+++ Transmission +++
* * * Next update: 24 November. In the meantime, find the global updates at 7 Days. * * *
The pre-print paper we presented on October 25 has been published in Science: Hou YJ, Chiba S, Halfmann P, et al. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo. Science 2020, published 12 November. Full-text: https://doi.org/10.1126/science.abe8499
This paper is a milestone work: Ralph Baric and colleagues (among the leading labs in the world) provide the possible explanation for the exploding numbers of SARS-CoV-2 infections. Engineering SARS-CoV-2 variants harboring the D614G substitution (the most prevalent SARS-CoV-2 strain circulating globally), they show that the D614G variant replicates more efficiency in primary human proximal airway epithelial cells and is more fit than wildtype virus in competition studies. Infection of human ACE2 transgenic mice and Syrian hamsters with the wildtype or D614G viruses produced similar titers in respiratory tissue and pulmonary disease. However, the D614G variant exhibited significantly faster droplet transmission between hamsters than the WT virus, early after infection. No more doubts that the SARS-CoV2 D614G substitution enhances infectivity, replication fitness, and early transmission.
Liu J, Li Y, Liu L, et al. Infection of human sweat glands by SARS-CoV-2. Cell Discov 6, 84 (2020). Full-text: https://doi.org/10.1038/s41421-020-00229-y
Manli Wang, Jia Liu and colleagues from Wuhan Institute of Virology describe skin autopsy samples from five patients with COVID-19. Immunofluorescence and immunohistochemical analyses detected SARS-CoV-2 spike proteins in three of the five patients. In these cases, the virus resided primarily in the sweat glands and sweat ducts with apparently higher amounts in the former than in the latter; in contrast, the virus was rarely detected in the epidermis or sebaceous glands. The authors conclude that “it is important to further assess the potential risk of viral transmission via perspiration and skin contact.” Editor’s note: This paper will not change my standard protection measures.
Letizia AG, Ramos I, Obla A, et al. SARS-CoV-2 Transmission among Marine Recruits during Quarantine. N Engl J Med 2020, published 11 November. Full-text: https://doi.org/10.1056/NEJMoa2029717
A two-week quarantine at home is not sufficient to prevent SARS-CoV-2 from entering into a closed college campus. That’s one of the results of a study by Stuart Sealfon, Andrew Letizia and colleagues who investigated SARS-CoV-2 infections among US Marine Corps. Around 2% of recruits who had had negative results for SARS-CoV-2 at the beginning of a supervised quarantine tested positive within two weeks. Most recruits who tested positive were asymptomatic, and no infections were detected through daily symptom monitoring. The author’s short conclusion: “Transmission clusters occur within platoons.”
See also the comment by Michael NL. SARS-CoV-2 in the U.S. Military — Lessons for Civil Society. N Engl J Med 2020, published 11 November. Full-text: https://doi.org/10.1056/NEJMe2032179
Kasper MR, Geibe JR, Sears CL, et al. An outbreak of Covid-19 on an aircraft carrier. N Engl J Med 2020, published 11 November. Full-text: https://doi.org/10.1056/NEJMoa2019375
Do you remember March 30? SARS-CoV-2 is spreading aboard the aircraft carrier USS Theodore Roosevelt. The ship’s commanding officer, Captain Brett Crozier, sends an email to three admirals in his chain of command, recommending that he be given permission to evacuate all non-essential sailors, to quarantine known COVID-19 cases, and sanitize the ship. “We are not at war. Sailors do not need to die,” writes Crozier in his four-page memo. The letter leaks to the media and generates several headlines. Three days later, 2 April, Captain Crozier is sacked.
You can now read the final report of the outbreak. A total of 1271 crew members (26.6% of the crew) tested positive for SARS-CoV-2. Among the crew members with laboratory-confirmed infection, 76.9% (978 of 1271) had no symptoms at the time that they tested positive and 55.0% had symptoms develop some time during the clinical course. Among the 1331 crew members with suspected or confirmed COVID-19, 23 (1.7%) were hospitalized, 4 (0.3%) received intensive care, and 1 died. Crew members who worked in confined spaces appeared more likely to become infected. The conclusion: transmission of SARS-CoV-2 is facilitated by close-quarters conditions and by asymptomatic and pre-symptomatic infected crew members.
