Viral load dynamics in healthcare workers with COVID-19 during Delta and Omicron era (preprint)

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, several variants of concern (VOC) have emerged and became the dominant strain. These are considered VOC because of traits like increased transmissibility, increased severity, and immune-evasion. Understanding their viral load dynamics, with the use of longitudinal follow-up data, can help to understand transmission and could inform policy makers on for example infection prevention guidelines. However, longitudinal follow-up studies are scarce. In this study, we were able to monitor the viral load dynamics of the Delta, Omicron BA.1 and BA.2 variants via an unique dataset that was obtained as a consequence of the implemented infection prevention guidelines for healthcare workers at our institution, based on longitudinal follow-up of viral load. We found that the dynamics are different between Delta, Omicron BA.1, and Omicron BA.2 variants, the latter having the highest viral load on day 5 (5.7 log10 copies/mL compared to 4.3 log10 copies/mL for Delta and 4.8 log10 copies/mL for BA.1) and day 7 (4.4 log10 copies/mL compared to 3.3 log10 copies/mL for Delta and 3.8 log10 copies/mL for BA.1). However, the infection duration does not appear to be different between these variants. Still, considerable viral loads even after the suggested quarantine period were observed, in particular for the Omicron BA.2 sub variant. This highlights the need for a tailored approach per variant as results of previously circulating variants do not always match. This is in particular important for healthcare workers as they can transmit SARS-CoV-2 to vulnerable patients. 

Increased Transmissibility of SARS-CoV-2 Alpha Variant (B.1.1.7) in Children: Three Large Primary School Outbreaks Revealed by Whole Genome Sequencing in the Netherlands (preprint)

Background: Variant of concern (VOC) SARS-CoV-2 alpha variant (B.1.1.7) was the dominant strain in the Netherlands between March 2021 – June 2021. We describe three primary school outbreaks due to the alpha variant using whole genome sequencing with evidence of large-scale transmission among children, teachers and their household contacts. MethodAll outbreaks described were investigated by the South Limburg Public Health Service, the Netherlands. A case was defined as an individual with a real-time polymerase chain reaction test or antigen test positive for SARS-CoV-2. Whole genome sequencing was performed on random samples from at least one child and one teacher of each affected class.ResultsPeak attack rates in classes were 53%, 33% and 39%, respectively. Specific genotypes were identified for each school across a majority of affected classes. Attack rates were high among staff members, likely to promote staff-to-children transmission. Cases in some classes were limited to children, indicating child-to-child transmission. At 39%, the secondary attack rate (SAR) in household contacts of infected children was remarkably high, similar to SAR in household contacts of staff members (42%). SAR of household contacts of asymptomatic children was only 9%. Conclusion Our findings suggest increased transmissibility of the alpha variant in children compared to preceding non-VOC variants, consistent with a substantial rise in the incidence of cases observed in primary schools and children aged 5-12 since the alpha variant became dominant in March 2021. Lack of mandatory masking, insufficient ventilation and lack of physical distancing also probably contributed to the school outbreaks. The rise of the delta variant (B.1.617.2) since July 2021 which is estimated to be 55% more transmissible than the alpha variant, provides additional urgency to adequate infection prevention in school settings.

Investigating SARS-CoV-2 breakthrough infections per variant and vaccine type (preprint)

Breakthrough SARS-CoV-2 infections have been reported in fully vaccinated individuals, in spite of the high efficacy of the currently available vaccines, proven in trials and real-world studies. Several variants of concern (VOC) have been proffered to be associated with breakthrough infections following immunization. In this study, we investigated 378 breakthrough infections recorded between January and July 2021 and compared the distribution of SARS-CoV-2 genotypes identified in 225 fully vaccinated individuals to the frequency of circulating community lineages in the region of South Limburg (The Netherlands) in a week-by-week comparison. Although the proportion of breakthrough infections was relatively low and stable when the Alpha variant was predominant, the rapid emergence of the Delta variant lead to a strong increase in breakthrough infections, with a higher relative proportion of individuals vaccinated with Oxford-AstraZeneca or J&J/Janssen being infected compared to those immunized with mRNA-based vaccines. A significant difference in median age was observed when comparing fully vaccinated individuals with severe symptoms (83 years) to asymptomatic cases (46.5 years) or individuals with mild-to-moderate symptoms (42 years). There was no association between SARS-CoV-2 genotype or vaccine type and disease symptoms. Interestingly, symptomatic individuals harbored significantly higher SARS-CoV-2 loads than asymptomatic vaccinated individuals and breakthrough infections caused by the Delta variant are associated with increased viral loads compared to those caused by the Alpha variant. Altogether, these results indicate that the emergence of the Delta variant might have lowered the efficiency of particular vaccine types to prevent SARS-CoV-2 infections and that, although rare, the elderly are particularly at risk of becoming severely infected as the consequence of a breakthrough infection.

