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Background:
Systematic Review

Does COVID-19 Vaccination Protect Contact Persons? A Systematic Review

by
Günter Kampf
University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse, 17475 Greifswald, Germany
Hygiene 2024, 4(1), 23-48; https://doi.org/10.3390/hygiene4010003
Submission received: 14 September 2023 / Revised: 14 November 2023 / Accepted: 21 December 2023 / Published: 9 January 2024
(This article belongs to the Section Public Health and Preventive Medicine)
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Abstract

:
The protective effect of COVID-19 vaccination for contact persons is controversial. Therefore, the aim of this review was to determine whether COVID-19 vaccination provides significant protection for them. A PubMed search was carried out using the terms “unvaccinated vaccinated covid” in combination with “viral load” and “transmission”. Studies were included if they reported original comparative data on the SARS-CoV-2 viral load, duration of SARS-CoV-2 detection, or SARS-CoV-2 transmission rates. A total of 332 articles were identified, of which 68 were included and analyzed. The differences in the viral load were equivocal in 57% of the 35 studies, significantly lower in the vaccinated in 11 studies and in the unvaccinated in 3 studies. The infectious virus levels were significantly lower in the vaccinated in two out of six studies. Virus clearance was significantly faster in vaccinated subjects in two of eight studies (detection of viral RNA) and two of four studies (detection of infectious virus). The secondary attack rates were significantly lower in vaccinated index cases in 6 of 15 studies. The vaccination status of contacts was described in two of the six studies and was 31.8% and 39.9% lower in households with an unvaccinated index case. The inconsistent and variable differences in the viral load, viral clearance and secondary attack rates between vaccinated and unvaccinated individuals, especially during the omicron predominance, suggests that COVID-19 vaccination is unlikely to prevent a relevant proportion of transmissions to contact persons, taking into account the relevance of the immunological status of the contact population (vaccination rates and previous infection).

1. Introduction

The primary goal of COVID-19 vaccination is to protect the vaccinated individual [1]. Self-protection is well established. Vaccination reduces the risk of symptomatic [2], severe [3] and fatal COVID-19 [3], although protection against SARS-CoV-2 infection declines from 83% at one month to only 22% at five months [4] and even faster for the omicron variant [5]. The personal motivation for COVID-19 vaccination was partly the expected self-protective effect. A substantial proportion of priority occupational groups, however, wanted to receive the COVID-19 vaccination mainly to protect their family members (76.2%) or colleagues (72.3%), and less often to protect themselves (49.1%) [6]. Official campaigns in some countries repeatedly claimed that the COVID-19 vaccination of index cases also protects contact persons [7,8].
However, the protective effect of the vaccination of individuals on the risk of contact persons acquiring COVID-19 is controversial. Several outbreaks have shown that vaccinated healthcare workers, for example, can still transmit SARS-CoV-2 to colleagues, patients or residents in nursing homes [9,10,11]. The WHO stated in 2021 that vaccines provide some protection against transmission [12]. However, it is currently not clear whether vaccinated individuals provide clinically relevant protection against infection to their contacts.
The aim of this review was therefore to find out whether full vaccination of individuals against COVID-19 provides clinically relevant protection for their contact persons, for example, by reducing the level of the viral load (RNA and infectious virus) in the event of infection (breakthrough infection), by shortening the duration of virus detection in respiratory tract specimens, or by preventing transmission from fully vaccinated individuals to close contacts, referred to as secondary attack rates.

2. Materials and Methods

2.1. Search Results

A literature search was conducted on PubMed using two combinations of terms: “unvaccinated vaccinated viral load covid” (30 November 2022) and “unvaccinated vaccinated transmission covid” (8 December 2022). The search protocol was developed for a previous search on a similar topic. Different combinations of search terms were initially evaluated, leading to the selection of the search terms used for this review. No changes were made during the review. The PRISMA statement standards were followed to conduct the systematic review.

2.2. Inclusion and Exclusion Criteria

Studies were included if they reported original comparative data on the SARS-CoV-2 viral load (cycle threshold values [Ct values], RNA copies per ml, infectious virus assessed by viral infectivity assays in cell culture) in both vaccinated and unvaccinated individuals, including those with a history of COVID-19 infection, if they reported the duration of SARS-CoV-2 detection (RNA, infectious virus) in both groups of vaccinated and unvaccinated individuals, including those with a history of infection, or if they reported the comparative secondary attack rates in vaccinated and unvaccinated individuals, including those with a history of previous infection. Fully vaccinated was defined as having received all the doses of the vaccine regime intended by the manufacturers at the time of vaccine approval. This means two doses of Comirnaty (BioNTech/Pfizer), Spikevax (Moderna), AZD1222 (AstraZeneca), CoronaVac/SinoVac (Sinovac Biotech), Sputnik V (Biocad), or CoviVac (Nanolek) or one dose of Jcovden (Janssen). For transmission studies, information on the COVID-19 vaccination status of contacts was included whenever possible. Studies were excluded if they did not meet the inclusion criteria, did not report original comparative human viral load or transmission data, were subsequently updated, were not in English, were based on modeling studies only, or were classified as reviews.

2.3. Data Extraction

The data were summarized in tables using a pre-specified data extraction table. The following data were extracted from the studies on the level of the viral load and on the duration of viral detection: viral load, including sample size, variant of SARS-CoV-2, study population, sampling period, country, number of vaccine doses administered, types of vaccine products, type of gene (PCR test), the duration of SARS-CoV-2 detection (if it was the endpoint) and the p-value. These data were extracted from the studies on the secondary attack rates: variant of SARS-CoV-2, study population, sampling period, country, vaccination status of index cases and sample size, vaccination status of contacts and sample size, type of contact, types of vaccine products, secondary attack rates per group, proportion of fully vaccinated contacts per group and p-value. Whenever possible, data on study participants with a previous COVID-19 infection were also extracted. The data in the tables were stratified according to the predominant SARS-CoV-2 variant at the time and place of the studies. When necessary, supplements were reviewed to identify more specific data, e.g., when relevant data such as the case numbers per vaccination group [13] or the types of vaccines were not described in the manuscript itself [14,15]. The search protocol was not registered.

2.4. Assessment of Study Quality

The risk of bias in each study was assessed using the Newcastle–Ottawa scale for cohort studies and the modified Newcastle–Ottawa scale for cross-sectional studies. The scales were adapted to the corresponding research questions and the type of study.
For cohort studies on the viral load and duration of detection, the following details were assessed: representativeness of the exposed cohort, selection of the non-exposed cohort, ascertainment of exposure (confirmation of vaccination or prior infection, respectively), comparability of cohorts based on design or analysis, assessment of outcome (always viral load), and adequacy of follow-up of cohorts. For cross-sectional studies on the viral load and duration of detection, the following details were assessed: representativeness of the sample, sample size, ascertainment of exposure (confirmation of vaccination), comparability of groups based on design or analysis, focusing on the time since symptom onset and additional relevant clinical parameters such as age, sex or comorbidities, assessment of outcome (measurement of viral load, test protocol) and a statistical test.
For cohort studies on the transmission and secondary attack rates, the following details were evaluated: representativeness of the exposed cohort, selection of the non-exposed cohort, ascertainment of exposure (complete vaccination of index case or prior infection, respectively), demonstration that the outcome of interest was not present at the start of the study (no detection of SARS-CoV-2 among any contact person), comparability of cohorts on the basis of the design or analysis (contact persons: vaccination status of contacts, duration and frequency of contacts, frequency of COVID tests; proportion of recovered contact persons; physical distancing behavior at home; hand hygiene behavior at home) and assessment of outcome (SARS-CoV-2 detection in contact persons). For cross-sectional studies on the transmission and secondary attack rates, the following details were evaluated: representativeness of the sample, sample size, ascertainment of exposure (complete vaccination of index case), comparability of cohorts on the basis of the design or analysis (vaccination status of contacts; other parameter may be duration and frequency of contacts, frequency of COVID tests; proportion of recovered contact persons; physical distancing behavior at home; hand hygiene behavior at home), assessment of outcome (confirmed COVID-19 case among contacts) and statistical test. Further details are provided in the four tables in the Supplementary Materials.

3. Results

3.1. Search Results

A total of 332 articles were found. Twenty-nine of them were removed as duplicate records so that 303 articles remained. A total of 200 articles were excluded because no comparative data on the viral load or transmission in the distinctive groups of vaccinated and unvaccinated individuals were found. Thirteen articles were reviews and so were excluded. Eleven articles were later updated and excluded. Seven articles described transmission based only on modeling efforts and so were excluded. Finally, four articles were in the Chinese language and so were excluded. Sixty-eight studies remained and were analyzed (Figure 1). Those were all observational studies; notably, no randomized controlled trials were identified in the search. Some studies might have appeared to meet the inclusion criteria but were excluded because the authors did not describe comparative data between vaccinated and unvaccinated subjects [16] or compared two heterogenous groups (vaccinated or boosted versus unvaccinated or unboosted parents) [17].

3.2. Level of Viral Load

The level of the viral load was described in 18 cohort studies and 22 cross-sectional studies of mostly moderate quality. The evaluations of the study quality can be found in the Supplementary Materials in Tables S1 and S2.

3.2.1. Ct Values According to Vaccination Status

In 30 studies, the comparative viral load was described with Ct values (Table 1). In the data sets of 20 studies, a lower viral load (higher Ct value; median or mean) was found among the vaccinated, with 10 of them reporting the difference as statistically significant, 10 of them being not significant and 3 of them without a p-value. In the data sets of 15 studies, a lower viral load was found among the unvaccinated, with three of those differences being significant, eleven of them being not significant and two of them without reporting results on statistical significance testing. Two studies described the same viral load in vaccinated and unvaccinated individuals.
With the ancestral strain, the Ct values in individuals infected with SARS-CoV-2 ranged between 13.9 and 26.6 [18]. Comparisons between vaccinated and unvaccinated individuals were not possible due to the lack of vaccines during the period of dominance of the ancestral strain. During the dominance of the beta variant, one study with two different vaccination protocols showed a significantly higher viral load (lower Ct value; median or mean) among the unvaccinated individuals [19].
During the alpha wave, five of six studies demonstrated a higher viral load among the unvaccinated subjects, with a significant difference in two of the studies [21,25], whereas in two other studies, no significant difference was found [20,22]. Among nursing home residents, a significantly lower viral load among the vaccinated individuals was found only when the vaccination completion was at least 28 days ago [23]. The viral load among vaccinated and unvaccinated healthcare workers was the same, with a median of 18.5 (interquartile range, IQR 13.5–24.0 and 16.0–26.0 for unvaccinated or vaccinated, respectively) in one study [24]. In an additional study without a description of the mean or median Ct values, the evaluation of 85 unvaccinated and 165 vaccinated cases during an outbreak in a nursing home with the alpha variant of SARS-CoV-2 revealed a lower mean Ct value among the vaccinated residents (3.04 cycles lower), but the difference was not significant (p = 0.38) [48].
Data obtained during the delta wave revealed an inconsistent picture. Overall, the data sets in 13 studies described a lower viral load among the vaccinated compared to the unvaccinated. The difference was significant in five studies [18,27,35,36,41], not significant in seven studies [10,26,27,28,37,39,42] and without reporting results of a statistical evaluation in two studies [22,31]. On the other hand, the data sets in 12 studies described a higher viral load among the vaccinated compared to the unvaccinated. The difference was significant in three studies [27,30,38], not significant in eight studies [20,26,29,30,33,34,35,40] and without reporting results of a statistical evaluation in two studies [22,32]. Among the boosted population (having received one dose of booster after the completion of the original course of vaccination), the effect of a lower viral load is insignificant within 61 to 120 days [49].
In three studies during the omicron period, no significant difference in the viral load was found between vaccinated and unvaccinated individuals [18,29,43]. Four data sets from three studies examined the viral load during various pandemic periods, resulting in data with multiple variants. In one data set, the viral load was significantly higher in unvaccinated subjects [46], whereas in the other data sets, no significant difference was found [44,45,46].

