Epidemiology: References – CR05

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New References (5^th Edition)

The following pages add short comments to the papers published since the previous edition (June-October). The comments are from https://covidreference.com/daily-science.After a selection of the best articles, find the new articles of the 5^th edition grouped according to the outline of the chapter.

Top Articles

Leadership vacuum

NEJM Editors. Dying in a Leadership Vacuum. N Engl J Med 2020; 383:1479-1480. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMe2029812

SARS-CoV-2 and the COVID-19 pandemic became a test of leadership. With no good options to combat a novel pathogen, countries were forced to make hard choices about how to respond. In the United States, the leaders have failed that test.

“Variolation”?

Bielecki M, Züst R, Siegrist D, et al. Social distancing alters the clinical course of COVID-19 in young adults: A comparative cohort study. Clin Inf Dis, June 29, 2020. Full-text: https://doi.org/10.1093/cid/ciaa889

Gandhi M, Rutherford GW. Facial Masking for Covid-19 — Potential for “Variolation” as We Await a Vaccine. NEJM September 8, 2020. Full-text: https://doi.org/10.1056/NEJMp2026913

Reducing the viral SARS-CoV-2 inoculum might not only reduce the probability of infection but also favor an asymptomatic infection while still generating immunity. This suggestion by Michel Bielecki et al. in June 2020 (Bielecki 2020) was later developed by Monica Gandhi and George W. Rutherford (Ghandi 2020). If facial masking may help reducing the size of the viral inoculum, universal facial masking might ensure that a greater proportion of new infections are asymptomatic. If universal masking could be proved to be a form of “variolation” (inoculation), it would be a giant leap to pandemic control.

SARS-CoV-2 Emergence in Europe and North America

Worobey M, Pekar J, Larsen BB, et al. The emergence of SARS-CoV-2 in Europe and North America. Science 2020, published 10 September. Full-text: https://doi.org/10.1126/science.abc8169

Despite the early successes in containment, SARS-CoV-2 eventually took hold in both Europe and North America during the first two months of 2020: first in Italy around the end of January, then in Washington State around the beginning of February, and followed by New York City later that month (Worobey 2020; see also Figure 6).

Brazil

Candido DS, Claro M, de Jesus JG, et al. Evolution and epidemic spread of SARS-CoV-2 in Brazil. Science 23 Jul 2020:eabd2161. Full-text: https://doi.org/10.1126/science.abd2161

Sequencing of hundreds of genomes showed that more than 100 international virus introductions in Brazil with 76% of Brazilian strains falling into three clades that were introduced from Europe between 22 February and 11 March 2020 (Candido 2020).

Mumbai, India

Kolthur-Seetharam U, Shah D, Shastri J, Juneja S, Kang G, Malani A, Mohanan M, Lobo GN, Velhal G, Gomare M. SARS-CoV2 Serological Survey in Mumbai by NITI-BMC-TIFR. Tata Institute of Fundamental Research (TIFR) 2020, published 29 June. Full-text: https://www.tifr.res.in/TSN/article/Mumbai-Serosurvey%20Technical%20report-NITI.pdf

In a cross-sectional survey in Mumbai, India, the prevalence of SARS-CoV-2 infection in three areas in Mumbai (called ‘wards’) was around 57% in the slum areas of Chembur, Matunga and Dahisar, and 16% in neighboring non-slums (Kolthur-Seetharam 2020). If these data are confirmed, some Mumbai areas would soon reach herd immunity and could return to a pre-COVID way of life. For many countries in the world, this would be the best piece of news since the beginning of the pandemic.

Frontline healthcare workers: US

Self WH, Tenforde MW, Stubblefield WB, et al. Seroprevalence of SARS-CoV-2 Among Frontline Health Care Personnel in a Multistate Hospital Network — 13 Academic Medical Centers, April–June 2020. MMWR. Full-text: http://dx.doi.org/10.15585/mmwr.mm6935e2

Many cases appear to go undetected: among 3,248 HCWs who routinely cared for COVID-19 patients in 13 US academic medical centers from February 1, 2020, 194 (6%) had evidence of previous SARS-CoV-2 infection, with considerable variation by location that generally correlated with community cumulative incidence. Among 194 participants who had SARS-CoV-2 antibodies, 56 (29%) did not recall any symptoms consistent with an acute viral illness in the preceding months and 133 (69%) did not have a previous positive test result demonstrating an acute SARS-CoV-2 infection. Prevalence of SARS-CoV-2 antibodies was lower among personnel who reported always wearing a face covering while caring for patients (6%), compared with those who did not (9%).

Frontline healthcare workers: London

Houlihan CF, Vora N, Byrne T, et al. Pandemic peak SARS-CoV-2 infection and seroconversion rates in London frontline health-care workers. Lancet July 09, 2020. Full-text: https://doi.org/10.1016/S0140-6736(20)31484-7

High-risk frontline healthcare workers (HCV) are really at high risk. In a prospective cohort study in an acute National Health Service hospital trust in London, 25% of HCWs were already seropositive at enrolment (26 March to 8 April) and a further 20% became seropositive within the first month of follow-up (Houlihan 2020). Most infections occurred between March 30 and April 5, the week with the highest number of new cases in London.

School Openings

Cheng SY, Wang J, Shen AC, et al. How to Safely Reopen Colleges and Universities During COVID-19: Experiences From Taiwan. Ann Int Med 2020, Jul 2. Full-text: https://doi.org/10.7326/M20-2927

Taiwan is one of the few countries where schools are functioning normally. To secure the safety of students and staff, the Ministry of Education in Taiwan established general guidelines, including a combination of strategies such as – our future? – active campus-based screening and access control; school-based screening and quarantine protocols; student and faculty quarantine when warranted; mobilization of administrative and health center staff; regulation of dormitories and cafeterias; and reinforcement of personal hygiene, environmental sanitation, and indoor air ventilation practices (Cheng SY 2020). Depressing (“un monde de con”), but probably necessary.

Second Wave

NCOMG. The national COVID-19 outbreak monitoring group. COVID-19 outbreaks in a transmission control scenario: challenges posed by social and leisure activities, and for workers in vulnerable conditions, Spain, early summer 2020. Eurosurveillance Volume 25, Issue 35, 03/Sep/2020. Full-text: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.35.2001545

From mid-June to 2 August, excluding single household outbreaks, 673 outbreaks were notified in Spain (NCOMG 2020). There were two main settings where over 55% of active outbreaks (303/551) and over 60% (3,815/6,208) of active outbreak cases originated: First, social settings such as family gatherings or private parties (112 outbreaks, 854 cases), followed by those linked to leisure venues such as bars, restaurants, or clubs (34 outbreaks, over 1,230 cases). Second, occupational settings (representing 20% of all active outbreaks), mainly among workers in the fruit and vegetable sector (31 outbreaks and around 500 cases) and workers at slaughterhouses or meat processing plants (12 outbreaks and around 360 cases).

Rigorous wildlife disease surveillance

Watsa M. Rigorous wildlife disease surveillance. Science 10 Jul 2020, 369: 145-147. Full-text: https://doi.org/10.1126/science.abc0017

Emerging infectious diseases (EID) associated with the wildlife trade remain the largest unmet challenge of current disease surveillance efforts. International or national conventions on pathogen screening associated with animals, animal products or their movements are urgently needed (Watsa 2020). Internationally recognized standard for managing wildlife trade on the basis of known disease risks should be established.

Introduction

McNeil Jr DG. A Viral Epidemic Splintering Into Deadly Pieces. The New York Times, 29 July 2020. Full-text: https://www.nytimes.com/2020/07/29/health/coronavirus-future-america.html

Some articles in the lay press are outstanding documents, and a few are better than two thirds of published and pre-published scientific articles about COVID-19. Read these 4,000 words thoughtfully put down by Donald G. McNeil Jr. If you don’t read it now, read it on the weekend.

