS-CoV-2 (severe acute respiratorysyndrome coronavirus 2) was diagnosed in northernItaly’s Lombardy region in a man in his 30s who had nohistory of possible exposure abroad. Within 14 days,many other cases of COVID-19 in the surrounding areawere diagnosed, including a substantial number of criti-cally ill patients.1 On the basis of the number of casesand of the advanced stage of the disease it was hypoth-esized that the virus had been circulating within thepopulation since January.
Another cluster of patients with COVID-19 was si-multaneously identified in Veneto, which bordersLombardy. Since then, the number of cases identified inItaly has rapidly increased, mainly in northern Italy, butall regions of the country have reported having pa-tients with COVID-19. After China, Italy now has the sec-ond largest number of COVID-19 cases2 and also hasa very high case-fatality rate.3 This Viewpoint reviewsthe Italian experience with COVID-19 with an emphasison fatalities.
Surveillance System and Overall Fatality RateAt the outset of the COVID-19 outbreak, the Italian Na-tional Institute of Health (Istituto Superiore di Sanità[ISS]) launched a surveillance system to collect informa-tion on all people with COVID-19 throughout the coun-try. Data on all COVID-19 cases were obtained from all19 Italian regions and the 2 autonomous provinces ofTrento and Bozen. COVID-19 cases were identified by re-verse transcriptase–polymerase chain reaction (RT-PCR)testing for the severe acute respiratory syndrome coro-navirus 2 (SARS-CoV-2). The fatality rate was defined asnumber of deaths in persons who tested positive forSARS-CoV-2 divided by number of SARS-CoV-2 cases.The overall fatality rate of persons with confirmedCOVID-19 in the Italian population, based on data up toMarch 17, was 7.2% (1625 deaths/22 512 cases).3 This rateis higher than that observed in other countries2 and maybe related to 3 factors.
Fatality Rate and Population AgeThe demographic characteristics of the Italian popula-tion differ from other countries. In 2019, approxi-mately 23% of the Italian population was aged 65 yearsor older. COVID-19 is more lethal in older patients, so theolder age distribution in Italy may explain, in part, Ita-ly’s higher case-fatality rate compared with that of othercountries. The Table shows the age-specific fatality ratein Italy compared with that of China.4
The overall case-fatality rate in Italy (7.2%) is sub-stantially higher than in China (2.3%). When data werestratified by age group, the case-fatality rate in Italy andChina appear very similar for age groups 0 to 69 years,but rates are higher in Italy among individuals aged70 years or older, and in particular among those aged80 years or older. This difference is difficult to explain.The distribution of cases is very different in the 2 coun-tries: individuals aged 70 years or older represent37.6% of cases in Italy and only 11.9% in China. In addi-tion, a relevant number of cases in Italy are in peopleaged 90 years or older (n = 687), and this age grouphas a very high fatality rate (22.7%); data on cases inthose aged 90 years or older were not reported inChina. In addition, the report from the WHO-ChinaJoint Mission on Coronavirus Disease 2019 Mortality,which presents data on 2114 COVID-19 related deathsamong 55 924 laboratory-confirmed cases in China,reported a fatality rate among patients aged 80 yearsor older that was similar to the rate in the Italian sample(21.9% in China vs 20.2% in Italy).5
Thus, the overall older age distribution in Italy rela-tive to that in China may explain, in part, the higher av-erage case-fatality rate in Italy.
Definition of COVID-19–Related DeathsA second possible explanation for the high Italian case-fatality rate may be how COVID-19–related deaths areidentified in Italy. Case-fatality statistics in Italy are basedon defining COVID-19–related deaths as those occur-ring in patients who test positive for SARS-CoV-2 viaRT-PCR, independently from preexisting diseases thatmay have caused death. This method was selected be-cause clear criteria for the definition of COVID-19–related deaths is not available.
Electing to define death from COVID-19 in this waymay have resulted in an overestimation of the case-fatality rate. A subsample of 355 patients with COVID-19who died in Italy underwent detailed chart review.Among these patients, the mean age was 79.5 years (SD,8.1) and 601 (30.0%) were women. In this sample, 117patients (30%) had ischemic heart disease, 126 (35.5%)had diabetes, 72 (20.3%) had active cancer, 87 (24.5%)had atrial fibrillation, 24 (6.8%) had dementia, and 34(9.6%) had a history of stroke. The mean number of pre-existing diseases was 2.7 (SD, 1.6). Overall, only 3 pa-tients (0.8%) had no diseases, 89 (25.1%) had a singledisease, 91 (25.6%) had 2 diseases, and 172 (48.5%) had3 or more underlying diseases. The presence of these co-morbidities might have increased the risk of mortality in-dependent of COVID-19 infection.
COVID-19–related deaths are not clearly defined inthe international reports available so far, and differences
VIEWPOINT
Graziano Onder, MD,PhDDepartment ofCardiovascular,Endocrine-MetabolicDiseases and Aging,Istituto Superiore diSanità, Rome, Italy.
Giovanni Rezza, MDDepartment ofInfectious Diseases,Istituto Superiore diSanità, Rome, Italy.
Silvio Brusaferro, MDOffice of the President,Istituto Superiore diSanità, Rome, Italy.
Video
CorrespondingAuthor: GrazianoOnder, MD, PhD,Department ofCardiovascular,Endocrine-MetabolicDiseases and Aging,Istituto Superiore diSanità, Via Giano dellaBella, 34-0161 Roma,Italy ([email protected]).
Opinion
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in definitions of what is or is not a COVID-19–related death might ex-plain variation in case-fatality rates among different countries. To bet-ter understand the actual causes of death, the ISS is now reviewingthe complete medical records of all patients with positive RT-PCR re-sults who have died in Italy.
