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Living Evidence - COVID-19 transmission

Living evidence tables provide high level summaries of key studies and evidence on a particular topic, and links to sources. They are reviewed daily and updated as new evidence and information is published.

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The flowchart depicts factors that influence the transmission of and immunological response to SARS-CoV-2, the virus that causes COVID-19.

It starts with a question: are effective physical barriers in place? If yes, there is no infection. If no, and there is exposure to SARS-CoV-2, a range of factors affect risk of infection and developing disease. What is the viral dose or time that a person is exposed to virus? What is the mode of transmission – is it through contact, droplets, aerosols or fomites?

A key question is whether there is effective innate immunity or circulating antibodies? If the answer to that question is yes, then there is no infection. If the answer is no, the virus is able to bind to host cells via the ACE2 receptor and enter.

The next question is whether there is an effective cell mediated immune response – do host cytotoxic T-cells and natural killer cells act to remove the infected cells? If yes, then the infection was only transient with no symptoms and the host would not have been infective? If no, then the virus replicates in the host cells and the host becomes infective – able to spread the virus. The extent of spread is shaped by the viral load, shedding, symptoms, and the secondary attack rate. Viral load also affects disease severity in the host.

The next question is whether the host recovers – mounting an effective humoral response with antibody production. If yes, then the host will be immune to the infecting strain, but may be affected by post-acute COVID-19 syndrome. If no, then the host dies.

Transmission concepts and current knowledge

TopicDefinition Current understanding for SARS-CoV-2 and COVID-19

Mode of transmission

The route or method of transfer by which infectious microorganisms (viruses, bacteria, parasites, etc) move or are carried from one place to another to reach a new host.

SARS-CoV-2 is primarily transmitted between people through respiratory droplets and contact routes.

Short-range aerosol transmission can occur under special circumstances, such as in crowded and inadequately ventilated spaces over a prolonged period of time (>30 mins) with infected persons.

Despite consistent evidence as to SARS-CoV-2 contamination of surfaces and the survival of the virus on certain surfaces, there is no direct evidence of fomite transmission.

No published reports of transmission through urine or faeces.

No strong evidence for intrauterine transmission of SARS-CoV-2 from infected pregnant women to their foetuses. No evidence of SARS-CoV-2 transmission through breast milk.

Setting-specific transmission

(See also secondary attack rate)

Patterns of disease spread associated with a particular context or situation

Studies usually compare secondary attack rates in different settings.

A systematic review showed households have the highest transmission rates, with a pooled secondary attack rate of 21.1%. It was significantly higher where the duration of household exposure exceeded 5 days.

Estimates of secondary attack rate for asymptomatic index cases were approximately a seventh, and for pre-symptomatic two thirds of those for symptomatic index cases. The review found some evidence for reduced transmission potential both from and to individuals under 20 years of age in the household context, which is more limited when examining all settings.

Minimal infectious dose (MID)

Smallest amount of a pathogen that is required to establish an infection

There is limited evidence that the minimum infective dose of COVID-19 in humans, is higher than 100 particles (pre-peer review, no direct experimental data in human)

Approval for a ‘challenge trial’, which will infect healthy volunteers in the UK was announced 17 February 2021.*

Dose response

The relationship between the infecting dose (the quantity of viable virus) and disease severity

Some observations support a dose response, but this is not established.

Observational studies of three clusters of individuals exposed to diverse inoculum, developed divergent clinical forms of disease. In clusters where physical distancing and wearing masks were not followed, a larger proportion of individuals developed severe disease.

Viral load

The amount of measurable virus inside an individual (often measured in a standard volume of plasma, or blood)

A systematic review reported viral load (RNA) in upper respiratory tract samples peaks around symptom onset or a few days thereafter, and becomes undetectable about two weeks after symptom onset. There is evidence of prolonged virus detection in stool samples, with unclear clinical significance.

Viral load and severity

Mixed evidence - some studies found viral load to be similar in asymptomatic and symptomatic cases. Other studies suggest an association between viral load and severity / mortality.

