Clinical Microbiology and Infection

BackgroungTo cope with the persistence of the Covid-19 epidemic and the decrease in antibody levels following vaccination, a third dose of vaccine has been recommended in the general population. However, several vaccine regimens had been used initially, and the heterologous ChadOx1-S/BNT162b2 regimen had shown better efficacy and immunogenicity than the homologous BNT162b2/BNT162b2 regimen. AimWe wanted to determine if this benefit was retained after the third dose. MethodsWe combined an observational study of SARS-COV-2 infections among vaccinated healthcare workers at the University-Hospital of Lyon, France, with an analysis of immunological parameters before and after the third mRNA vaccine dose. ResultsFollowing the second vaccine dose, heterologous vaccination regimens were more protective against infection than homologous regimens, but this was no longer the case after the third dose. RBD-specific IgG levels and serum neutralization capacity against different SARS-CoV-2 variants were higher after the third dose than after the second dose in the homologous regimen group, but not in the heterologous group. ConclusionThe advantage conferred by heterologous vaccination is lost after the third dose both in terms of protection and immunogenicity. Immunological measurements suggest that heterologous vaccination induces maximal immunity after the second dose, whereas the third dose is required to reach the same level in individuals with a homologous regimen.

A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. During the study period (November 2022-January 2024), 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p=0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p=0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Day-28 mortality of JN.1-infected patients was 14.6%.

ObjectivesWe aimed to determine risk factors for the development of long coronavirus disease (COVID) in healthcare workers (HCWs). MethodsWe conducted a case-control study among HCWs who had confirmed COVID-19 infection working in a Brazilian healthcare system between March 1, 2020 and July 15, 2022. Cases were defined as those having long COVID per the Centers for Disease Control and Prevention definition. Controls were defined as HCWs who had documented COVID-19 infection but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up. ResultsOf 7,051 HCWs diagnosed with COVID-19 infection, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with development of long COVID were female sex (OR 1.21 [CI95 1.05-1.39]), age (OR 1.01 [CI95 1.00-1.02]), and two or more COVID-19 infections (1.27 [CI95 1.07-1.50]). Those infected with the Delta variant (OR 0.30 [CI95 0.17-0.50]) or the Omicron variant (OR 0.49 [CI95 0.30-0.78]), and those receiving four COVID-19 vaccine doses prior to infection (OR 0.05 [CI95 0.01-0.19]) were significantly less likely to develop long COVID. ConclusionsLong COVID can be prevalent among HCWs. We found that acquiring more than one COVID-19 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.

BackgroundThe SARS-CoV-2 Delta variant (B.1.617.2), initially identified in India, has become predominant in several countries, including Portugal. Few studies have compared the effectiveness of mRNA vaccines against Delta versus Alpha variant of concern (VOC) and estimated variant-specific viral loads in vaccine infection breakthroughs cases. In the context of Delta dominance, this information is critical to inform decision-makers regarding the planning of restrictions and vaccination roll-out. MethodsWe developed a case-case study to compare mRNA vaccines effectiveness against Delta (B.1.617.2) versus Alpha (B.1.1.7) variants. We used RT-PCR positive cases notified to the National Surveillance System between 17th of May and 4th of July 2021 (week 20 to 26) and information about demographics and vaccination status through the electronic vaccination register. Whole-genome sequencing (WGS) or spike (S) gene target failure (SGTF) data were used to classify SARS-CoV-2 variants. The odds of vaccinated individuals to become infected (odds of vaccine infection breakthrough) in Delta cases compared to Alpha SARS-CoV-2 cases was estimated by conditional logistic regression adjusted for age group, sex, and matched by the week of diagnosis. As a surrogate of viral load, mean RT-PCR Ct values were stratified and compared between vaccine status and VOC. ResultsOf the 2 097 SARS-CoV-2 RT-PCR positive cases included in the analysis, 966 (46.1%) were classified with WGS and 1131 (53.9%) with SGTF. Individuals infected with the Delta variant were more frequently vaccinated 162 (12%) than individuals infected with the Alpha variant 38 (5%). We report a statistically significant higher odds of vaccine infection breakthrough for partial (OR=1.70; CI95% 1.18 to 2.47) and complete vaccination (OR=1.96; CI95% 1.22 to 3.14) in the Delta cases when compared to the Alpha cases, suggesting lower mRNA vaccine effectiveness against Delta cases. On our secondary analysis, we observed lower mean Ct values for the Delta VOC cases versus Alpha, regardless the vaccination status. Additionally, the Delta variant cases revealed a Ct-value mean increase of 2.24 (CI95% 0.85 to 3.64) between unvaccinated and fully vaccinated breakthrough cases contrasting with 4.49 (CI95% 2.07 to 6.91) in the Alpha VOC, suggesting a lower impact of vaccine on viral load of Delta cases. ConclusionsWe found significantly higher odds of vaccine infection breakthrough in Delta cases when compared to Alpha cases, suggesting lower effectiveness of the mRNA vaccines in preventing infection with the Delta variant. Additionally, the vaccine breakthrough cases are estimated to be of higher mean Ct values, suggesting higher infectiousness with the Delta variant infection. These findings can help decision-makers weigh on the application or lifting of control measures and adjusting vaccine roll-out depending on the predominance of the Delta variant and the coverage of partial and complete mRNA vaccination.