3.2.2. Viral RNA Copies According to Vaccination Status

Across all the variants, nine studies described the viral load by calculating the number of viral RNA copies per ml (Table 2). In nine data sets from seven studies, a lower viral load was found among the vaccinated, with seven of those differences being significant and two of them being not significant. In the data sets of three studies, a lower viral load was found among the unvaccinated, with all of them being not significant.
During the delta predominance, a lower viral load was found among the vaccinated in three studies [14,50,51], which was in one study not associated with a specific vaccine [14]. The effect, however, was waning within five months [51], although it could be restored by a booster dose [51]. During the omicron predominance, almost all the data sets from two studies showed a similar viral load for unvaccinated, fully vaccinated and boosted [18,51], with the exception of those who received the second dose 14 to 149 days before their infection (mean difference [95%-CI]: −1 [–1.7 to −0.3]), as based on a regression model. In investigations with multiple SARS-CoV-2 variants, the number of RNA copies from vaccinated individuals was lower in two studies [52,53], higher in one study [47], and equal to the viral load in vaccinated individuals in one study [45], with one of those differences showing a lower viral load in vaccinated individuals being statistically significant [53].
Table 2. Log10 viral copies per ml from respiratory tract samples of COVID-19 cases according to the vaccination status and the SARS-CoV-2 variant.
Table 2. Log10 viral copies per ml from respiratory tract samples of COVID-19 cases according to the vaccination status and the SARS-CoV-2 variant.
SARS-CoV-2 VariantType of GeneSampling Period (Country)Type of PopulationLog10 Viral Copies per mL According to the Number of Vaccination Doses (Number of Samples)p-ValueSource
None1 Dose2 Doses3 Doses
DeltaE gene6/21–12/21 (Switzerland)Any individual with symptomsApprox. 8.5 [SD: 0.8] * (127) -Approx. 8.2 [SD: 1.0] * (104)-0.0002[18]
DeltaN gene12/20–4/22 (USA)Healthcare workers, essential frontline workers, uninfected upon inclusion4.1 * (78)-3.0 * (27) #
4.2 * (165) ##		3.2 * (18)“significant”
n.s.
n.s.		[51]
DeltaN gene10/20–8/21 (USA)General population7.4 [IQR: 3.3–10.8] ** (36)-4.7 [IQR: approx. 1.0–10.6] * (56)-<0.0001[14]
Mainly deltaN gene7/21–9/21 (France)Patients7.1 [IQR: 5.7–7.9] ** (2619)7.0 ** [IQR: 5.6–7.8] ** (636)6.6 [IQR: 5.5–7.6] ** (520)-<0.0001
for delta variant
(0 versus 2)		[50]
Mainly deltaN genes12/20–9/21 (USA)General population1.1 [95% CI: approx. 0.7–1.6] * (160)-0.3 * [95% CI: approx. 0.3–0.8] * (112)-0.02[41]
OmicronN gene12/20–4/22 (USA)Healthcare workers, essential frontline workers, uninfected upon inclusion3.5 * (109)-2.8 * (42) #
3.3 * (209) ##		3.1 * (383)“significant”
n.s.
n.s.		[51]
Omicron BA.1E gene12/21–2/22 (Switzerland)General populationApprox. 7.6 [SD: approx. 0.8] * (33)-Approx. 7.8
[SD: approx. 0.8] * (91)		Approx. 7.7
[SD: approx. 0.7] * (30)		n.s.[18]
Multiple variantsORF1ab, N and S gene12/20–4/21 USA)General population3.8 [SD: 1.7] * (155)2.3 [SD: 1.7] * (16) ***--“significant”[53]
Multiple variantsN gene2/21–6/21 (USA)General population and patients6.6 * (1061)-6.6 * (121)-0.99[45]
Multiple variantsNot described11/20–8/21 (USA)Participants of the occupational health program of the National Basketball Association, infected upon inclusion8.0 [95% CI: 8.2–11.5] * (136)-8.1 [95% CI: 7.9–11.5] * (37)-n.s.[47]
Multiple variantsN gene9/20–9/21 (USA)General population, infected non-hospitalized7.5 [IQR: 0.004–108.0] ** (52)-1.0 [IQR: 0.2–32.0] ** (32)-0.39[52]
Multiple variantsE gene9/20–9/21 (USA)General population, infected non-hospitalized1.2 [IQR: 0.005–27.4] ** (52)-0.6 [IQR: 0.07–23.3] ** (32)-0.88[52]
* mean with 95% confidence interval (95% CI) or standard deviation (SD); ** median with interquartile range (IQR); *** at least 1 dose; # received 2nd dose 14–149 days before infection; ## received 2nd dose ≥ 150 days before infection; patients were defined as those who are treated in hospitals (inpatients) or asked for medical treatment (outpatients); n.s. = not significant.

3.2.3. Infectious Virus According to Vaccination Status

Five studies measured the load of infectious SARS-CoV-2 in the vaccinated and unvaccinated populations (Table 3). In seven data sets of four studies, a lower load of infectious virus was found among the vaccinated or boosted. Five of those differences described in three studies were significant [18,37,51] and two were not significant [51,52]. In the data sets of two studies, a lower load of infectious virus was found among the unvaccinated compared to those who received two doses, without reaching statistical significance [18,38].

3.3. Duration of Viral Detection

The duration of viral detection was described in nine cohort studies of mostly moderate quality. The evaluations of the study quality can be found in the Supplementary Materials in Table S1.

3.3.1. Detection of SARS-CoV-2 Genes

In three studies during the delta predominance, vaccinated COVID-19 cases had a shorter duration of RNA detection compared to unvaccinated or partly vaccinated control cases (Table 4) [15,30,33]. The difference, however, was significant in only one study [33]. Five studies described the duration of RNA detection with various SARS-CoV-2 variants. Here, all the data sets indicated a shorter RNA detection duration in the partly vaccinated [53] and fully vaccinated [47,52,54,55], with the difference being significant in two of the four studies [47,54].

3.3.2. Detection of Infectious SARS-CoV-2

Four studies described the duration of detection of infectious SARS-CoV-2 in vaccinated and unvaccinated subjects (Table 5). Two studies with the delta variant found a shorter duration of detection in fully vaccinated subjects compared to the group of unvaccinated and partly vaccinated subjects (median: 5 versus 11 days [15]; median: 1.8 versus 4.4 days [30]). The difference, however, was significant in only one study [15]. Two other studies described the persistence of infectious virus with various viral variants. A shorter duration of detection was found in fully vaccinated compared to the unvaccinated subjects (median: 5 versus 7 days [52]; mean: 0.8 versus 2.8 days [56]). The difference was significant in one study [56].

3.4. Transmission from COVID-19 Cases

The secondary attack rates from both unvaccinated and vaccinated index cases were described in nine cohort studies and seven cross-sectional studies. They were mostly of moderate quality. The results of the study quality evaluations are described in Tables S3 and S4 in the Supplementary Materials.
Without any vaccination, the secondary attack rate in households was described to be as high as 64.3% [57]. In both of the included studies that were conducted during the alpha variant predominance (Table 6), the secondary attack rates were significantly lower when the index case was vaccinated compared to unvaccinated index cases (19% versus 42% [58]; 22.2% versus 66.7% [48]). The contact persons were all unvaccinated in one of the two studies [48].
An additional study was found during the alpha variant dominance without a complete description of the case numbers [17]. A transmission analysis revealed that among 127 households, no household with secondary cases was found in three households with the primary case being fully vaccinated, one household with secondary cases was found in five households with the primary case being partially vaccinated and nine households with secondary cases were found in 11 households with the primary case being unvaccinated [59]. In households with children, the vaccination status of the parents was associated with a lower COVID-19 case number (mainly alpha variant) among the unvaccinated children (risk reduction when one parent is vaccinated: −26.0%; risk reduction when both parents are vaccinated: −71.7%) [17]. In addition, in households of healthcare workers, less secondary cases were found among unvaccinated household members when the index case was vaccinated [60].
Table 6. Secondary attack rates with 95% confidence intervals (95% CI) or standard deviation (SD) from COVID-19 cases with different vaccination statuses infected with different SARS-CoV-2 variants.
Table 6. Secondary attack rates with 95% confidence intervals (95% CI) or standard deviation (SD) from COVID-19 cases with different vaccination statuses infected with different SARS-CoV-2 variants.
SARS-CoV-2
Variant		Study Period (Country)Vaccination Status Index Cases (n)Type of ContactSecondary Attack Rate per GroupProportion of Fully Vaccinated Contacts (Group)p-ValueSource
Mainly alpha12/20–4/21 (Israel)Unvaccinated (200)
Fully vaccinated (15)		Household contacts of healthcare workers42.0% *** [95% CI: 38%–46%]
19.0% *** [95% CI: 9%–34%]		-significant[58]
Mainly alpha1/21–3/21 (Germany)Unvaccinated (11)
Fully vaccinated (5)		Household contacts66.7%
22.2%		0% ** (all contacts)
0% ** (all contacts)		0.046[48]
Alpha and delta1/21–8/21 (UK)Unvaccinated (218,946)
Partially vaccinated (91,394)
Fully vaccinated (63,775)		“Close contacts” of infected adult patients46.4%
28.0%
26.8%		27.8% (all contacts with PCR tests)- *[13]
Delta9/20–9/21 (UK)Unvaccinated (63)
Partially vaccinated (25)
Fully vaccinated (50)		Mainly household contacts23.0%
37.1%
24.6%		63.0% (contacts of unvaccinated index cases)
54.3% (contacts of partially vaccinated index cases)
62.3% (contacts of fully vaccinated index cases)		n.s. #[61]
Delta2/21–5/21 (The Netherlands)Unvaccinated (110,872)
Partially vaccinated (2088)
Fully vaccinated (622)		Household contacts30.8%
28.9%
11.2%		2.1% (all contacts)-[62]
Delta6/21–10/21 (Denmark)Unvaccinated (16,431)
Fully vaccinated (8262)		Household contacts22.3%
20.1%		Correlation coefficient of 0.72 of the vaccination status between primary cases and contacts among individuals of ≥13 years of age-[63]
Delta6/21–7/21 (USA)Unvaccinated (61)
Fully and partially vaccinated (22)		Household contacts57.8%
16.7%		35.7% (contacts of unvaccinated index cases)
75.0% (contacts of fully vaccinated index cases)		<0.01[64]
Delta6/21–10/21 (Denmark)Unvaccinated (8611)
Fully vaccinated, no previous infection (8765)
Boosted (528)
Unvaccinated, previous infection (145)
Fully vaccinated, previous infection (58)		Household contacts21.5%
20.2%
18.0%
7.5%
7.5%		48.7% (all contacts, delta and omicron)-[65]
Delta3/20–11/21 (Republic of Korea)Unvaccinated (100)
Partially vaccinated (10)
Fully vaccinated (43)		Healthcare setting27.0%
20.0%
7.0%		-0.03[30]
Delta8/21–9/21 (The Netherlands)Unvaccinated (2641)
Partially vaccinated (540)
Fully vaccinated (1740)		Household contacts17.7%
7.9%
12.4%		35.3% (contacts of unvaccinated index cases)
67.3% (contacts of partially vaccinated index cases)
79.6% (contacts of fully vaccinated index cases)		-[66]
Delta9/21–1/22 (Republic of Korea)Partially or unvaccinated (30)
Fully vaccinated (19)		“Close contacts”14.1%
3.7%		-0.001[15]
Omicron11/21–12/21 (Denmark)Unvaccinated (1166)
Fully vaccinated, no previous infection (6934)
Boosted (468)
Unvaccinated, previous infection (128)
Fully vaccinated, previous infection (414)		Household contacts30.8%
29.5%
31.8%
15.0%
16.0%		48.7% (all contacts, delta and omicron)-[65]
Omicron11/21–2/22 (USA)Unvaccinated (36)
Fully vaccinated (12) ****
Boosted (57)		Household contacts63.9%
43.6%
42.7%		35.1% (all contacts); an additional 26.0% were boosted.-[67]
Omicron12/21–1/22 (Germany)Unvaccinated (202)
Fully vaccinated (202)
Boosted (204)		“Close contacts”47.9%
49.5%
34.8%		--[68]
Multiple variants9/20–1/22 (USA)Unvaccinated (21)
Fully vaccinated (21)		Household contacts45.0% [95% CI: 29.0%–62.0%]
41.4% [95% CI: 25.0%–59.0%]		20.0% (contacts of unvaccinated index cases)
85.3% (contacts of fully vaccinated index cases)		0.60[69]
Multiple variants4/21–9/21 (Thailand)Unvaccinated (177)
Fully vaccinated (231)		Household contacts46.8%
50.8%		3.1% (contacts of unvaccinated index cases)
14.7% (contacts of fully vaccinated index cases)		0.177[70]
Multiple variants12/20–8/21 (Germany)Unvaccinated (357)
Fully vaccinated (357)		“close contacts”37.8%
10.1%		Significantly more secondary cases among unvaccinated contacts (p < 0.001)<0.001[46]
* significantly lower transmission rate ratios (multivariable model) for partly and fully vaccinated index cases; ** vaccine was prioritized in January 2021 for selected population groups only; *** mean number of infected contacts per index case; **** vaccinated < 5 months before index date; # based on vaccine effectiveness estimate for secondary attack rates; n.s. = not significant.
Significantly lower secondary attack rates were also found during the period when both the alpha and delta variants were present for both the fully and partly vaccinated index cases [13].
During the delta variant predominance, eight studies were carried out (Table 6). The secondary attack rates were lower from fully vaccinated index cases in all of those studies, with three of them being statistically significant [15,30,64] and four of them without a statistical evaluation [62,63,65,66]. In one study, the secondary attack rate was higher from fully vaccinated index cases but the difference was not significant or not statistically evaluated [61].
An additional transmission analysis was performed during the delta wave between index cases and contacts in households. The proportion of COVID-19 cases among contacts was not significantly different between vaccinated and unvaccinated index cases [71]. In households with children, the vaccination status of the parents was associated with a lower COVID-19 case number (mainly delta variant) among the unvaccinated children (risk reduction when one parent is vaccinated: −20.8%; risk reduction when both parents are vaccinated: −58.1%) [17]. One additional study did not describe the secondary attack rates but a significantly higher mean number of infected contacts per unvaccinated index case [72].
When the omicron variant became predominant in the second half of 2021, three studies were carried out (Table 6), with a lower secondary attack rate from fully vaccinated individuals compared to the unvaccinated in two studies (29.5% versus 30.8% [65]; 43.6% versus 63.9% [67]) and a higher secondary attack rate in one study (49.5% versus 47.9% [68]). Boosted index cases revealed a lower secondary attack rate compared to fully vaccinated index cases in two studies (42.7% versus 43.6% [67]; 34.8% versus 49.5% [68]) and a higher secondary attack rate in one study (31.8% versus 29.5% [65]).
Three more studies with multiple SARS-CoV-2 variants described a lower secondary attack rate from vaccinated index cases compared to the unvaccinated in two studies (41.4% versus 45.0% [69]; 10.1% versus 37.8% [46]) and a higher rate in the other study (50.8% versus 46.8% [70]; Table 6). A significant difference, however, was described only in one study [46].
Several transmission studies did not report the vaccination status or the history of any past SARS-CoV-2 infection of the contact persons. In five studies, however, the majority of contact persons of fully vaccinated index cases were also fully vaccinated, whereas the vaccination rate in households from unvaccinated index cases was much lower [63,64,66,69,72]. In one study, however, the proportion of vaccinated households’ contacts was similar for vaccinated and unvaccinated index cases [61].

