Overzicht van een serie belangwekkende studies via contactonderzoek

opgesteld door de Schotse virologe Dr. Muge Cevik

Samenvatting van de resultaten, zoals compleet achterin vermeld: Nummer 1: China (Ningbo) 4 maart 2020 http://html.rhhz.net/zhlxbx/028.htm

2147 nauwe contacten van 157 patienten zijn opgevolgd: - 6% was besmet

o Onder vrienden was het 22% o Binnen huishouden was het 18%

Belangrijkste risicofactoren o In huishouden 13% o Transport 11% o Dineren 7%

Nummer 3: China (Shenzen) gepubliceerd 27 maart 2020 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30287-5/fulltext 1286 nauwe contacten van 319 patienten zijn opgevolgd

o 11,5% van leden huishouden zijn besmet o Kinderen in even grote mate

Nummer 4: China (Guangzhou) gepubliceerd 11 april 2020 https://www.medrxiv.org/content/10.1101/2020.04.11.20056010v1 349 cases in 195 clusters

o 17% in huishouden besmet o 7% buiten het huishouden o Onder 20 jaar 5% o Boven 60 jaar 18%

Nummer 5: China gepubliceerd 17 april 2020 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa450/5821281

392 contacten binnen huishoudens van 105 cases.

o 16% in huishouden besmet o 28% van partners o 17% van volwassenen in huishouden o 4% van onder 18 jaar

Nummer 7: Taiwan gepubliceerd 1 mei 2020 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2765641?utm_campaign=articlePDF%26utm_medium%3darticlePDFlink%26utm_source%3darticlePDF%26utm_content%3djamainternmed.2020.2020

2761 contacten van 100 cases.

o 22 gevallen o 4,7% binnen de huishoudens

Nummer 10: IJsland gepubliceerd 14 april 2020 https://www.nejm.org/doi/full/10.1056/NEJMoa2006100

Bevolkingsonderzoek: 9199 getest

o 13.7% van de volwassenen besmet o 6,7% van de kinderen onder 10 jaar

Nummer 13: VS, gepubliceerd 27 april 2020 https://jamanetwork.com/journals/jama/fullarticle/2765378

408 personen getest in een opvangplek voor thuislozen, die daar 2 dagen waren

o 36% waren positief o Meerderheid had geen symptomen

Nummer 14: VS, gepubliceerd 24 april 2020 https://www.nejm.org/doi/full/10.1056/NEJMoa2008457

In een verzorgingshuis 23 dagen na het eerste geval zijn 76 getest.

o 64% positief o 50% bewoners had geen symptomen

Samenvatting van de bevindingen door Dr. Muge Cevik: Nummer 15: Om besmet te worden is een langdurig contact in een gesloten ruimte vereist. Meeste risico binnen: Huishouden, zorginstellingen, openbaar vervoer Nummer 16: Korte informele kontakten zijn niet de belangrijkste oorzaak van de epidemie Nummer 17: Verhoogde infectiecijfers in gesloten omgevingen zijn in overeenstemming met de

hoge infectiecijfers in megasteden, achterstandsgebieden en opvangcentra. Het lijkt erop dat de intensiteit van de epidemie sterk wordt gevormd door de drukte.

Nummer 18: Indicatie dat het risico om besmet te worden boven de 60 jaar het hoogst is. Kinderen

duidelijk minder. Nummer 19: De meeste gevallen van de besmetting ontstaan bij nauw contact met iemand met

symptomen, met name in de eerste 5 dagen van de symptomen. Dit is een belangwekkend nieuw paper hierover: https://www.medrxiv.org/content/10.1101/2020.04.25.20079103v1

In een reactie op deze informatie stelt de viroloog/epidemioloog/microbioloog Dan Diekema van de Universiteit van Iowa ( @dan_diekema) het volgende;

Besmetting komt het meest op de volgende wijze voor:

o Via Airborne transmissies o Nauw contact, gedurende een langere periode. Dat komt het meest voor binnen

huishoudens, veel minder bij contacten in de gezondheidzorg Besmetting vindt plaats binnen 5 dagen na start van symptomen.