BackgroundA comprehensive assessment of COVID-19 in healthcare workers (HCWs) including the investigation of viral shedding duration is critical. MethodsA longitudinal study including 319 HCWs was conducted. After SARS-CoV-2 screening with RT-PCR assay, other respiratory pathogens were tested with a multiplex molecular panel. For SARS-CoV-2 positive HCWs, the normalized viral load was determined weekly; viral culture and virus neutralization assays were also performed. For 190 HCWs tested negative, SARS-CoV-2 serological testing was performed one month after the inclusion. FindingsOf the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; two of them developed severe COVID-19. The proportion of smell and taste dysfunction was significantly higher in SARS-CoV-2 positive HCWs than in negative ones (38.8% vs 9.5% and 37.3% vs 10.7%, respectively, p<0.001). Of the 67 positive patients, 9.1% were tested positive for at least another respiratory pathogen (vs 19.5%, p=0.07). The proportion of HCWs with a viral load > 5.0 log10 cp/ml (Ct value <25) was less than 15% at 8 days after symptom onset; 12% of them were still positive after 40 days (Ct >37). More than 90% of culturable virus had a viral load > 4.5 log10 cp/ml (Ct < 26) and were collected within 10 days after symptom onset. From HCWs tested negative, 6/190 (3.2%) exhibited seroconversion for IgG antibodies. InterpretationOur data suggest that the determination of normalized viral load (or its estimation through Ct values) can be useful for discontinuing isolation of HCWs and facilitating their safe return to work. HCWs presenting mild COVID-19 are unlikely infectious 10 days after symptom onset. FundingFondation des Hospices Civils de Lyon. bioMerieux provided diagnostic kits.

IntroductionHealthcare workers (HCW) were amongst the first prioritized for COVID-19 vaccination but data on COVID-19 vaccine effectiveness among HCW is still limited. This study aims to estimate the COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 symptomatic infection among HCW from Portuguese hospitals. MethodsIn this prospective cohort study, we analysed data from HCW (all professional categories) from two central hospitals in the Lisbon and Tagus Valley and Centre regions of mainland Portugal between December 2020 and November 2021. VE against symptomatic SARS-CoV-2 infection was estimated as one minus the confounder adjusted hazard ratios by Cox models considering age group, sex, presence of chronic disease and occupational exposure to patients diagnosed with COVID-19 as adjustment variables. ResultsDuring the 11 months of follow up, the 2213 HCW contributed a total of 1950 person-years at risk and 171 SARS-CoV-2 events occurred. The COVID-19 incidence rate for unvaccinated HCW was 348.7 per 1000 person-years while for fully vaccinated HCW was 43.0 per 1000 person-years. We observed a VE against symptomatic SARS-CoV-2 infection of 73.9% (95% CI: 26.2-90.8%) for complete vaccination status. ConclusionThis cohort study found a high COVID-19 VE against symptomatic SARS-CoV-2 infection in Portuguese HCW, which is in concordance with previous studies from other countries. Monitoring of VE in this HCW cohort continues during the winter 2021/2022 to evaluate potential VE decay and booster vaccine effect.