3.5. Previous COVID-19 Infection

Three studies have addressed the level of the viral load in reinfections compared to unvaccinated and fully vaccinated COVID-19 cases (Table 7). Patients with a COVID-19 reinfection mostly had a lower viral load, as indicated by the higher Ct values compared to unvaccinated cases with a primary infection (29.8 versus 28.0, p = 0.0004 [54]; 29.9 versus 23.6, p < 0.001, [19]; 32.8 versus 28.7, no p-value [22]), although another study demonstrated a higher viral load for the same comparison (22.3 versus 25.7, no p-value, [22]). The comparison of the viral load in reinfections and fully vaccinated but previously uninfected revealed a lower viral load in reinfections in two data sets [19] and a higher viral load in three data sets (Table 7) [22].
Another study described the viral load in healthcare workers, with 46 of them being neither vaccinated nor previously infected, 45 being unvaccinated but previously infected, 26 being fully vaccinated without a previous infection and 26 being fully vaccinated and previously infected. There was no significant difference between all four groups regarding the Ct values of various genes [43].

4. Discussion

Some scientists and politicians repeatedly spoke out in favor of COVID-19 vaccination in order to protect contact persons. Protection of contact persons became the main motivation for vaccination in some population groups [6]. A lower risk of transmission from vaccinated subjects may be explained by a lower viral load, a shorter viral persistence or a reduced transmission in a defined setting such as a household.
The viral load substantially contributed to human-to-human transmission, with a higher viral load posing a greater risk of onward transmission [73]. For example, a significantly higher viral load (lower Ct values) was described in index cases from households with a secondary transmission (N gene: 23.1; ORF1ab gene: 23.2) compared index cases from households without a secondary transmission (N gene: 27.1; ORF1ab gene: 29.1) [74]. But the vaccination status does obviously not have a consistent and relevant impact on the viral load of individuals infected with SARS-CoV-2. In 2021, during the beta and alpha variant dominance, three of seven studies showed a statistically significantly lower viral load among the vaccinated as demonstrated by higher Ct values. Data obtained during the delta and omicron waves, however, found a significantly lower viral load in the vaccinated in the data sets of five studies and a significantly higher viral load in the vaccinated in the data sets of three studies with regard to the Ct values. These findings were confirmed by the results from more than 460,000 individuals, showing that the effect of a recent vaccination on the viral load of the omicron variant is rapidly waning and thereby raising doubts about the effect of vaccination on viral transmissibility [75]. This is why an expected lower viral load as a single parameter does not seem to reduce the risk of transmission to a great extent.
A major limitation regarding the interpretation of Ct values is that the values obtained from the same samples can vary substantially depending on the investigated gene. For example, significantly lower Ct values were detected in samples from vaccinated individuals when the RdRp gene or the N gene were tested, whereas no significant difference was found when the E gene was tested [27]. Similar results were obtained by Bollinger et al. [35]. Caution has been advised when interpreting single Ct values as a proxy for infectivity, especially in intermittently positive test results and in different stages of infection with a variable decline of viral RNA [76]. In the current review, however, the Ct values are not analyzed as single results per person to determine the person’s current individual infectivity. It is likely that additional factors contribute to transmission, such as physical distance or duration of contact [77,78]. An analysis of 602 PCR test samples was performed from COVID-19 cases among students. Contact tracing information was available for 195 index cases, with 101 of them being non-spreaders and 94 of them being spreaders. The mean Ct values of the spreaders and the non-spreaders were nearly identical, suggesting that the Ct values do not predict the transmissibility of SARS-CoV-2 [79].
Viral clearance, including the detection of infectious virus, has been described to be faster in the vaccinated population so that their expectable duration as a possible source for transmission is mostly shorter. Viral shedding, however, is continuously decreasing with time over the course of infection [80]. This is why the overall relevance of a somewhat faster clearance of viral RNA or infectious SARS-CoV-2 to the transmissibility of SARS-CoV-2 is not clear.
An analysis of the secondary attack rates provided some evidence that in household settings, vaccination of the index cases was associated with fewer secondary cases in their household contacts compared to no vaccination of the index cases. The difference was significant in 6 of the 16 studies. But with a lack of data obtained from RCTs, the causality of the observed findings remains uncertain. One possibility is that the vaccination of the index cases has caused the lower attack rate among contact persons. But it may as well be the vaccination status of the contact persons that has caused lower secondary attacks rates among household members of vaccinated index cases, i.e., vaccination coverage of the contact persons confounding the results of lower secondary attack rates when the index was vaccinated.
Two of the six studies with a significant difference were performed during the alpha wave, when COVID-19 vaccination was not broadly available yet [48,58], while three of the studies were conducted during the delta wave, with small sample sizes of 153 [30], 83 [64] or 49 index cases [15]. The proportions of fully vaccinated contact persons are, however, not described in any of the three studies. One study with a significant difference included data from multiple SARS-CoV-2 variants. It was based on 714 index cases. The authors provided a possible explanation for their finding because they found significantly more secondary cases among unvaccinated contacts (p < 0.001) [46]. Although the authors focused in all studies on the vaccination status of the index cases, they did not always adequately take into account the vaccination status of the contact persons.
In five of the 16 studies, the vaccination coverage of the contact persons was described according to the vaccination status of the index cases. Four of the studies indicated that contact persons were more often vaccinated when the index case was also vaccinated. The differences in vaccination rates varied between 11.6% [70], 39.3% [64], 44.3% [66] and 65.3% [69]. Population-based data from Denmark also described a correlation coefficient of 0.72 for the vaccination status between primary cases and contacts among individuals of ≥ 13 years of age [63]. It is therefore plausible to assume that the vaccination status of the contact persons may be a more suitable factor to explain the observation of lower secondary attack rates in contacts to vaccinated index persons. This assumption is supported by a finding from South Korea. A population-based study during the omicron predominance indicated that fully vaccinated and boosted contacts have a lower incidence ratio compared to unvaccinated contacts [81]. This assumption is supported by the finding that those who encouraged their families and friends to get vaccinated are more likely to accept a COVID-19 vaccination [82]. The presence of symptoms may also be relevant for a secondary transmission from index cases, as symptomatic infections have been described to increase transmissibility from the index cases [83]. Finally, the behavior may be different between households of vaccinated and unvaccinated index cases. It has been described that those who are willing to get vaccinated have a higher adherence to physical distancing guidelines compared to the unvaccinated [84]. In addition, mitigation behaviors such as masking, physical distancing and hand hygiene are significantly more performed by the vaccinated [85]. Keeping more physical distance may also have a relevant impact on the incidence of secondary cases [77]. It is therefore highly questionable if the partly observed lower secondary attack rates in contact populations of vaccinated index cases, which are based entirely on observational studies, are best explained by the vaccination status of the index cases, as there remain other and more plausible factors to explain the observed differences.
This interpretation is strongly supported by recent data on secondary transmission rates obtained during four COVID-19 waves among 50,973 index cases and 111,674 contacts. The authors considered the immune status of the index cases and their contacts and categorized the results accordingly. Vaccination of index cases reduced their infectiousness by 1.3% to 6.5% depending on the variant of SARS-CoV-2 and the timing of vaccination. A previous infection of index cases yielded a stronger reduction in their infectiousness (4.3% to 11.3%). Recent vaccination of the contact persons reduced their susceptibility to being infected significantly by 9.5% (delta variant) and 12.9% (alpha variant), whereas it increased susceptibility to be infected during the omicron wave significantly by 6.9%. Vaccination at least six months ago increased the susceptibility to being infected strongly during the omicron wave significantly by 13.3%. A previous infection provided consistently a stronger reduction in susceptibility to being infected compared to vaccination [86]. This is why the knowledge of the immune status of the contact persons is indispensable for the analysis of secondary transmission rates in the studies described above.
Another aspect with relevance to transmission may be a previous COVID-19 infection of the index case resulting in natural immunity. A previous COVID-19 infection reduced the duration of viral RNA detection from 26.4 to 13.7 days [55], a magnitude of reduction not observed among the fully vaccinated (Table 4). Household transmission studies described a lower secondary attack rate from unvaccinated index cases with a previous infection compared to unvaccinated index cases without a previous infection (delta variant: 7.5% versus 21.5% [65]; omicron variant: 15.0% versus 30.8% [65]; omicron 40.9% versus 63.9% [67]). Importantly, the secondary attack rates from vaccinated index cases without a previous infection were consistently higher than those from unvaccinated index cases with a previous infection (delta variant: 20.2% versus 7.5% [65]; omicron variant: 29.5% versus 15.0% [65]; omicron 43.6% versus 40.9% [67]). Natural immunity has been described to be at least as effective as vaccination [87]. One of the reasons may be that natural immunity results in local tissue immunity (nose, mouth, saliva, lungs) as a first-line defense against SARS-CoV-2, which is not generated by intramuscular injection [87].
Only some of the included studies considered the time since vaccination as a factor to account for the waning of vaccine effectiveness over time with respect to our main outcomes [13,22,30,61]. In those, this information was incorporated in multivariate models or included in the stratified reporting of data. A decline in the effect of vaccination on the viral burden was shown in one study [22], while another study showed no effect of the time since vaccination on the viral burden [30]. Vaccine effectiveness against transmission was found to decline substantially after 12 weeks since the second dose of BNT162b2 or ChAdOx1 [13], while another study indicated that the protective effect of the full vaccination of the contacts with BNT162b2 or ChAdOx1 declined in a likewise manner within two to three months [61].
The phase 3 COVID-19 vaccine trials were carried out in 2020 and found a significant reduction in symptomatic COVID-19 cases among the vaccinated [88,89,90,91]. This may have led to the assumption that transmission of SARS-CoV-2 can be slowed down or prevented by the increasingly vaccinated population, as was then soon perpetrated in official campaigns in numerous countries during 2021. In one of the trials, however, it was already described that the proportion of asymptomatic COVID-19 was the same among the vaccinated (1.0%) and the unvaccinated (1.0%), suggesting that the proportion of asymptomatic viral carriers may not be affected by vaccination status [88]. The epidemiology of COVID-19 has changed in the meantime and the epidemiological relevance of the vaccinated population as a possible source of transmission is increasingly recognized [92]. Only a few countries provided epidemiological data on the COVID-19 incidence per 100,000 unvaccinated, vaccinated or boosted. The UK is one of them. The case rates were published in the weekly COVID-19 vaccine report until week 13 in 2022 [93]. It describes the unadjusted case rates among persons vaccinated with at least 3 doses per 100,000 and among unvaccinated persons also per 100,000 (between week 9 and week 12 2022, omicron period). The proportion of confirmed cases in each of the two groups indicates their epidemiological relevance as possible sources of transmission. Among the boosted population in the UK, the COVID-19 case rates per 100,000 were much higher compared to the unvaccinated (all age groups of ≥ 18 years) [93]. For example, in citizens of 30 to 39 years, 4325 cases per 100,000 were found among the boosted and 1086 among the unvaccinated [93]. Based on the UK data, the possible sources for COVID-19 transmission are overall more likely among the boosted compared to the unvaccinated population.
A limitation of this review may be that studies were only identified and extracted from PubMed. The inclusion of other sources may have added more relevant information on the topic, which may have resulted in an even broader compilation of evidence and a possible different overall result.
A further limitation of this work is that no randomized controlled trials on this topic were found. This is why the causality of the observed findings remains undetermined. Linked to this, it has to be considered that only a portion of the included studies controlled for potential confounders for differences in the Ct values such as age and sex [22] or the time between onset of illness and specimen collection [51] and potential confounders as the type of exposure and characteristics of contacts of an index person [13]. In most of the included studies, however, the outcomes were reported and compared as unadjusted estimates of the respective values of the viral load or secondary transmission.