Testing StrategiesA third possible explanation for variation in country-specific case-fatality rates are the differing strategies used for SARS-CoV-2 RT-PCRtesting. After an initial, extensive testing strategy of both sympto-matic and asymptomatic contacts of infected patients in a very earlyphase of the epidemic, on February 25, the Italian Ministry of Healthissued more stringent testing policies. This recommendation priori-tized testing for patients with more severe clinical symptoms whowere suspected of having COVID-19 and required hospitalization.Testing was limited for asymptomatic people or those who had lim-ited, mild symptoms. This testing strategy resulted in a high pro-portion of positive results, ie, 19.3% (positive cases, 21 157 of 109 170tested as of March 14, 2020), and an apparent increase in the case-fatality rate because patients who presented with less severe clini-cal disease (and therefore with lower fatality rate) were no longertested (case-fatality rate changed from 3.1% on February 24 to 7.2%on March 17). These more mild cases, with low fatality rate, were thusno longer counted in the denominator.
Other countries have different testing strategies. For example,the Republic of Korea has adopted a strategy of widely testing for
SARS-CoV-2. This may have led to the identification of a large num-ber of individuals who had mild or limited symptoms, but a muchlower case-fatality rate compared with Italy (1.0% vs 7.2%) be-cause many patients with mild disease who would not be tested inItaly were included in the denominator in Korea.2
ConclusionsIn conclusion, the current data illustrate that Italy has a high pro-portion of older patients with confirmed COVID-19 infection and thatthe older population in Italy may partly explain differences in casesand case-fatality rates among countries. Within Italy, COVID-19deaths are mainly observed among older, male patients who alsohave multiple comorbidities. However, these data are limited andwere derived from the first month of documented COVID-19 casesin Italy. In addition, some patients who are currently infected maydie in the near future, which may change the mortality pattern.
From a research perspective, the comparisons discussed high-light the need for transparency in reporting testing policies, withclear reporting of the denominators used to calculate case-fatalityrates and the age, sex, and clinical comorbid status of affected per-sons when comparing COVID-19 case and mortality rates betweendifferent countries and regions. Finally, because the outbreak isnew, continued surveillance, with transparent and accurate report-ing of patient characteristics and testing policies, is needed frommultiple countries to better understand the global epidemiology ofCOVID-19.
ARTICLE INFORMATION
Published Online: March 23, 2020.doi:10.1001/jama.2020.4683
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank the followingmembers of the COVID-19 Surveillance Group whowere involved in the collection of data used in thisreport: Xanthi Andrianou, Antonino Bella, StefaniaBellino, Stefano Boros, Marco Canevelli, Maria RitaCastrucci, Alessandra Ciervo, Fortunato D'Ancona,Martina Del Manso, Chiara Donfrancesco, MassimoFabiani, Antonietta Filia, Cinzia Lo Noce, AlbertoMateo Urdiales, Luigi Palmieri, Patrizio Pezzotti,Ornella Punzo, Valeria Raparelli, Flavia Riccardo,Maria Cristina Rota, Andrea Siddu, Paola Stefanelli,Brigid Unim, Nicola Vanacore.
REFERENCES
1. Grasselli G, Pesenti A, Cecconi M. Critical careutilization for the COVID-19 outbreak in Lombardy,Italy: early experience and forecast during anemergency response. JAMA. Published online March13, 2020. doi:10.1001/jama.2020.4031
2. Coronavirus disease 2019 (COVID-19): situationreport-57. Published March 17, 2020. AccessedMarch 18, 2020. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200317-sitrep-57-covid-19.pdf?sfvrsn=a26922f2_2
3. Livingston E, Bucher K. Coronavirus disease2019 (COVID-19) in Italy. JAMA. Published onlineMarch 17, 2020. doi:10.1001/jama.2020.4344
4. Novel Coronavirus Pneumonia EmergencyResponse Epidemiology Team. Vital surveillances:
the epidemiological characteristics of an outbreakof 2019 novel coronavirus diseases(COVID-19)—China, 2020. China CDC Weekly.2020;2(8):113-122. Accessed March 18, 2020.http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51
5. Report of the WHO-China Joint Mission onCoronavirus Disease 2019 (COVID-19). PublishedFebruary 16, 2020. Accessed March 18, 2020.https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf
Table. Case-Fatality Rate by Age Group in Italy and Chinaa
Italy as of March 17, 2020 China as of February 11, 2020No. of deaths(% of total)
Case-fatalityrate, %b
No. of deaths(% of total)
Case-fatalityrate, %b
All 1625 (100) 7.2 1023 (100) 2.3
Age groups, y
0-9 0 0 0 0
10-19 0 0 1 (0.1) 0.2
20-29 0 0 7 (0.7) 0.2
30-39 4 (0.3) 0.3 18 (1.8) 0.2
40-49 10 (0.6) 0.4 38 (3.7) 0.4
50-59 43 (2.7) 1.0 130 (12.7) 1.3
60-69 139 (8.6) 3.5 309 (30.2) 3.6
70-79 578 (35.6) 12.8 312 (30.5) 8.0
≥80 850 (52.3) 20.2 208 (20.3) 14.8
a Data from China are from ChineseCenter for Disease Control andPrevention.4 Age was not availablefor 1 patient.
b Case-fatality rate calculated asnumber of deaths/number of cases.
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Characteristics of COVID-19 patients dying in Italy Report based on available data on March 26th, 2020
1. Sample
The present report describes characteristics of 6801 COVID-19 patients dying in Italy.* Geographic distribution across the 19 regions and 2 autonomous provinces of Trento and Bozen is presented in the table below. Data are update to March 26th, 2020.
Tabel 1. Geographic distribution of deceased patients COVID-2019 positive
REGIONS N %
Lombardia
4484
65.9
Emilia-Romagna
1068
15.7
Veneto
301
4.4
Piemonte
194
2.9
Liguria
180
2.6
Marche
97
1.4
Lazio
88
1.3
Friuli-Venezia Giulia 66
1.0
Puglia
61
0.9
Toscana
59
0.9
Bolzano
46
0.7
Trento
46
0.7
Campania
40
0.6
Sicilia
15
0.2
Sardegna
13
0.2
Abruzzo
12
0.2
Umbria
11
0.2
Molise
8
0.1
Calabria
6
0.1
Valle d'Aosta
6
0.1
Total
6801
100.0 * COVID-19 related deaths presented in this report are those occurring in patients who test positive for SARSCoV-2 RT by PCR, independently from pre-existing diseases.