BackgroundOn January 31st the first case of COVID-19 was detected in Spain, an imported case from Germany in Canary Islands, and thereafter on February 25th the first case was detected in Madrid. The first case of COVID-19 was confirmed at the Hospital Universitario 12 de Octubre on March 1st, a large public hospital with 1200 beds, covering an area over 400000 inhabitants in southern Madrid. During March 2020 highly active circulation of SARS-CoV-2 was experienced in Madrid with 24090 cases officially reported by March 29th. MethodsSince the beginning of the epidemics the Occupational Health and Safety Service (OHSS) organized the consulting and testing of the hospital personnel with confirmed exposure and also those presenting symptoms suggestive of viral respiratory infection. For molecular diagnosis of SARS-CoV-2 infection both nasopharyngeal and oropharyngeal swabs were obtained from suspected cases and processed at the Microbiology Laboratory by automatized specific PCR methods that was operative from February 25th as part of the preparedness. ResultsFrom a total of 6800 employees of the hospital, 2085 (30,6 %) were tested during the period 1-29 March 2020, some of them repeatedly (2286 total samples). The first HCW infected was confirmed on March 9th. A total of 791 HCW and personnel were confirmed to be infected by March 29th, representing 38% of those tested and 11,6 % of all the hospital workers. The proportion of infected individuals was estimated among the different groups of occupational exposure and the evolution of the cases during the expansive epidemic wave was compared between HCW and those patients attending at the Emergency Department (ER) during the same period and adjusted by the same age range. There were no statistically significant differences in the proportion of SARS- CoV-2 positive PCR detection between HCW from high risk areas involved in close contact with COVID-19 patients in comparison with clerical, administrative or laboratory personnel without direct contact with patients. The curves of evolution of accumulated cases between patients and HCW during March 2020 showed an almost parallel shape. DiscussionThe recommendation from our OHSS did not include testing of asymptomatic cases but was highly proactive in testing even patients with minor symptoms therefore, a high proportion of HCW and non-sanitary personnel was tested in March 2020 during the rapid period of expansion of the epidemics in Madrid, accounting for a total of 30,6 % of the hospital employees. Most of the COVID-19 cases among the hospital HCW and personnel were mild and managed at home under self-isolation measures, however 23 (3%) required hospitalization mostly due to severe bilateral interstitial pneumonia, two of those cases required mechanical ventilation at the ICU. No fatalities occurred during the study period. Although there were some cases of highly probable transmission from COVID-19 patients to HCWs, mainly at the first phase of the epidemics, there were no significant differences on the infection rates of HCW and hospital personnel that can be related to working in areas of high exposure risk. Furthermore, the evolution of cases during the same time period (March 2020) between patients attending the ER and hospital staff suggests that both groups were driven by the same dynamics. This experience is similar to the communicated from Wuhan verified by the WHO Joint Mission and also from recent experiences at hospital in the Netherlands, where most of the infections of HCW were related to household or community contacts. SignificanceSince the collective of hospital HCW are exhaustively screened in specific centers, their rate of infection for SARS-CoV-2 could be an indicator of the epidemic dynamics in the community. There appears to be a close connection between HCW infection and the driving forces of transmission in the community. Although we cannot exclude an additional risk factor of infection by SARS-CoV-2 due to the fact of the hospital environment, the similar proportions of positive cases among all the areas of the hospital and the evolutive wave of infection, as compared with the community, are clear arguments against a major factor of occupational risk. Exhaustive testing, such as the one carried out in our institution, covering over one third of all the workers, could be used as a reference of the population infected in the community. Since a significant proportion of COVID-19 cases can be asymptomatic and not all the hospital employees were actually tested, it is highly likely that this 11,6 % is a minimum estimation of the impact of SARS-CoV-2 circulation in Madrid during the first 4 weeks of the epidemics. This is in high and clear contrast with the official figures circulating at national and international levels. This has important implications to more precisely estimate the actual number of cases in the community and to develop public health policies for containment, treatment and recovery.

ObjectivesTo assess the effectiveness of tecovirimat (TPOXX) for treating mpox in terms of difference in healing time and extent of viral clearance. DesignEmulation of a target trial based on observational data. SettingItaly ParticipantsForty-one men hospitalized for mpox as of September 29th, 2022. Main outcome measuresMain outcome was the time to clinical recovery. Secondary outcome was the variation in viral load in the upper respiratory tract (URT) after treatment. ResultsThe median time from symptoms onset to hospital admission and to initiation of TPOXX was 4 days (IQR 2-6) and 10 days (IQR 8-11), respectively. Fifteen patients completed a course of therapy. No deaths were observed; the overall median healing time was 21 days (IQR 17-26). We found no evidence for a significant improvement in recovery time in treated vs. untreated patients, with an estimated mean of 14.7 days for both groups. A subset of 13 patients had URT samples at T1 (median of 5 days (IQR 3-7) from symptoms onset) and T2 (median 7 days (IQR 7-9) from T1). Overall, mean viral load was 4.65 (0.30) vs. 4.91 (0.35) (log2 scale of cycle threshold) at T1 and T2, respectively. In the unadjusted analysis, variation over T1-T2 was lower in the treated 0.13 log2 (SD=0.53) vs. untreated 0.37 (0.50), although not statistically significant (unpaired t-test p=0.41). After controlling for confounding, there was no evidence for a difference in the potential changes over T1-T2 by treatment arm, and our estimate of the average treatment effect (ATE) was consistent with no difference by treatment group, although with large 95% CI around these estimates. ConclusionsOur analysis seems to exclude a clinically important effect of TPOXX in hospitalized mpox patients when compared to no treatment. These data are one of the valuable currently available sources of evidence to guide treatment decisions in patients hospitalized with TPOXX. Pending more robust data from randomized comparisons, the use of TPOXX should be restricted to the clinical trials setting. Trial registration"MpoxCohort" observational study protocol: approval number 40z, Register of Non-Covid Trials 2022.