5. Conclusions

At the beginning of the COVID-19 pandemic, it seemed possible and plausible to assume that COVID-19 vaccination has partially slowed down transmission by reducing the number of symptomatic cases. But considering the differences in the viral load, viral clearance and secondary attack rates between vaccinated and unvaccinated, and considering the limitations regarding the interpretation of the studies, it can be assumed that COVID-19 vaccination is unlikely to prevent a relevant proportion of transmissions to contact persons when taking into account the relevance of the immunological status of the contact population (rates of vaccination and previous infection) and the previously described higher adherence level to physical distancing, masking and hand hygiene guidelines in the vaccinated population.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/hygiene4010003/s1: Table S1: Summary of quality assessment based on the Newcastle-Ottawa quality assessment scale for cohort studies on viral load and duration of detection; Table S2: Summary of quality assessment based on the Newcastle-Ottawa quality assessment scale for cross-sectional studies on viral load and duration of detection; Table S3: Summary of quality assessment based on the Newcastle-Ottawa quality assessment scale for cohort studies on transmission and secondary attack rates; Table S4: Summary of quality assessment based on the Newcastle-Ottawa quality assessment scale for cross-sectional studies on transmission and secondary attack rates.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The author is very grateful for the significant support provided by Andreas Hoffmann, who double-checked many of the extracted data and provided relevant aspects regarding the interpretation of the results.

Conflicts of Interest

The author has received an honorarium from Schülke & Mayr, Germany, outside the submitted work.