Nissen K, Krambrich J, Akaberi D, et al. Long-distance airborne dispersal of SARS-CoV-2 in COVID-19 wards. Sci Rep 10, 19589 (2020). Full-text: https://doi.org/10.1038/s41598-020-76442-2
Detection of coronavirus RNA, including SARS-CoV-2, in hospital and other ventilation systems has been reported. Here, Erik Salaneck, Karolina Nissen and colleagues present further evidence for SARS-CoV-2’s ability to disperse from patients to ward vent openings. They detected viral RNA in ventilation exhaust filters located at least 50 m from patient room vent openings. Although the authors did not isolate infectious virus, they suggest that there may be a risk for airborne dissemination and transmission, especially at much closer distances to contagious persons in confined spaces, both in and outside hospital environments.
Chang S, Pierson E, Koh PW. Mobility network models of COVID-19 explain inequities and inform reopening. Nature (2020). Full-text: https://doi.org/10.1038/s41586-020-2923-3
A small minority of “superspreader” events account for a large majority of infections. What we have known for a long time is now being confirmed by a mobility network model which mapped the hourly movements of 98 million people from neighborhoods to points of interest (POIs) such as restaurants and religious establishments. Jure Leskovec, Serina Chang and colleagues, connected 57,000 neighborhoods to 553,000 POIs and found that restricting maximum occupancy at each POI would be more effective than uniformly reducing mobility. Their model also correctly predicted higher infection rates among disadvantaged racial and socioeconomic groups: disadvantaged groups cannot reduce mobility as sharply as other groups and the POIs they visit are more crowded.
See also the comment by Ma KC, Lipsitch M. Big data and simple models used to track the spread of COVID-19 in cities. Nature 2020, published 10 November. Full-text: https://www.nature.com/articles/d41586-020-02964-4
See also Cyranoski D. How to stop restaurants from driving COVID infections. Nature 2020, published 10 November. Full-text: https://www.nature.com/articles/d41586-020-03140-4 | US mobile data suggests restaurants, gyms and cafes can be COVID hotspots — and reveals strategies for limiting spread.
Tufekci Z. We Need to Talk About Ventilation. The Atlantic 2020, published 30 July. Full-text: https://www.theatlantic.com/health/archive/2020/07/why-arent-we-talking-more-about-airborne-transmission/614737/
Published more than three months ago but still instructive.
Harvey AP, Fuhrmeister ER, Cantrell M, et al. Longitudinal monitoring of SARS-CoV-2 RNA on high-touch surfaces in a community setting. medRxiv 2020, posted 1 November. Full-text: https://doi.org/10.1101/2020.10.27.20220905
The estimated risk of infection from touching a contaminated surface was less than 5 in 10,000 in a study by Amy Pickering, Abigail Harvey and colleagues. From April to June 2020, they repeatedly sampled 33 surfaces in public places like liquor and grocery stores, banks, gas stations, laundromats, restaurants and on metro doors and crosswalk buttons. Twenty-nine of 348 (8.3 %) surface samples were positive for SARS-CoV-2. The authors suggest that fomites might play only a minimal role in SARS-CoV-2 community transmission.
A second, not less important point: The weekly percentage of positive samples in one postal district peaked about 7 days before a spike in new SARS-CoV-2 cases. Surveillance on high-touch surfaces might therefore provide precious early warning clues.
SARS-CoV-2 transmission among high-risk contacts
Excellent retrospective cohort study by Vernon Lee, Oon Tek Ng and colleagues Between Jan 23 and April 3, 2020, the authors identified 7,518 close contacts (1779 [23%] household contacts, 2231 [30%] work contacts, and 3508 [47%] social contacts) linked to 1114 PCR-confirmed index cases.
Ng OT, Marimuthu K, Koh V, et al. SARS-CoV-2 seroprevalence and transmission risk factors among high-risk close contacts: a retrospective cohort study. Lancet Infect Dis 2020, published 2 November. Full-text: https://doi.org/10.1016/S1473-3099(20)30833-1
The secondary clinical attack rate:
Household contacts: 5.9% (95% CI 4.9–7.1).
Particular risk factors:
- Sharing a bedroom (multivariable odds ratio [OR] 5.38)
- Being spoken to by an index case for 30 min or longer (7.86)
Non-household contact: Work contacts, 1.3% (0.9–1.9); social contacts, 1.3% (1.0–1.7).
Particular risk factors:
- Exposure to more than one case (3.92)
- Being spoken to by an index case for 30 min or longer (2.67)
- Sharing a vehicle with an index case (3.07).