Adam D. A guide to R — the pandemic’s misunderstood metric. Nature News. 03 July 2020. Full-text: https://www.nature.com/articles/d41586-020-02009-w

Nice article about what R, the reproduction number, can and can’t tell us about managing COVID-19 (Adam 2020). Politicians seem to have embraced R with enthusiasm but it’s far more important to watch for clusters of cases and to set up comprehensive systems to test people, trace their contacts and isolate those infected, than to look at R.

Yu X, Wei D, Chen Y, et al. Retrospective detection of SARS-CoV-2 in hospitalized patients with influenza-like illness. Emerging Microbes & Infections 2020, Full-text: https://doi.org/10.1080/22221751.2020.1785952

There was no ‘stealthy’ SARS-CoV-2 transmission before the outbreak in Wuhan, China. In a retrospective screening for SARS-CoV-2 RNA in 1,271 nasopharyngeal swab samples, as well as the prevalence of IgM, IgG, and total antibodies against SARS-CoV-2 in 357 matched serum samples collected from hospitalized patients with influenza-like illness between December 1, 2018 and March 31, 2020 in Shanghai Ruijin Hospital, the onset date of the earliest COVID-19 case was January 25 (Yu X 2020).

Worobey M, Pekar J, Larsen BB, et al. The emergence of SARS-CoV-2 in Europe and North America. Science 2020, published 10 September. Full-text: https://doi.org/10.1126/science.abc8169

Dawood FS, Ricks P, Njie GJ, et al. Observations of the global epidemiology of COVID-19 from the prepandemic period using web-based surveillance: a cross-sectional analysis. Lancet Infect Dis 2020, published 29 July. Full-text: https://doi.org/10.1016/S1473-3099(20)30581-8

Fatimah Dawood and colleagues describe the global spread of SARS-CoV-2 and characteristics of COVID-19 cases and clusters before WHO declared COVID-19 as a pandemic on 11 March 2020 (i.e., pre-pandemic). They identified cases of COVID-19 from official websites, press releases, press conference transcripts, and social media feeds of national ministries of health or other government agencies. Cases with travel links to China, Italy, or Iran accounted for almost two-thirds of the first reported COVID-19 cases from affected countries (Dawood 2020). There were many clusters of household transmission among early cases; however, clusters in occupational or community settings tended to be larger.

Deng X, Gu W,Federman S, et al. Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California. Science 08 Jun 2020. Full-text: https://doi.org/10.1126/science.abb9263

Early genomic surveillance revealed the cryptic introduction of at least 7 different SARS-CoV-2 lineages into California (Deng X 2020).

Candido DS, Claro M, de Jesus JG, et al. Evolution and epidemic spread of SARS-CoV-2 in Brazil. Science 23 Jul 2020:eabd2161. Full-text: https://doi.org/10.1126/science.abd2161

Seroprevalence

Italy

Sabbadini LL, Romano MC, et al. [First results of the seroprevalence survey about SARS-CoV-2] (Primi risultati dell’indagine di sieroprevalenza sul SARS-CoV-2). Italian Health Ministery and National Statistics Institute 2020, published 3 August. Full-text (Italian): https://www.istat.it/it/files//2020/08/ReportPrimiRisultatiIndagineSiero.pdf

According to a representative study by the Italian Ministry of Health (64,000 participants), 1.5 million people (2.5% of the population) had SARS-CoV-2 antibodies during the study period from May 25 to July 15 (Sabbadini 2020). This figure is higher than the currently reported 250,000 cases. If these figures are true, the infection fatality rate (IFR, the proportion of deaths among all the infected individuals) in Italy would be 2.3% (35,000 deaths/1,500,000 infections). This is higher than in other European countries and needs to be addressed in future studies.

Bassi F, Arbia G, Falorsi PD. Observed and estimated prevalence of Covid-19 in Italy: How to estimate the total cases from medical swabs data. Sci Total Environ. 2020 Oct 8:142799. PubMed: https://pubmed.gov/33066965. Full-text: https://doi.org/10.1016/j.scitotenv.2020.142799

A national survey in Italy from May to July 2020 (see previous article) found a nationwide seropositivity rate of 2.5% (Sabbadini 2020). Insiders never believed these figures and favored a seropositivity rate of 5-10% like in Spain or in France. Now we have a new estimate of COVID-19 prevalence in Italy by Francesca Bassi and colleagues: 9%, corresponding to almost 6 million Italians.

Percivalle E, Cambiè G, Cassaniti I, et al. Prevalence of SARS-CoV-2 specific neutralising antibodies in blood donors from the Lodi Red Zone in Lombardy, Italy, as at 06 April 2020. Euro Surveill. 2020 Jun;25(24):2001031. PubMed: https://pubmed.gov/32583766. Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.24.2001031

In the highly affected “Lodi Red Zone” in Italy (an area of 169 km², including 10 municipalities and 51,500 inhabitants, which went into lockdown in February 2020), 91 of 390 blood donors (23%) aged 19–70 years were antibody positive (Percivalle 2020).

Spain

Pollán M, Pérez-Gómez B, Pastor-Barriuso R, et al. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. The Lancet 2020, July 06, 2020. Full-text: https://doi.org/10.1016/S0140-6736(20)31483-5

The vast majority (95%) of the Spanish population is seronegative, even in hotspot areas. In a nationwide, representative study, 61,075 participants were tested. Seroprevalence was 5.0% (95% CI 4.7–5.4) by the point-of-care test and 4.6% (4.3–5.0) by immunoassay, with a lower seroprevalence in children younger than 10 years (< 3.1% by the point-of-care test) (Pollán 2020). There was high geographical variability, with higher prevalence around Madrid (> 10%) and lower in coastal areas (< 3%).

Soriano V, Meiriño R, Corral O, Guallar MP. SARS-CoV-2 antibodies in adults in Madrid, Spain. Clin Infect Dis. 2020 Jun 16:ciaa769. PubMed: https://pubmed.gov/32544951. Full-text: https://doi.org/10.1093/cid/ciaa769

Even in regions that were hard hit by the first SARS-CoV-2 wave (like the Madrid area with with 65,000 confirmed cases and 9,000 deaths up to May 10^th), only roughly 11% of adults had SARS-CoV-2 antibodies at the time of lockdown release on May 10^th (Soriano 2020).

US

Ng DL, Goldgof GM, Shy BR, et al. SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood. Nat Commun. 2020 Sep 17;11(1):4698. PubMed: https://pubmed.gov/32943630. Full-text: https://doi.org/10.1038/s41467-020-18468-8

In April 2020, SARS-CoV-2 seroprevalence was low in the San Francisco Bay Area (0.26% in 387 hospitalized patients; 0.1% in 1,000 blood donors) (Ng DL 2020). Charles Y. Chiu, Dianna Ng and colleagues also describe the longitudinal dynamics of immunoglobulin-G (IgG), immunoglobulin-M (IgM), and in vitro neutralizing antibody titers in COVID-19 patients. The median time to seroconversion ranged from 10.3–11.0 days for these 3 assays. The authors provide evidence that seropositive results using SARS-CoV-2 anti-nucleocapsid protein IgG and anti-spike IgM assays are generally predictive of in vitro neutralizing capacity.

Havers FP, Reed C, Lim T, et al. Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States, March 23-May 12, 2020. JAMA Intern Med. 2020 Jul 21. PubMed: https://pubmed.gov/32692365. Full-text: https://doi.org/10.1001/jamainternmed.2020.4130

In a cross-sectional study, the proportion of seropositive persons ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1) (Havers 2020). The estimated number of SARS-CoV-2 infections is around 10 times the number of reported cases.