2. Demographics
Mean age of patients dying for COVID-2019 infection was 78 (median 79, range 30-100, IQR 73 -85). Women were 2,012 (29.6%). Figure 1 shows that median age of patients dying for COVID-2019 infection was more than 15 years higher as compared with the national sample diagnosed with COVID-2019 infection (median age 63 years). Figure 2 shows the absolute number of deaths by age group. Women dying for COVID-2019 infection had an older age than men (median age women 82 - median age men 78). Figure 1. Median age of patients with COVID-2019 infection and COVID-19 positive deceased patients
Figure 2. Absolute number of deaths by age group
0 20 40 60 80 100 120
Median age (years)
COVID19-Diagnosed
COVID19-Deaths
3 18 53 154
556
894
334
14 49 190
607
1847 1808
274
17 67 243
761
2403
2702
608
0
500
1000
1500
2000
2500
3000
30-39 40-49 50-59 60-69 70-79 80-89 90+
Women
Men
All
Age group
3. Pre-existing conditions
Table 1 presents most common comorbidities diagnosed before COVID-2019 infection. Data on diseases were based on chart review and was available on 710 patients dying in-hospital for whom it was possible to analyse clinic charts. Mean number of diseases was 2.7 (median 3, SD 1.6). Overall, 2.1% of the sample presented with a no comorbidities, 21.3% with a single comorbidity, 25.9% with 2, and 50.7% with 3 or more.
Before hospitalization, 30% of COVID-19 positive deceased patients followed ACE-inhibitor therapy and 17% angiotensin receptor blockers-ARBs therapy. This information can be underestimated because data on drug treatment before admission were not always described in the chart.
Table 1. Most common comorbidities observed in COVID-19 positive deceased patients
Diseases N %
Ischemic heart disease 249 27.8
Atrial Fibrillation 213 23.7
Heart failure 153 17.1
Stroke 101 11.3
Hypertension 655 73.0
Diabetes 281 31.3
Dementia 130 14.5
COPD 150 16.7
Active cancer in the past 5 years 155 17.3
Chronic liver disease 37 4.1
Chronic renal failure 199 22.2
Number of comorbidities
0 comorbidities 15 2.1
1 comorbidity 151 21.3
2 comorbidities 184 25.9
3 comorbidities and over 360 50.7
4. Symptoms Figure 3 shows symptoms most commonly observed at hospital admission. Fever, dyspnoea and cough were the most commonly observed symptoms, while diarrhoea and haemoptysis were less commonly observed. Overall, 6.4% of patients did not present any symptoms at hospital admission.
Figure 3. Most common symptoms observed in COVID-19 positive deceased patients
5. Acute conditions
Acute Respiratory Distress syndrome was observed in the majority of patients (96.4% of cases),
followed by acute renal failure (24.7%). Superinfection was observed in 10.4% and acute cardiac injury in
10.1% of cases.
6. Treatments
Antibiotics were used by 86% of patients during hospital stay, while less used were antivirals (54%) and corticosteroids (35%). Concomitant use of these 3 treatments was observed in 8.1% of cases.
1
6
40
71
75
0 20 40 60 80 100
Fever
Dyspnoea
Cough
Diarrhea
Hemoptysis
(%)
7. Time-line
Figure 4 shows, for COVID-19 positive deceased patients, the median times, in days, from the onset of symptoms to death (9 days), from the onset of symptoms to hospitalization (4 days) and from hospitalization to death (5 days). The time from hospitalization to death was 2 days longer in those who were transferred to intensive care than those who were not transferred (6 days vs. 4 days).
Figure 5. Median hospitalization times (in days) in COVID-19 positive deceased patients
8. Deaths under the age of 50 years
As of March 26th, 84 out of the 6801 (1.2%) positive COVID-19 patients under the age of 50 died. In
particular, 17 of these were less than 40 years, 14 men and 3 women (age range between 30 and 39
years). For 5 patients under the age of 40 years no clinical information is available; the remaining 8 had
serious pre-existing pathologies (cardiovascular, renal, psychiatric pathologies, diabetes, obesity) and 1
had no major pathologies.
This report was produced by COVID-19 Surveillance Group
Members of the COVID-19 Surveillance Group
Luigi Palmieri, Xanthi Andrianou, Pierfrancesco Barbariol, Antonino Bella, Stefania Bellino, Eva Benelli,
Luigi Bertinato, Stefano Boros, Gianfranco Brambilla, Giovanni Calcagnini, Marco Canevelli, Maria Rita
Castrucci, Federica Censi, Alessandra Ciervo, Elisa Colaizzo, Fortunato D'Ancona, Martina Del Manso,
Chiara Donfrancesco, Massimo Fabiani, Antonietta Filia, Tiziana Grisetti, Martin Langer, Ilaria Lega, Cinzia
Lo Noce, Pietro Maiozzi, Valerio Manno, Margherita Martini, Alberto Mateo Urdiales, Eugenio Mattei,
Claudia Meduri, Giada Minelli, Manuela Nebuloni, Lorenza Nisticò, Marino Nonis, Graziano Onder, Nicola
Petrosillo, Patrizio Pezzotti, Ornella Punzo, Valeria Raparelli, Giovanni Rezza, Flavia Riccardo, Maria
Cristina Rota, Debora Serra, Andrea Siddu, Paola Stefanelli, Dorina Tiple, Brigid Unim, Luana Vaianella,
Nicola Vanacore, Monica Vichi, Silvio Brusaferro.
