ABSTRACT
Purpose: COViK - a prospective hospital-based multicenter case-control study in Germany - aims to assess the effectiveness of COVID-19 vaccines against severe disease. Here, we report vaccine effectiveness (VE) against COVID-19-caused hospitalization and intensive care treatment during the Omicron wave. Methods: We analyzed data from 276 cases with COVID-19 and 494 control patients recruited in 13 hospitals from 1 December 2021 to 5 September 2022. We calculated crude and confounder-adjusted VE estimates. Results: 21% of cases (57/276) were not vaccinated, compared to 5% of controls (26/494; p < 0.001). Confounder-adjusted VE against COVID-19-caused hospitalization was 55.4% (95% CI: 12-78%), 81.5% (95% CI: 68-90%) and 95.6% (95% CI: 88-99%) after two, three and four vaccine doses, respectively. VE against hospitalization due to COVID-19 remained stable up to one year after three vaccine doses. Conclusion: Three vaccine doses remained highly effective in preventing severe disease and this protection was sustained; a fourth dose further increased protection.
Subject(s)
COVID-19ABSTRACT
While current guidelines recommend the use of respiratory tract specimens for the direct detection of SARS-CoV-2 infection, saliva has recently been suggested as preferred sample type for the sensitive detection of SARS-CoV-2 B.1.1.529 (Omicron). Here, we compare the clinical diagnostic sensitivity of paired buccal saliva swabs and combined oro-/nasopharyngeal swabs from hospitalized, symptomatic COVID-19 patients collected at median six days after symptom onset by real-time polymerase chain reaction (PCR) and antigen test. Of the tested SARS-CoV-2 positive sample pairs, 55.8% were identified as Omicron BA.1 and 44.2% as Omicron BA.2. Real-time PCR from buccal swabs generated significantly higher quantification cycle (Cq) values compared to those from matched combined oro-/nasopharyngeal swabs and resulted in an increased number of false-negative PCR results. Reduced diagnostic sensitivity of buccal swabs by real-time PCR was observed already at day one after symptom onset. Similarly, detection rates using the Abbott COVID-19 Ag Rapid Test Device were reduced in buccal swabs compared to those using combined oro-/nasopharyngeal swabs. Our results suggest reduced clinical diagnostic sensitivity of saliva from buccal swabs in comparison to combined oro-/nasopharyngeal swabs in the detection of Omicron in symptomatic individuals.
Subject(s)
COVID-19ABSTRACT
BACKGROUNDIn November 2021, the first case of SARS-CoV-2 "variant of concern" (VOC) B.1.1.529 ("Omicron") was reported in Germany, alongside global reports of reduced vaccine efficacy against infections with this variant. The potential threat posed by the rapid spread of this variant in Germany remained, at the time, elusive. METHODSWe developed a variant-dependent population-averaged susceptible-exposed-infected-recovered (SEIR) infectious disease model. The model was calibrated on the observed fixation dynamics of the Omicron variant in December 2021, and allowed us to estimate potential courses of upcoming infection waves in Germany, focusing on the corresponding burden on intensive care units (ICUs) and the efficacy of contact reduction strategies. RESULTSA maximum median incidence of approximately 300 000 (50% PI in 1000: [181,454], 95% PI in 1000: [55,804]) reported cases per day was expected with the median peak occurring in the mid of February 2022, reaching a cumulative Omicron case count of 16.5 million (50% PI in mio: [11.4, 21.3], 95% PI in mio: [4.1, 27.9]) until Apr 1, 2022. These figures were in line with the actual Omicron waves that were subsequently observed in Germany with respective peaks occurring in mid February (peak: 191k daily new cases) and mid March (peak: 230k daily new cases), cumulatively infecting 14.8 million individuals during the study period. The model peak incidence was observed to be highly sensitive to variations in the assumed generation time and decreased with shorter generation time. Low contact reductions were expected to lead to containment. Early, strict, and short contact reductions could have led to a strong "rebound" effect with high incidences after the end of the respective non-pharmaceutical interventions. Higher vaccine uptake would have led to a lower outbreak size. To ensure that ICU occupancy remained below maximum capacity, a relative risk of requiring ICU care of 10%-20% was necessary (after infection with Omicron vs. infection with Delta). CONCLUSIONSWe expected a large cumulative number of infections with the VOC Omicron in Germany with ICU occupancy likely remaining below capacity nevertheless, even without additional non-pharmaceutical interventions. Our estimates were in line with the retrospectively observed waves. The results presented here informed legislation in Germany. The methodology developed in this study might be used to estimate the impact of future waves of COVID-19 or other infectious diseases.
Subject(s)
COVID-19 , Communicable DiseasesABSTRACT
We included 852 patients in a prospectively recruiting multicenter matched case-control study in Germany to assess vaccine effectiveness (VE) in preventing COVID-19-associated hospitalization (Delta-variant dominance). Two-dose VE was 89% (95%CI 84-93%) overall, 79% in patients with >2 comorbidities and 77% in adults aged 60-75 years. A third dose increased VE to >93% in all patient-subgroups.