Moscola J, Sembajwe G, Jarrett M, et al. Prevalence of SARS-CoV-2 Antibodies in Health Care Personnel in the New York City Area. JAMA 2020, published 6 August. https://doi.org/10.1001/jama.2020.14765

Health care personnel (HCP) have a high exposure risk for SARS-CoV-2 infection. In New York, the prevalence of SARS-CoV-2 was 13.7 (5523 of 40,329 HCWs tested) which was similar to that among adults randomly tested in New York State (14.0%). (Moscola 2020).

India

Faroe Islands

Petersen MS, Strøm M, Christiansen DH, Fjallsbak JP, Eliasen EH, Johansen M, et al. Seroprevalence of SARS-CoV-2–specific antibodies, Faroe Islands. Emerg Infect Dis 2020 Nov. Published August 2020. Full-text: https://doi.org/10.3201/eid2611.202736

In the Faroe Islands, an autonomous territory within the Kingdom of Denmark with a population of around 50,000, only 6 out of 1,075 randomly selected participants (0.6%) tested seropositive for antibodies to SARS-CoV-2 (Petersen 2020). At present, small islands tend to have low seropositivity rates.

UK

Ward H, Atchison C, Whitaker M, et al. Antibody prevalence for SARS-CoV-2 following the peak of the pandemic in England: REACT2 study in 100,000 adults. Imperial College London 2020. Pre-print: https://www.imperial.ac.uk/media/imperial-college/institute-of-global-health-innovation/Ward-et-al-120820.pdf

By the end of June 2020, an estimated 3.4 million people, or slightly under 6% of the UK population, had antibodies to the virus and had likely had COVID-19. London had the highest numbers (13%), while the South West had the lowest (3%) (Ward 2020). Black, Asian and minority ethnic (BAME) individuals were between two and three times as likely to have had SARS-CoV-2 infection compared to white people. An interesting trend: young people aged 18-24 had the highest rates (8%), while older adults aged 65 to 74 were least likely to have been infected (3%).

China

Xu X, Sun J, Nie S, et al. Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China. Nat Med. 2020 Jun 5. PubMed: https://pubmed.gov/32504052. Full-text: https://doi.org/10.1038/s41591-020-0949-6

At the end of the 2020 winter epidemic, the seropositivity (IgM and IgG antibodies ) in Wuhan was low, varying between 3.2% and 3.8% in different sub-cohorts (Xu X 2020).

Switzerland

Stringhini S, Wisniak A, Piumatti G, et al. The Lancet, June 11, 2020. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study. Full-text: https://doi.org/10.1016/S0140-6736(20)31304-0

Geneva was a COVID-19 hot spot in Switzerland (5000 cases over < 2.5 months in half a million people). The seroprevalence increased from about 5% to about 11% over five consecutive weekly sero-surveys among 2,766 randomly selected participants from a previous population-representative survey, and 1,339 household members aged 5 years and older (Stringhini 2020). Of note, young children (5–9 years) and older people (≥ 65 years) had significantly lower seroprevalence than the other age groups. Authors estimated that there were 11 infections for every COVID-19 confirmed case.

Hotspots of SARS-CoV-2 Transmission

Hospitals

Nagano T, Arii J, Nishimura M, et al. Diligent medical activities of a publicly designated medical institution for infectious diseases pave the way for overcoming COVID-19: A positive message to people working at the cutting edge. Clin Infect Dis. 2020 May 31. PubMed: https://pubmed.gov/32474577. Full-text: https://doi.org/10.1093/cid/ciaa694

Standard preventive measures against infectious diseases can prevent SARS-CoV-2 exposure in medical staff. Of 509 medical staff members working to treat COVID-19 patients at the Hyogo Prefectural Kakogawa Medical Center, a large medical institution for infectious diseases in Japan (mean number of hospitalized COVID-19 patients was 20), none had IgG antibodies for SARS-CoV-2 on May 1-8 (Nagano 2020).

Callaghan AW, Chard AN, Arnold P, et al. Screening for SARS-CoV-2 Infection Within a Psychiatric Hospital and Considerations for Limiting Transmission Within Residential Psychiatric Facilities – Wyoming, 2020. MMWR Morb Mortal Wkly Rep. 2020 Jul 3;69(26):825-829. PubMed: https://pubmed.gov/32614815. Full-text: https://doi.org/10.15585/mmwr.mm6926a4

Implementing expanded admission screening and infection prevention and control procedures is effective even within a psychiatric ward (Callaghan 2020).

Rincón A, Moreso F, López-Herradón A. The keys to control a coronavirus disease 2019 outbreak in a haemodialysis unit. Clinical Kidney Journal, 13 July 2020. Full-text: https://doi.org/10.1093/ckj/sfaa119

In an hemodialysis unit in Barcelona, 18% of patients receiving treatment became infected (Rincón 2020). The main risk factors for SARS-CoV-2 infection were sharing health-care transportation, living in a nursing home and having been admitted to the reference hospital within the previous 2 weeks.

Vahidy FS, Bernard DW, Boom ML, et al. Prevalence of SARS-CoV-2 Infection Among Asymptomatic Health Care Workers in the Greater Houston, Texas, Area. JAMA Netw Open. 2020 Jul 1;3(7):e2016451. PubMed: https://pubmed.gov/32716512. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.16451

Among clinical HCWs, 5.4% from COVID-19 units and 0.6% from non–COVID units had RT-PCR test results positive for SARS-CoV-2 (Vahidy 2020).

Long-term care facilities

Marossy A, Rakowicz S, Bhan A, et al. A study of universal SARS-CoV-2 RNA testing of residents and staff in a large group of care homes in South London. J Infect Dis. 2020 Sep 5:jiaa565. PubMed: https://pubmed.gov/32889532. Full-text: https://doi.org/10.1093/infdis/jiaa565

In one of the largest studies of care homes in Europe which involved 2,455 individuals, residents and staff from 37 care homes in the London Borough of Bromley were tested irrespective of symptoms. Overall, the point prevalence of SARS-CoV-2 infection was 6.5% with a higher rate in residents (9.0%) than in staff (4.7%) (Marossy 2020).

Fisman DN, Bogoch I, Lapointe-Shaw L, et al. Risk Factors Associated With Mortality Among Residents With Coronavirus Disease 2019 (COVID-19) in Long-term Care Facilities in Ontario, Canada. JAMA, published July 22, Full-text: https://doi.org/10.1001/jamanetworkopen.2020.15957

Hotspot LTCF. In a study from Ontario, Canada, the incidence of mortality was more than 13 times greater than that seen in community-living adults older than 69 years during a similar period (Fisman 2020).

Graham NSN, Junghans C, McLaren R, et al. High rates of SARS-CoV-2 seropositivity in nursing home residents. J Infection August 26, 2020a. Full-text: https://doi.org/10.1016/j.jinf.2020.08.040

Some nursing homes in the UK achieved fairly high seropositivity rates. In one study, 72% percent of nursing home residents were anti-SARS-CoV-2 IgG antibody positive (Graham 2020). Seropositivity was not associated with the presence of comorbidities.

ECDC Public Health Emergency Team, Danis K, Fonteneau L, et al. High impact of COVID-19 in long-term care facilities, suggestion for monitoring in the EU/EEA. May 2020. Eurosurveillance, Volume 25, Issue 22, 04/Jun/2020 Article. Full-text: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.22.2000956

Residents in long-term care facilities contribute 30–60% of all COVID-19 deaths in many European countries (ECDC 2020). Surveillance and infection prevention and control measures are paramount: identify clusters early, decrease the spread within and between facilities and reduce the size and severity of outbreaks.