IntroductionInformation on vaccine effectiveness and viral loads in a context of novel variants of concern (VOC) emergence is of key importance to inform public health policies. This study aimed to estimate a measure of comparative vaccine effectiveness between Omicron (BA.1) and Delta (B.1.617.2 and sub-lineages) VOC according to vaccination exposure (primary or booster) and time since primary vaccination and to compare cycle threshold (Ct) values between Omicron and Delta VOC infections according to the vaccination status as an indirect measure of viral load. MethodsWe developed a case-case study using data on RT-PCR SARS-CoV-2 positive cases notified in Portugal during weeks 49-51 2021. The odds of vaccination in Omicron cases were compared to Delta using logistic regression adjusted for age group, sex, region and week of diagnosis and laboratory of origin. RT-PCR Ct values were compared by vaccination status and variant using linear regression model. ResultsHigher odds of vaccination were observed in cases infected by Omicron (BA.1) VOC compared to Delta (B.1.617.2) VOC cases for both complete primary vaccination (OR=2.1; CI 95% :1.8 to 2.4) and booster dose (OR= 5.2; CI 95%: 3.1 to 8.8), indicating vaccine effectiveness reduction against Omicron. No differences in distribution of Ct-values between these two VOC were observed for any vaccination exposure categories. ConclusionConsistent lower VE was observed against Omicron infection. Complete primary vaccination may not be protective against SARS-CoV-2 infection in regions where Omicron variant is dominant, but a massive rollout of booster vaccination campaign can contribute to reduce SARS-CoV-2 incidence in the population.

IntroductionSelf-testing for COVID-19 (C19ST) based on antigen detecting diagnostics could significantly support controlling the SARS-CoV-2 pandemic. To inform the World Health Organization in developing a C19ST guideline, we performed a systematic review and meta-analysis of the available literature. MethodsWe electronically searched Medline and the Web of Science core collection, performed secondary reference screening, and contacted experts for further relevant publications. Any study published between December 1, 2020 and November 30, 2021 assessing the epidemiological impact and clinical utility of C19ST was included. Study quality was evaluated using the Newcastle Ottawa Scale (NOS). The review was registered on PROSPERO (CRD42022299977). Results11 studies only from high-income countries with an overall low quality (median of 3/9 stars on the NOS) were found. Pooled C19ST positivity was 0.2% (95% CI 0.1% to 0.4%; eight data sets) in populations where otherwise no dedicated testing would have occurred. The impact of self-testing on virus transmission was uncertain. Positive test results mainly resulted in people having to isolate without further confirmation of results (eight data sets). When testing was voluntary by study design, pooled testing uptake was 53.2% (95% CI 36.7% to 68.9%; five data sets. Outside direct health impacts, C19ST reduced quarantine duration and absenteeism from work, and made study participants feel safer. Study participants favored self-testing and were confident that they performed testing and sampling correctly. ConclusionsThe present data suggests that C19ST could be a valuable tool in reducing the spread of COVID-19, as it can achieve good uptake, may identify additional cases, and was generally perceived as positive by study participants. However, data was very limited and heterogenous, and further research especially in low- and middle-income countries is needed to assess the clinical utility and epidemiological impact of C19ST in more detail. CONTRIBUTIONS TO THE LITERATURE- COVID-19 self-testing (C19ST) using antigen detection could conceivably support pandemic control. A current PubMed search found no systematic evidence synthesis of studies assessing the epidemiological impact and clinical utility of C19ST implementation - We systematically reviewed and meta-analyzed 11 studies including more than 1.1 million persons tested - C19ST can achieve good uptake, may identify additional cases, and was general perceived as positive by study participants, suggesting it to be a valuable tool in reducing the spread of SARS-CoV-2 - Further data especially from low- and middle-income countries is needed to understand the impact of C19ST in more detail

The authors have withdrawn this manuscript because analytic strategies for this project have changed. Therefore, the authors do not wish this work to be cited as reference for the project.