6
4
5
4
9
0 5 10 15
Onset of symptoms --> Death
Onset of symptoms --> hospitalization
Hospitalization --> Death
Hospitalization --> Death (NO ICU)
Hospitalization --> Death (YES ICU)
Median number of days
Characteristics of and Important Lessons From theCoronavirus Disease 2019 (COVID-19) Outbreak in ChinaSummary of a Report of 72 314 Cases From the ChineseCenter for Disease Control and Prevention
The Chinese Center for Disease Control and Preven-tion recently published the largest case series to date ofcoronavirus disease 2019 (COVID-19) in mainland China(72 314 cases, updated through February 11, 2020).1 ThisViewpoint summarizes key findings from this report anddiscusses emerging understanding of and lessons fromthe COVID-19 epidemic.
Epidemiologic Characteristicsof the COVID-19 OutbreakAmong a total of 72 314 case records (Box), 44 672were classified as confirmed cases of COVID-19 (62%;diagnosis based on positive viral nucleic acid test resulton throat swab samples), 16 186 as suspected cases(22%; diagnosis based on symptoms and exposuresonly, no test was performed because testing capacity isinsufficient to meet current needs), 10 567 as clinicallydiagnosed cases (15%; this designation is being used inHubei Province only; in these cases, no test was per-formed but diagnosis was made based on symptoms,exposures, and presence of lung imaging features con-sistent with coronavirus pneumonia), and 889 asasymptomatic cases (1%; diagnosis by positive viralnucleic acid test result but lacking typical symptomsincluding fever, dry cough, and fatigue).1
Most case patients were 30 to 79 years of age(87%), 1% were aged 9 years or younger, 1% were aged10 to 19 years, and 3% were age 80 years or older.Most cases were diagnosed in Hubei Province (75%)and most reported Wuhan-related exposures (86%;ie, Wuhan resident or visitor or close contact withWuhan resident or visitor). Most cases were classifiedas mild (81%; ie, nonpneumonia and mild pneumonia).However, 14% were severe (ie, dyspnea, respiratoryfrequency �30/min, blood oxygen saturation �93%,partial pressure of arterial oxygen to fraction of inspiredoxygen ratio <300, and/or lung infiltrates >50% within24 to 48 hours), and 5% were critical (ie, respiratoryfailure, septic shock, and/or multiple organ dysfunctionor failure) (Box).1
The overall case-fatality rate (CFR) was 2.3% (1023deaths among 44 672 confirmed cases). No deaths oc-curred in the group aged 9 years and younger, but casesin those aged 70 to 79 years had an 8.0% CFR andcases in those aged 80 years and older had a 14.8% CFR.No deaths were reported among mild and severe cases.The CFR was 49.0% among critical cases. CFR was el-evated among those with preexisting comorbid condi-tions—10.5% for cardiovascular disease, 7.3% for diabe-tes, 6.3% for chronic respiratory disease, 6.0% for
hypertension, and 5.6% for cancer. Among the 44 672cases, a total of 1716 were health workers (3.8%), 1080of whom were in Wuhan (63%). Overall, 14.8% of con-firmed cases among health workers were classified assevere or critical and 5 deaths were observed.1
COVID-19 rapidly spread from a single city tothe entire country in just 30 days. The sheer speed ofboth the geographical expansion and the sudden in-crease in numbers of cases surprised and quickly over-whelmed health and public health services in China, par-ticularly in Wuhan City and Hubei Province. Epidemiccurves reflect what may be a mixed outbreak pattern,with early cases suggestive of a continuous commonsource, potentially zoonotic spillover at Huanan Sea-food Wholesale Market, and later cases suggestive of apropagated source as the virus began to be transmit-ted from person to person (Figure 1).1
Comparison of COVID-19 With SARS and MERSThe current COVID-19 outbreak is both similar and dif-ferent to the prior severe acute respiratory syndrome
Box. Key Findings From the Chinese Centerfor Disease Control and Prevention Report
72 314 Cases (as of February 11, 2020)• Confirmed cases: 44 672 (62%)• Suspected cases: 16 186 (22%)• Diagnosed cases: 10 567 (15%)• Asymptomatic cases: 889 (1%)
Age distribution (N = 44 672)• �80 years: 3% (1408 cases)• 30-79 years: 87% (38 680 cases)• 20-29 years: 8% (3619 cases)• 10-19 years: 1% (549 cases)• <10 years: 1% (416 cases)
Spectrum of disease (N = 44 415)• Mild: 81% (36 160 cases)• Severe: 14% (6168 cases)• Critical: 5% (2087 cases)
Case-fatality rate• 2.3% (1023 of 44 672 confirmed cases)• 14.8% in patients aged �80 years (208 of 1408)• 8.0% in patients aged 70-79 years (312 of 3918)• 49.0% in critical cases (1023 of 2087)
Health care personnel infected• 3.8% (1716 of 44 672)• 63% in Wuhan (1080 of 1716)• 14.8% cases classified as severe or critical
(247 of 1668)• 5 deaths
VIEWPOINT
Zunyou Wu, MD, PhDChinese Center forDisease Control andPrevention, Beijing,China.
Jennifer M.McGoogan, PhDChinese Center forDisease Control andPrevention, Beijing,China.
Viewpointpages 1245, and 1243
Related articlepage 1313
CorrespondingAuthor: ZunyouWu, MD, PhD,Chinese Centerfor Disease Controland Prevention,155 Changbai Rd,Beijing 102206, China([email protected]).
Opinion
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Figu
re1.