Graham N, Junghans C, Downes R, et al. SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes. J Infect 2020b, Jun 3:S0163-4453(20)30348-0. PubMed: https://pubmed.gov/32504743. Full-text: https://doi.org/10.1016/j.jinf.2020.05.073

Hotspot nursing home. In one UK investigation involving 394 residents and 70 staff in 4 nursing homes in central London, 26% of residents died over a two-month period (Graham 2020). Systematic testing identified 40% of residents as positive for SARS-CoV-2 and of these, 43% were asymptomatic and 18% had only atypical symptoms during the two weeks prior to testing. Of note, this was also true of many residents in the days leading up to death indicating that even in severe COVID-19, fever and cough were commonly absent. 4% of asymptomatic staff also tested positive.

Dora AV, Winnett A, Jatt LP, et al. Universal and Serial Laboratory Testing for SARS-CoV-2 at a Long-Term Care Skilled Nursing Facility for Veterans – Los Angeles, California, 2020. MMWR Morb Mortal Wkly Rep. 2020 May 29;69(21):651-655. PubMed: https://pubmed.gov/32463809. Full-text: https://doi.org/10.15585/mmwr.mm6921e1

Again and again: Test them all, immediately. After an outbreak at a long-term care nursing facility, all residents, regardless of symptoms, underwent serial (approximately weekly) nasopharyngeal SARS-CoV-2 RT-PCR testing. Nineteen of 99 (19%) residents had positive test results for SARS-CoV-2 (Dora 2020). Fourteen of the 19 residents with COVID-19 were asymptomatic at the time of testing. Among these, eight developed symptoms 1-5 days after specimen collection and were later classified as presymptomatic.

Leisure venues (bars, clubs, choirs, karaoke, discos, etc.)

Hotspot Movida. From mid-June to 2 August, excluding single household outbreaks, 673 outbreaks were notified in Spain (NCOMG 2020). There were two main settings where over 55% of active outbreaks (303/551) and over 60% (3,815/6,208) of active outbreak cases originated: First, social settings such as family gatherings or private parties (112 outbreaks, 854 cases), followed by those linked to leisure venues such as bars, restaurants, or clubs (34 outbreaks, over 1,230 cases). Second, occupational settings (representing 20% of all active outbreaks), mainly among workers in the fruit and vegetable sector (31 outbreaks and around 500 cases) and workers at slaughterhouses or meat processing plants (12 outbreaks and around 360 cases).

Data from Japan showed that of a total of 61 COVID-19 clusters, 18 (30%) were in healthcare facilities; 10 (16%) in care facilities of other types, such as nursing homes and day care centers; 10 (16%) in restaurants or bars; 8 (13%) in workplaces; 7 (11%) in music-related events, such as live music concerts, chorus group rehearsals, and karaoke parties; 5 (8%) in gymnasiums; 2 (3%) in ceremonial functions; and 1 (2%) in transportation-related incident in an airplane (Furuse 2020). Of note, 41% of probable primary case-patients were pre-symptomatic or asymptomatic at the time of transmission. 45% had cough. Many clusters were associated with heavy breathing in close proximity.

Kang CR, Lee JY, Park Y, Huh IS, Ham HJ, Han JK, et al. Coronavirus disease exposure and spread from nightclubs, South Korea. Emerg Infect Dis. 2020 Sep. Full-text: https://doi.org/10.3201/eid2610.202573

Superspreading events in nightclubs have the potential to spark local resurgence of cases. Large-scale testing (41,612 total tests!) for active case-finding among persons who visited 5 Itaewon nightclubs in downtown Seoul found positive results in 0.19% (67/35,827) of nightclub visitors, 0.88% (51/5,785) of their contacts, and 0.06% (1/1,627) of anonymously tested persons (Kang 2020). In total, 246 COVID-19 cases were associated with the reopening of nightclubs in Seoul.

Lewis M, Sanchez R, Auerbach S, et al. COVID-19 Outbreak Among College Students After a Spring Break Trip to Mexico — Austin, Texas, March 26–April 5, 2020. MMWR Morb Mortal Wkly Rep. ePub: 24 June 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6926e1

Asymptomatic persons or those with mild symptoms likely played an important role in sustaining transmission. A college trip is an ideal environment for SARS-CoV-2 transmission (64 cases on one trip, 14 asymptomatic and 50 symptomatic; Lewis 2020).

Workplaces

Waltenburg MA, Victoroff T, Rose CE, et al. Update: COVID-19 Among Workers in Meat and Poultry Processing Facilities – United States, April–May 2020. MMWR Morb Mortal Wkly Rep. ePub: 7 July 2020. Full-text: https://www.cdc.gov/mmwr/volumes/69/wr/mm6927e2.htm

Meat and poutry processing facilities are SARS-CoV-2 hotspots. One study reported 16,233 COVID-19 cases and 86 COVID-19–related deaths among workers in 239 facilities (Waltenburg 2020). The percentage of workers with COVID-19 ranged from 3.1% to 24.5% per facility.

Among seven facilities that implemented facility-wide testing, the crude prevalence of asymptomatic or presymptomatic infections among 5,572 workers who had positive SARS-CoV-2 test results was 14.4% (Waltenburg 2020).

Steinberg J, Kennedy ED, Basler C, et al. COVID-19 Outbreak Among Employees at a Meat Processing Facility — South Dakota, March–April 2020. MMWR Morb Mortal Wkly Rep 2020;69:1015–1019. Full-text: http://dx.doi.org/10.15585/mmwr.mm6931a2

Early outbreak in a meat processing facility in the US. From March 16 to April 25, 25.6% (929) of employees and 8.7% (210) of their contacts were diagnosed with COVID-19; two employees died (Steinberg 2020). The highest attack rates occurred among employees who worked < 6 feet (2 meters) from one another on the production line.

Schools

Davies NG, Klepac P, Liu Y et al. Age-dependent effects in the transmission and control of COVID-19 epidemics. Nat Med 2020, June 16. https://doi.org/10.1038/s41591-020-0962-9

Children have a lower susceptibility to infection. Using epidemic data from Canada, China, Italy, Japan, Singapore, and South Korea, one group found that susceptibility to infection in individuals under 20 years of age was approximately half that of adults aged over 20 years, and clinical symptoms manifest in 21% of infections in 10- to-19-year-olds, rising to 69% of infections in people aged over 70 years (Davis 2020).

Panovska-Griffiths J, Kerr CC, Stuart RM, et al. Determining the optimal strategy for reopening schools, the impact of test and trace interventions, and the risk of occurrence of a second COVID-19 epidemic wave in the UK: a modelling study. Lancet Child Adolesc Health 2020, August 03, 2020. Full-text: https://doi.org/10.1016/S2352-4642(20)30250-9

Reopening of schools must be accompanied by large-scale, population-wide testing of symptomatic individuals and effective tracing of their contacts, followed by isolation of diagnosed individuals. Without these levels of testing and contact tracing, reopening of schools together with gradual relaxing of the lockdown measures are likely to induce a second wave that would peak in December 2020 (Panovska-Griffiths).

Brown NE, Bryant-Genevier J, Bandy U, Browning CA, Berns AL, Dott M, et al. Antibody responses after classroom exposure to teacher with coronavirus disease, March 2020. Emerg Infect Dis. 2020 Sep [date cited]. https://doi.org/10.3201/eid2609.201802

No big surprise: classroom interaction between an infected teacher and students might result in virus transmission. After returning from Europe to the United States on March 1, 2020, a symptomatic teacher received positive test results. In total 2/21 students exposed to the teacher in the classroom had positive serologic results.