A study using nasopharyngeal swabs showed for each additional unit of viral RNA detected (log10 per mL), there was a 7% increase in the risk of mortality.

Viral load and infectivity

At least four studies have described the correlation between decreased viral loads and reduced infectivity.

Modelling studies suggest the threshold viral load for a 50% probability of transmission is approximately 10 7.5 viral RNA copies/mL and that infected persons are likely to be above this threshold for only about 1 day.

Viral load and vaccines

Single dose of BNT162b2 (Pfizer-BioNTech) vaccine was associated with a significantly lower nasopharyngeal viral load (-2.4 mean log10) than without vaccine (p=0.004) in nursing home residents.

Viral load was substantially reduced for infections occurring 12–37 days after the first dose of the BNT162b2 (Pfizer-BioNTech) vaccine.

Viral shedding

The expulsion and release of viable virus progeny following successful reproduction during a host-cell infection. It can refer to viral release from one infected cell; from one part of the body to another; and from an infected host into the environment.

During COVID-19, shedding has also been used to refer to the release of non-viable viral genetic material or particles into the environment

A systematic review, published in January 2021 reported mean SARS-CoV-2 RNA shedding duration was 17·0 days (maximum shedding duration 83 days) in upper respiratory tract, 14·6 days (maximum 59 days) in lower respiratory tract, 17·2 days (maximum 126 days) in stool, and 16·6 days (maximum 60 days) in serum samples. Pooled mean SARS-CoV-2 shedding duration was positively associated with age.

No study has detected live virus beyond day 9 of illness, despite persistently high viral loads. SARS-CoV-2 viral load in the upper respiratory tract appears to peak in the first week of illness.

Data are mixed about the dynamics of viral shedding in those with persistently asymptomatic infection. One study which analysed serial nasopharyngeal samples of people in quarantine showed asymptomatic cases had faster viral clearance than symptomatic cases while another found asymptomatic cases had longer duration of shedding. Studies use PCR, rather than culturing methods so may be overstating shedding of live virus.

Incubation period

The time between exposure to the virus and symptom onset,

The median incubation period for COVID-19 is 4.9 – 7 days, with a range of 1 – 14 days. Most people who are infected will develop symptoms within 14 days of infection. A recent systematic review reported that the weighted pooled mean incubation period is 6.5 (95% CI: 5.9, 7.1).

Pre-symptomatic

Refers to the period before symptoms appear among infected individuals

Multiple studies have shown that people infect others before becoming ill (WHO). However, estimates of the proportion of secondary cases acquired from presymptomatic persons vary:

  • A study of 77 infectee-infector pairs (assuming an incubation period of 5.2 days) estimated that 44% of secondary cases were acquired from cases that were presymptomatic at the time of transmission.
  • Clinical and epidemiological investigation of all 243 cases reported in Singapore over a six week period from 23 January 2020 concluded that 6.4% of secondary cases resulted from pre-symptomatic transmission.

Asymptomatic

Without signs or symptoms of disease

How many COVID-19 cases are asymptomatic?

The extent of truly asymptomatic infection in the community remains unknown.

Early studies reported that many cases were asymptomatic, based on the lack of symptoms at the time of testing; however, 75-100% of these people later developed symptoms.

One systematic review estimated that the proportion of truly asymptomatic cases ranges from 4% to 41%, with a pooled estimate of 17% (14%–20%).

A second systematic review concluded that at least one third of infections are asymptomatic. Of 14 studies with longitudinal data, nearly three quarters of positive cases who had no symptoms at the time of testing remained asymptomatic. The highest-quality evidence comes from nationwide, representative serosurveys of England (n= 365 104) and Spain (n= 61 075), which suggest that at least one third of SARS-CoV-2 infections are asymptomatic.

Are asymptomatic cases infectious?

Transmission can occur from persistently asymptomatic persons, although they seem to be less likely to transmit. The secondary attack rate of symptomatic index cases was higher than asymptomatic cases (RR: 3.23; 95% CI: 1.46, 7.14).

Infectiousness

The capacity to spread disease by transmitting a pathogen to others.

Persons who have SARS-CoV-2 with or without symptoms can transmit.

