Tackling hepatitis B co-infection in PLHIV after COVID: an audit and updated guidelines

Background: 5-20% of people living with HIV (PLWH) are co-infected with Hepatitis B (HBV) and coinfection is associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC), incidence of which is 5 to 6 times higher. COVID-19 led to a lapse in surveillance of this population, warranting a reassessment. Method(s): BHIVA and EACS guidelines were combined to create a standard to audit against. All people under the care of the HIV team with co-infection were included, and analysed for the prior six months. Local ethics approval was granted. The results were then presented to clinicians, and local guidelines created to reflect the most recent research on co-infection which were shared with the department. A re-audit was then conducted against the modified guidelines. Result(s): 42 people were living with co-infection of HBV and HIV, with a 50:50 gender split;32 were of Black African ethnicity (76%). The median age was 50.5. Nobody had a HBV resistance profile done at baseline. 3 people did not have suppressed HIV viral load (VL), and 8 people did not have a suppressed HBV VL. In the previous 6 months only 26 (62%) had had a HBV VL, 20 (48%) had had an alfa-fetoprotein (AFP) check, and 21 (36%) had had an ultrasound liver. An US had been requested in 21 (50%) of patients. 100% were on a tenofovir-containing drug regimen. Following presentation and rewriting of guidelines, performance of investigations improved. An US had been requested in 26 (62%) cases although only performed in 16 (38%) and an AFP had been measured in 25 (60%). Vaccination of partners had also improved. Conclusion(s): The provision of care of those with coinfection was significantly impacted by the COVID pandemic, but reinforcement of information, and re-issuing of guidelines improved patient care. Attendance of appointments for blood tests and scans remains a major challenge for improving patient care. Literature aimed at our local population to reinforce the importance of HCC screening is being developed.

Cell culture systems for isolation of SARS-CoV-2 clinical isolates and generation of recombinant virus.

A simple and robust cell culture system is essential for generating authentic SARS-CoV-2 stocks for evaluation of viral pathogenicity, screening of antiviral compounds, and preparation of inactivated vaccines. Evidence suggests that Vero E6, a cell line commonly used in the field to grow SARS-CoV-2, does not support efficient propagation of new viral variants and triggers rapid cell culture adaptation of the virus. We generated a panel of 17 human cell lines overexpressing SARS-CoV-2 entry factors and tested their ability to support viral infection. Two cell lines, Caco-2/AT and HuH-6/AT, demonstrated exceptional susceptibility, yielding highly concentrated virus stocks. Notably, these cell lines were more sensitive than Vero E6 cells in recovering SARS-CoV-2 from clinical specimens. Further, Caco-2/AT cells provided a robust platform for producing genetically reliable recombinant SARS-CoV-2 through a reverse genetics system. These cellular models are a valuable tool for the study of SARS-CoV-2 and its continuously emerging variants.

Development of a biomarker signature using grating-coupled fluorescence plasmonic microarray for diagnosis of MIS-C.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can develop 4-6 weeks after a school age child becomes infected by SARS-CoV-2. To date, in the United States more than 8,862 cases of MIS-C have been identified and 72 deaths have occurred. This syndrome typically affects children between the ages of 5-13; 57% are Hispanic/Latino/Black/non-Hispanic, 61% of patients are males and 100% have either tested positive for SARS-CoV-2 or had direct contact with someone with COVID-19. Unfortunately, diagnosis of MIS-C is difficult, and delayed diagnosis can lead to cardiogenic shock, intensive care admission, and prolonged hospitalization. There is no validated biomarker for the rapid diagnosis of MIS-C. In this study, we used Grating-coupled Fluorescence Plasmonic (GCFP) microarray technology to develop biomarker signatures in pediatric salvia and serum samples from patients with MIS-C in the United States and Colombia. GCFP measures antibody-antigen interactions at individual regions of interest (ROIs) on a gold-coated diffraction grating sensor chip in a sandwich immunoassay to generate a fluorescent signal based on analyte presence within a sample. Using a microarray printer, we designed a first-generation biosensor chip with the capability of capturing 33 different analytes from 80  µ L of sample (saliva or serum). Here, we show potential biomarker signatures in both saliva and serum samples in six patient cohorts. In saliva samples, we noted occasional analyte outliers on the chip within individual samples and were able to compare those samples to 16S RNA microbiome data. These comparisons indicate differences in relative abundance of oral pathogens within those patients. Microsphere Immunoassay (MIA) of immunoglobulin isotypes was also performed on serum samples and revealed MIS-C patients had several COVID antigen-specific immunoglobulins that were significantly higher than other cohorts, thus identifying potential new targets for the second-generation biosensor chip. MIA also identified additional biomarkers for our second-generation chip, verified biomarker signatures generated on the first-generation chip, and aided in second-generation chip optimization. Interestingly, MIS-C samples from the United States had a more diverse and robust signature than the Colombian samples, which was also illustrated in the MIA cytokine data. These observations identify new MIS-C biomarkers and biomarker signatures for each of the cohorts. Ultimately, these tools may represent a potential diagnostic tool for use in the rapid identification of MIS-C.