Cheng SY, Wang J, Shen AC, et al. How to Safely Reopen Colleges and Universities During COVID-19: Experiences From Taiwan. Ann Int Med 2020, Jul 2. Full-text: https://doi.org/10.7326/M20-2927

Torres JP, Piñera C, De La Maza V, et al. SARS-CoV-2 antibody prevalence in blood in a large school community subject to a Covid-19 outbreak: a cross-sectional study. Clin Infect Dis. 2020 Jul 10:ciaa955. PubMed: https://pubmed.gov/32649743. Full-text: https://doi.org/10.1093/cid/ciaa955

School-based outbreak are common with cases among teachers, children and parents. In some situations, the index cases were teachers and/or parents (Torres 2020). Reopening schools should focus on avoiding new cases among teachers

Mass gatherings

Anonymous. Deutsche Box-Olympiamannschaft mit Coronavirus infiziert. Die Zeit 2020, published 12 September. Full-text: https://www.zeit.de/sport/2020-09/trainingslager-oesterreich-deutsche-box-olympiamannschaft-coronavirus-infektion-quarantaene

In an unintentional experiment, the German national team of amateur boxers has proved that you can achieve a 100% transmission rate in a small group within days. In a training camp, some of the 18 athletes and 7 coaches and supervisors had cold symptoms four days ago. Now all 25 persons have tested positive for SARS-CoV-2. So far, no serious cases.

Mubarak N, Zin CS. Religious tourism and mass religious gatherings – The potential link in the spread of COVID-19. Current perspective and future implications. Travel Med Infect Dis. 2020 Jun 9;36:101786. PubMed: https://pubmed.gov/32531422. Full-text: https://doi.org/10.1016/j.tmaid.2020.101786

Religious mass gatherings should probably postponed. Of particular concern are pilgrims returning to home countries with inadequate quarantine and diagnostic infrastructure, especially those over 50 years old or suffering from chronic disease such as diabetes or cardiovascular disease (Mubarak 2020).

Khan A, Bieh KL, El-Ganainy A, et al. Estimating the COVID-19 Risk during the Hajj Pilgrimage. Journal of Travel Medicine, 05 September 2020. Full-text: https://doi.org/10.1093/jtm/taaa157

A religious gathering that attracts 2.5 million pilgrims from over 150 countries has clearly the potential to create a giga-spreading event. Designated ward and ICU beds could be saturated within days. Reducing the number of pilgrims and excluding foreign pilgrims is a wise decision (Khan 2020)

Nayar KR, Koya SF, Ramakrishnan V, et al. Call to avert acceleration of COVID-19 from India’s Sabarimala pilgrimage of 25 million devotees. Journal of Travel Medicine, 05 September 2020, taaa153. Full-text: https://doi.org/10.1093/jtm/taaa153

Hajj or the Sabarimala annual 41-day long Hindu pilgrimage attended by an average of 25 million pilgrims (Nayar 2020). How would proceed to require a negative SARS-CoV-2 antigen test from all pilgrims?

Closed and densely populated spaces

Njuguna H, Wallace M, Simonson S, et al. Serial Laboratory Testing for SARS-CoV-2 Infection Among Incarcerated and Detained Persons in a Correctional and Detention Facility — Louisiana, April–May 2020. MMWR Morb Mortal Wkly Rep. ePub: 29 June 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6926e2

High COVID-19 attack rates in prisons. Among 98 incarcerated and detained persons in Louisiana who were quarantined because of virus exposure, 71 (72%) had lab-confirmed SARS-CoV-2 infection identified through serial testing, among them 45% without any symptoms at the time of testing (Njuguna 2020). Serial testing of contacts of persons with COVID-19 in correctional and detention facilities can identify asymptomatic and presymptomatic persons who would be missed through symptom screening alone.

Jiménez MC, Cowger TL, Simon LE, Behn M, Cassarino N, Bassett MT. Epidemiology of COVID-19 Among Incarcerated Individuals and Staff in Massachusetts Jails and Prisons. JAMA Netw Open 2020;3(8). Full-text: https://doi.org/10.1001/jamanetworkopen.2020.18851

In July 2020, the rate of COVID-19 among incarcerated individuals was nearly 3 times that of the Massachusetts general population and 5 times the US rate (Jiménez 2020). Of 14,987 individuals incarcerated across Massachusetts prison facilities, 1032 confirmed cases of COVID-19 were reported among incarcerated individuals (n = 664) and staff (n = 368).

Saloner B, Parish K, Ward JA. COVID-19 Cases and Deaths in Federal and State Prisons. JAMA July 8, 2020. Full-text: https://doi.org/10.1001/jama.2020.12528

By June 6, 2020, there had been 42,107 cases of COVID-19 and 510 deaths among 1.3 million prisoners in the US (Saloner 2020).

Maxmen A. California’s San Quentin prison declined free coronavirus tests and urgent advice — now it has a massive outbreak. Nature NEWS 07 July 2020. Full-text: https://doi.org/10.1038/d41586-020-02042-9

In July 2020, more than one-third of the inmates and staff (1,600 people) in San Quentin Prison tested positive (Maxmen 2020). Six had died.

Rogers JH, Link AC, McCulloch D, et al. Characteristics of COVID-19 in Homeless Shelters : A Community-Based Surveillance Study. Ann Intern Med. 2020 Sep 15. PubMed: https://pubmed.gov/32931328. Full-text: https://doi.org/10.7326/M20-3799

In this cross-sectional, community-based surveillance study of 14 homeless shelters in King County, Washington, Helen Chu, Julia Rogers and colleagues divided the number of positive cases by the total number of participant encounters, regardless of symptoms. Among 1434 encounters, 29 (2%) cases of SARS-CoV-2 infection were detected across 5 shelters. Eighty-six percent of persons with positive test results slept in a communal space rather than in a private or shared room (Rogers 2020).

Payne DC, Smith-Jeffcoat SE, Nowak G, et al. SARS-CoV-2 Infections and Serologic Responses from a Sample of U.S. Navy Service Members — USS Theodore Roosevelt, April 2020. MMWR Morb Mortal Wkly Rep. ePub: 9 June 2020. Full-text: https://www.cdc.gov/mmwr/volumes/69/wr/mm6923e4.htm

In late March 2020, a large outbreak on the aircraft carrier USS Theodore Roosevelt was characterized by widespread transmission with relatively mild symptoms and asymptomatic infection among mostly young, healthy adults with close, congregate exposures. One fifth of infected participants reported no symptoms. Preventive measures, such as using face-coverings and observing social distancing, reduced risk for infection: among 382 service members, those who reported taking preventive measures had a lower infection rate than did those who did not report taking these measures (e.g., wearing a face-covering, 56% versus 81%; avoiding common areas, 54% versus 68%; and observing social distancing, 55% versus 70%, respectively) (Payne 2020).

Special Aspects of the Pandemic

Preparedness

Pham QT, Rabaa MA, Duong HL, et al. The first 100 days of SARS-CoV-2 control in Vietnam. Clin Infect Dis 2020, published 1 August. Full-text: https://doi.org/10.1093/cid/ciaa1130

Vietnam did remarkably well. One hundred days after the first SARS-CoV-2 case was reported in Vietnam on January 23^rd, 270 cases were confirmed, with no deaths. Although there was a high proportion of asymptomatic and imported cases as well as evidence for substantial pre-symptomatic transmission, Vietnam controlled SARS-CoV-2 spread through the early introduction of mass communication, meticulous contact-tracing with strict quarantine, and international travel restrictions (Pham QT 2020). A lesson for the world?

Looi MK. Covid-19: Japan ends state of emergency but warns of “new normal”. BMJ. 2020 May 26;369:m2100. PubMed: https://pubmed.gov/32457055. Full-text: https://doi.org/10.1136/bmj.m2100

Japan has done a good job. Public adherence to the rules, along with cluster tracing and a ban on mass gatherings, seems to have achieved success in bringing the outbreak under control,

If, as in Japan, widespread mask use and hygiene is a normal part of etiquette, combatting SARS-CoV-2 is easier (Looi 2020).