References

  1. WHO. Vaccines and Immunization: What Is Vaccination? Available online: https://www.who.int/news-room/questions-and-answers/item/vaccines-and-immunization-what-is-vaccination (accessed on 1 August 2022).
  2. Korang, S.K.; von Rohden, E.; Veroniki, A.A.; Ong, G.; Ngalamika, O.; Siddiqui, F.; Juul, S.; Nielsen, E.E.; Feinberg, J.B.; Petersen, J.J.; et al. Vaccines to prevent COVID-19: A living systematic review with Trial Sequential Analysis and network meta-analysis of randomized clinical trials. PLoS ONE 2022, 17, e0260733. [Google Scholar] [CrossRef]
  3. Ghazy, R.M.; Ashmawy, R.; Hamdy, N.A.; Elhadi, Y.A.M.; Reyad, O.A.; Elmalawany, D.; Almaghraby, A.; Shaaban, R.; Taha, S.H.N. Efficacy and Effectiveness of SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis. Vaccines 2022, 10, 350. [Google Scholar]
  4. Ssentongo, P.; Ssentongo, A.E.; Voleti, N.; Groff, D.; Sun, A.; Ba, D.M.; Nunez, J.; Parent, L.J.; Chinchilli, V.M.; Paules, C.I. SARS-CoV-2 vaccine effectiveness against infection, symptomatic and severe COVID-19: A systematic review and meta-analysis. BMC Infect. Dis. 2022, 22, 439. [Google Scholar] [CrossRef]
  5. Accorsi, E.K.; Britton, A.; Fleming-Dutra, K.E.; Smith, Z.R.; Shang, N.; Derado, G.; Miller, J.; Schrag, S.J.; Verani, J.R. Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants. JAMA 2022, 327, 639–651. [Google Scholar] [CrossRef]
  6. Štěpánek, L.; Janošíková, M.; Nakládalová, M.; Ivanová, K.; Macík, J.; Boriková, A.; Vildová, H. Motivation for COVID-19 vaccination in priority occupational groups: A cross-sectional survey. Int. J. Environ. Res. Public Health 2021, 18, 11726. [Google Scholar]
  7. Bundesministerium für Gesundheit. Gemeinschaftsschutz durch Corona-Schutzimpfung. Available online: https://www.zusammengegencorona.de/impfen/gemeinschaftsschutz-solidaritaet-in-der-coronavirus-pandemie/ (accessed on 30 November 2022).
  8. Hütten, F. Weitergabe des Virus—Warum man mit einer Corona-Impfung auch andere schützt. Available online: https://www.derbund.ch/warum-man-mit-einer-corona-impfung-auch-andere-schuetzt-414879400098 (accessed on 30 November 2022).
  9. Zürcher, K.; Abela, I.A.; Stange, M.; Dupont, C.; Mugglin, C.; Egli, A.; Trkola, A.; Egger, M.; Fenner, L. Alpha variant coronavirus outbreak in a nursing home despite high vaccination coverage: Molecular, epidemiological and immunological studies. Clin. Infect. Dis. 2022, 77, ciab1005. [Google Scholar] [CrossRef]
  10. Park, S.Y.; Kim, T.H.; Lee, E.; Loeb, M.; Jeong, Y.S.; Kim, J.H.; Oh, S.M.; Cheong, S.; Park, H.; Jo, S.Y.; et al. A SARS-CoV-2 outbreak associated with vaccine breakthrough in an acute care hospital. Am. J. Infect. Control 2022, 50, 1006–1012. [Google Scholar] [CrossRef]
  11. Shitrit, P.; Zuckerman, N.S.; Mor, O.; Gottesman, B.S.; Chowers, M. Nosocomial outbreak caused by the SARS-CoV-2 Delta variant in a highly vaccinated population, Israel, July 2021. Eurosurveillance 2021, 26, 2100822. [Google Scholar] [CrossRef]
  12. World Health Organization. Vaccine Efficacy, Effectiveness and Protection. Available online: https://www.who.int/news-room/feature-stories/detail/vaccine-efficacy-effectiveness-and-protection (accessed on 30 November 2022).
  13. Eyre, D.W.; Taylor, D.; Purver, M.; Chapman, D.; Fowler, T.; Pouwels, K.B.; Walker, A.S.; Peto, T.E.A. Effect of COVID-19 Vaccination on Transmission of Alpha and Delta Variants. N. Engl. J. Med. 2022, 386, 744–756. [Google Scholar] [CrossRef]
  14. Rife Magalis, B.; Rich, S.; Tagliamonte, M.S.; Mavian, C.; Cash, M.N.; Riva, A.; Marini, S.; Amador, D.M.; Zhang, Y.; Shapiro, J.; et al. Severe Acute Respiratory Syndrome Coronavirus 2 Delta Vaccine Breakthrough Transmissibility in Alachua County, Florida. Clin. Infect. Dis. 2022, 75, 1618–1627. [Google Scholar] [CrossRef]
  15. Kang, S.W.; Kim, J.Y.; Park, H.; Lim, S.Y.; Kim, J.; Bae, S.; Jung, J.; Kim, M.J.; Chong, Y.P.; Lee, S.O.; et al. Comparison of outward transmission potential between vaccinated and partially vaccinated or unvaccinated individuals with the SARS-CoV-2 delta variant infection. J. Infect. 2022, 85, e69. [Google Scholar] [CrossRef]
  16. Adams, C.; Chamberlain, A.; Wang, Y.; Hazell, M.; Shah, S.; Holland, D.P.; Khan, F.; Gandhi, N.R.; Fridkin, S.; Zelner, J.; et al. The Role of Staff in Transmission of SARS-CoV-2 in Long-term Care Facilities. Epidemiology 2022, 33, 669–677. [Google Scholar] [CrossRef]
  17. Hayek, S.; Shaham, G.; Ben-Shlomo, Y.; Kepten, E.; Dagan, N.; Nevo, D.; Lipsitch, M.; Reis, B.Y.; Balicer, R.D.; Barda, N. Indirect protection of children from SARS-CoV-2 infection through parental vaccination. Science 2022, 375, 1155–1159. [Google Scholar] [CrossRef]
  18. Puhach, O.; Adea, K.; Hulo, N.; Sattonnet, P.; Genecand, C.; Iten, A.; Jacquérioz, F.; Kaiser, L.; Vetter, P.; Eckerle, I.; et al. Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral, Delta or Omicron SARS-CoV-2. Nat. Med. 2022, 28, 1491–1500. [Google Scholar] [CrossRef]
  19. Abu-Raddad, L.J.; Chemaitelly, H.; Ayoub, H.H.; Tang, P.; Coyle, P.; Hasan, M.R.; Yassine, H.M.; Benslimane, F.M.; Al-Khatib, H.A.; Al-Kanaani, Z.; et al. Relative infectiousness of SARS-CoV-2 vaccine breakthrough infections, reinfections, and primary infections. Nat. Commun. 2022, 13, 532. [Google Scholar] [CrossRef]
  20. Luo, C.H.; Morris, C.P.; Sachithanandham, J.; Amadi, A.; Gaston, D.C.; Li, M.; Swanson, N.J.; Schwartz, M.; Klein, E.Y.; Pekosz, A.; et al. Infection With the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta Variant Is Associated With Higher Recovery of Infectious Virus Compared to the Alpha Variant in Both Unvaccinated and Vaccinated Individuals. Clin. Infect. Dis. 2022, 75, e715–e725. [Google Scholar] [CrossRef]
  21. Muhsen, K.; Maimon, N.; Mizrahi, A.; Bodenneimer, O.; Cohen, D.; Maimon, M.; Grotto, I.; Dagan, R. Effectiveness of BNT162b2 mRNA COVID-19 vaccine against acquisitions of SARS-CoV-2 among health care workers in long-term care facilities: A prospective cohort study. Clin. Infect. Dis. 2022, 75, e755–e763. [Google Scholar] [CrossRef]
  22. Pouwels, K.B.; Pritchard, E.; Matthews, P.C.; Stoesser, N.; Eyre, D.W.; Vihta, K.D.; House, T.; Hay, J.; Bell, J.I.; Newton, J.N.; et al. Effect of Delta variant on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK. Nat. Med. 2021, 27, 2127–2135. [Google Scholar] [CrossRef]
  23. Shrotri, M.; Krutikov, M.; Palmer, T.; Giddings, R.; Azmi, B.; Subbarao, S.; Fuller, C.; Irwin-Singer, A.; Davies, D.; Tut, G.; et al. Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): A prospective cohort study. Lancet. Infect. Dis. 2021, 21, 1529–1538. [Google Scholar] [CrossRef]
  24. Ioannou, P.; Karakonstantis, S.; Astrinaki, E.; Saplamidou, S.; Vitsaxaki, E.; Hamilos, G.; Sourvinos, G.; Kofteridis, D.P. Transmission of SARS-CoV-2 variant B.1.1.7 among vaccinated health care workers. Infect. Dis. 2021, 53, 876–879. [Google Scholar] [CrossRef]
  25. Regev-Yochay, G.; Amit, S.; Bergwerk, M.; Lipsitch, M.; Leshem, E.; Kahn, R.; Lustig, Y.; Cohen, C.; Doolman, R.; Ziv, A.; et al. Decreased infectivity following BNT162b2 vaccination: A prospective cohort study in Israel. Lancet Reg. Health-Eur. 2021, 7, 100150. [Google Scholar] [CrossRef]
  26. Acharya, C.B.; Schrom, J.; Mitchell, A.M.; Coil, D.A.; Marquez, C.; Rojas, S.; Wang, C.Y.; Liu, J.; Pilarowski, G.; Solis, L.; et al. Viral Load Among Vaccinated and Unvaccinated, Asymptomatic and Symptomatic Persons Infected With the SARS-CoV-2 Delta Variant. Open Forum Infect. Dis. 2022, 9, ofac135. [Google Scholar] [CrossRef]
  27. Levine-Tiefenbrun, M.; Yelin, I.; Alapi, H.; Katz, R.; Herzel, E.; Kuint, J.; Chodick, G.; Gazit, S.; Patalon, T.; Kishony, R. Viral loads of Delta-variant SARS-CoV-2 breakthrough infections after vaccination and booster with BNT162b2. Nat. Med. 2021, 27, 2108–2110. [Google Scholar] [CrossRef]
  28. Chia, P.Y.; Ong, S.W.X.; Chiew, C.J.; Ang, L.W.; Chavatte, J.M.; Mak, T.M.; Cui, L.; Kalimuddin, S.; Chia, W.N.; Tan, C.W.; et al. Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: A multicentre cohort study. Clin. Microbiol. Infect. 2022, 28, 612.e1–612.e7. [Google Scholar] [CrossRef]
  29. Fall, A.; Eldesouki, R.E.; Sachithanandham, J.; Morris, C.P.; Norton, J.M.; Gaston, D.C.; Forman, M.; Abdullah, O.; Gallagher, N.; Li, M.; et al. The displacement of the SARS-CoV-2 variant Delta with Omicron: An investigation of hospital admissions and upper respiratory viral loads. EBioMedicine 2022, 79, 104008. [Google Scholar] [CrossRef]
  30. Jung, J.; Kim, J.Y.; Park, H.; Park, S.; Lim, J.S.; Lim, S.Y.; Bae, S.; Lim, Y.-J.; Kim, E.O.; Kim, J.; et al. Transmission and Infectious SARS-CoV-2 Shedding Kinetics in Vaccinated and Unvaccinated Individuals. JAMA Netw. Open 2022, 5, e2213606. [Google Scholar] [CrossRef]
  31. Griffin, J.B.; Haddix, M.; Danza, P.; Fisher, R.; Koo, T.H.; Traub, E.; Gounder, P.; Jarashow, C.; Balter, S. SARS-CoV-2 Infections and Hospitalizations Among Persons Aged ≥16 Years, by Vaccination Status—Los Angeles County, California, May 1-July 25, 2021. MMWR Morb. Mortal. Wkly. Rep. 2021, 70, 1170–1176. [Google Scholar] [CrossRef]
  32. Sriraman, K.; Shaikh, A.; Vaswani, S.; Mestry, T.; Patel, G.; Sakthivel, S.; Oswal, V.; Kadam, P.; Nilgiriwala, K.; Shah, D.; et al. Impact of COVID-19 vaccination on transmission risk of breakthrough infections: Lessons from adapted N95 mask sampling for emerging variants and interventions. J. Med. Virol. 2022, 95, e28188. [Google Scholar] [CrossRef]
  33. Koh, T.; Ooi, X.Y.; Vasoo, S.; Yeo, S.C. Impact of Variant of Concern and Vaccination Status on COVID-19 Infection Virological Dynamics in End Stage Kidney Disease Patients Receiving Haemodialysis. Nephrology 2022, 27, 804–809. [Google Scholar] [CrossRef]
  34. Li, J.; Zhang, Y.; Jiang, L.; Cheng, H.; Li, J.; Li, L.; Chen, Z.; Tang, F.; Fu, Y.; Jin, Y.; et al. Similar aerosol emission rates and viral loads in upper respiratory tracts for COVID-19 patients with Delta and Omicron variant infection. Virol. Sin. 2022, 37, 762–764. [Google Scholar] [CrossRef]
  35. Bollinger, M.; Saile, P.; Shapeton, A.D.; Kohl, M.; Kumle, B. Sensitivity of severe acute respiratory syndrome coronavirus type 2 rapid antigen point-of-care tests in vaccinated patients. Eur. J. Emerg. Med. 2022, 29, 285–290. [Google Scholar] [CrossRef]
  36. Elliott, P.; Haw, D.; Wang, H.; Eales, O.; Walters, C.E.; Ainslie, K.E.C.; Atchison, C.; Fronterre, C.; Diggle, P.J.; Page, A.J.; et al. Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant. Science 2021, 374, eabl9551. [Google Scholar] [CrossRef]
  37. Plante, J.A.; Machado, R.R.G.; Mitchell, B.M.; Shinde, D.P.; Walker, J.; Scharton, D.; McConnell, A.; Saada, N.; Liu, J.; Khan, B.; et al. Vaccination Decreases the Infectious Viral Load of Delta Variant SARS-CoV-2 in Asymptomatic Patients. Viruses 2022, 14, 2071. [Google Scholar] [CrossRef]
  38. Riemersma, K.K.; Haddock, L.A.; Wilson, N.A.; Minor, N.; Eickhoff, J.; Grogan, B.E.; Kita-Yarbro, A.; Halfmann, P.J.; Segaloff, H.E.; Kocharian, A.; et al. Shedding of infectious SARS-CoV-2 despite vaccination. PLoS Pathog. 2022, 18, e1010876. [Google Scholar] [CrossRef]