Bacterial contamination on used face masks among nursing home healthcare personnel.

Objectives: Since the beginning of the COVID-19 pandemic, face masks have been worn by many in public areas and for prolonged periods by healthcare workers (HCWs). This may facilitate bacterial contamination and transmission to and from patients in nursing homes where clinical care areas with strict precautions and residential and activity areas are interconnected. We assessed and compared bacterial mask colonization in HCWs belonging to different demographic categories and professions (clinical and nonclinical) and among HCWs who had worn the mask for different periods of time. Design setting and participants: We conducted a point-prevalence study of 69 HCW masks at the end of a typical work shift in a 105-bed nursing home serving postacute care and rehabilitation patients. Information collected about the mask user included profession, age, sex, length of time the mask was worn, and known exposure to patients with colonization. Results: In total, 123 distinct bacterial isolates were recovered (1-5 isolates per mask), including Staphylococcus aureus from 11 masks (15.9%) and gram-negative bacteria of clinical importance from 22 masks (31.9%). Antibiotic resistance rates were low. There were no significant differences in the number of clinically important bacteria among masks worn more or less than 6 hours, and there were no significant differences among HCWs with different job functions or exposure to colonized patients. Conclusions: Bacterial mask contamination was not associated with HCW profession or exposure and did not increase after 6 hours of mask wearing in our nursing home setting. Bacteria contaminating HCW masks may differ from those colonizing patients.

Trends in coronary calcium score and coronary CT angiography imaging volume during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic disrupted the delivery of preventative care and management of acute diseases. This study assesses the effect of the COVID-19 pandemic on coronary calcium score and coronary CT angiography imaging volume. MATERIALS AND METHODS: A single institution retrospective review of consecutive patients presenting for coronary calcium score or coronary CT angiography examinations between January 1, 2020 to January 4, 2022 was performed. The weekly volume of calcium score and coronary CT angiogram exams were compared. RESULTS: In total, 1,817 coronary calcium score CT and 5,895 coronary CT angiogram examinations were performed. The average weekly volume of coronary CTA and coronary calcium score CT exams decreased by up to 83% and 100%, respectively, during the COVID-19 peak period compared to baseline (P < 0.0001). The post-COVID recovery through 2020 saw weekly coronary CTA volumes rebound to 86% of baseline (P = 0.024), while coronary calcium score CT volumes remained muted at only a 53% recovery (P < 0.001). In 2021, coronary CTA imaging eclipsed pre-COVID rates (P = 0.012), however coronary calcium score CT volume only reached 67% of baseline (P < 0.001). CONCLUSIONS: A significant decrease in both coronary CTA and coronary calcium score CT volume occurred during the peak-COVID-19 period. In 2020 and 2021, coronary CTA imaging eventually superseded baseline rates, while coronary calcium score CT volumes only reached two thirds of baseline. These findings highlight the importance of resumption of screening exams and should prompt clinicians to be aware of potential undertreatment of patients with coronary artery disease.

Facial Dermal Filler Injection and Vaccination: A 12-Year Review of Adverse Event Reporting and Literature Review.