Stoke EK, Zambrano LD, Anderson KN. Coronavirus Disease 2019 Case Surveillance — United States, January 22–May 30, 2020. MMWR June 15, 2020. Full-text: https://www.cdc.gov/mmwr/volumes/69/wr/mm6924e2.htm

In June, the CDC reported data on 1,320,488 laboratory-confirmed COVID-19 cases. Overall, 184,673 (14%) patients were hospitalized, 29,837 (2%) were admitted to an intensive care unit (ICU), and 71,116 (5%) died. Hospitalizations were six times higher among patients with a reported underlying condition (45.4%) than those without reported underlying conditions (7.6%). Deaths were 12 times higher among patients with reported underlying conditions (19.5%) compared with those without reported underlying conditions (1.6%) (Stoke 2020).

Unwillingness to prepare/denial (UK, USA, Brazil)

NEJM Editors. Dying in a Leadership Vacuum. N Engl J Med 2020; 383:1479-1480. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMe2029812

Yehya N, Venkataramani A, Harhay MO. Statewide Interventions and Covid-19 Mortality in the United States: An Observational Study. Clin Infect Dis. 2020 Jul 8. PubMed: https://pubmed.gov/32634828. Full-text: https://doi.org/10.1093/cid/ciaa923

Every day counts. In this large, nationwide study, later statewide emergency declarations and school closures were associated with higher COVID-19 mortality. Each day of delay increased mortality risk by 5 to 6% (Yehya 2020).

Maxmen A. Why the United States is having a coronavirus data crisis. Nature 2020, published 25 August. Full-text: https://www.nature.com/articles/d41586-020-02478-z

To respond to a pandemic, you need reliable information on who is infected, why and where. Unfortunately, many countries suffered from a dearth of data (Maxmen 2020).

Splendid isolation (New Zealand, Australia)

Baker MG, Anglemyer A. Successful Elimination of Covid-19 Transmission in New Zealand. N Engl J Med 2020, published 7 August. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMc2025203

Heywood AE, Macintyre CR. Elimination of COVID-19: what would it look like and is it possible? Lancet 2020, published 6 August. Full-text: https://doi.org/10.1016/S1473-3099(20)30633-2

Is elimination of SARS-CoV-2 possible (Hewyood 2020)? Geographical isolated islands or island states should be the identical candidates for elimination trials. However, even New Zealand which viewd itself in the post-elimination stage and where public life had returned to near normal (Baker 2020), was suddenly called back into COVID-19 reality when new cases were discovered in early August. The elimination of any infectious disease is ambitious, requiring substantial resources. They suggest a zero-case scenario of not less than three months before declaring an area SARS-CoV-2-free. For obvious reasons, islands or island states have the best chances to achieve this goal (Hewyood 2020).

Seemann T, Lance CR, Sherry NL, et al. Tracking the COVID-19 pandemic in Australia using genomics. Nat Commun 11, 4376 (2020). Full-text: https://doi.org/10.1038/s41467-020-18314-x

Multiple SARS-CoV-2 importations by returned international travelers drove transmission in Australia, with travel-related cases responsible for establishing ongoing transmission lineages (each with 3–9 cases) accounting for over half of locally acquired cases (Seemann 2020).

The unknown (?) outcome

Kalk A, Schultz A. SARS-CoV-2 epidemic in African countries—are we losing perspective? Lancet, August 07, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30563-6

Lockdown for everybody? Maybe not. In the Democratic Republic of the Congo and Malawi, for instance, only 2-3% of the population is older than 65 years. Under these circumstances, full lockdown measures might cause more harm than SARS-CoV-2 itself (Kalk 2020).

Twahirwa Rwema JO, Diouf D, Phaswana-Mafuya N, et al. COVID-19 Across Africa: Epidemiologic Heterogeneity and Necessity of Contextually Relevant Transmission Models and Intervention Strategies. Ann Intern Med. 2020 Jun 18. PubMed: https://pubmed.gov/32551812. Full-text: https://doi.org/10.7326/M20-2628

Europe without Russia has a surface of roughly 6 million km², Africa has 30 million km². That should explain by itself that the burden and outcomes associated with COVID-19 in Africa shows substantial variations across African countries (Twahirwa 2020).

Walker PG, Whittaker C, Watson OJ, et al. The impact of COVID-19 and strategies for mitigation and suppression in low- and middle-income countries. Science 12 Jun 2020. Full-text: https://DOI.ORG/10.1126/science.abc0035

The impact of the SARS-CoV-2 pandemic in low- and middle-income countries (LMIC) is still unknown. On one hand, we have an overall younger population, on the other hand, there is a higher burden of infectious diseases such as AIDS and TB already, and of poverty-related determinants of poorer health outcomes such as malnutrition (Walker 2020). There is also a more persistent spread to older age categories (higher levels of household-based transmissions) and poorer quality health care and lack of health care capacity.

The SARS-CoV-2 pandemic: Past and Future

Natural course of a pandemic

Barbarossa MV, Fuhrmann J, Meinke JH, et al. Modeling the spread of COVID-19 in Germany: Early assessment and possible scenarios. PLoS One. 2020 Sep 4;15(9):e0238559. PubMed: https://pubmed.gov/32886696. Full-text: https://doi.org/10.1371/journal.pone.0238559

Without restrictive measures, about 32 million total infections and 730,000 deaths could result in Germany alone over the course of the epidemic (Barbarossa 2020).

The 2020 Lockdowns

Sudharsanan N, Didzun O, Bärnighausen T Geldsetzer P. The Contribution of the Age Distribution of Cases to COVID-19 Case Fatality Across Countries – A 9-Country Demographic Study. Ann Intern Med 2020, published 22 July. Full-text: https://doi.org/10.7326/M20-2973

The overall observed case-fatality rates (CFR) vary widely, with the highest rates in Italy (9.3%) and the Netherlands (7.4%) and the lowest rates in South Korea (1.6%) and Germany (0.7%). This cross-sectional study of population-based data from China, France, Germany, Italy, the Netherlands, South Korea, Spain, Switzerland, and the US finds that age distribution of cases explains 66% of the variation of across countries, with a resulting age-standardized median CFR of 1.9%. See also the editorial by David N. Fisman, Amy L. Greer, and Ashleigh R. Tuite: Age Is Just a Number: A Critically Important Number for COVID-19 Case Fatality; full-text: https://doi.org/10.7326/M20-4048.

David N. Fisman, Amy L. Greer, and Ashleigh R. Tuite: Age Is Just a Number: A Critically Important Number for COVID-19 Case Fatality; full-text: https://doi.org/10.7326/M20-4048.

During the first European wave of the SARS-CoV-2 pandemic, case-fatality rates (CFR) varied widely, with the highest rates in Italy (9.3%) and the Netherlands (7.4%) and the lowest rates in South Korea (1.6%) and Germany (0.7%) (Sudharsanan 2020, Fisman 2020). The study also found that age distribution of cases explains 66% of the variation of across countries.

Kissler SM, Kishore N, Prabhu M, et al. Reductions in commuting mobility correlate with geographic differences in SARS-CoV-2 prevalence in New York City. Nat Commun. 2020 Sep 16;11(1):4674. PubMed: https://pubmed.gov/32938924. Full-text: https://doi.org/10.1038/s41467-020-18271-5

SARS-CoV-2 prevalence varied substantially between New York City boroughs between 22 March and 3 May 2020 (for example, Manhattan: 11.3%; South Queens: 26.0%). These differences in prevalence correlate with antecedent reductions in commuting-style mobility between the boroughs. Prevalence was lowest in boroughs with the greatest reductions in morning movements out of and evening movements into the borough (Kissler 2020).