Transmission can occur from persistently asymptomatic persons, although they are less likely to transmit (due to lower viral load, and the absence of expectoration/ coughing, etc). One study (pre-print) found that for both symptomatic and asymptomatic individuals, viral titers normally peak within 3 days of the first positive test.

Among symptomatic patients, a report of 3410 close contacts of 391 case patients in China found that the secondary attack rate increased with the severity of the index case and that the specific symptoms of fever and expectoration were associated with a higher risk of secondary infections.

A study which analysed 77 infector-infectee pairs (and assumed an incubation period of 5.2 days) inferred that transmissibility peaks around 2 days before and 1 day after symptom onset. The same study found that infectiousness declined rapidly within a week of symptom onset. No cases of late transmissions, occurring after a patient has had symptoms for a week, have been documented.

The period of infectiousness is much shorter than the duration of detectable RNA particle shedding.

Transmission dynamics

The pattern and rate of spread from infectious to susceptible hosts.

The virus has heterogeneous transmission dynamics.

Most persons do not transmit virus, whereas some cause many secondary cases in transmission clusters called “superspreading events.

Early estimates suggested 80% of secondary infections arose from 8.9% of index cases. Subsequent modelling estimated approximately 10% of cases lead to 80% of secondary transmissions.

A systematic review on setting specific transmission rates estimated secondary attack rates for asymptomatic index cases were approximately a seventh, and for pre-symptomatic two thirds of those for symptomatic index cases.

Secondary attack rate

A measure of the frequency of new cases among the contacts of known patients

In households

A meta-analysis of 54 studies with 77 758 participants, the estimated overall household secondary attack rate was 16.6%. Secondary attack rates were higher in households from symptomatic index cases than asymptomatic index cases, to adult contacts than to child contacts, to spouses than to other family contacts, and in households with 1 contact than households with 3 or more contacts.

Another systematic review estimated the household secondary attack rate to be 18.1% (95% CI: 15.7%, 20.6%).

In other settings

In healthcare settings, the secondary attack rate was 0.7% (95% CI: 0.4%, 1.0%).

There are a limited number of studies in other settings, and therefore no pooled analyses. However high secondary attack rates (suggesting high risk setting) were observed in a meeting (84.6%), a chalet (73.3%), and at choirs (70.4%, 53.3%). In other settings, relatively high SARs were reported in eating (38.8%, 28.6%) and traveling (80.8%, 46.6%) with a case, as well as a study evaluating a religious event (14.8%).

SARs were much lower in encounters with relatives (3.5% to 6.6%), social contacts (0.9% to 2.2%), and at workplace or school (0% to 5.3%).

Methods

An initial PubMed search for Systematic reviews was conducted on the 17 February 2021 using a combination of words for ‘transmission’ AND ‘COVID-19’ (full search string below). Supplementary topic specific searches were undertaken when evidence in systematic reviews was not sufficient and individual studies were included, but these do not represent a complete list of studies. Grey literature including publications from key organisations such as the World Health Organisation were also included. Living evidence tables are monitored and updated daily. To monitor the evidence, a PubMed search has been set up to receive automatic alerts daily, the Critical Intelligence Unit daily evidence digest database is searched daily, and grey literature is monitored through targeted searches.

Search string: (transmission[ti] OR "viral shedding"[ti] OR "viral load"[ti] OR asymptomatic[ti]) AND (2019-nCoV[title/abstract] or nCoV*[title/abstract] or covid-19[title/abstract] or covid19[title/abstract] OR "covid 19"[title/abstract] OR "coronavirus"[MeSH Terms] OR "coronavirus"[title/abstract] OR sars-cov-2[title/abstract] OR “severe acute respiratory syndrome coronavirus 2”[Supplementary Concept]) Filters: Systematic Review.

Living evidence tables include some links to low quality sources and an assessment of the original source has not been undertaken. Sources are monitored daily but due to rapidly emerging information, tables may not always reflect the most current evidence. The tables are not peer reviewed, and inclusion does not imply official recommendation nor endorsement of NSW Health.

Last updated on 8 Apr 2021

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