  39. Caserta, L.C.; Martins, M.; Cronk, B.; Anderson, R.; Eldridge, H.; Gallow, D.; Kruppa, F.; Plocharczyk, E.; Diel, D.G. Infection and Transmission of SARS-CoV-2 B.1.617.2 Lineage (Delta Variant) among Fully Vaccinated Individuals. Microbiol. Spectr. 2022, 10, e0056322. [Google Scholar] [CrossRef]
  40. Altawalah, H.; Alfouzan, W.; Al-Fadalah, T.; Ezzikouri, S. Diagnostic Performance of Automated SARS-CoV-2 Antigen Assay in Nasal Swab during COVID-19 Vaccination Campaign. Diagnostics 2021, 11, 2110. [Google Scholar] [CrossRef]
  41. Bramante, C.T.; Proper, J.L.; Boulware, D.R.; Karger, A.B.; Murray, T.; Rao, V.; Hagen, A.; Tignanelli, C.J.; Puskarich, M.; Cohen, K.; et al. Vaccination Against SARS-CoV-2 Is Associated With a Lower Viral Load and Likelihood of Systemic Symptoms. Open Forum Infect. Dis. 2022, 9, ofac066. [Google Scholar] [CrossRef]
  42. Brown, C.M.; Vostok, J.; Johnson, H.; Burns, M.; Gharpure, R.; Sami, S.; Sabo, R.T.; Hall, N.; Foreman, A.; Schubert, P.L.; et al. Outbreak of SARS-CoV-2 Infections, Including COVID-19 Vaccine Breakthrough Infections, Associated with Large Public Gatherings—Barnstable County, Massachusetts, July 2021. MMWR Morb. Mortal. Wkly. Rep. 2021, 70, 1059–1062. [Google Scholar] [CrossRef]
  43. Laura, L.; Dalmatin-Dragišić, M.; Martinović, K.; Tutiš, B.; Herceg, I.; Arapović, M.; Arapović, J. Does pre-existing immunity determine the course of SARS-CoV-2 infection in health-care workers? Single-center experience. Infection 2023, 51, 323–339. [Google Scholar] [CrossRef]
  44. Colavita, F.; Meschi, S.; Gruber, C.E.M.; Rueca, M.; Vairo, F.; Matusali, G.; Lapa, D.; Giombini, E.; De Carli, G.; Spaziante, M.; et al. Virological and Serological Characterisation of SARS-CoV-2 Infections Diagnosed After mRNA BNT162b2 Vaccination Between December 2020 and March 2021. Front. Med. 2022, 8, 815870. [Google Scholar]
  45. Servellita, V.; Morris, M.K.; Sotomayor-Gonzalez, A.; Gliwa, A.S.; Torres, E.; Brazer, N.; Zhou, A.; Hernandez, K.T.; Sankaran, M.; Wang, B.; et al. Predominance of antibody-resistant SARS-CoV-2 variants in vaccine breakthrough cases from the San Francisco Bay Area, California. Nat. Microbiol. 2022, 7, 277–288. [Google Scholar] [CrossRef]
  46. Hsu, L.; Grüne, B.; Buess, M.; Joisten, C.; Klobucnik, J.; Nießen, J.; Patten, D.; Wolff, A.; Wiesmüller, G.A.; Kossow, A.; et al. COVID-19 breakthrough infections and transmission risk: Real-world data analyses from Germany’s largest public health department (Cologne). Vaccines 2021, 9, 1267. [Google Scholar] [CrossRef]
  47. Kissler, S.M.; Fauver, J.R.; Mack, C.; Tai, C.G.; Breban, M.I.; Watkins, A.E.; Samant, R.M.; Anderson, D.J.; Metti, J.; Khullar, G.; et al. Viral Dynamics of SARS-CoV-2 Variants in Vaccinated and Unvaccinated Persons. N. Engl. J. Med. 2021, 385, 2489–2491. [Google Scholar] [CrossRef]
  48. Meyer, E.D.; Sandfort, M.; Bender, J.; Matysiak-Klose, D.; Dörre, A.; Bojara, G.; Beyrer, K.; Hellenbrand, W. BNT162b2 vaccination reduced infections and transmission in a COVID-19 outbreak in a nursing home in Germany, 2021. Influenza Other Respir. Viruses 2022, 17, e13051. [Google Scholar] [CrossRef]
  49. Levine-Tiefenbrun, M.; Yelin, I.; Alapi, H.; Herzel, E.; Kuint, J.; Chodick, G.; Gazit, S.; Patalon, T.; Kishony, R. Waning of SARS-CoV-2 booster viral-load reduction effectiveness. Nat. Commun. 2022, 13, 1237. [Google Scholar] [CrossRef]
  50. Migueres, M.; Dimeglio, C.; Trémeaux, P.; Raymond, S.; Lhomme, S.; Da Silva, I.; Mendes, K.O.; Abravanel, F.; Félicé, M.P.; Mansuy, J.M.; et al. Influence of the Delta Variant and Vaccination on the SARS-CoV-2 Viral Load. Viruses 2022, 14, 323. [Google Scholar] [CrossRef]
  51. Thompson, M.G.; Yoon, S.K.; Naleway, A.L.; Meece, J.; Fabrizio, T.P.; Caban-Martinez, A.J.; Burgess, J.L.; Gaglani, M.; Olsho, L.E.W.; Bateman, A.; et al. Association of mRNA Vaccination With Clinical and Virologic Features of COVID-19 Among US Essential and Frontline Workers. JAMA 2022, 328, 1523–1533. [Google Scholar] [CrossRef]
  52. Garcia-Knight, M.; Anglin, K.; Tassetto, M.; Lu, S.; Zhang, A.; Goldberg, S.A.; Catching, A.; Davidson, M.C.; Shak, J.R.; Romero, M.; et al. Infectious viral shedding of SARS-CoV-2 Delta following vaccination: A longitudinal cohort study. PLoS Pathog. 2022, 18, e1010802. [Google Scholar] [CrossRef]
  53. Thompson, M.G.; Burgess, J.L.; Naleway, A.L.; Tyner, H.; Yoon, S.K.; Meece, J.; Olsho, L.E.W.; Caban-Martinez, A.J.; Fowlkes, A.L.; Lutrick, K.; et al. Prevention and Attenuation of COVID-19 with the BNT162b2 and mRNA-1273 Vaccines. N. Engl. J. Med. 2021, 385, 320–329. [Google Scholar] [CrossRef]
  54. Maier, H.E.; Plazaola, M.; Lopez, R.; Sanchez, N.; Saborio, S.; Ojeda, S.; Barilla, C.; Kuan, G.; Balmaseda, A.; Gordon, A. SARS-CoV-2 infection-induced immunity and the duration of viral shedding: Results from a Nicaraguan household cohort study. Influenza Other Respir. Viruses 2022, 17, e13074. [Google Scholar] [CrossRef]
  55. Tian, X.; Zhang, Y.; Wang, W.; Fang, F.; Zhang, W.; Zhu, Z.; Wan, Y. The impacts of vaccination status and host factors during early infection on SARS-CoV-2 persistence:a retrospective single-center cohort study. Int. Immunopharmacol. 2022, 114, 109534. [Google Scholar] [CrossRef]
  56. Ke, R.; Martinez, P.P.; Smith, R.L.; Gibson, L.L.; Achenbach, C.J.; McFall, S.; Qi, C.; Jacob, J.; Dembele, E.; Bundy, C.; et al. Longitudinal Analysis of SARS-CoV-2 Vaccine Breakthrough Infections Reveals Limited Infectious Virus Shedding and Restricted Tissue Distribution. Open Forum Infect. Dis. 2022, 9, ofac192. [Google Scholar] [CrossRef]
  57. Kolodziej, L.M.; van Lelyveld, S.F.L.; Haverkort, M.E.; Mariman, R.; Sluiter-Post, J.G.C.; Badoux, P.; de Koff, E.M.; Koole, J.C.D.; Miellet, W.R.; Swart, A.N.; et al. High Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Household Transmission Rates Detected by Dense Saliva Sampling. Clin. Infect. Dis. 2022, 75, e10–e19. [Google Scholar] [CrossRef]
  58. Layan, M.; Gilboa, M.; Gonen, T.; Goldenfeld, M.; Meltzer, L.; Andronico, A.; Hozé, N.; Cauchemez, S.; Regev-Yochay, G. Impact of BNT162b2 Vaccination and Isolation on SARS-CoV-2 Transmission in Israeli Households: An Observational Study. Am. J. Epidemiol. 2022, 191, 1224–1234. [Google Scholar] [CrossRef]
  59. McCormick, D.W.; Konkle, S.L.; Magleby, R.; Chakrabarti, A.K.; Cherney, B.; Lindell, K.; Namageyo-Funa, A.; Visser, S.; Soto, R.A.; Donnelly, M.A.P.; et al. SARS-CoV-2 infection risk among vaccinated and unvaccinated household members during the Alpha variant surge—Denver, Colorado, and San Diego, California, January–April 2021. Vaccine 2022, 40, 4845. [Google Scholar] [CrossRef]
  60. Salo, J.; Hägg, M.; Kortelainen, M.; Leino, T.; Saxell, T.; Siikanen, M.; Sääksvuori, L. The indirect effect of mRNA-based COVID-19 vaccination on healthcare workers’ unvaccinated household members. Nat. Commun. 2022, 13, 1162. [Google Scholar] [CrossRef]
  61. Singanayagam, A.; Hakki, S.; Dunning, J.; Madon, K.J.; Crone, M.A.; Koycheva, A.; Derqui-Fernandez, N.; Barnett, J.L.; Whitfield, M.G.; Varro, R.; et al. Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: A prospective, longitudinal, cohort study. Lancet Infect. Dis. 2022, 22, 183–195. [Google Scholar] [CrossRef]
  62. de Gier, B.; Andeweg, S.; Joosten, R.; ter Schegget, R.; Smorenburg, N.; van de Kassteele, J.; Hahné, S.J.M.; van den Hof, S.; de Melker, H.E.; Knol, M.J.; et al. Vaccine effectiveness against SARS-CoV-2 transmission and infections among household and other close contacts of confirmed cases, The Netherlands, February to May 2021. Eurosurveillance 2021, 26, 2100640. [Google Scholar] [CrossRef]
  63. Lyngse, F.P.; Mølbak, K.; Denwood, M.; Christiansen, L.E.; Møller, C.H.; Rasmussen, M.; Cohen, A.S.; Stegger, M.; Fonager, J.; Sieber, R.N.; et al. Effect of vaccination on household transmission of SARS-CoV-2 Delta variant of concern. Nat. Commun. 2022, 13, 3764. [Google Scholar] [CrossRef]
  64. Baker, J.M.; Shah, M.M.; O’Hegarty, M.; Pomeroy, M.; Keiser, P.; Ren, P.; Weaver, S.C.; Maknojia, S.; Machado, R.R.G.; Mitchell, B.M.; et al. Primary and Secondary Attack Rates by Vaccination Status after a SARS-CoV-2 B.1.617.2 (Delta) Variant Outbreak at a Youth Summer Camp—Texas, June 2021. J. Pediatr. Infect. Dis. Soc. 2022, 11, piac086. [Google Scholar] [CrossRef]
  65. Lyngse, F.P.; Mortensen, L.H.; Denwood, M.J.; Christiansen, L.E.; Møller, C.H.; Skov, R.L.; Spiess, K.; Fomsgaard, A.; Lassaunière, R.; Rasmussen, M.; et al. Household transmission of the SARS-CoV-2 Omicron variant in Denmark. Nat. Commun. 2022, 13, 5573. [Google Scholar] [CrossRef]
  66. De Gier, B.; Andeweg, S.; Backer, J.A.; Hahné, S.J.M.; van den Hof, S.; de Melker, H.E.; Knol, M.J. Vaccine effectiveness against SARS-CoV-2 transmission to household contacts during dominance of Delta variant (B.1.617.2), the Netherlands, August to September 2021. Eurosurveillance 2021, 26, 2100977. [Google Scholar] [CrossRef]
  67. Baker, J.M.; Nakayama, J.Y.; O’Hegarty, M.; McGowan, A.; Teran, R.A.; Bart, S.M.; Mosack, K.; Roberts, N.; Campos, B.; Paegle, A.; et al. SARS-CoV-2 B.1.1.529 (Omicron) Variant Transmission Within Households—Four U.S. Jurisdictions, November 2021–February 2022. Morb. Mortal. Wkly. Rep. 2022, 71, 341–346. [Google Scholar] [CrossRef]
  68. Grüne, B.; Grüne, J.; Kossow, A.; Joisten, C. Vaccination and Transmission Risk during the Outbreak of B.1.1.529 (Omicron). Vaccines 2022, 10, 1003. [Google Scholar] [CrossRef]
  69. Kelly, J.D.; Lu, S.; Anglin, K.; Garcia-Knight, M.; Pineda-Ramirez, J.; Goldberg, S.A.; Tassetto, M.; Zhang, A.; Donohue, K.; Davidson, M.C.; et al. Magnitude and determinants of SARS-CoV-2 household transmission: A longitudinal cohort study. Clin. Infect. Dis. 2022, 75, S193–S204. [Google Scholar] [CrossRef]
  70. Muadchimkaew, M.; Siripongboonsitti, T.; Wongpatcharawarakul, S.; Boonsankaew, C.; Tawinprai, K.; Soonklang, K.; Mahanonda, N. Effect of Inactivated SARS-CoV-2 Vaccines and ChAdOx1 nCoV-19 Vaccination to Prevent COVID-19 in Thai Households (VacPrevent trial). Int. J. Infect. Dis. 2022, 124, 190–198. [Google Scholar] [CrossRef]
  71. Ng, O.T.; Koh, V.; Chiew, C.J.; Marimuthu, K.; Thevasagayam, N.M.; Mak, T.M.; Chua, J.K.; Ong, S.S.H.; Lim, Y.K.; Ferdous, Z.; et al. Impact of Delta Variant and Vaccination on SARS-CoV-2 Secondary Attack Rate Among Household Close Contacts. Lancet Reg. Health West. Pac. 2021, 17, 100299. [Google Scholar] [CrossRef]
  72. Hsu, L.; Hurraß, J.; Kossow, A.; Klobucnik, J.; Nießen, J.; Wiesmüller, G.A.; Grüne, B.; Joisten, C. Breakthrough infections with the SARS-CoV-2 Delta variant: Vaccinations halved transmission risk. Public Health 2022, 204, 40–42. [Google Scholar] [CrossRef]
  73. Puhach, O.; Meyer, B.; Eckerle, I. SARS-CoV-2 viral load and shedding kinetics. Nat. Rev. Microbiol. 2023, 21, 147–161. [Google Scholar] [CrossRef]