BACKGROUND: Following authorization of 2 COVID-19 vaccines in December 2020, media attention increased towards postvaccine adverse events (AEs) in patients with facial dermal filler injections. OBJECTIVES: The purpose of this study was to characterize vaccine-related facial dermal filler AEs by scrutinizing the FDA's Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: The MAUDE database was queried from January 1, 2011 to January 28, 2023 for facial dermal filler medical device reports (MDRs) discussing vaccination-related AEs. A PubMed (National Institutes of Health, Bethesda, MD) literature review on dermal filler AEs was then conducted. Data were analyzed with descriptive statistics. RESULTS: Of 10,637 MDRs identified, 33 were included. There were 25 MDRs (75.8%) related to COVID-19 vaccination. Hyaluronic acid-based fillers were described in 31 MDRs (93.9%). AEs were mostly reported within days postinjection (n = 7, 21.2%), but ranged from immediately (n = 2, 6.1%) to months (n = 6, 18.2%) postinjection. Most AEs were reported postvaccine (n = 17, 51.5%) vs postfiller (n = 14, 42.4%). In 26 reports (78.8%), AEs occurred at the site of filler injection. Most MDRs described inflammation/swelling (n = 21, 28.0%). The literature review returned 302 articles, of which 14 were included. Only 1 article (7.1%) was published in a plastic surgery journal. CONCLUSIONS: Although the pandemic brought attention to COVID-19 vaccine-related facial dermal filler AEs, this study shows a low incidence compared with the millions of vaccine and filler injections administered. Reactions with non-COVID-19 vaccines were also documented. Increased awareness may help providers counsel patients undergoing vaccination and dermal filler implantation.

Post-COVID-19 condition in the German working population: A cross-sectional study of 200k registered stem cell donors.

BACKGROUND: The SARS-CoV-2 pandemic has strained health systems worldwide, and infection numbers continue to rise. While previous data have already shown that many patients suffer from symptoms for months after an acute infection, data on risk factors and long-term outcomes are incomplete, particularly for the working population. OBJECTIVES: We aimed to provide information on the prevalence of post COVID-19 conditions in a subset of the German working-age population (18-61 years old) and to analyze risk-factors. METHODS: We conducted an online survey with a health questionnaire among registered potential stem cell donors with or without a self-reported history of PCR-confirmed SARS-CoV-2 infection. Logistic regression models were used to examine the risks of severity of acute infection, sex, age, body mass index, diabetes mellitus and arterial hypertension medication on post COVID-19 symptoms. RESULTS: 199,377 donors reported evaluable survey questionnaires: 12,609 cases had a history of SARS-CoV-2 infection and 186,768 controls had none. Overall, cases reported physical, cognitive and psychological complaints more frequently compared to controls. Increased rates of complaints persisted throughout 15 months post infection, e.g. 28.4/19.3% of cases/controls reported fatigue (p<0.0001) and 9.5/3.6% of cases/controls reported loss of concentration (p<0.0001). No significant differences were observed in the frequency of reported symptoms between three- and 15-months post-infection. Multivariate analysis revealed a strong influence of the severity of the acute SARS-CoV-2 infection episode and age on the risk for post-COVID-19 conditions. CONCLUSION: We report the prevalence of post-COVID-19 conditions in mainly unvaccinated individuals with SARS-CoV-2 infections between February 2020 and August 2021. Severity of the acute course and age were major risk factors. Vaccinations may reduce the risk of post-COVID-19 conditions by reducing the risk for severe infections. This article is protected by copyright. All rights reserved.

Development & Implementation of a Biomarker-based Remotely-delivered Antimicrobial Stewardship (AMS) Strategy during the COVID-19 Pandemic