ObjectivesAn IFN-2b and IFN-{gamma} combination has demonstrated favorable pharmacodynamics for genes underlying antiviral activity which might be involved in the defense of a host from a SARS-CoV-2 infection. Considering this synergy, we conducted a randomized controlled clinical trial for efficacy and safety evaluation of subcutaneous IFN - 2b and IFN-{gamma} administration in patients positive for SARS-CoV-2. MethodsWe enrolled 19-82 years-old inpatients at the Military Central Hospital Luis Diaz Soto, Havana, Cuba. They were hospitalized after confirmed diagnosis for SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction. Patients were randomly assigned in a 1:1 ratio to receive either, subcutaneous treatment with a co-lyophilized combination of 3.0 MIU IFN-2b and 0.5 MIU IFN-{gamma} (HeberFERON, CIGB, Havana, Cuba), twice a week for two weeks, or thrice a week intramuscular injection of 3.0 MIU IFN-2b (Heberon(R) Alpha R, CIGB, Havana, Cuba). Additionally, all patients received lopinavir-ritonavir (200/50 mg every 12 h) and chloroquine (250 mg every 12 h, i.e.standard of care). The primary endpoints were, from the start of treatment, the time to elimination of viral RNA and the time to progression to severe COVID-19. The protocol was approved by the Ethics Committee on Clinical Investigation from the Hospital and the Center for the State Control of Medicines, Equipment and Medical Devices in Cuba. Informed consent was obtained from each participant (INSTITUTION PROTOCOL IG/IAG/CV/2001). ResultsA total of 79 patients with laboratory-confirmed SARS-CoV-2 infection, including symptomatic or asymptomatic conditions, fulfilled the inclusion criteria and underwent randomization. Thirty-three subjects were assigned to the HeberFERON group, and 33 to the Heberon Alpha R group. Sixty-three patients were analyzed for viral elimination, of these 78.6% in the HeberFERON group eliminated the virus after 4 days of treatment versus 40.6% of patients in the Heberon Alpha R groups (p=0.004). Time to reach the elimination of SARS-CoV-2, as measured by RT-PCR was 3.0 and 5.0 days for the HeberFERON and Heberon Alpha R groups, respectively. A significant improvement in the reduction of time for virus elimination was attributable to HeberFERON (p=0.0027, Log-rank test) with a Hazard Ratio of 3.2 and 95% CI of 1.529 to 6.948, as compared to the Heberon Alpha R treated group. Worsening of respiratory symptoms was detected in two (6.6%) and one (3.3%) patients in HeberFERON and IFN-2b groups, respectively. However, none of the subjects transited to severe COVID-19 during the study or during the following clinical evaluation (21 more days). RT-PCR on day 14 after the start of the treatment was negative to SARS-CoV-2 in 100% and 91% of patients of the combination of IFNs and IFN-2b, respectively. Elimination in HeberFERON treated patients was related to a significant increase in lymphocytes counts and also a significant reduction in CRP as early as 7 days after commencing the therapeutic schedule. All the patients in both cohorts recovered and had their laboratory parameters return to normal values by day 14 after treatment initiation. Adverse events were identified in 31.5% of patients, 28.5% in the control group, and 34.4% in the HeberFERON group, with the most frequent adverse event being headaches (17.4%). ConclusionsIn a cohort of 63 hospitalized patients between 19 to 82 years-old with positive SARS-CoV-2, HeberFERON significantly eliminated the virus on day 4 of treatment when compared to treatment with IFN-2b alone. However, Heberon Alpha R alone also showed efficacy for the treatment of the viral infection. Both treatments were safe and positively impacted on the resolution of the symptoms. None of the patients developed severe COVID-19.