  74. Li, D.; Li, A.E.; Li, Z.Q.; Bao, Y.; Liu, T.; Qin, X.R.; Yu, X.J. SARS-CoV-2 Delta Variant in Jingmen City, Hubei Province, China, 2021: Children Susceptible and Vaccination Breakthrough Infection. Front. Microbiol. 2022, 13, 856757. [Google Scholar] [CrossRef]
  75. Woodbridge, Y.; Amit, S.; Huppert, A.; Kopelman, N.M. Viral load dynamics of SARS-CoV-2 Delta and Omicron variants following multiple vaccine doses and previous infection. Nat. Commun. 2022, 13, 6706. [Google Scholar] [CrossRef]
  76. Hawken, S.E.; Sellers, S.A.; Smedberg, J.R.; Ward, J.D.; Elliott, A.M.; Whinna, H.C.; Fischer, W.A.; Miller, M.B. Longitudinal SARS-CoV-2 Testing among the Unvaccinated Is Punctuated by Intermittent Positivity and Variable Rates of Increasing Cycle Threshold Values. Microbiol. Spectr. 2022, 10, e0271521. [Google Scholar] [CrossRef]
  77. Chu, D.K.; Akl, E.A.; Duda, S.; Solo, K.; Yaacoub, S.; Schünemann, H.J.; El-harakeh, A.; Bognanni, A.; Lotfi, T.; Loeb, M.; et al. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: A systematic review and meta-analysis. Lancet 2020, 395, 1973–1987. [Google Scholar] [CrossRef]
  78. Mousa, A.; Winskill, P.; Watson, O.J.; Ratmann, O.; Monod, M.; Ajelli, M.; Diallo, A.; Dodd, P.J.; Grijalva, C.G.; Kiti, M.C.; et al. Social contact patterns and implications for infectious disease transmission—A systematic review and meta-analysis of contact surveys. eLife 2021, 10, e70294. [Google Scholar] [CrossRef]
  79. Tian, D.; Lin, Z.; Kriner, E.M.; Esneault, D.J.; Tran, J.; DeVoto, J.C.; Okami, N.; Greenberg, R.M.; Yanofsky, S.; Ratnayaka, S.; et al. Ct Values Do Not Predict Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmissibility in College Students. J. Mol. Diagn. 2021, 23, 1078–1084. [Google Scholar] [CrossRef]
  80. Boucau, J.; Marino, C.; Regan, J.; Uddin, R.; Choudhary, M.C.; Flynn, J.P.; Chen, G.; Stuckwisch, A.M.; Mathews, J.; Liew, M.Y.; et al. Duration of Shedding of Culturable Virus in SARS-CoV-2 Omicron (BA.1) Infection. N. Engl. J. Med. 2022, 387, 275–277. [Google Scholar] [CrossRef]
  81. Lim, D.S.; Choe, Y.J.; Kim, Y.M.; Lee, S.E.; Jang, E.J.; Kim, J.; Park, Y.-J. Household Secondary Attack Rates of SARS-CoV-2 Omicron Variant, South Korea, February 2022. Emerg. Infect. Dis. 2022, 28, 1731–1734. [Google Scholar] [CrossRef]
  82. Cai, H.; Bai, W.; Liu, S.; Liu, H.; Chen, X.; Qi, H.; Liu, R.; Cheung, T.; Su, Z.; Ng, C.H.; et al. Attitudes Toward COVID-19 Vaccines in Chinese Adolescents. Front. Med. 2021, 8, 691079. [Google Scholar] [CrossRef]
  83. Wright, E.; Pollard, G.; Robertson, H.; Anuradha, S. Household transmission of the Delta COVID-19 variant in Queensland, Australia: A case series. Epidemiol. Infect. 2022, 150, e173. [Google Scholar] [CrossRef]
  84. Freeman, D.; Loe, B.S.; Chadwick, A.; Vaccari, C.; Waite, F.; Rosebrock, L.; Jenner, L.; Petit, A.; Lewandowsky, S.; Vanderslott, S.; et al. COVID-19 vaccine hesitancy in the UK: The Oxford coronavirus explanations, attitudes, and narratives survey (Oceans) II. Psychol. Med. 2022, 52, 3127–3141. [Google Scholar] [CrossRef]
  85. Hall, P.A.; Meng, G.; Sakib, M.N.; Quah, A.C.K.; Agar, T.; Fong, G.T. Do the vaccinated perform less distancing, mask wearing and hand hygiene? A test of the risk compensation hypothesis in a representative sample during the COVID-19 pandemic. Vaccine 2022, 41, 4027–4030. [Google Scholar] [CrossRef]
  86. Mongin, D.; Bürgisser, N.; Laurie, G.; Schimmel, G.; Vu, D.L.; Cullati, S.; Courvoisier, D.S. Effect of SARS-CoV-2 prior infection and mRNA vaccination on contagiousness and susceptibility to infection. Nat. Commun. 2023, 14, 5452. [Google Scholar] [CrossRef]
  87. Sette, A.; Crotty, S. Immunological memory to SARS-CoV-2 infection and COVID-19 vaccines. Immunol. Rev. 2022, 310, 27–46. [Google Scholar] [CrossRef]
  88. Voysey, M.; Clemens, S.A.C.; Madhi, S.A.; Weckx, L.Y.; Folegatti, P.M.; Aley, P.K.; Angus, B.; Baillie, V.L.; Barnabas, S.L.; Bhorat, Q.E.; et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021, 397, 99–111. [Google Scholar] [CrossRef]
  89. Baden, L.R.; El Sahly, H.M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.; Creech, C.B.; et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N. Engl. J. Med. 2021, 384, 403–416. [Google Scholar] [CrossRef]
  90. Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Pérez Marc, G.; Moreira, E.D.; Zerbini, C.; et al. Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine. N. Engl. J. Med. 2020, 383, 2603–2615. [Google Scholar] [CrossRef]
  91. Logunov, D.Y.; Dolzhikova, I.V.; Shcheblyakov, D.V.; Tukhvatulin, A.I.; Zubkova, O.V.; Dzharullaeva, A.S.; Kovyrshina, A.V.; Lubenets, N.L.; Grousova, D.M.; Erokhova, A.S.; et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: An interim analysis of a randomised controlled phase 3 trial in Russia. Lancet 2021, 397, 671–681. [Google Scholar] [CrossRef]
  92. Kampf, G. The epidemiological relevance of the COVID-19-vaccinated population is increasing. Lancet Reg. Health Eur. 2021, 11, 100272. [Google Scholar] [CrossRef]
  93. UK Health Security Agency. COVID-19 Vaccine Surveillance Report—Week 13. Available online: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1066759/Vaccine-surveillance-report-week-13.pdf (accessed on 20 December 2023).
Hygiene 04 00003 g001
Figure 1. Flow diagram of the study selection, exclusion and inclusion within the systematic review (PRISMA).
Figure 1. Flow diagram of the study selection, exclusion and inclusion within the systematic review (PRISMA).
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Table 1. Ct values from respiratory tract samples of COVID-19 cases according to their vaccination status and the SARS-CoV-2 variant (different data sets may be derived from the same study).
Table 1. Ct values from respiratory tract samples of COVID-19 cases according to their vaccination status and the SARS-CoV-2 variant (different data sets may be derived from the same study).
SARS-CoV-2 VariantType of GeneSampling Period (Country)Type of PopulationCt Values According to Number of Applied Vaccine Doses (Number of Samples)p-ValueSource
None1 Dose2 Doses3 Doses
Ancestral variantE gene4/20–9/20 (Switzerland)Any individual with symptoms13.9–26.6 * (118)----[18]
Mainly betaN, ORF1ab and S gene2/20–7/21 (Qatar)General population24.0 [95% CI: 23.8–24.2] ** (4035)-25.0 [95% CI: 24.8–25.2] ** (4035 #)-<0.001[19]
Mainly betaN, ORF1ab and S gene2/20–7/21 (Qatar)General population26.8 [95% CI: 25.9–27.6] ** (265)-30.3 [95% CI: 29.6–31.0] ** (265 ##)-<0.001[19]
AlphaN gene1/21–9/21 (USA)PatientsApprox. 20.9 *** (470)-Approx. 21.0 *** (94)-n.s.[20]
AlphaORF1ab gene9/20–1/21 (Israel)Healthcare workers26.7 [IQR: approx. 23–31] *** (40) 32.0 [IQR: approx. 28–33.5] *** (20) 0.008[21]
Alpha B.1.1.7N, ORF1ab and S gene12/10–5/21 (UK)General population28.7 [IQR: 20.4–32.9] *** (10,853)31.6 (IQR: 26.6–33.7] *** (577)33.3 [IQR: 31.6–34.0] *** (56)--[22]
Alpha B.1.1.7Various genes ###12/20–3/21 (UK)Nursing home residents26.6 [95% CI: 26.0–27.1] ** (552)25.9 [95% CI: 25.2–26.6] ** (411; 0–27 days after vaccination with dose 1)--0.158[23]
Alpha B.1.1.7Various genes ###12/20–3/21 (UK)Nursing home residents26.6 [95% CI: 26.0–27.1] ** (552)31.3 [95% CI: 29.6–33.0] ** (107; ≥28 days after vaccination with dose 1)--<0.0001[23]
Mainly alphaN, ORF1ab and S gene1/21–4/21 (Greece)Healthcare workers18.5 [IQR: 13.5–24.0] *** (31)-18.5 [IQR: 16.0–26.0] *** (24)-0.70[24]
Mainly alphaN gene12/20–3/21 (Israel)Healthcare workers22.2 [SD: 1.0] *** (163) 27.3 [SD: 2.2] *** (31) <0.001[25]
DeltaE gene6/21–12/21 (Switzerland)Any individual with symptoms13.8–26.3 * (127)-16.3–26.1 * (104)-0.0002[18]
DeltaN gene6/21–8/21 (USA)General population23.4 [IQR: approx. 19.0–28.5] *** (198)-23.1 [IQR: approx. 17.0–27.0] *** (171)-0.54[26]
DeltaN gene6/21–8/21 (USA)General population (HYT cohort)25.4 [IQR: approx. 23.0–28.0] *** (375)-25.5 [IQR: approx. 23.0–29.0] *** (125)-0.80[26]
DeltaN gene1/21–9/21 (USA)PatientsApprox. 21 *** (134) 20.5 *** (117) n.s.[20]
DeltaRdRp gene6/21–9/21 (Israel)Patients27.7 [SD: 5.0] ** (3100) 26.9 [SD: 5.0] ** (12,934)29.1 [SD: 4.7] ** (519)<0.05
(0 versus 2 doses)
<0.001
(0 versus 3 doses)		[27]
DeltaN gene6/21–9/21 (Israel)Patients25.1 [SD: 5.0] ** (3100) 25.4 [SD: 5.0] ** (12,934)27.5 [SD: 4.7] ** (519)<0.05
(0 versus 2)
<0.001
(0 versus 3)		[27]
DeltaE gene6/21–9/21 (Israel)Patients22.7 [SD: 4.9] ** (3100) 22.9 [SD: 4.9] ** (12,934)25.2 [SD: 4.6] ** (519)n.s.
(0 versus 2)
<0.001
(0 versus 3)		[27]
Delta B.1.617.2 (early period)N, ORF1ab and S gene12/10–5/21 (UK)General population21.5 [IQR: 16.4–31.7] *** (75)30.1 [IQR: 18.6–31.7] *** (110)32.2 [IQR: 26.0–34.0] *** (104)--[22]
Delta B.1.617.2 (late period)N, ORF1ab and S gene12/10–5/21 (UK)General population25.7 [IQR: 19.1–30.8] *** (326)24.7 [IQR: 18.8–31.3] *** (705)25.3 [IQR: 19.1–31.3] *** (1593)--[22]
DeltaN and S gene4/21–6/21 (Singapore)Patients18.8 [IQR: 14.9–22.7] *** (130)-19.2 [IQR: 15.2–22.2] *** (71)-0.929[28]
DeltaN gene11/21–12/21 (USA)PatientsApprox. 18.5
[IQR: approx. 15.0–21.5] *** (400)		-Approx. 17
[IQR: approx. 15.0–21.0] *** (230)		-n.s.[29]
Mainly deltaN and S gene3/20–11/21 (Republic of Korea)Healthcare worker, inpatients, caregivers20 [IQR: 15.0–29.0] *** (109)-19 [IQR: 16.0–24.0] *** (45)-0.64[30]
Mainly delta (May 2021)ORF1ab gene
N gene		5/21–7/21 (USA)General population22.8 [IQR: approx. 18.0–31.0] *** (-)
24.0 [IQR: approx. 18.0–33.0] *** (-)		36.6 [IQR: approx. 28.0–37.0] *** (-)
36.0 [IQR: approx. 33.0–37.0] *** (-)		27.7 [IQR: approx. 23.0–37.0] *** (-)
30.6 [IQR: approx. 23.0–36.0] *** (-)		-
-		-
-		[31]
Mainly delta (July 2021)ORF1ab gene
N gene		5/21–7/21 (USA)General population18.8 [IQR: approx. 16.0–24.0] *** (-)
19.3 [IQR: approx. 16.0–25.0] *** (-)		17.8 [IQR: approx. 16.0–23.0] *** (-)
18.6 [IQR: approx. 14.0–29.0] *** (-)		19.0 [IQR: approx. 15.0–26.0] *** (-)
19.5 [IQR: approx. 16.0–23.0] *** (-)		-
-		-
-		[31]
Mainly deltaN and O genes7/21–9/21 (India)Patients24 [IQR: 20.5–28.6] *** (14)19 [IQR: 17.0–23.0] *** (31)21 [IQR: 16.0–24.0] *** (50)--[32]
DeltaN and S gene7/21–11/21 (Republic of Korea)Healthcare worker, inpatients, caregivers25 [IQR: 18.0–32.0] *** (28)-19 [IQR: 16.0–26.0] *** (44)-0.04[30]
DeltaNot described2/20–9/21 (Singapore)Hemodialysis patients19.0 [SD: 3.0] ** (10)-17.0 [SD: 3.5] ** (24)-0.37[33]
DeltaORF1ab gene2021 (China)PatientsApprox. 28 [SD: approx. 7.5] ** (14)-Approx. 26 [SD: approx. 6.5] ** (6)-0.528[34]
DeltaN gene2021 (China)PatientsApprox. 27 [SD: approx. 7.5] ** (14)-Approx. 25 [SD: approx. 7.5] ** (6)-0.427[34]
DeltaN gene11/21 (Germany)Patients23.2 [SD: 6.0] ** (107)-27.5 [SD: 6.1] ** (127)-0.012[35]
DeltaORF1a region11/21 (Germany)Patients22.9 [SD: 6.1] ** (107)-27.0 [SD: 6.0] ** (127)-0.019[35]
DeltaN1 gene11/21 (Germany)Patients24.4 [SD: 6.7] ** (107)-23.8 [SD: 5.8] ** (127)-0.80[35]
DeltaN2 gene11/21 (Germany)Patients26.1 [SD: 5.8] ** (107)-25.5 [SD: 5.0] ** (127)-0.42[35]
DeltaE gene11/21 (Germany)Patients24.6 [SD: 6.0] ** (107)-23.8 [SD: 4.9] ** (127)-0.37[35]