Among both household and non-household contacts, indirect contact, meal sharing, and lavatory co-usage were not independently associated with SARS-CoV-2 transmission.
Wang Y, Xu G, Huang YW. Modeling the load of SARS-CoV-2 virus in human expelled particles during coughing and speaking. PLoS One. 2020 Oct 30;15(10):e0241539. PubMed: https://pubmed.gov/33125421 . Full-text: https://doi.org/10.1371/journal.pone.0241539
The authors investigated the dependence of airborne viral load on the size distributions of the human expelled particles from coughing and speaking. Of note, differentiating “aerosols” and “droplets” using a specific size, e.g., 5 μm, did not reflect the actual evolution of virus-containing particles over time and space, because a large number of particles above 5 μm remained airborne after an extended period of time. Simulation showed that after ten seconds of a cough, although most evaporated particles are larger than 5 μm, 59.5% of the original virus-containing particles were still able to remain airborne. Simulation also showed that wearing a mask can effectively reduce the spread of the viruses. The results challenge the false dichotomy of using aerosols and droplets to separate the modes of disease transmission.
Grijalva CG, Rolfes MA, Zhu Y, et al. Transmission of SARS-COV-2 Infections in Households — Tennessee and Wisconsin, April–September 2020. MMWR Morb Mortal Wkly Rep. ePub: 30 October 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6944e1
Important study (because prospective). After enrollment, 101 index patients and 191 household members were trained remotely by study staff members to complete symptom diaries and obtain self-collected specimens, nasal swabs only or nasal swabs and saliva samples, daily for 14 days. In this preliminary analysis of the first 7 days, transmission of SARS-CoV-2 among household members was common, and secondary infection rates were higher (35%) than have been previously reported. Secondary infections occurred rapidly and were high across all racial/ethnic groups or rage groups. The authors conclude that persons who suspect that they might have COVID-19 should isolate, stay at home, and use a separate bedroom and bathroom if feasible. Isolation should begin before seeking testing and before test results become available. All household members, including the index patient, should start wearing a mask in the home, particularly in shared spaces where appropriate distancing is not possible. Close household contacts of the index patient should also self-quarantine, to the extent possible, particularly staying away from those at higher risk of getting severe COVID-19.
Shah ASV, Wood R, Gribben C. Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study. BMJ October 28, 2020;371:m3582. Full-text: http://dx.doi.org/10.1136/bmj.m3582
This large cohort from Scotland comprising 158,445 healthcare workers (HCW) and 229,905 household members revealed that HCW and their households contributed a sixth of all COVID-19 cases admitted to hospital. Patient facing HCW and their household members had threefold and twofold increased risks of admission with COVID-19. However, the absolute risk of admission was low overall, being 0.20% (181/90733), 0.07% (23/32615), and 0.11% (39/35097) in patient facing, non-patient facing, and undetermined HCW.
Goldstein E, Lipsitch M, Cevik M, et al. On the effect of age on the transmission of SARS-CoV-2 in households, schools and the community. J Inf Dis 29 October 2020, jiaa691. Full-text: https://doi.org/10.1093/infdis/jiaa691
Literature review of all papers published before October 5, 2020. Compared to younger/middle aged adults, susceptibility to infection for children aged less than 10 years of age seems to be significantly lower, while estimated susceptibility to infection in adults aged over 60 years is higher. There is some evidence that given limited control measures, SARS-CoV-2 may spread robustly in secondary/high schools, and to a lesser degree in primary schools, with class size possibly affecting that spread. There is also evidence of more limited spread in schools when some mitigation measures are implemented. Several potential biases that may affect these studies are discussed.
Lee EC, Wada NI, Grabowski MK, Gurley ES, Lessler J. The engines of SARS-CoV-2 spread. Science. 2020 Oct 23;370(6515):406-407. PubMed: https://pubmed.gov/33093098. Full-text: https://doi.org/10.1126/science.abd8755
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mostly transmitted within households and household-like settings. A decreasing proportion of transmission events take place at increasing spatial scales, but these events become more critical for sustaining the pandemic. Discover the fundamental engines that drive the SARS-CoV-2 pandemic in this Science Perspective.
Teran RA, Ghinai I, Gretsch S, et al. COVID-19 Outbreak Among a University’s Men’s and Women’s Soccer Teams — Chicago, Illinois, July–August 2020. MMWR Morb Mortal Wkly Rep. ePub: 27 October 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6943e5
Investigation of 17 COVID-19 cases among a university’s men’s and women’s soccer team identified numerous social gatherings as possible transmission events. Minimal mask use and social distancing resulted in rapid spread among students who live, practice, and socialize together. Nothing truly new – we should stop reporting on SARS-CoV-2 transmission during social gatherings.