IntroductionEarly reports showed that Omicron (BA.1) SARS-CoV-2 could be less severe. However, the magnitude of risk reduction of hospitalization and mortality of Omicron (BA.1) infections compared with Delta (B.1.617.2) is not yet clear. This study compares the risk of severe disease among patients infected with the Omicron (BA.1) variant with patients infected with Delta (B.1.617.2) variant in Portugal. MethodsWe conducted a cohort study in individuals diagnosed with SARS-CoV-2 infection between 1st and 29th December 2021. Cases were individuals with a positive PCR test notified to the national surveillance system. SARS-CoV-2 variants were classified first by whole genomic sequencing (WGS) and, if this information was unavailable, by detecting the S gene target failure. We considered a hospitalization for all the patients admitted within the 14 days after the SARS-CoV-2 infection; after that period, they were censored. The comparison of the risk of hospitalization between Omicron (BA.1) and Delta (B.1.617.2) VOC was estimated using a Cox proportional hazards model. The mean length of stay was compared using linear regression, and the risk of death between Omicron and Delta patients was estimated with a penalized logistic regression. All models were adjusted for sex, age, previous infection, and vaccination status. ResultsWe included 15 978 participants aged 16 or more years old, 9 397 infected by Delta (B.1.617.2) and 6 581 infected with Omicron (BA.1). Within the Delta (B.1.617.2) group, 148 (1.6%) were hospitalized, and 16 (0.2%) were with the Omicron (BA.1). A total of 26 deaths were reported, all in participants with Delta (B.1.617.2) infection. Adjusted HR for hospitalization for the Omicron (BA.1) variant compared with Delta (B.1.617.2) was 0.25 (95%CI 0.15 to 0.43). The length of stay in hospital for Omicron (BA.1) patients was significantly shorter than for Delta (confounding-adjusted difference -4.0 days (95%CI -7.2 to -0.8). The odds of death were 0.14 (95% CI 0.0011 to 1.12), representing a reduction in the risk of death of 86% when infected with Omicron (BA.1) compared with Delta (B.1.617.2). ConclusionOmicron (BA.1) was associated with a 75% risk reduction of hospitalization compared with Delta (B.1.617.2) and reduced length of hospital stay.

IntroductionThe B.1.617.2 variant (Delta) was associated with increased transmissibility and lower vaccine effectiveness than the B.1.1.7 variant (Alpha). However, the effect of the B.1.617.2 variant on disease severity remains unclear. This study aims to assess whether infection with the B.1.617.2 variant was associated with a higher risk of serious illness, compared with other co-circulating variants, measured through hospitalization and death by COVID-19 in Portugal. MethodsWe conducted a matched cohort study in adult individuals diagnosed with SARS-CoV-2/COVID-19 infection between March 29 and August 1, 2021. Cases were individuals with a positive PCR test notified to the surveillance system. SARS-CoV-2 variants were classified first by genomic sequencing (WGS) and, if this information was unavailable, by detecting the S gene target failure. Delta (B.1.617.2) and Alpha (B.1.1.7) cases were matched on the week of diagnosis at a 1 to k ratio (k being the maximum number of unexposed available in that week) to maximize the inclusion of unexposed, using the nearest-neighbor algorithm. The hazard risk and 95% confidence intervals of hospitalization and death among those infected with the Delta (B.1.617.2) variant vs. Alpha (B.1.1.7) was estimated using a Cox proportional hazards model, adjusting for confounding for sex, age, and vaccination status. ResultsA total of 2,778 cases were included in the study. Of the total, 1 742 (68%) were identified as B.1.617.2 variant cases and 3 629 (32%) as B.1.1.7 variant. Within the B.1.1.7 variant cases 106 (2.9%) were hospitalized, and 110 (6.3%) within the B.1.617.2 variant cases. A total of 29 deaths were reported, 8 (0.2%) in patients infected with B.1.1.7 variant and 21 (1.2%) in patients with the B.1.617.2 variant. The confounding adjusted risk of hospitalization, in persons infected with the B.1.617.2 variant was 2.44 (95%CI 1.85; 3.20) times higher than the risk of hospitalization among B.1.1.7 variant cases, and the confounding-adjusted risk of death for B.1.617.2 variant cases was 5.20 (95%CI 2.20; 12.29) times higher than the risk of death in patients infected by B.1.1.7 variant. ConclusionThe B.1.617.2 variant is associated with an increased risk of hospitalization and death compared with the B.1.1.7 variant.

IntroductionTo analyse the effectiveness of a dose of adenovirus vector ChAdOx1 vaccine (AVChOx1) in an outbreak of SARS-CoV-2 detected in a prison. MethodsObservational study carried out at Brians-1 Prison, Barcelona. After detecting a case of infection, rt-PCR was administered to all prisoners (some of whom had been vaccinated 21-23 days previously with a dose of AVChOx1) and to staff. Infection rates in vaccinated and unvaccinated populations were calculated, as was vaccine effectiveness. ResultsOne hundred and eighty-four asymptomatic prisoners (50.3% vaccinated) and 33 staff were screened. Forty-eight (25.9%) infections by the SCV-B.1.17 variant were recorded in prisoners and none in staff. Infection rates were higher in younger prisoners, immigrants, and those admitted [&ge;]7 days previously. In all, 22.6% of vaccinated subjects were infected vs. 29.3% of unvaccinated. Vaccine effectiveness was 23%. Only 6.2 cases would have been prevented by vaccinating the unvaccinated individuals. At seven days, the rt-PCR was negative in 46.2% of vaccinated subjects vs. 13.6% of unvaccinated (p = 0.02). DiscussionIn a prison outbreak, a dose of AVChAdOx1 administered 21-23 days earlier did not significantly prevent the occurrence of infections, but did reduce the duration of rt-PCR positivity. Maintaining post-vaccination preventive measures is essential.