Background. Increased antibiotic usage during the COVID-19 pandemic and resultant infection control measures derailed the existing antimicrobial stewardship program which involved in person post prescription review and feedback. We performed a time series analysis using Procalcitonin as a tool for a remotely delivered antimicrobial stewardship program by a clinical pharmacist. Methods. This study was conducted in a tertiary care 3500 bedded teaching hospital in southern India. In the baseline phase, all COVID-19 in-patients receiving antibiotics > 48 hours were screened via the electronic records by a pharmacist and antimicrobial consumption indices like days of therapy (DOT) and length of therapy (LOT) were measured. In the intervention phase, if a patient was on antimicrobials, then a PCT was sent. An alert was sent to the treating team based on the procalcitonin levels and a screening of electronic records by a clinical pharmacist to either continue/ de-escalate or discontinue an antibiotic under supervision of an Infectious Diseases physician. Figure 1 Guideline for continuing or stopping antibiotics based on procalcitonin levels Figure 2 Guideline for continuing or stopping antibiotics based on procalcitonin levels Study Flow Results. About 481 patients were enrolled in the pre intervention phase of the study from July to October 2020 (peak of the pandemic) and 90 patients in the intervention phase December 2020 - March 2021 (decline of the pandemic. The baseline characteristics are shown in Figure3. The DOT/1000 patient days (PD) for all antibiotics was 9269 (DOT-6915) in the baseline and 2032 (DOT-886) in the intervention arm. The total length of therapy (LOT) for antimicrobial consumption significantly reduced from 3779 in the pre-intervention phase to 657 in the intervention phase (Figure 4). Out of the 90 recommendations given in the intervention phase, 82 (91.1%) were accepted by the treating team. For Azithromycin and Doxycycline, DOT significantly reduced from 3319 to 486 per 1000 PD and 602 to 158 per 1000 PD respectively. The DOT of the reserve antibiotics according to the WHO AWaRe classification like Polymyxins and Carbapenems decreased from 323 to 67 and 777 to 443 per 1000 PD days in the intervention phase. Conclusion. This study demonstrated the utility of a novel biomarker driven antimicrobial stewardship strategy by clinical pharmacists during the COVID pandemic when access to patients was restricted to both infection control physicians and pharmacists.

Outreach for Science Facilities: Armagh Observatory and Planetarium's programme for the Cherenkov Telescope Array

We describe an outreach programme being delivered by the Armagh Observatory and Planetarium (AOP) for the Cherenkov Telescope Array (CTA). Founded in 1790 and with a rich astronomical heritage, AOP today combines the research and education arms of our organisation to bring a research-informed outreach programme to the public, most often through our planetarium-related activities. We have developed and written, in-house, a short full dome planetarium show ("Exploring the High-Energy Universe”) that describes the science of gamma-ray astronomy and introduces the CTA as the first ground-based gamma-ray observatory open to the whole scientific community. In parallel, we are engaged in developing a series of short videos to introduce the scientists and the science of the UK CTA consortium, again designed for public audiences. These videos can be accessed through our social media channels. Delivery of such outreach programme in bite-sized pieces is an essential element in attracting and engaging audiences. We explain how we have developed the skill set to do this in our Education Team at AOP whilst our facility has been closed for the past year, a result of the Covid-pandemic. There is also scope in extending these concepts for providing outreach support for other science facilities. © Copyright owned by the author(s) under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0)

Spike and nsp6 are key determinants of SARS-CoV-2 Omicron BA.1 attenuation.

The SARS-CoV-2 Omicron variant is more immune evasive and less virulent than other major viral variants that have so far been recognized1-12. The Omicron spike (S) protein, which has an unusually large number of mutations, is considered to be the main driver of these phenotypes. Here we generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron (BA.1 lineage) in the backbone of an ancestral SARS-CoV-2 isolate, and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escaped vaccine-induced humoral immunity, mainly owing to mutations in the receptor-binding motif; however, unlike naturally occurring Omicron, it efficiently replicated in cell lines and primary-like distal lung cells. Similarly, in K18-hACE2 mice, although virus bearing Omicron S caused less severe disease than the ancestral virus, its virulence was not attenuated to the level of Omicron. Further investigation showed that mutating non-structural protein 6 (nsp6) in addition to the S protein was sufficient to recapitulate the attenuated phenotype of Omicron. This indicates that although the vaccine escape of Omicron is driven by mutations in S, the pathogenicity of Omicron is determined by mutations both in and outside of the S protein.

Investigating measurement invariance of the Emotion Regulation Questionnaire-8 (ERQ-8) across 29 countries.

The widely used Emotion Regulation Questionnaire (ERQ) measures the habitual use of cognitive reappraisal and expressive suppression. Recently, a more economical 8-item version of the ERQ was proposed that showed good model fit. We assessed whether the latent constructs of the ERQ-8 are generalizable across different countries and cultures. To this end, we used data from the COVIDiSTRESS survey and investigated measurement invariance of the ERQ-8 in a large sample that included 11,288 individuals from 29 countries with diverse cultural backgrounds. Our analyses revealed configural and metric invariance of the ERQ-8 in 14 countries. The results suggest that emotion regulation strategies may not readily converge across all cultures. This underscores the importance of testing measurement invariance before interpreting observed differences and similarities between countries. Supplementary information: The online version contains supplementary material available at 10.1007/s12144-022-04220-6.