DeltaN gene6/21–7/21 (UK)General population23.1 [95% CI: 20.3–25.8] **** (28)27.4 [95% CI: 24.8–30.0] **** (76)27.6 [95% CI: 25.5–29.7] **** (145)-0.01
(2 versus 0)
0.04
(1 versus 0)		[36]
DeltaS gene6/21–8/21 (USA)General population and patients19.0 [SD: 3.0] ** (59)-20.0 [SD: 3.5] ** (28)-n.s.[37]
DeltaN gene6/21–12/21 (USA)General population22.9 [95% CI: 22.8–23.0] ** (11,084)-22.1 [95% CI: 22.0–23.2] ** (9347)-<0.0001[38]
DeltaNot described7/21–8/21 (USA)PatientsApprox. 23 *** (25) ####-Approx. 24 *** (47)-n.s.[39]
DeltaRdRp/ORF1ab gene9/21–10/21 (Republic of Korea)Healthcare workers (61), inpatients (18), caregivers (15) in an outbreak situation19.9 [SD: 5.4] ** (24)-20.9 [SD: 6.3] ** (70)-0.52[10]
Mainly deltaN gene5/21–7/21 (Kuwait)General population19.7 [range: approx. 13.0–33.0] *** (91)-19.6 [range: approx. 10.0–33.0] *** (59)-0.42[40]
Mainly deltaN genes12/20–9/21 (USA)General population23.1 [IQR: 19.4–29.0] *** (160)-25.8 [IQR: 20.6–31.2] *** (112)-0.02[41]
Mainly deltaNot described7/21 (USA)General population21.5 [IQR: approx. 19.0–26.0] *** (84) ##### 22.8 [IQR: approx. 18.0–27.0] *** (127) n.s.[42]
OmicronN gene11/21–12/21 (USA)PatientsApprox. 18.4
[IQR: approx.16.0–22.0] *** (166)		-Approx. 17
[IQR: approx. 15.0–19.0] *** (229)		-n.s.[29]
Omicron BA.1E gene12/21–2/22 (Switzerland)Any individual with symptoms16.6–26.7 * (33)-14.6–26.7 * (121) ***** n.s.[18]
Mainly omicronRdRp gene1/22 (Bosnia and Herzegovina)Healthcare workers (141)Approx. 32.0
[IQR: approx. 28.0–34.0] *** (44)		-Approx. 30.5
[IQR: approx. 27.5–33.0] (26)		-n.s.[43]
Mainly omicronE gene1/22 (Bosnia and Herzegovina)Healthcare workers (141)Approx. 27.5
[IQR: approx. 22.0–29.0] *** (44)		-Approx. 24.0
[IQR: approx. 22.0–27.0] (26)		-n.s.[43]
Mainly omicronN gene1/22 (Bosnia and Herzegovina)Healthcare workers (141)Approx. 28.0
[IQR: approx. 26.0–32.0] *** (44)		-Approx. 27.0
[IQR: approx. 25.5–30.5] (26)		-n.s.[43]
Multiple variantsORF1ab gene12/20–3/21 (Italy)General population19.4 [IQR: 18.0–28.7] *** (31)-21.2 [IQR: 17.5–31.3] *** (54)-0.20[44]
Multiple variantsN gene2/21–6/21 (USA)General population and patients23.1 ** (1061)-23.1 ** (121) 0.99[45]
Multiple variantsNot described12/20–8/21 (Germany)General population, index cases25.7 [SD: 6.6] ** (287)-29.5 [SD: 7.5] ** (300)-<0.001[46]
Multiple variantsNot described12/20–8/21 (Germany)General population, contact persons of index cases25.6 [SD: 6.5] ** (270)-26.2 [SD: 7.3] ** (56)-0.599[46]
Multiple variantsNot described11/20–8/21 (USA)Participants of the occupational health program of the National Basketball Association, infected upon inclusion20.7 [95% CI: 19.8–20.2] ** (136)-20.5 [95% CI: 19.0–21.0] ** (37)-n.s.[47]
* range; ** mean with 95% confidence interval (95% CI) or standard deviation (SD); *** median with interquartile range (IQR); **** comparison between unvaccinated, partly vaccinated and fully vaccinated; ***** with 30 boosted subjects; # vaccinated with BNT162b2; ## vaccinated with mRNA 1273; ### data from 13 laboratories using 6 different validated assays; #### includes unvaccinated and not fully vaccinated; ##### includes unvaccinated, not fully vaccinated and whose vaccination status was unknown; patients were defined as those who are treated in hospitals (inpatients) or asked for medical treatment (outpatients); n.s. = not significant.
Table 3. Log10 infectious virus titer per ml from respiratory tract samples of COVID-19 cases according to the vaccination status and the SARS-CoV-2 variant.
Table 3. Log10 infectious virus titer per ml from respiratory tract samples of COVID-19 cases according to the vaccination status and the SARS-CoV-2 variant.
SARS-CoV-2 VariantSampling Period (Country)Type of PopulationLog10 Infectious Virus Titer per ml According to Vaccination Status (Number of Samples)p-ValueSource
None1 Dose2 Doses3 Doses
Delta6/21–12/21 (Switzerland)Any individual with symptomsApprox. 2.5 [SD: 1.2] * (127)-Approx. 1.7 [SD: 1.3] * (104)-<0.0001[18]
Delta6/21–8/21 (USA)PatientsApprox. 2.9 [SD: approx. 1.0] * (59)-Approx. 2.4 [SD: approx. 1.0] * (28)-<0.05[37]
Delta12/20–4/22 (USA)Healthcare workers, essential frontline workers, uninfected upon inclusion4.8 * (36)-3.8 * (9) #
4.1 * (61) ##		3.1 * (10)n.s.
“significant”
“significant”		[51]
Delta6/21–12/21 (USA)General populationApprox. 2.3 ** (24)-Approx. 2.4 ** (23)-n.s.[38]
Omicron BA.112/21–2/22 (Switzerland)Any individual with symptomsApprox. 1.6 [SD: 1.2] ** (33)-Approx. 1.7 [SD: 1.2] ** (91)Approx. 0.9 [SD: 0.9] ** (30)0.038[18]
Multiple variants9/20–10/21 (USA)General population, infected non-hospitalized3.9 [IQR: 0.0–5.4] ** (52)-3.2 [IQR: 0.0–6.1] ** (32)-0.60[52]
* mean with standard deviation (SD); ** median with interquartile range (IQR); # received 2nd dose 14–149 days before infection; ## received 2nd dose ≥ 150 days before infection; patients were defined as those who are treated in hospitals (inpatients) or asked for medical treatment (outpatients); n.s. = not significant.
Table 4. Duration of SARS-CoV-2 gene detection from respiratory tract samples of COVID-19 cases according to the vaccination status and the SARS-CoV-2 variant.
Table 4. Duration of SARS-CoV-2 gene detection from respiratory tract samples of COVID-19 cases according to the vaccination status and the SARS-CoV-2 variant.
SARS-CoV-2 VariantType of GeneSampling Period (Country)Type of PopulationDuration of SARS-CoV-2 Detection (Days) According to Vaccination Status (Number of Samples)p-ValueSource
None1 Dose2 DosesPrior Infection
DeltaNot described2/20–9/21 (Singapore)Hemodialysis patients32 [IQR: 30.0–34.0] * # (10)-24 [IQR: 21.0–26.0] * # (24)-<0.01[33]
DeltaN and S gene9/21–1/22 (Republic of Korea)Patients, infected upon inclusion->26 [95% CI: 18–NA] * (30) **15 [95% CI: 12–NA] * (19)-0.15[15]
DeltaN and S gene3/20–11/21 (Republic of Korea)Patients≥10 (28)≥10 (11)≥ 10 (6)-n.s.[30]
Multiple variantsORF1ab, N and S gene12/20–4/21 USA)Healthcare workers, essential frontline workers, uninfected upon inclusion8.9 [SD: 10.2] *** (155)2.7 [SD: 3.0] *** (16) ****--significant[53]
Multiple variantsNot described11/20–8/21 (USA)Participants of the occupational health program of the National Basketball Association7.5 [95% CI: 6.8–8.2] *** (136)-5.5 [95% CI: 4.6–6.5] *** (37)-significant[47]
Multiple variantsN and E genes9/20–10/21 (USA)General population, infected non-hospitalized9.0 [IQR: 7.0–12.0] * (52)-8.0 [IQR: 4.5–12.0] * (32)-0.52[52]
Multiple variantsORF1ab and N gene5/20–3/22 (Nicaragua)General population28.2 [IQR: 16.5–43.1] *-12.9 [IQR: 7.6–19.8] * significant[54]
Multiple variantsORF1ab and N gene1/20–1/22 (China)Hospitalized patients19.0 [IQR: 12.0–24.5] * (171) *****
Approx. 16 * ******		-17.0 [IQR: 12.3–19.5] * (165) *****
Approx. 16 * ******		-0.038
-		[55]
* median with interquartile range (IQR) or 95% confidence interval (95% CI); ** partly vaccinated and unvaccinated; *** mean with standard deviation (SD) or 95% confidence interval (95% CI); **** at least 1 dose; ***** moderate COVID-19; ****** mild COVID-19; # two negative swabs at least 24 h apart; patients were defined as those who are treated in hospitals (inpatients) or asked for medical treatment (outpatients); n.s. = not significant.
Table 5. Duration of detection of infectious SARS-CoV-2 from respiratory tract samples of COVID-19 cases according to the vaccination status.
Table 5. Duration of detection of infectious SARS-CoV-2 from respiratory tract samples of COVID-19 cases according to the vaccination status.
SARS-CoV-2 VariantSampling Period (Country)Type of PopulationDuration of SARS-CoV-2 Detection (Days) According to Vaccination Status (Number of Samples)p-ValueSource
None1 Dose2 Doses
Delta9/21–1/22 (Republic of Korea)Patients, infected upon inclusion-11 [95% CI: 9.0–15.0] * (30) **5 [95% CI: 4.0–NA] * (19)0.0013[15]
Delta3/20–11/21 (Republic of Korea)Inpatients-4.4 [95% CI: 2.0–7.0] * (39) **1.8 [95% CI: 1.0–NA] * (6)0.42[30]
Multiple variants9/20–10/21 (USA)General population, infected non-hospitalized7.0 [IQR: 0.0–8.0] * (52)-5.0 [IQR: 0.0–7.0] * (32)0.12[52]
Multiple variants12/20–3/21 (USA)Students and university staff who tested positive2.8 *** (70)-0.8 *** (12)< 0.01[56]
* median; ** partly vaccinated and unvaccinated; *** mean.
Table 7. Ct values from respiratory tract samples of unvaccinated COVID-19 cases having a reinfection compared unvaccinated COVID-19 cases (primary infection) and to fully vaccinated COVID-19 cases with a breakthrough infection.
Table 7. Ct values from respiratory tract samples of unvaccinated COVID-19 cases having a reinfection compared unvaccinated COVID-19 cases (primary infection) and to fully vaccinated COVID-19 cases with a breakthrough infection.
SARS-CoV-2 VariantNumber of Samples (Reinfection in Unvaccinated)Type of ControlNumber of Samples from ControlType of GeneCt Values (Reinfection in Unvaccinated)Ct Values (Control Group)p-ValueSource
Mainly beta1686Primary infection in unvaccinated1686N, ORF1ab and S gene29.9 * [IQR: 22.3–33.5]23.6 * [IQR: 18.5–29.9]<0.001[19]
Mainly beta761BNT162b2 breakthrough infections761N, ORF1ab and S gene29.5 * [IQR: 22.0–33.4]26.4 * [IQR: 20.2–31.9]<0.001[19]
Mainly beta85mRNA-1273 breakthrough infections85N, ORF1ab and S gene33.0 * [IQR: 29.4–34.4]31.6 * [IQR: 24.1–34.2]<0.001[19]
Alpha B.1.1.768Primary infection in unvaccinated10,853N, ORF1ab and S gene32.8 * [IQR: 30.9–34.2]28.7 * [IQR: 20.4–32.9]-[22]
Alpha B.1.1.768BNT162b2 and ChAdOx1 breakthrough infections56N, ORF1ab and S gene32.8 * [IQR: 30.9–34.2]33.3 * [IQR: 31.6–34.0]-[22]
Delta B.1.617.2 (early period)5Primary infection in unvaccinated75N, ORF1ab and S gene30.8 * [IQR: 29.5–34.3]21.5 * [IQR: 16.4–31.7]-[22]
Delta B.1.617.2 (early period)5BNT162b2 and ChAdOx1 breakthrough infections104N, ORF1ab and S gene30.8 * [IQR: 29.5–34.3]32.2 * [IQR: 26.0–34.0]-[22]
Delta B.1.617.2 (late period)20Primary infection in unvaccinated326N, ORF1ab and S gene22.3 * [IQR: 16.5–30.3]25.7 * [IQR: 19.1–30.8]-[22]
Delta B.1.617.2 (late period)20BNT162b2 and ChAdOx1 breakthrough infections1593N, ORF1ab and S gene22.3 * [IQR: 16.5–30.3]25.3 * [IQR: 19.1–31.3]-[22]
Multiple variants443 **Primary infection in mostly unvaccinated302 ***ORF1ab and N gene29.8 ****28.0 ****0.0004[54]
* median with interquartile ranges (IQR); ** 49 subjects (11.1%) were fully vaccinated *** 4 subjects (1.3%) were fully vaccinated; **** mean.
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Kampf, G. Does COVID-19 Vaccination Protect Contact Persons? A Systematic Review. Hygiene 2024, 4, 23-48. https://doi.org/10.3390/hygiene4010003

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Kampf G. Does COVID-19 Vaccination Protect Contact Persons? A Systematic Review. Hygiene. 2024; 4(1):23-48. https://doi.org/10.3390/hygiene4010003

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Kampf, Günter. 2024. "Does COVID-19 Vaccination Protect Contact Persons? A Systematic Review" Hygiene 4, no. 1: 23-48. https://doi.org/10.3390/hygiene4010003

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