SARS-CoV-2 transmission on an aircraft
If you had seen this selection of seats, wouldn’t you have felt safe? This was a 7.5 h flight into Ireland, with a passenger occupancy of 17% (49/283 seats). Astonishingly, the flight-associated attack rate was 9.8–17.8%, leading to 13 cases (in flight-transmission was proven by 99% homology across the virus genome in five cases travelling from three different continents). A mask was worn during the flight by nine cases, not worn by one (a child), and unknown for three. Spread to 46 non-flight cases occurred country-wide.
Murphy N, Boland M, Bambury N, et al. A large national outbreak of COVID-19 linked to air travel, Ireland, summer 2020. Euro Surveill 2020;25(42):pii=2001624. Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.42.2001624
Copyright: ECDC. Reproduced with permission.
+ + +
Hou YJ, Chiba S, Halfmann P, et al. SARS-CoV-2 D614G Variant Exhibits Enhanced Replication ex vivo and Earlier Transmission in vivo. bioRxiv. 2020 Sep 29:2020.09.28.317685. PubMed: https://pubmed.gov/33024969. Full-text: https://doi.org/10.1101/2020.09.28.317685.
This is a pre-print and not a peer reviewed par. However, this milestone work from Ralph Baric and colleagues (among the leading labs world-wide) probably provides the explanation for the exploding numbers. The D614G substitution in the S protein is now the most prevalent SARS-CoV-2 strain circulating globally. Engineering SARS-CoV-2 variants harboring the D614G substitution, the Baric group shows that the D614G variant replicates more efficiency in primary human proximal airway epithelial cells and is more fit than wildtype virus in competition studies. Infection of human ACE2 transgenic mice and Syrian hamsters with the wildtype or D614G viruses produced similar titers in respiratory tissue and pulmonary disease. However, the D614G variant exhibited significantly faster droplet transmission between hamsters than the WT virus, early after infection. No more doubts that the SARS-CoV2 D614G substitution enhances infectivity, replication fitness, and early transmission. Phantastic work, but probably the worst news during the last months.
Pringle JC, Leikauskas J, Ransom-Kelley S, et al. COVID-19 in a Correctional Facility Employee Following Multiple Brief Exposures to Persons with COVID-19 — Vermont, July–August 2020. MMWR Morb Mortal Wkly Rep. ePub: 21 October 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6943e1
On August 11, 2020, a young male correctional officer was found to be infected. Some days earlier, he had multiple brief encounters with six infected incarcerated or detained persons (IDPs). Other infection routes were ruled out. Why is this of interest? Because detailed video surveillance footage was available! It showed that the officer had no close contact (being within 6 feet of infectious persons for ≥15 consecutive minutes) but numerous brief (approximately 1-minute) encounters. During his 8-hour shift, he was within 6 feet of an infectious IDP an estimated 22 times while the cell door was open, for an estimated 17 total minutes of cumulative exposure. IDPs wore microfiber cloth masks during most interactions with the correctional officer that occurred outside a cell; however, during several encounters IDPs did not wear masks. During all interactions, the correctional officer wore a microfiber cloth mask, gown, and eye protection (goggles). He also wore gloves during most interactions. This is bad news because we can’t rely on definitions of “close contacts”.
Poole S, Brendish NJ, Tanner AR, et al. Physical distancing in schools for SARS-CoV-2 and the resurgence of rhinovirus. Lancet Resp Med October 22, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30502-6
Stephen Poole and colleagues from Southampton compared the rate of respiratory virus detection in 2020 with the same period in 2019. Among 3,898 adult patients who were tested between March and September, they observed a drop in the rate of detection of all respiratory viruses including rhinovirus following the nationwide lockdown. Around 2 weeks after the concurrent re-opening of state primary and secondary schools in early September, there was a sharp increase in the number of detections similar to that seen in 2019. Two conclusions: 1. children are a major reservoir for rhinovirus infection, and a key driver of transmission to adults. 2. Current physical distancing measures adopted by schools do not effectively prevent rhinovirus transmission.
From student cluster to vulnerable population
The title says it all: a substantial SARS-CoV-2 outbreak coincided with the return to in-person instruction at three local academic institutions. From 111 sequenced genomes the authors identified rapid transmission of the virus into more vulnerable populations. One of the variants made its way into two care homes, infecting 8 residents. Two died. MedRxiv article – not yet peer reviewed.