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Feb 11, 2020
Feb 10, 2020
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Feb 7, 2020
Feb 6, 2020
Feb 5, 2020
Feb 4, 2020
Feb 3, 2020
Feb 2, 2020
Feb 1, 2020
Jan 31, 2020
Jan 30, 2020
Jan 29, 2020
Jan 28, 2020
Jan 27, 2020
Jan 26, 2020
Jan 25, 2020
Jan 24, 2020
Jan 23, 2020
Jan 22, 2020
Jan 21, 2020
Jan 20, 2020
Jan 19, 2020
Jan 18, 2020
Jan 17, 2020
Jan 16, 2020
Jan 15, 2020
Jan 13, 2020
Jan 12, 2020
Jan 11, 2020
Jan 10, 2020
Jan 9, 2020
Jan 8, 2020
Jan 7, 2020
Jan 6, 2020
Jan 5, 2020
Jan 4, 2020
Jan 3, 2020
Jan 2, 2020
Jan 1, 2020
Dec 31, 2019
Dec 30, 2019
Dec 29, 2019
Dec 28, 2019
Dec 27, 2019
Dec 26, 2019
Dec 25, 2019
Dec 24, 2019
Dec 23, 2019
Dec 22, 2019
Dec 21, 2019
Dec 20, 2019
Dec 19, 2019
Dec 18, 2019
Dec 17, 2019
Dec 16, 2019
Dec 15, 2019
Dec 14, 2019
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Dec 12, 2019
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Opinion Viewpoint
1240 JAMA April 7, 2020 Volume 323, Number 13 (Reprinted) jama.com
© 2020 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ by Eleanor Kennedy on 04/16/2020
(SARS; 2002-2003) and Middle East respiratory syndrome (MERS;2012-ongoing) outbreaks. SARS was initiated by zoonotic transmis-sion of a novel coronavirus (likely from bats via palm civets) inmarkets in Guangdong Province, China. MERS was also tracedto zoonotic transmission of a novel coronavirus (likely from bats viadromedary camels) in Saudi Arabia. All 3 viral infections commonlypresent with fever and cough, which frequently lead to lower respi-ratory tract disease with poor clinical outcomes associated witholder age and underlying health conditions. Confirmation of infec-tion requires nucleic acid testing of respiratory tract samples(eg, throat swabs), but clinical diagnosis may be made based onsymptoms, exposures, and chest imaging. Supportive care forpatients is typically the standard protocol because no specificeffective antiviral therapies have been identified.
The World Health Organization (WHO) declared the SARS out-break contained on July 5, 2003. A total of 8096 SARS cases and774 deaths across 29 countries were reported for an overall CFR of9.6%. MERS is still not contained and is thus far responsible for2494 confirmed cases and 858 deaths across 27 countries for aCFR of 34.4%. Despite much higher CFRs for SARS and MERS,COVID-19 has led to more total deaths due to the large number ofcases. As of the end of February 18, 2020, China has reported72 528 confirmed cases (98.9% of the global total) and 1870deaths (99.8% of the global total). This translates to a currentcrude CFR of 2.6%. However, the total number of COVID-19 cases islikely higher due to inherent difficulties in identifying and countingmild and asymptomatic cases. Furthermore, the still-insufficienttesting capacity for COVID-19 in China means that many suspectedand clinically diagnosed cases are not yet counted in thedenominator.2 This uncertainty in the CFR may be reflected by theimportant difference between the CFR in Hubei (2.9%) comparedwith outside Hubei (0.4%).1,2 Nevertheless, all CFRs still need to beinterpreted with caution and more research is required.
Most secondary transmission of SARS and MERS occurred inthe hospital setting. Transmission of COVID-19 is occurring in thiscontext as well—3019 cases have been observed among healthworkers as of February 11, 2020 (of whom there have been 1716confirmed cases and 5 deaths).1 However, this is not a major meansof COVID-19 spread. Rather, it appears that considerable transmis-sion is occurring among close contacts. To date, 20 provincesoutside of Hubei have reported 1183 case clusters, 88% of whichcontained 2 to 4 confirmed cases. Of note, 64% of clusters docu-mented thus far have been within familial households (ChineseCenter for Disease Control and Prevention presentation made tothe WHO Assessment Team on February 16, 2020). Thus, althoughCOVID-19 seems to be more transmissible than SARS and MERS, andmany estimates of the COVID-19 reproductive number (R0) have al-ready been published, it is still too soon to develop an accurate R0
estimate or to assess the dynamics of transmission. More researchis needed in this area as well.
Response to the COVID-19 EpidemicSince 2003, the Chinese government has improved its epidemicresponse capacity. Some of these efforts are evident in theresponse to COVID-19 (Figure 2). For example, in the 2002-2003SARS outbreak, 300 cases and 5 deaths already had occurred bythe time China reported the outbreak to the WHO, whereas in theCOVID-19 outbreak, only 27 cases and zero deaths had occurred
when the WHO was notified (January 3, 2020) (Figure 2). From thetime of WHO notification, 2 months elapsed before SARS-CoV wasidentified compared with only 1 week from the time of WHO notifi-cation until 2019-nCoV was identified.
The timing of the COVID-19 outbreak, prior to China’s annualLunar New Year holiday, was an important factor as China consid-ered how to respond to the outbreak. Culturally, this is the largest andmost important holiday of the year. It is the expectation that peoplereturn to their family homes, which is the cause for the several bil-lion person-trips made by residents and visitors during this time,mostly on crowded planes, trains, and buses. Knowing this meanteach infected person could have numerous close contacts over a pro-tracted time and across long distances, the government needed toquickly act. However, it was not only the speed of the government’sresponse, but also the magnitude of that response that were influ-enced by the impending holiday travel time. Knowing that specifictreatment and prevention options, such as targeted antiviral drugsand vaccines, were not yet available for COVID-19, China focused ontraditional public health outbreak response tactics—isolation, quar-antine, social distancing, and community containment.3-5
Identified case patients with COVID-19 were immediately iso-lated in designated wards in existing hospitals, and 2 new hospitalswere rapidly built to isolate and care for the increasing numbers ofcases in Wuhan and Hubei. People who had been in contact withCOVID-19 cases were asked to quarantine themselves at home orwere taken to special quarantine facilities, where they could bemonitored for onset of symptoms. Enormous numbers of largegatherings were canceled, including all Lunar New Year celebra-tions, and traffic in Wuhan and in cities across Hubei was restrictedand closely monitored. Virtually all transportation was subse-quently restricted at a national level. All of these measures wereinstituted to achieve social distancing. In addition, an estimated40 million to 60 million residents of Wuhan and 15 other surround-ing cities within Hubei Province were subjected to community con-tainment measures. Although these types of traditional outbreakresponse actions have been successfully used in the past, theyhave never been executed on such a large scale.