BackgroundHealth-care workers (HCW) are at increased risk for SARS-CoV-2 infection, but few studies have evaluated prevalence of antibodies against SARS-CoV-2 among them. ObjectiveTo determine the seroprevalence against SARS-CoV-2 in all HCW. MethodsCross-sectional study (April 14th- 27th, 2020) of all HCW at Hospital Universitario Fundacion Alcorcon, a second level teaching hospital in Madrid, Spain. SARS-CoV-2 IgG was measured by ELISA. HCW were classified by professional category, working area, and risk for SARS-CoV-2 exposure. ResultsAmong 2919 HCW, 2590 (90.5%) were evaluated. Mean age was 43.8 years (SD 11.1) and 73.9% were females. Globally, 818 (31.6%) workers were IgG positive, with no differences for age, sex or previous diseases. Among them, 48.5% did not report previous symptoms. Seropositivity was more frequent in high (33.1%) and medium (33.8%) than in low-risk areas (25.8%, p = 0.007), but no difference was found for hospitalization areas attending COVID-19 and non-COVID-19 patients (35.5 vs 38.3% p = NS). HCW with a previous SARS-CoV2 PCR positive test were IgG seropositive in 90.8%. By multivariate logistic regression analysis, seropositivity was associated with being physicians (OR 2.37, CI95% 1.61-3.49), nurses (OR 1.67, CI95% 1.14-2.46), or nurse- assistants (OR 1.84, CI95% 1.24-2.73), HCW working at COVID-19 hospitalization areas (OR 1.71, CI95% 1.22-2.40), non-COVID-19 hospitalization areas (OR 1.88, CI95% 1.30-2.73), and at the Emergency Room (OR 1.51, CI95% 1.01-2.27) ConclusionsSeroprevalence uncovered a high rate of infection previously unnoticed among HCW. Patients not suspected of having COVID-19 as well as asymptomatic HCW may be a relevant source for nosocomial SARS-CoV-2 transmission.

BackgroundSARS-CoV-2 vaccines are highly effective at preventing COVID-19-related morbidity and mortality. As no vaccine is 100% effective, breakthrough infections are expected to occur. MethodsWe analyzed the virological characteristics of 161 vaccine breakthrough infections in a population of 24,706 vaccinated healthcare workers (HCWs), using RT-PCR and virus culture. ResultsThe delta variant (B.1.617.2) was identified in the majority of cases. Despite similar Ct-values, we demonstrate lower probability of infectious virus detection in respiratory samples of vaccinated HCWs with breakthrough infections compared to unvaccinated HCWs with primary SARS-CoV-2 infections. Nevertheless, infectious virus was found in 68.6% of breakthrough infections and Ct-values decreased throughout the first 3 days of illness. ConclusionsWe conclude that rare vaccine breakthrough infections occur, but infectious virus shedding is reduced in these cases.

BackgroundThe Co-HCW study is a prospective, longitudinal single center observational study on the SARS-CoV-2 seroprevalence and infection status in staff members of Jena University Hospital (JUH) in Jena, Germany. Material and MethodsThis follow-up study covers the observation period from 19th May 2020 to 22nd June 2021. At each out of three voluntary study visits, participants filled out a questionnaire on individual SARS-CoV-2 exposure. In addition, serum samples to assess specific SARS-CoV-2 antibodies were collected. Participants with antibodies against nucleocapsid and/or spike protein without previous vaccination and/or a reported positive SARS-CoV-2 PCR test were regarded as participants with detected SARS-CoV-2 infection. Multivariable logistic regression modeling was applied to identify potential risk factors for infected compared to non-infected participants. ResultsOut of 660 participants that were included during the first study visit, 406 participants (61.5%) were eligible for final analysis as they did not change the COVID-19 risk area (high-risk n=76; intermediate-risk n=198; low-risk n=132) during the study. Forty-four participants (10.8%, 95% confidence interval (95%CI) 8.0%-14.3%) had evidence of a current or past SARS-CoV-2 infection detected by serology (n=40) and/or PCR (n=28). No association of any SARS-CoV-2 infection with the COVID-19 risk group according to working place could be detected. But exposure to a SARS-CoV-2 positive household member (adjusted OR (AOR) 4.46, 95%CI 2.06-9.65) or colleague (AOR 2.30, 95%CI 1.10-4.79) significantly increased the risk of a SARS-CoV-2 infection. ConclusionOur results demonstrate that non-patient-related SARS-CoV-2 exposure imposed the highest infection risk in hospital staff members of JUH.