A novel B.1.1.523 SARS-CoV-2 variant that combines many spike mutations linked to immune evasion with current variants of concern (preprint)

In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic several variants have emerged that are linked to increased transmissibility and immune evasion. These variants are recognized as variants of concern (VOC). In this study, we describe a B.1.1.523 variant that shares many spike mutations with current VOC. Receptor-binding domain mutations E484K and S494P were observed but also a deletion (position 156-158) in the N-terminal antigenic supersite that is similar to the delta-variant. These mutations are linked to immune evasion in VOC that could lead to less effective vaccines. This variant has been reported in various different countries and continents despite the dominance of B.1.1.7 (alpha) and B.1.617.2 (delta) variant. Furthermore, the B.1.1.523 pangolin lineage as a whole is recognized as a variant under monitoring since 14th of July 2021.

Linked Nosocomial COVID-19 Outbreak in Three Facilities for People with Intellectual and Developmental Disabilities Due to SARS-CoV-2 Variant B.1.1.519 with Spike Mutation T478K in the Netherlands (preprint)

Background: Individuals with intellectual and developmental disabilities (IDD) living in congregated settings have increased risk of COVID-19 infection and mortality. Little is known about variant B.1.1.519 with spike mutation T478K, dominant in Mexico. We describe a linked SARS-CoV-2 B.1.1.519 outbreak in three IDD facilities in the Netherlands. Methods: Following notification of the index, subsequent cases were identified through serial PCR group testing. Positive specimens were submitted for whole-genome-sequencing. Clinical information was gathered through interviews with staff members of the three facilities. Results: Attack rate (AR) in clients of the index facility was 92% (23/25), total AR in clients 45% (33/73) and in staff members 24% (8/34). 55% (18/33) of client cases were asymptomatic, versus 25% (2/8) of staff members. Five client cases (15%) were hospitalized, two died (6%). Sequencing yielded the same specific B.1.1.519 genotype in all three facilities. No significant difference in median viral load was established comparing the B.1.1.519 variant with other circulating variants. The index of the linked outbreak reported no travel history or link to suspected or confirmed cases suggesting regional surveillance. Observed peak regional prevalence of B.1.1.519 during the outbreak supports this. Conclusion: AR, morbidity and mortality prior to control measures taking effect were high, probably related to the specific characteristics of the IDD setting and its clients. We assessed no evidence for intrinsic contributing properties of variant B.1.1.519. Our study argues for enhanced infection prevention protocols in the IDD setting, and prioritization of this group for vaccination against COVID-19.

Applying the electronic nose for pre-operative SARS-CoV-2 screening (preprint)

Background: Infection with SARS-CoV-2 causes Corona Virus Disease (COVID-19). The most standard diagnostic method is reverse transcription-polymerase chain reaction (RT-PCR) on a nasopharyngeal and/or an oropharyngeal swab. The high occurrence of false-negative results due to the non-presence of SARS-CoV-2 in the oropharyngeal environment renders this sampling method not ideal. Therefore, a new sampling device is desirable. This proof-of-principle study investigated the possibility to train machine-learning classifiers with an electronic nose (Aeonose) to differentiate between COVID-19 positive- and negative persons based on volatile organic compounds (VOCs) analysis.Methods: Between April and June 2020, participants were invited for breath analysis when a swab for RT-PCR was collected. If the RT-PCR resulted negative, presence of SARS-CoV-2 specific antibodies was checked to confirm the negative result. All participants breathed through the Aeonose for five minutes. This device contains metal-oxide sensors that change in conductivity upon reaction with VOCs in exhaled breath. These conductivity changes are input data for machine-learning and used for pattern recognition. The result is a value between -1 and +1, indicating the infection probability.Results: 219 participants were included, 57 of which COVID-19 positive. A sensitivity of 0.86 and a negative predictive value (NPV) of 0.92 were found. Adding clinical variables to machine-learning classifier via multivariate logistic regression analysis, the NPV improved to 0.96. Conclusions: The Aeonose can distinguish COVID-19 positive from negative participants based on VOC patterns in exhaled breath with a high NPV. The Aeonose might be a promising, non-invasive, and low-cost triage tool for excluding SARS-CoV-2 infection in patients elected for surgery. 

Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort; MaastrICCht (preprint)

BackgroundThe course of the disease in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort; MaastrICCht. We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with SARS-CoV-2 infection. Study populationMechanically ventilated patients admitted to the Intensive Care with SARS- CoV-2 infection. Main messageWe will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, electrocardiograms, echocardiography as well as other imaging modalities to assess heterogeneity of the natural course of SARS-CoV-2 infection in critically ill patients. The MaastrICCht cohort is, also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national Intensive Care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. ConclusionThe spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS- CoV-2 infection in mechanically ventilated patients. Our design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht cohort. Strengths and limitations of this studyO_LISerial measurements that characterize the disease course of SARS-CoV-2 infection in mechanically ventilated patients C_LIO_LIData collection and analysis according to a predefined protocol C_LIO_LIFlexible, evolving design enabling the study of multiple aspects of SARS-CoV-2 infection in mechanically ventilated patients C_LIO_LISingle centre, including only ICU patients C_LI