Czeisler MÉ, Tynan MA, Howard ME, et al. Public Attitudes, Behaviors, and Beliefs Related to COVID-19, Stay-at-Home Orders, Nonessential Business Closures, and Public Health Guidance – United States, New York City, and Los Angeles, May 5-12, 2020. MMWR Morb Mortal Wkly Rep. 2020 Jun 19;69(24):751-758. PubMed: https://pubmed.gov/32555138. Full-text: https://doi.org/10.15585/mmwr.mm6924e1

Most people agreed: during the week of May 5–12, 2020, a survey among 2,402 adults in New York City and Los Angeles and broadly across the United States found widespread support of stay-at-home orders and nonessential business closures and high degree of adherence to COVID-19 mitigation guidelines (Czeisler 2020). 74-82% reported they would not feel safe if these restrictions were lifted nationwide at the time the survey was conducted. In addition, among those who reported that they would not feel safe, some indicated that they would nonetheless want community mitigation strategies lifted and would accept associated risks (13-17%, respectively).

Moreland A, Herlihy C, Tynan MA, et al. Timing of State and Territorial COVID-19 Stay-at-Home Orders and Changes in Population Movement – United States, March 1-May 31, 2020. MMWR Morb Mortal Wkly Rep. 2020 Sep 4;69(35):1198-1203. PubMed: https://pubmed.gov/32881851 . Full-text: https://doi.org/10.15585/mmwr.mm6935a2

US Americans were compliant to mandatory stay-at-home orders. Based on location data from mobile devices, in 97.6% of counties these orders were associated with decreased median population movement (Moreland 2020).

Flaxman S, Mishra S, Gandy A, et al. Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe. Nature. 6/2020 Jun 8. PubMed: https://pubmed.gov/32512579. Full-text: https://doi.org/10.1038/s41586-020-2405-7

According to one study, between 12 and 15 million individuals in Europe had been infected with SARS-CoV-2 by May 4th, representing between 3.2% and 4.0% of the population (Flaxman 2020). Percentages of total population infected were for Austria 0.76% (0.59% – 0.98%), Belgium 8.0 % (6.1% – 11%), Denmark 1.0% (0.81% – 1.4%), France 3.4% (2.7% – 4.3%), Germany 0.85% (0.66% – 1.1%), Italy 4.6% (3.6% – 5.8%), Norway 0.46% (0.34% – 0.61%), Spain 5.5% (4.4% – 7.0%), Sweden 3.7% (2.8% – 5.1%), Switzerland 1.9% (1.5% – 2.4%) and United Kingdom 5.1% (4.0% – 6.5%).

Habib H. Has Sweden’s controversial covid-19 strategy been successful? BMJ. 2020 Jun 12;369:m2376. PubMed: https://pubmed.gov/32532807. Full-text: https://doi.org/10.1136/bmj.m2376

Has Sweden’s controversial covid-19 strategy been successful? After a negative press at the beginning of the 2020 summer (Habib 2020) which stressed that the country was still far away from herd immunity and the death toll 5 to 10 times higher than in neighboring Denmark and Finland, the evaluation in October has changed…

First autumn, first winter

Verdery AM, Smith-Greenaway E, Margolis R, Daw J. Tracking the reach of COVID-19 kin loss with a bereavement multiplier applied to the United States. Proc Natl Acad Sci U S A. 2020 Jul 10:202007476. PubMed: https://pubmed.gov/32651279. Full-text: https://doi.org/10.1073/pnas.2007476117

In the US, every death from COVID-19 will leave approximately nine bereaved, i.e., people who lost a grandparent, parent, sibling, spouse, or child (Verdery 2020).

Measuring the epidemic

Westhaus S, Weber FA, Schiwy S, et al. Detection of SARS-CoV-2 in raw and treated wastewater in Germany – Suitability for COVID-19 surveillance and potential transmission risks. Sci Total Environ 2020 August 18;751:141750. PubMed: https://pubmed.gov/32861187. Full-text: https://doi.org/10.1016/j.scitotenv.2020.141750

SARS-CoV-2 can be detected in wastewater in Germany using RT-qPCR. The total load of gene equivalents in wastewater correlated with the cumulative and the acute number of COVID-19 cases reported in the respective catchment areas. Thus, wastewater-based epidemiology can be regarded as a complementary measure to survey the outbreak (Westhaus 2020). (Important note: wastewater is no route for SARS-CoV-2 transmission to humans! All replication tests were negative tests for replication.)

Thomas LJ, Hunag O, Yin F, et al. Spatial heterogeneity can lead to substantial local variations in COVID-19 timing and severity. PNAS September 10, 2020. Full-text: https://doi.org/10.1073/pnas.2011656117

Relaxation of mitigation measures leading to a resumption of “normal” diffusion may initially appear to have few negative effects, only to lead to deadly outbreaks weeks or months later (Thomas 2020). Public health messaging may need to stress that apparent lulls in disease progress are not necessarily indicators that the threat has subsided, and that areas “passed over” by past outbreaks could be impacted at any time.

Herd immunity: Not yet

Brett TS, Rohani P. Transmission dynamics reveal the impracticality of COVID-19 herd immunity strategies. Proc Natl Acad Sci U S A. 2020 Sep 22:202008087. PubMed: https://pubmed.gov/32963094. Full-text: https://doi.org/10.1073/pnas.2008087117

Achieving herd immunity without overwhelming hospital capacity leaves little room for error, as the author of one paper put it (Brett 2020). In other words: their modeling did not support achieving herd immunity as a practical objective, requiring an unlikely balancing of multiple poorly defined forces.

Eckerle I, Meyer B. SARS-CoV-2 seroprevalence in COVID-19 hotspots. The Lancet July 06, 2020. Full-text: https://doi.org/10.1016/S0140-6736(20)31482-3

Comment on these findings. Most of the population appears to have remained unexposed to SARS-CoV-2, even in areas with widespread virus circulation. Any proposed approach to achieve herd immunity through natural infection is not only highly unethical, but also unachievable (Eckerle 2020). With a large majority of the population being infection-naïve, virus circulation can quickly return to early pandemic dimensions in a second wave once measures are lifted.

Buss LF, Prete Jr CA, Abrahim CMM, et al. COVID-19 herd immunity in the Brazilian Amazon. medRxiv 2020, posted 21 September. Full-text: https://doi.org/10.1101/2020.09.16.20194787

As much as 66% of the population of Manaus (two million people), Brazil, could have been infected with SARS-CoV-2. Ester Sabino, Lewis Buss and colleagues show that the transmission of SARS-CoV-2 in Manaus increased quickly during March and April and declined more slowly from May to September. In June, one month following the epidemic peak, 44% of the population was seropositive for SARS-CoV-2. After correcting for confounding factors, the authors estimate the epidemic size to be 66% by early August 2020. Note that these findings have not yet been peer reviewed and that the results have recently been questioned.

Remember: herd immunity is defined as the proportion of a population that must be immune to an infectious disease, either by natural infection or vaccination, such that new cases decline and R₀falls below 1 (see also https://www.nature.com/articles/d41586-020-02009-w).

“Variolation” – Finding of the year?

Important finding that was long suspected: viral inoculum during infection or mode of transmission may be key factors determining the clinical course of COVID-19. The authors prospectively studied an outbreak in Switzerland among a population of 508 predominantly male soldiers with a median age of 21 years. Infections were followed in two spatially separated cohorts with almost identical baseline characteristics – before and after implementation of stringent social distancing. Results: of 354 soldiers infected prior to the implementation of social distancing, 30% fell ill. In contrast, none out of 154 soldiers in which infections (confirmed by NP swabs or serology) appeared after implementation of social distancing developed COVID-19.