There have been some questions about whether these actionsare reasonable and proportional responses to the outbreak. Somehave argued that a number of these approaches may infringe on thecivil liberties of citizens, and some of these measures have been re-ferred to as “draconian.” However, it is not only individual rights thatmust be considered. The rights of those who are not infected, butat risk of infection, must be considered as well. Whether these ap-proaches have been effective (eg, in terms of reduced infections anddeaths averted), and whether these potential benefits have out-weighed the costs (eg, economic losses), will be debated for years.4,5
Next StepsImportantly, another major goal of China’s current outbreakresponse activities is to help “buy time” for science to catch upbefore COVID-19 becomes too widespread. China must now focuson adjusting tactics and strategies as new evidence becomesavailable.3,6 Much remains to be done and many questionsremain unanswered. China is very grateful for the help it is receiv-ing from the international scientific, health, and public healthcommunities. The global society is more interconnected than ever,and emerging pathogens do not respect geopolitical boundaries.
Viewpoint Opinion
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Proactive investment in public health infrastructure and capacityis crucial to effectively respond to epidemics like COVID-19, andit is critical to continue to improve international surveillance, coop-
eration, coordination, and communication about this major out-break and to be even better prepared to respond to future newpublic health threats.
ARTICLE INFORMATION
Published Online: February 24, 2020.doi:10.1001/jama.2020.2648
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was supported by theNational Health Commission of the People’sRepublic of China (2018ZX10721102).
Role of the Funder/Sponsor: The funder had norole in the preparation, review, or approval of themanuscript, or the decision to submit themanuscript for publication.
Disclaimer: The opinions expressed herein reflectthe collective views of the coauthors and do notnecessarily represent the official position of theChinese Center for Disease Control and Prevention.
Additional Contributions: We thank China CDCWeekly for its permission to re-create the epidemiccurve with modifications.
REFERENCES
1. Novel Coronavirus Pneumonia EmergencyResponse Epidemiology Team. Vital surveillances:the epidemiological characteristics of an outbreakof 2019 novel coronavirus diseases(COVID-19)—China, 2020. China CDC Weekly.Accessed February 20, 2020. http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51
2. Battegay M, Kuehl R, Tschudin-Sutter S, HirschHH, Widmer AF, Neher RA. 2019-Novel coronavirus(2019-nCoV): estimating the case fatality rate:a word of caution. Swiss Med Wkly. 2020;150:w20203. doi:10.4414/smw.2020.20203
3. McCloskey B, Heymann DL. SARS to novelcoronavirus: old lessons and new lessons. EpidemiolInfect. 2020;148:e22. doi:10.1017/S0950268820000254
4. Du Z, Wang L, Cauchemez S, et al. Risk fortransportation of 2019 novel coronavirus diseasefrom Wuhan to other cities in China. Emerg Infect Dis.2020;26(5). doi:10.3201/eid2605.200146
5. Wilder-Smith A, Freedman DO. Isolation,quarantine, social distancing and communitycontainment: pivotal role for old-style public healthmeasures in the novel coronavirus (2019-nCoV)outbreak. J Travel Med. 2020;taaa020. doi:10.1093/jtm/taaa020
6. Cowling BJ, Leung GM. Epidemiological researchpriorities for public health control of the ongoingglobal novel coronavirus (2019-nCoV) outbreak.Euro Surveill. 2020;25(6). doi:10.2807/1560-7917.ES.2020.25.6.2000110
Figure 2. Timeline Comparing the Severe Acute Respiratory Syndrome (SARS) and Coronavirus Disease 2019(COVID-19) Outbreaks
Nov
Dec
Jan
Feb
Mar
Apr
May
Jun
Jul
Dec 8: First case Onset of symptoms in first known casea of pneumonia with unknown etiology in Wuhan City, Hubei Province, China
Jan 7: New virus identifiedChinese scientists identify the pathogen as a novel coronavirus
Jan 30: WHO global alertWHO declares a “public health emergency of international concern”China
7736 confirmed cases 170 deaths
Feb 20: Current statusChina
74 675 confirmed cases 2121 deaths
Dec 31: Reported to WHOChina reports a cluster of cases of pneumonia with unknown etiology in Wuhan to WHOChina
27 cases0 deaths
Outside China82 confirmed cases0 deaths
Outside China1073 confirmed cases8 deaths
Nov 16: First case First known casea of atypical pneumonia in Foshan City, Guangdong Province, China
Mar 12: WHO global alertWHO issues a global alert on “cases of severe respiratory illness [that] may spread to hospital staff”
Jul 5: Final statusWHO declares worldwide containmentChina
5327 cases 349 deaths
Feb 11: Reported to WHOChina reports an outbreak of acute respiratory symptoms in Guangdong to WHOChina
300 cases5 deaths
Outside China2769 cases425 deaths
Apr 16: New virus identifiedWHO scientists identify the pathogen as a novel coronavirus
May 28: >8000 cumulative cases worldwide
Apr 28: >5000 cumulative cases worldwide
Apr 2: >2000 cumulative cases worldwide
SARS outbreak 2002-2003 COVID-19 outbreak 2019-2020
The timeline of events for the SARSoutbreak (left) from first case to finalworldwide containment. The timelineof events for the COVID-19 outbreak(right) from the onset of symptomsfor the first case on December 8,2019, to status on February 20,2020. Over the course of the first2 months, more than 70 000 caseshave been confirmed and many moreare suspected. WHO indicates WorldHealth Organization.a Identified later retrospectively.
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Covid-19 and Diabetes: Interim Care Home Guidance 28th April 2020
____________________________________________
Background
The epidemiology of Covid-19 incidence, severity of illness and mortality seem to be shifted towards older people particularly those with multiple comorbidities such as diabetes, hypertension, and cardiovascular disease.