Optimized ACE2 decoys neutralize antibody-resistant SARS-CoV-2 variants through functional receptor mimicry and treat infection in vivo.

As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) evolves to escape natural antibodies, it also loses sensitivity to therapeutic antibody drugs. By contrast, evolution selects for binding to ACE2, the cell-surface receptor required for SARS-CoV-2 infection. Consistent with this, we find that an ACE2 decoy neutralizes antibody-resistant variants, including Omicron, with no loss in potency. To identify design features necessary for in vivo activity, we compare several enzymatically inactive, Fc effector-silenced ACE2-Fc decoys. Inclusion of the ACE2 collectrin-like domain not only improves affinity for the S protein but also unexpectedly extends serum half-life and is necessary to reduce disease severity and viral titer in Syrian hamsters. Fc effector function is not required. The activity of ACE2 decoy receptors is due, in part, to their ability to trigger an irreversible structural change in the viral S protein. Our studies provide a new understanding of how ACE2 decoys function and support their development as therapeutics to treat ACE2-dependent coronaviruses.

Virtual Tumor Board Increases Provider Attendance and Case Presentations.

PURPOSE: Many cancer centers engage in multidisciplinary tumor board meetings to determine the optimal approach to complex cancer care. With the onset of the COVID-19 pandemic, many institutions changed the format of these meetings from in-person to virtual. The aim of this study was to determine if the change to a virtual meeting format had an impact on attendance and cases presented. METHODS: Tumor board records were analyzed to obtain attendance and case presentation information at a National Cancer Institute-designated Comprehensive Cancer Center. Twelve-month in-person tumor board data were compared with 12-month virtual tumor board data to assess for difference in attendance and case presentation patterns. RESULTS: Seven separate weekly tumor board meetings at the beginning of the study (breast, GI, gynecology, liver, lung, melanoma, and urology) were expanded to nine meetings on the virtual platform (+endocrine and pancreas). Overall attendance increased by 46% on the virtual platform compared with in-person meetings (4,030 virtual attendances v 2,753 in-person, P < .001). Increased attendance was present across all specialties on the virtual platform. In addition, the number of patient cases discussed increased from 2,127 in in-person meeting to 2,656 on the virtual platform (a 20% increase, P < .001). CONCLUSION: A significant increase was observed in overall tumor board attendance and in case presentations per meeting, requiring the expansion of additional weekly meetings. Furthermore, in a major cancer center with multiple community affiliates, virtual tumor boards may encourage increased participation from remote sites with the benefit of obtaining expert specialist advice as compared with geographically challenging in-person meetings.

Alterations in the Kynurenine-Tryptophan Pathway and Lipid Dysregulation Are Preserved Features of COVID-19 in Hemodialysis.

Coronavirus disease 2019 (COVID-19)-induced metabolic alterations have been proposed as a source for prognostic biomarkers and may harbor potential for therapeutic exploitation. However, the metabolic impact of COVID-19 in hemodialysis (HD), a setting of profound a priori alterations, remains unstudied. To evaluate potential COVID-19 biomarkers in end-stage kidney disease (CKD G5), we analyzed the plasma metabolites in different COVID-19 stages in patients with or without HD. We recruited 18 and 9 asymptomatic and mild, 11 and 11 moderate, 2 and 13 severely affected, and 10 and 6 uninfected HD and non-HD patients, respectively. Plasma samples were taken at the time of diagnosis and/or upon admission to the hospital and analyzed by targeted metabolomics and cytokine/chemokine profiling. Targeted metabolomics confirmed stage-dependent alterations of the metabolome in non-HD patients with COVID-19, which were less pronounced in HD patients. Elevated kynurenine levels and lipid dysregulation, shown by an increase in circulating free fatty acids and a decrease in lysophospholipids, could distinguish patients with moderate COVID-19 from non-infected individuals in both groups. Kynurenine and lipid alterations were also associated with ICAM-1 and IL-15 levels in HD and non-HD patients. Our findings support the kynurenine pathway and plasma lipids as universal biomarkers of moderate and severe COVID-19 independent of kidney function.

Public Stigmatization of People With Intellectual Disability During the COVID-19 Pandemic.