Protecting people at risk

Nguyen LH, Drew DA, Graham MS, et al. Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study. Lancet Public Health. 2020 Sep;5(9):e475-e483. PubMed: https://pubmed.gov/32745512. Full-text: https://doi.org/10.1016/S2468-2667(20)30164-X

Front-line health care workers are at increased risk of SARS-CoV-2 infection. In a prospective, observational cohort study in the UK and the USA, front-line health care workers were at increased risk for reporting a positive COVID-19 test (adjusted HR 11.6) (Nguyen 2020). An increased risk (HR 3.4) was even found after accounting for differences in testing frequency between front-line health care workers and the general community. Post-hoc analyses showed that Black, Asian, and minority ethnic health care workers are at especially high risk of SARS-CoV-2 infection, with at least a fivefold (!) increased risk of COVID-19 compared with the non-Hispanic white general community.

Emeruwa UN, Ona S, Shaman JL, et al. Associations Between Built Environment, Neighborhood Socioeconomic Status, and SARS-CoV-2 Infection Among Pregnant Women in New York City. JAMA 2020, June 18, 2020. Full-text: https://doi.org/10.1001/jama.2020.11370

In a cross-sectional study of 396 pregnant New York City residents, large household membership, household crowding, and low socioeconomic status were associated with a 2-3 fold higher risk of infection (Emeruwa 2020).

Hatcher SM, Agnew-Brune C, Anderson M, et al. COVID-19 Among American Indian and Alaska Native Persons — 23 States, January 31–July 3, 2020. MMWR Morb Mortal Wkly Rep 2020, published 19 August 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6934e1

American Indian and Alaska Native (AI/AN) persons appear to be disproportionately affected by the COVID-19 pandemic. In one study, the overall COVID-19 incidence among AI/AN persons was 3.5 times that among white persons (594 per 100,000 AI/AN population compared with 169 per 100,000 white population) (Hatcher 2020).

Grasso D, Zafra M, Ferrero B, et al. Covid de ricos, covid de pobres: las restricciones de la segunda ola exponen las desigualdades de Madrid. El País 2020, published 17 September. Full-text: https://elpais.com/espana/madrid/2020-09-16/covid-de-ricos-covid-de-pobres-las-restricciones-de-la-segunda-ola-exponen-las-desigualdades-de-madrid.html

The authors explain that the number of infections is higher in the most vulnerable areas, where possible limitations will weigh the most.

Prevention: Testing, tracing, isolating

Lash RR, Donovan CV, Fleischauer AT, et al. COVID-19 Contact Tracing in Two Counties – North Carolina, June-July 2020. MMWR Morb Mortal Wkly Rep. 2020 Sep 25;69(38):1360-1363. PubMed: https://pubmed.gov/32970654. Full-text: https://doi.org/10.15585/mmwr.mm6938e3

Despite aggressive efforts by health departments, many COVID-19 patients do not report contacts, and many contacts cannot be reached (Lash 2020). Staff members in North Carolina/US have investigated 5,514 (77%) persons with COVID-19 in Mecklenburg County and 584 (99%) in Randolph Counties: during periods of high COVID-19 incidence, 48% and 35% of patients reported no contacts, and 25% and 48 % of contacts were not reached. Median interval from index patient specimen collection to contact notification was 6 days. Improved timeliness of contact tracing, community engagement, and community-wide mitigation are needed to reduce SARS-CoV-2 transmission.

Clapham H, Hay J, Routledge I, et al. Seroepidemiologic Study Designs for Determining SARS-COV-2 Transmission and Immunity. Emerg Infect Dis. 2020 Jun 16;26(9). PubMed: https://pubmed.gov/32544053. Full-text: https://doi.org/10.3201/eid2609.201840

Test, test, test… but how accurate are the tests? Numerous challenges exist in terms of sample collection, what the presence of antibodies actually means, and appropriate analysis and interpretation to account for test accuracy and sampling biases (Clapham 2020). The authors review strengths and limitations of different assay types and study designs

Liang LL, Tseng CH, Ho HJ, Wu CY. Covid-19 mortality is negatively associated with test number and government effectiveness. Sci Rep. 2020 Jul 24;10(1):12567. PubMed: https://pubmed.gov/32709854. Full-text: https://doi.org/10.1038/s41598-020-68862-x

In a worldwide cross-sectional study (Liang LL 2020), the authors find that COVID-19 mortality is

Negatively associated with
- Test number per 100 people
- Government effectiveness score
- Number of hospital beds
Positively associated with
- Proportion of population aged 65 or older
- Transport infrastructure quality score

Remember: Government effectiveness!

Jingwen Li, Chengbi Wu, Xing Zhang, Lan Chen, Xinyi Wang, Xiuli Guan, Jinghong Li, Zhicheng Lin, Nian Xiong. Post-pandemic testing of SARS-CoV-2 in Huanan Seafood Market area in Wuhan, China. Clinical Infectious Diseases 2020, published 25 July 2020. Full-text: https://doi.org/10.1093/cid/ciaa1043

Citywide mass nucleic acid testing of SARS-CoV-2 for all citizens is possible as shown in Wuhan city (14 May to 1 June 2020). The results are sometimes meager, revealing just 6 persons who test positive for SARS-CoV-2 (0.006% of 107,662 residents around the Huanan Seafood Market), but are able to suffocate a nascent epidemic (Jingwen L 2020).

Perkins TA, Cavany SM, Moore SM, et al. Estimating unobserved SARS-CoV-2 infections in the United States. PNAS August 21, 2020. Full-text: https://doi.org/10.1073/pnas.2005476117

Testing was a major limiting factor in assessing the extent of SARS-CoV-2 transmission during its initial invasion into the US (Perkins 2020). After a national emergency was declared, fewer than 10% of locally acquired, symptomatic infections in the US may were detected over a period of a month. This gap in surveillance during a critical phase of the epidemic resulted in a large, unobserved reservoir by early March.

Curfews

Andronico A, Kiem CT, Paireaux J, et al. Evaluating the impact of curfews and other measures on SARS-CoV-2 transmission in French Guiana. medRxiv 2020, posted 12 October. Full-text: https://doi.org/10.1101/2020.10.07.20208314

Might curfews be a less costly alternative, both economically and socially? In French Guiana, an overseas départment, a combination of curfews and targeted lockdowns in June and July 2020 was sufficient to avoid saturation of hospitals. On weekdays, residents were first ordered to stay at home 11 p.m., then at 9 p.m., later again at 7 p.m., and finally at 5 p.m. On weekends, everyone had to stay at home from 1 p.m. on Saturday (Andronico 2020). Whether curfews can be successfully adapted to other areas than French Guaiana, is not known. French Guaiana is a young territory with a median age is 25 years and the risk of hospitalisation following infection was only 30% that of France. About 20% of the population had been infected with SARS-CoV- by July 2020 (Andronico 2020). Be prepared though to see some curfews orders over the coming six months.

Outlook

Horton R. Offline: The second wave. Lancet 2020, June 27, 395, ISSUE 10242, P1960. Full-text: https://doi.org/10.1016/S0140-6736(20)31451-3

In June, scientists predicted a second SARS-CoV-2 wave in Europe. They were right. We should now hope that the current epidemic doesn’t follow the scenario of the 1918 influenza pandemic (Horton 2020).

Petersen E, Koopmans M, Go U, et al. Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics. Lancet Inf Dis 2020, July 03, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30484-9

How long will a combination of physical distancing, enhanced testing, quarantine, and contact tracing be needed? Historical evidence from prior influenza pandemics indicates that pandemics tend to come in waves over the first 2–5 years as population immunity builds-up (naturally or through vaccination) and that this is the most likely trajectory for SARS-CoV-2 (Petersen 2020).