Residents of care homes (both residential and nursing) are a highly co-morbid population who are particularly vulnerable to Covid-19 infection. A quarter of residents have diabetes and two-thirds may have frailty which is better predictor of intensive care unit (ICU) outcomes than age or other factors.
This guidance is designed to support clinical decision-making in care homes. As such, the guidance will take into account the availability of skilled personnel, access to monitoring of blood glucose (sugar) and ketones, fluid administration limits, and overall level of care likely to be available.
__________________________________________
Prevention and Control Issues
Care homes represent a major challenge to ensuring that
Covid-19 prevention and control issues are optimal. Advice
on special precautions to be taken can be found at: https://www.gov.uk/government/publications/coronavirus
-covid-19-admission-and-care-of-people-in-care-homes
Communication between all relevant parties (care homes,
community services, primary care) may be enhanced by
technology for virtual reviews/case conferences to
minimise contacts for healthcare professionals.
____________________________________________
Advice for care home managers
A Covid-19 Response Action – Diabetes Management in Care Homes
A National Stakeholders Covid-19 Response Group Interim Guidance
This guidance was prepared by a
multidisciplinary stakeholder group in order to:
• Minimise morbidity and mortality from
Covid-19 in care home residents with
diabetes
• Alert care homes that those residents with
diabetes are at very high risk of Covid-19
infection
• Emphasise that those at the highest risk of
poor outcomes from Covid-19 are those
who have: frailty, several existing medical
conditions such as cardiovascular disease or
respiratory disease, diabetes-complications,
treatment with steroids, a life expectancy
<6 months
• Maintain the safety of all those living and
working within the care home
Addressed to: Care home managers, other care
home staff, community nursing and diabetes
staff, primary care providers including general
practitioners
• Equip your care home with sufficient capillary
blood glucose (sugar) strips (with a meter),
and strips for ketones if possible
• Have available a hypoglycaemia treatment kit
plus intramuscular (IM) glucagon, and
replenishing this every time it is has been used
• Maintain a written record of a resident’s blood
glucose, medications, temperature, food chart
and body weight
• Have a daily foot care surveillance plan in
place for all residents with diabetes to ensure
good foot health
• Ensure good communication with your local
diabetes specialist nurses, the community
nursing service, and with your primary care
team who want to provide you and your staff
with support and guidance at all times
Covid-19 and Diabetes: Interim Care Home Guidance 28th April 2020
_______________________________________________________________________________________________
Effect of Covid-19 on individual residents and their diabetes management
Covid-19 can cause a serious acute illness in residents with diabetes by:
o increasing the risk of a rapid worsening of diabetes control which can lead to life-threatening conditions called diabetic
ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS)
o increasing susceptibility to other infections including pneumonia, chest and foot infections, and sepsis
o worsening symptoms and signs in those with frailty, kidney disease and/or cardiovascular (heart) disease.
_______________________________________________________________________________________________
Management of your residents with diabetes
Usual management of each resident with diabetes should aim to ensure that they:
o receive plenty of oral fluids to maintain good hydration
o maintain a daily appropriate exercise and nutritional plan with regular meals or if appetite reduced, have food ‘little
and often’
o receive their usual diabetes treatment
o have regular twice daily capillary blood glucose testing with the aim to keep the level between 7 and 12 mmol/l
o have daily foot checks to ensure early detection of poor blood supply, infection, and regular changes of dressings
o have the opportunity to have their wishes documented in any anticipated future emergency (e.g. hospital admission) by
completion of a ReSPECT form or similar.
Table A – General areas of concern
Area of Concern Potential Effect of Covid-19 ACTION
‘Higher Risk’ residents with Diabetes
Increase their vulnerability to more serious life-threatening disease
Extra vigilance and surveillance looking for any deterioration in health by twice-daily assessment of symptoms, blood glucose and ketones where possible
Diabetes control (glucose targets)
Risk of worsening diabetes control by causing higher glucose levels
Aim for random sugar (glucose) levels of 7-12 mmol/l
Hospital Admission Will increase need for specialist review and referral to hospital in residents with acute illness
Persistent fever, increasing shortness of breath, or persistent diarrhoea and/or vomiting. Also see ‘Special Note’
Best place of care: care home v hospital
Increase the risk of acute illness with or without major changes in glucose control
Decision to admit to hospital based on a shared decision basis with manager, nursing advice, resident and/or carer: threshold for hospital admission LOW in residential (non-nursing) homes
Special Note: residents with diabetes and Covid-19 who are:
• generally unwell, very thirsty, look dehydrated with deep breathing, and blood
sugar ≥ 11 mmol/l, may have diabetic ketoacidosis (DKA) – check urine for raised
ketones if strips available
• very dehydrated, confused or more drowsy than usual, and with blood sugar ≥ 30
mmol/l, may have hyperosmolar hyperglycaemia state (HHS).
Please consult your local diabetes nurse specialist or primary care team for immediate
assessment and treatment guidance and arrangements for hospital admission as
appropriate.
!