2/ 445 close contacts of 10

1/ 2147 close contacts of 157

data tell us about actual probability of

4 May 20 • 23 tweets • Dr Muge Cevik

mugecevik/status/1257392347010215947

A lot of discussion recently about transmission dynamics, most of which are extrapolated from viral loads & estimates. What does contact tracing/community testing

#COVID19 transmission(infection rate), high risk environments/age? [thread]

#COVID19 cases were followed up: Overall infection rate was

6%, higher infection rate among friends (22%) and household (18%), and main risk factors include contact in household (13%), transport (11%), dining (7%). html.rhhz.net/zhlxbx/028.htm (4/3/20)

#COVID19 cases were followed up, of those 54 (12%) developed

symptoms, suggesting secondary attack rate of 0.45%, household attack rate of 10.5%. No other close contacts incl community members, HCWs were positive.

Active Monitoring of Persons Exposed to Patients with Confirmed... CDC and public health authorities have learned more about COVID-19 through active contact tracing and monitoring of people who have been exposed to the virus that causes COVID-19. https://www.cdc.gov/mmwr/volumes/69/wr/mm6909e1.htm?s_cid=mm6909e1_w

(6/3/20)

5/ Among 392 household contacts of 105 index

4/ Among 349

3/ Based on 1286 close contacts of 319 #COVID19 cases; household and transport contacts had higher risk of transmission (80% of infections caused by 9% of cases), household attack rate of 11.5%, children were as likely to be infected

Epidemiology and transmission of COVID-19 in 391 cases and 1286 of … Our data on cases as well as their infected and uninfected close contacts provide key insights into the epidemiology of SARS-CoV-2. This analysis shows that isolation and contact tracing reduce the t… https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30287-5/fulltext

(27/3/20) #COVID19 cases in 195 clusters, household attack rate was very high (17%),

non-household attack rate 7%. Secondary attack rate was lower in <20y (5%) and highest in >60y (18%), suggesting susceptibility increases with age. https://www.medrxiv.org/content/10.1101/2020.04.11.20056010v1 (15/04/20) Preprint

#COVID19 cases, overall household attack rate was 16%, the secondary attack rate was highest in spouse (28%), all adults (17%) and

7/ Among 2761 close contacts of 100 confirmed

6/ A symptomatic index

was lower in <18 age group (4%). characteristics of household transmission of COVID-19 AbstractBackground. Since December 2019, SARS-CoV-2 virus has extended to most parts of China with more than 80 thousand cases and to at least 100 countries wi https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa450/5821281

(17/4/20)

#COVID19 case, her husband who subsequently acquired infection and their 350 close contacts were followed up, 43 developed symptoms, none tested positive, suggesting close & prolonged exposure is required for transmission.

First known person-to-person transmission of severe acute respirator… Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptoma… https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30607-3/fulltext

(13/3/20) #COVID19 pts in Taiwan, 22 secondary

cases were identified, household attack rate was 4.7%, rates were higher in close family, >40y, if exposed within 5d after symptom onset (0 infection after 5d)

tested) contacts, 1 had

Contact Tracing Assessment of COVID-19 Transmission Dynamics in T… This study delineates the transmission dynamics of coronavirus disease 2019 (COVID-19) and evaluates the transmission risk at different exposure window periods before and after symptom onset. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2765641?utm_camp…

(1/5/20)

8/ In a French chalet cluster, 11/15 contacts tested positive (all adult), 75% attack rate. One child (9y) was negative, attended 3 schools & ski class while symptomatic, among 172 (73

#COVID19, while 33% had influenza!

Cluster of coronavirus disease 2019 (Covid-19) in the French Alps, 2020 AbstractBackground. On 07/02/2020, French Health authorities were informed of a confirmed case of SARS-CoV-2 coronavirus in an Englishman infected in Singapore https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa424/5819060

(11/4/20) 9/ Among 31 household transmission clusters, 9.7% (3/31) were identified as having a paediatric index case (none was identified in Singapore), suggesting that children are unlikely to be driving the household transmission. https://www.medrxiv.org/content/10.1101/2020.03.26.20044826v1 (30/3/20) Preprint

#COVID19

10/ In a population-based study in Iceland in which 9199 were tested, of the 564 children <10y, 38 (6.7%) tested positive, vs 1183/8635 (13.7%) adolescents and adults tested positive, suggesting lower incidence in children.