This study aimed to examine the level of discrimination against people with intellectual disability during COVID-19, and assessed stereotypes, levels of familiarity with people with intellectual disability, and personal experiences with COVID-19 as potential correlates. A cross-sectional study was conducted using a large sample from the Dutch population (n = 1,797). Salient stereotype factors of people with intellectual disability were "friendly" and "in need of help," but not "give nuisance." Those respondents who were unfamiliar with people with intellectual disability in real life demonstrated higher levels of discrimination, perceiving them as more of a nuisance and as being less in need of help, in comparison to those who were more familiar. People with intellectual disability were judged by an ambivalent set of stereotypes during the COVID-19 pandemic that were in line with pre-COVID-19 findings and as such seemed to be fairly persistent and robust. There is a pressing need to both raise awareness of stereotypes towards and discrimination against people with intellectual disability via advocacy and education, and to facilitate positive encounters.

Simultaneous Detection of SARS-CoV-2 and Influenza Virus in Wastewater of Two Cities in Southeastern Germany, January to May 2022.

Dependent on the excretion pattern, wastewater monitoring of viruses can be a valuable approach to characterizing their circulation in the human population. Using polyethylene glycol precipitation and reverse transcription-quantitative PCR, the occurrence of RNA of SARS-CoV-2 and influenza viruses A/B in the raw wastewater of two treatment plants in Germany between January and May 2022 was investigated. Due to the relatively high incidence in both exposal areas (plant 1 and plant 2), SARS-CoV-2-specific RNA was determined in all 273 composite samples analyzed (concentration of E gene: 1.3 × 104 to 3.2 × 106 gc/L). Despite a nation-wide low number of confirmed infections, influenza virus A was demonstrated in 5.2% (concentration: 9.8 × 102 to 8.4 × 104 gc/L; plant 1) and in 41.6% (3.6 × 103 to 3.0 × 105 gc/L; plant 2) of samples. Influenza virus B was detected in 36.0% (7.2 × 102 to 8.5 × 106 gc/L; plant 1) and 57.7% (9.6 × 103 to 2.1 × 107 gc/L; plant 2) of wastewater samples. The results of the study demonstrate the frequent detection of two primary respiratory viruses in wastewater and offer the possibility to track the epidemiology of influenza by wastewater-based monitoring.

Investigating the cause of a 2021 winter wave of COVID-19 in a border region in Eastern Germany: a mixed-methods study, August to November 2021 (preprint)

In winter 2020 and 2021 many countries worldwide experienced a COVID-19 pandemic wave which led to severe burdens on healthcare systems and huge economic losses. Yet, it remains unclear how the winter waves started and many debates are ongoing about actions necessary to prevent future winter waves. In this study we deciphered the dynamic course of a winter wave in 2021 in Saxony, a state in Eastern Germany neighboring Czech Republic and Poland. The information we achieved might help future pandemic prevention. The dynamic course of the 2021 winter wave in Saxony was investigated through integration of multiple virus genomic epidemiology approaches and functional evaluations of locally circulating variants. Through international collaborations, we performed genomic epidemiology analysis on a weekly base with samples from Saxony and also from one neighbor region in the Czech Republic. Phylogeny analyses were used to track transmission chains, monitor virus genetic changes and identify emerging variants. Phylodynamic approaches have been applied to track the dynamic changes of transmission clusters. For identified local variants of interest, active viruses were isolated and functional evaluations were performed. Genomic epidemiology studies revealed multiple long-lasting community transmission clusters acting as the major driving forces for the winter wave 2021. Analysis of the dynamic courses of two representative long-lasting community transmission clusters indicated similar dynamic changes. In the first 6-8 weeks, the relevant variant was mainly circulating in a small region among young and middle-aged people; after eight weeks, the ratio of people aged above 60 years in the infected population markedly increased, and the virus got more widely spread to distant regions. On the other hand, the transmission cluster caused by a locally occurring variant showed a different transmission pattern. It got geographically widely distributed within six weeks, with many people aged above 60 years being infected since the beginning of the cluster, indicating a higher risk for escalating healthcare burdens. This variant displayed a relative growth advantage compared to co-circulating Delta sub-lineages. Functional analyses revealed a replication advantage, but no advantage in immune evasion ability. This study indicated that long-lasting community transmission clusters starting between August and October caused by imported variants as well as locally occurring variants all contributed to the development of the 2021 winter wave in Saxony. In particular, the cluster derived from a locally occurring variant with certain growth advantage might have stressed local healthcare systems.