Richmond CS, Sabin AP, Jobe DA, et al. SARS-CoV-2 sequencing reveals rapid transmission from college student clusters resulting in morbidity and deaths in vulnerable populations. medRxiv 2020, posted 14 October. Full-text: https://doi.org/10.1101/2020.10.12.20210294
Superspreading event in Ho Chi Minh City
St. Patrick’s Day, March 14. Bar X. Ho Chi Minh City. The bar had 2 indoor areas for clients, a 300-m2 area downstairs and an 50-m2 area upstairs, with no mechanical ventilation. During open hours, the left and right entrances were typically kept closed to facilitate cooling with air conditioners that recycled indoor air; the middle entrance was kept open. The bar also has naturally ventilated outdoor spaces. A 43-year old SARS-CoV-2 man enters the bar at 10:00 PM and participates in the celebration until 2:30AM. The result: 12 additional SARS-CoV-2 infections. The authors conclude that persons in crowded indoor settings with poor ventilation may be considered to be at high risk for SARS-CoV-2 transmission.
Chau NVV, Hong NTT, Ngoc NM, , et al. Superspreading event of SARS-CoV-2 infection at a bar, Ho Chi Minh City, Vietnam. Emerg Infect Dis. 2021 Jan. Full-text: https://doi.org/10.3201/eid2701.203480
SARS CoV-2 transmission in music clubs
Bad news for music clubs: asymptomatically infected persons can transmit the virus as soon as 2 days after infection. Substantial exposure can even occur within a few hours. Nobuhiko Sugano and colleagues from Osaka/Japan describe 108 cases linked to 4 various music clubs. Fifty-one cases attended a live music club only once and all index cases for secondary transmission were asymptomatic at the time of contact with other people. Substantial exposure occurred within a few hours.
Sugano N, Ando W, Fukushima W. Cluster of Severe Acute Respiratory Syndrome Coronavirus 2 Infections Linked to Music Clubs in Osaka, Japan. J Infect Dis. 2020 Oct 13;222(10):1635-1640. PubMed: https://pubmed.gov/32840606. Full-text: https://doi.org/10.1093/infdis/jiaa542
Atrubin D, Wiese M, Bohinc B. An Outbreak of COVID-19 Associated with a Recreational Hockey Game — Florida, June 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6941a4
On June 16, 2020, a recreational ice hockey game was played between two teams, each consisting of 11 players (typically six on the ice and five on the bench at any given time). The players were men aged 19–53 years. During the 5 days after the game, 15 persons (14 of the 22 players and a rink staff member) experienced signs and symptoms compatible with coronavirus disease 2019 (COVID-19).
Do you remember our September 12 Top 10? In an unintentional experiment, the German national team of amateur boxers 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. All 25 persons tested positive for SARS-CoV-2. If you read German, read 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
Top 10 Special: Transmission
Wilson RF, Sharma AJ, Schluechtermann S, et al. Factors Influencing Risk for COVID-19 Exposure Among Young Adults Aged 18–23 Years — Winnebago County, Wisconsin, March–July 2020. MMWR Morb Mortal Wkly Rep. ePub: 9 October 2020. DOI: http://dx.doi.org/10.15585/mmwr.mm6941e2
Still in the US: Which are the drivers of behaviors that might influence risk for COVID-19 exposure among young adults? In a remote US County, these were low severity of disease outcome; peer pressure; and exposure to misinformation, conflicting messages, or opposing views regarding masks. A scientifically inspired national prevention policy would have been helpful.
Wang L, Didelot X, Yang J, et al. Inference of person-to-person transmission of COVID-19 reveals hidden super-spreading events during the early outbreak phase. Nat Commun 11, 5006 (2020). Full-text: https://doi.org/10.1038/s41467-020-18836-4
Super-spreading events are an important phenomenon in the transmission of many diseases (such as SARS-CoV-1, MERS-CoV, Ebola virus, etc.), in which certain individuals infect a disproportionately large number of people. Here Yuhai Bi, Liang Wang and colleagues show that super-spreading events played an important role in the early stage of the COVID-19 outbreak. They estimated the dispersion parameter to be 0.23 (95% CI: 0.13–0.39). (What is the dispersion parameter? Check this FT article: To beat Covid-19, find today’s superspreading ‘Typhoid Marys’)