Spread of SARS-CoV-2 in the Icelandic Population | NEJM Original Article from The New England Journal of Medicine — Spread of SARS- CoV-2 in the Icelandic Population https://www.nejm.org/doi/full/10.1056/NEJMoa2006100

(14/4/20) 11/ In Singapore, 3 clusters of 28 cases were identified (2 churches, 1 family gathering). In all clusters, transmission accounted for 1 close contact w a symptomatic case, suggesting

#COVID19 case attended a

transmission largely occurs in close contact in congregation.

https://www.thelancet.com/action/showPdf?pii=S1473-3099%2820%2930273-5 (21/4/20)

12/ 15 confirmed/probable cases were identified after the index funeral (3h), shared a meal (2h), birthday party while having mild symptoms, suggesting family gatherings likely plays an important role in transmission

Community Transmission of SARS-CoV-2 at Two Family Gatherings ... Investigation of COVID-19 cases in Chicago identified a cluster of 16 confirmed or probable cases, including three deaths, likely resulting from one introduction. https://tinyurl.com/yaswk4hh

(17/04/20) 13/ 408 individuals residing at the shelter over a 2-day period were tested, 36% were positive, suggesting infection could likely be transmitted within homeless shelter easily. In addition, the majority of individuals did not have symptoms.

demonstrates that

close & prolonged contact is required for

14/ In a nursing home facility, 23d after the first resident with

Prevalence of SARS-CoV-2 Infection in a Large Homeless Shelter in Bo… This study characterizes the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected on polymerase chain reaction (PCR) screening of a large homeless shelter pop… https://jamanetwork.com/journals/jama/fullarticle/2765378

(27/4/20) #COVID19, among 84

residents (76 tested), 48 were positive. This facilty had 64% prevalence of Covid-19 among residents. 50% of residents had no symptoms at the time of testing.

Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled … Original Article from The New England Journal of Medicine — Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility https://www.nejm.org/doi/full/10.1056/NEJMoa2008457

(24/4/20) 15/ In summary: While the infectious inoculum required for infection is unknown, these studies indicate that

#COVID19 transmission. The risk is highest in enclosed environments; household, long-term care facilities and public transport. 16/ High infection rates seen in household, friend & family gatherings, transport suggest that closed contacts in congregation is likely the key driver of productive transmission. Casual, short interactions are not the main driver of the epidemic though keep social distancing! 17/ Increased rates of infection seen in enclosed & connected environments is in keeping with high infection rates seen in megacities, deprived areas, shelters. A recent preprint

#COVID19 epidemic intensity is strongly shaped by crowding

https://www.medrxiv.org/content/10.1101/2020.04.15.20064980v1 18/ Although limited, these studies so far indicate that susceptibility to infection increases with age (highest >60y) and growing evidence suggests children are less susceptible, are infrequently responsible for household transmission, are not the main drivers of this epidemic. 19/ Finally, these studies indicate that most transmission is caused by close contact with a symptomatic case, highest risk within first 5d of symptoms. To note: this preprint suggests

that most infections are not asymptomatic during infection https://www.medrxiv.org/content/10.1101/2020.04.25.20079103v1 20/ In conclusion, contact tracing data is crucial to understand real transmission dynamics. Cautionary note: This data & interpretation is based on the available evidence as of May 4th. Our understanding might change based on community testing/lifting lockdown measures. END Addendum: While we have limited data, similar high risk transmission pattern could be seen in other crowded & connected indoor environments such as crowded office spaces, other workplace environment, packed restaurants/cafes, cramped apartment buildings etc. Conclusion 2: (a) we need to redesign our living/working spaces & rethink how to provide better, ventilated living/working environment for those who live in deprived & cramped areas; (b) avoid close, sustained contact indoors & in public transport, & maintain personal hygiene.

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