Covid-19 and Diabetes: Interim Care Home Guidance 28th April 2020
• Give fast acting carbohydrates such as 60mls of Gluco juice, 200 ml of pure fruit juice, or 5-6 dextrose (glucose) tablets
• Wait 10 to 15mins, re-check capillary blood glucose (BG)
• Repeat treatment until BG >4 mmol/L
• Then give 20 g long-acting carbohydrate, such as 2 biscuits or a slice of bread
• Review medications, discuss de-escalation of glucose-lowering treatments with team responsible for diabetes care
Awake and able to
drink
If uncooperative:
• Squeeze half a tube of glucogel into the inside of the cheek and massage
• Wait 10 to 15mins, re-check BG
• Repeat treatment until BG >4mmol/L
• Then give 20 g of long-acting carbohydrate, such as 2 biscuits or a slice of bread
• Review medications, discuss de-escalation of glucose-lowering treatments with team responsible for diabetes care
Awake, able to drink but
confused or agitated
• Ask for help and dial 999
• Place patient in recovery position
• Stop any scheduled insulin
• Give 1mg glucagon IM once only if possible
• If becomes awake, give 20 g of long-acting carbohydrate, such as 2 biscuits or a slice of bread
• Liaise with paramedics on arrival for further management
Unconscious, may
be fitting
Table B – Managing hyperglycaemia (high glucose levels) in varying circumstances (clinical scenarios)
*please liaise with your local community nursing team and/or diabetes specialist nurse advice to manage the resident; ** for example,
canagliflozin, dapagliflozin, empagliflozin; ***for more detailed advice, please visit: https://abcd.care/coronavirus; ∆ monitoring frequency
and glucose target range dependent on shared decision making, staff resources and health status of resident
Management of hypoglycaemia (low blood sugar, <4 mmol/l)
Residents receiving insulin or certain glucose-lowering tablets called sulphonylureas (e.g. gliclazide, glipizide) or glinides (e.g.
nateglinide) have a higher risk of hypoglycaemia particularly if their usual meal pattern is disturbed through acute illness or
nausea. A guide to management is given below:
Suggested Initial Actions in different Clinical Scenarios Clinical scenario Initial Actions required
Stable non-COVID-19 resident Continue usual diabetes treatment; maintain close monitoring for COVID-19 symptoms.
COVID-19 positive and stable resident
Continue usual diabetes treatment even if they have reduced appetite, but regular monitoring is required to avoid high (i.e. ≥12 mmol/l) and low blood sugars (i.e. <4 mmol/l).
COVID-19 positive and unwell resident on oral therapy*
Initially, adjust oral hypoglycaemic medications and ensure regular and frequent testing of blood sugar (2-
4 hourly ∆): A Stop metformin in patients with fever and acute illness to minimise risk of lactic acidosis. B Stop SGLT-2 inhibitors** particularly in those with diarrhoea and vomiting due to an increased risk of dehydration and/or DKA C Consider adding a different oral hypoglycaemic treatment as necessary (e.g. linagliptin) D Alert your local diabetes nursing team if sugar levels continue to rise and remain above 12 mmol/l, as commencement of insulin may be necessary at some stage
COVID-19 positive and unwell resident on insulin*
A Seek local diabetes nursing team support/advice for further management; test blood sugar frequently
(e.g. 2-4 hourly ∆)
B Continue insulin at usual dose, closely monitor blood glucose (every 2-4 hours ∆) and depending on insulin regimen present, adjust insulin up or down initially by 2-4 units or as advised by your local diabetes
nursing team, every 6 hours if blood sugar outside target range of 7-12mmol/L.*** ∆
COVID-19 positive and unwell resident, unable to take oral therapy*
A Seek local diabetes nursing team support/advice for further management; test blood sugar frequently
(e.g. 2-4 hourly ∆) B Replace oral therapy by a basal long-acting analogue insulin starting at a daily dose of 0.15 units/Kg body weight (e.g 0.15 x 80kg given as 12 units once daily or 6 units twice daily). Aim to maintain blood
sugar levels within the target range of 7-12 mmol/l.∆
COVID-19 positive on any therapy but with erratic eating patterns and fluctuating surges of blood glucose*
A Seek local diabetes nursing team support/advice for further management; test blood sugar frequently (e.g. 4-6 hourly) B Continue their usual hypoglycaemic therapy. C Short-acting insulin can be given subcutaneously as required in boluses of up to 6 units or greater depending on local diabetes nursing advice, every 6 hours when blood sugar levels are ≥15mmol/L***
Covid-19 and Diabetes: Interim Care Home Guidance 28th April 2020
_______________________________________________________________________________________________
Management of foot care and end of life
Residents with diabetes and Covid-19 require strict attention to foot care to detect early any changes in blood supply to the feet
or any signs of infection which might lead to sepsis. Some residents may also be at end of life and this will alter how diabetes
care is delivered. A guide to key management aspects are given below:
_________________________________________________________________________________________________________
National Stakeholders Writing Group and Contributors
Professor Alan Sinclair (Co-Chair), Professor Ketan Dhatariya (Co-Chair), Olivia Burr, Dr Dinesh Nagi, Professor Partha Kar,
David Jones, Dr Philip Newland-Jones, Dr Kath Higgins, Dr Mayank Patel, Dr Ahmed Abdelhafiz, Dr David Hopkins, Dan
Howarth, Catherine Gooday
_________________________________________________________________________________________________________
• For residents with type 2 diabetes, stop all oral glucose-lowering therapy and GLP-1
RA (glucagon-like peptode-1 receptor agonist, e.g. exenatide, liraglutide) injections;
for those taking a small dose of daily insulin, consideration should also be given to
stopping this insulin by discussion with local team responsible for diabetes care .
• For residents with type 1 diabetes, treatment with insulin should be continued but
consideration given to simplifying the regimen and switching to a once-daily dose
long-acting insulin analogue such Insulin Glargine (Lantus) or Insulin Degludec
(Tresiba)
• Stop all routine blood sugar testing in those with type 2 diabetes on diet and/or
metformin; in other cases where there are no prospects of recovery, consideration
should be given to stopping all blood sugar testing
• For further advice on diabetes care at end of life, seek guidance from your local
diabetes and palliative care team, or visit: Diabetes UK, End Of Life Diabetes Care, 3rd
Edition, 2018 at: https://www.diabetes.org.uk/resources-s3/2018-
03/EoL_Guidance_2018_Final.pdf
Foot Care
End of Life
Residents with diabetes are at high risk of diabetes foot disease which can be exacerbated by Covid-19. Please ensure that each foot is protected from trauma or other injury and arrange daily inspection for:
• skin discolouration - might indicate diminished blood supply (limb ischaemia)
• infection
For more information and support with glucose and ketone testing or managing your residents with diabetes when they become Covid-19 positive, please consult with your local community nursing service, local diabetes specialist nurses, or primary care team.
Further Advice
