Infection

This section is aimed at assisting public health professionals and is based on an ongoing rapid review of the latest evidence.

Transmission

(Last update 15 August 2022)

SARS-CoV-2 is mainly spread via respiratory droplets, including aerosols, from an infected person who sneezes, coughs, speaks, sings, or breathes in close proximity to other people [1]. Exposure may occur via the inhalation of respiratory droplets or aerosol particles, deposition of respiratory droplets and particles on exposed mucous membranes (mouth, nose, eyes) and/or by touching mucous membranes after being contaminated by contact with surfaces with infectious virus on them.

The relative risk of environmental SARS-CoV-2 transmission (or fomite transmission) from contaminated surfaces is considered low compared with direct contact, droplet transmission, or airborne transmission [2]. Numerous studies have investigated how long SARS-CoV-2 can survive on various porous and non-porous surfaces. On porous surfaces, studies are unable to detect viable SARS-CoV-2 within minutes to hours of exposure to the virus. On non-porous surfaces, viable virus has been detected for days after exposure. However, the amount of viable virus declines over time, and it is rarely present on surfaces in sufficient amounts to cause infection [2]. Infection may occur when a person touches their nose, mouth, or eyes with their hands if their hands have been contaminated by fluids containing the virus or by touching surfaces contaminated with the virus.

Incubation period

(Latest update: 15 August 2022)

Based on systematic reviews and meta-analyses in studies investigating infections with ancestral strains of SARS-CoV-2, the incubation period of COVID-19 is, on average, five to six days, with most studies reporting a range of two to 14 days [3-7].

Recent evidence suggests that the incubation period of emerging SARS-CoV-2 variants can differ from that of ancestral strains [8-12]. For example, several studies have determined the Delta variant to have a shorter incubation period of around four days [10,13,14]. This information is important for determining when to test after a known exposure. Evidence from studies of the Omicron variant suggest an even shorter incubation period of approximately three days, but further studies are ongoing to verify these findings [15-17].

Infectivity and viral kinetics

(Latest update: 15 August 2022)

Infectivity

 The period during which people can transmit SARS-CoV-2 to others may vary between virus variants and individuals. An infected person can transmit the virus up to two days before they experience symptoms, as well as while they have symptoms [18,19]. It is dependent on numerous factors, such as disease severity and pre-existing immunity through vaccination or prior infection [20-22]. Patients with severe COVID-19 and immunocompromised patients have been shown to be infectious for a longer period [20,23,24].

Viral load and viral RNA shedding

One of the most frequently used diagnostic tests to detect SARS-CoV-2 infection is the nucleic acid amplification test (NAAT), which detects viral genetic material (RNA) in a specimen. Real-time reverse transcription PCR tests are the gold standard for the detection of COVID-19 and provide both a qualitative result (detected/not detected) and a quantitative result in the form of a cycle threshold (Ct) value (number of amplification cycles required for the detection signal to cross the background level - i.e. to generate a positive result). As Ct values are determined by the amount of viral RNA in the sample, they can be used as a proxy for the viral load (defined as the quantity of virus particles or viral genome copies in a given volume of the specimen) and can relate to the amount of virus present in the specimen. However, using Ct values as a proxy for viral RNA load should be done with care as a number of key factors (e.g. sampling procedure, viral transport media, time-to-processing) will have an effect on the Ct value.

It is important to note that the presence of SARS-CoV-2-RNA identified through RT-PCR in a patient (i.e. viral RNA shedding) does not necessarily indicate the presence of infectious SARS-CoV-2 (viable viral shedding). Some COVID-19 patients have positive RT-PCR results long after clinical diagnosis (e.g. 60 to >100 days) but this does not mean that they are still infectious [25-31].

Studies have reported that viral loads peak around the time of symptom onset and then gradually decrease [32-34]. It has been shown that the amount of viral RNA is highest three to six days after symptom onset [35]. Patients with severe disease tend to have higher viral loads than patients with mild disease [36]. Advanced age (>60 years) has also been associated with delayed viral clearance and disease severity [34,37,38]. Children have viral loads similar to those of adults [39]. Prolonged viral shedding with high viral load has been associated with poor outcomes in hospitalised patients [34].