The healthcare workers are considered as a high-risk group for infection with SARS-CoV-2, so they were included in the first stage of the National Plan for Vaccination against COVID-19 in Colombia. An ongoing prospective cohort study to evaluate immune response to vaccination included 490 workers from health institutions in Bogota, Colombia, vaccinated between March and June 2021 with BNT162b2 (Pfizer-BioNtech). Multiple samples were collected during a follow-up period of 6 months after immunization. We report cases of asymptomatic and symptomatic SARS-CoV-2 infections detected in this cohort. For each participant demographic data, vaccination dates, results for SARS-CoV-2 RT-PCR, and detection of antibody (IgG) tests during the follow-up period were collected. SARS-CoV-2 infection was detected in 38 (7.7 %) volunteers. Of these, 81.6% had a positive RT-PCR for SARS-CoV-2, and 18.4% were confirmed by detection of IgG anti-SARS-CoV-2 nucleoprotein; 76.3% of infections occurred after 7 days of second dose. A total of 57.9% of the cases were asymptomatic. No hospitalizations or deaths were registered. When infection occurred, 81.6% of infected participants had presence of IgG anti-S antibodies. In 12 samples in which genomic characterization was achieved, 83.4% corresponded to the variant Mu, 8.3% Gamma, and 8.3% Delta. All findings agree with other reports in different studies that show the benefit of COVID-19 vaccines, protecting specially against severe disease but not against infection or re-infection.

IntroductionRapid antigen detection tests (RDT) are suitable for large-scale testing for SARS-CoV-2 among the population and recent studies have shown that self-testing with RDT in the general population is feasible and yields acceptable sensitivities with high specificity. We aimed to determine the accuracy of two different RDTs, with two different sample collection methods for one of the RDTs among healthcare workers (HCW). Secondary objectives were to determine the accuracy of RDT using a viral load cut-off as proxy of infectiousness and to identify predictors for a false negative RDT. MethodsCenters that participated were secondary care hospitals, academic teaching hospitals, and long-term care facilities. All HCW that met inclusion criteria were asked to perform a RDT self-test next to a regular SARS-CoV-2 nucleic acid amplification test (NAAT). Three study groups were created. Study group 1; Veritor(tm) System, Becton Dickinson, Franklin Lakes, USA (BD-RDT) with combined oropharyngeal - mid-turbinate nasal sampling, group 2; BD-RDT with mid-turbinate nasal sampling only and group 3; SD Biosensor SARS-CoV-2 Rapid Antigen Test, Roche, Basel, Switzerland (Roche-RDT) with combined oropharyngeal - mid-turbinate nasal sampling. RDT accuracy was calculated using NAAT as reference standard. For samples processed in the cobas(R) 6800/8800 platform (Roche Diagnostics, Basel, Switzerland), established cycle threshold values (Ct-values) could be converted into viral loads. A viral load cut-off of [&ge;]5.2 log10 SARS-CoV-2 E gene copies/ml was used as proxy of infectiousness. Logistic regression analysis was performed to identify predictors for a false negative RDT. ResultsIn total, 7,196 HCW were included. Calculated sensitivities were 61.5% (95%CI 56.6%-66.3%), 50.3% (95%CI 42.8%-57.7%) and 74.2% (95%CI 66.4%-80.9%) for study groups 1, 2 and 3, respectively. After application of a viral load cut-off as a proxy for infectiousness for samples processed in the cobas(R) 6800/8800 platform sensitivities increased to 82.2% (95%CI 76.6-86.9%), 61.9% (95%CI 48.8%-73.9%) and 90.2% (95%CI 76.9%-97.3%) for group 1, group 2 and group 3, respectively. Multivariable regression analysis showed that use of Roche-RDT (p <0.01), combined oropharyngeal - mid-turbinate nasal sampling (p <0.05) and the presence of COVID-19 like symptoms at the time of testing (p <0.01) significantly reduced the likeliness of a false-negative RDT result. ConclusionSARS-CoV-2 RDT has proven able to identify infectious individuals, especially when upper respiratory specimen is collected through combined oropharyngeal - mid-turbinate sampling. Reliability of self-testing with RDT among HCW seems to depend on the type of RDT, the sampling method and the presence of COVID-19 like symptoms at the time of testing.