Detection of both viral RNA and infectious virus has been reported in pre-symptomatic patients (before the onset of symptoms) and even in asymptomatic individuals [40,41]. Asymptomatic individuals can have viral loads that are just as high as those of symptomatic cases, indicating that asymptomatic carriers can play a major role in transmitting SARS-CoV-2 [42-45]. In fact, several studies have shown that secondary transmissions from an index case (the first case identified in a cluster of cases) could occur up to two days before the onset of symptoms in the index case, indicating that the pre-symptomatic phase of SARS-CoV-2 is highly infectious [46-49].

Viral RNA has been detected in upper and lower respiratory tract, as well as gastrointestinal specimens. The period of detectable viral RNA shedding varies among specimen types and may also vary among SARS-CoV-2 variants and patients [25].

Impact of variants of concern on viral kinetics

Transmissibility, incubation period, duration of infectiousness, and peak viral load may differ among virus variants. For example, increased viral loads have been reported with the Alpha and Delta variants of concern (VOC), with Delta showing 10-15-fold higher viral loads compared to the ancestral strain [50]. Epidemiological evidence has shown that the Delta VOC was more transmissible than the ancestral and Alpha strains, with transmissibility nearly double that of the wild-type SARS-CoV-2 virus that circulated during autumn 2020 [10,51-54]. This increased transmissibility was a key factor in the rapid dominance of the Delta VOC in 2021. Compared to Delta, the Omicron variant may be up to three times more transmissible [55], with a shorter incubation period and lower viral loads at diagnosis [56]. Recent studies have shown that infection with Omicron resulted in a shorter viral RNA shedding period and lower peak viral RNA concentrations in comparison to the Delta variant [57,58]. These findings are in line with a study, where only infectious viral loads were assessed, showing significantly lower viral loads in Omicron BA.1 breakthrough cases (infections occurring after vaccination) compared to Delta breakthrough cases [50]. In combination, these results indicate that the observed high transmissibility of Omicron BA.1 is not caused by elevated viral loads and the mechanism behind the higher transmissibility lies in the higher binding affinity with the human ACE2 receptor [59]. Furthermore, it has been shown that Omicron is less fusogenic (prone to facilitate fusion) than Delta and the ancestral strains of SARS-CoV-2, meaning that the fusogenicity and S1/S2 cleavage efficacy of SARS-CoV-2 may be linked to the degree of its pathogenicity [60].

Assessing the virological characteristics of newly emerging variants of concern is challenging. Due to the increase in immunity against SARS-CoV-2 in the population, it is difficult to determine whether differences are attributable to immunity in a largely vaccinated or/and infected population or due to the intrinsic characteristics of the different variants of concern.

Impact of vaccination on viral kinetics

Studies of viral load in SARS-CoV-2-infected individuals conducted from late 2020 to early 2021 indicate that it is reduced in those who have received a COVID-19 vaccine. In a study conducted in Switzerland from April 2020 to February 2022, it was shown that full vaccination significantly reduced infectious viral load in Delta breakthrough infection cases compared to unvaccinated individuals [50]. A shorter duration of viral RNA shedding and a faster viral clearance in vaccinated individuals has been suggested by several studies conducted during the period when the Delta VOC was the dominant variant [22,61]. A more rapid viral clearance may have implications on how long vaccinated and unvaccinated individuals remain infectious, which may indicate that vaccinated individuals, even if infected, transmit the virus for a shorter time than unvaccinated individuals.

A recent large population-based household transmission study from Denmark during the circulation of Omicron VOC found ‘an increased transmission for unvaccinated individuals, and a reduced transmission for booster-vaccinated individuals, compared to fully vaccinated individuals. This finding shows that vaccinated individuals, particularly those recently having received a booster dose (or third dose), do not transmit the virus to the same extent as unvaccinated individuals [62]. A further study has shown that Omicron BA.1 breakthrough infections in patients who have completed the primary course of vaccination resulted in significantly lower infectious viral loads (14-fold) [50], suggesting that mechanisms other than increased infectious viral load contribute to the high infectiousness of SARS-CoV-2 Omicron BA.1. Moreover, a significantly lower infectious viral load was observed for booster-vaccinated individuals (5.3-fold) compared to fully vaccinated subjects [50], so the higher transmissibility of Omicron BA.1 seems to be unrelated to an increased shedding of infectious viral particles in vaccinated individuals.

References