Subject(s)
COVID-19ABSTRACT
Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections and bronchiolitis in young children. The seasonal pattern of RSV is shaped by short-lived immunity, seasonally varying contact rates and pathogen viability. The magnitude of each of these parameters is not fully clear. The disruption of the regular seasonality of RSV during the COVID pandemic in 2020 due to control measures, and the ensuing delayed surge in RSV cases provides an opportunity to disentangle these factors and to understand the implication for vaccination strategies. A better understanding of the drivers of RSV seasonality is key for developing future vaccination strategies. Methods: We developed a mathematical model of RSV transmission, which simulates the sequential re-infection (SEIRRS4) and uses a flexible Von Mises function to model the seasonal forcing. Using MCMC we fit the model to laboratory confirmed RSV data from 2010-2022 from NSW while accounting for the reduced contact rates during the pandemic with Google mobility data. We estimated the baseline transmission rate, its amplitude and shape during RSV season as well as the duration of immunity. The resulting parameter estimates were compared to a fit to pre-pandemic data only, and to a fit with a cosine forcing function. We then simulated the expected shifts in peak timing and amplitude under two vaccination strategies: continuous and seasonal vaccination. Results: We estimate that RSV dynamics in NSW can be best explained by a high effective baseline transmission rate (2.94/d, 95% CrI 2.72-3.19) and a narrow peak with a maximum 13% increase compared to the baseline transmission rate. We also estimate the duration of post infection temporary but sterilizing immunity to be 412 days (95% CrI 391-434). A cosine forcing resulted in a similar fit and posterior estimates. Excluding the data from the pandemic period in the fit increased parameter correlation and yielded less informative posterior distributions. The continuous vaccination strategy led to more extreme seasonal incidence with a delay in the peak timing and a higher amplitude whereas seasonal vaccination flattened the incidence curves. Conclusion: Quantifying the parameters that govern RSV seasonality is key in determining potential indirect effects from immunization strategies as those are being rolled out in the next few years.
Subject(s)
Bronchiolitis , Respiratory Syncytial Virus Infections , Respiratory Tract InfectionsABSTRACT
Background The SARS-CoV-2 Omicron variant is currently the dominant variant globally. This 3 rd interim analysis of a living systematic review summarizes evidence on COVID-19 vaccine effectiveness (VE) and duration of protection against Omicron. Methods We systematically searched the COVID-19 literature for controlled studies evaluating the effectiveness of COVID-19 vaccines approved in the European Union up to 14/01/2022, complemented by hand-searches of websites and metasearch engines up to 11/02/2022. We considered the following comparisons: full primary immunization vs. no vaccination; booster immunization vs. no vaccination; booster vs. primary immunization. VE against any confirmed SARS-CoV-2 infection, symptomatic, and severe COVID-19 (i.e. COVID-19-related hospitalization, ICU-admission, or death) was indicated providing estimate ranges. Meta-analysis was not performed due to high study heterogeneity. Risk of bias was assessed with ROBINS-I, certainty of evidence evaluated using GRADE. Results We identified 26 studies, including 430 to 2.2 million participants. VE against any confirmed SARS-CoV-2 infection compared to no vaccination ranged between 0-62% after full primary immunization, and between 34-66% after a booster dose. VE-range for booster vs. primary immunization was 34-54.6%. Against symptomatic COVID-19, VE ranged between 6-76% after full primary immunization, and between 19-73.9% after booster immunization, if compared to no vaccination. When comparing booster vs. primary immunization VE ranged between 56-69%. VE against severe COVID-19 compared to no vaccination ranged between 3-84% after full primary immunization, and between 12-100% after a booster dose. One study compared booster vs. primary immunization (VE 100%, 95% CI 71.4-100). VE was characterized by a moderate to strong decline within three to six months for SARS-CoV-2 infections and symptomatic COVID-19. Against severe COVID-19 protection remained robust at least for up to six months. Waning immunity was more profound after primary than booster immunization. Risk of bias was moderate to critical across studies and outcomes. GRADE-certainty was very low for all outcomes. Author’s conclusions Under the Omicron variant, effectiveness of EU-licensed COVID-19 vaccines in preventing any SARS-CoV-2 infection or mild disease is low and only short-lasting after primary immunization, but can be improved by booster vaccination. VE against severe COVID-19 remains high and is long-lasting, especially after receiving the booster vaccination.
Subject(s)
COVID-19ABSTRACT
After having affected the population for two years, the COVID-19 pandemic has reached a phase where a considerable number of people in Germany have been either infected with a SARS-CoV-2 variant, vaccinated, or both. Yet the full extent to which the population has been in contact with either virus or vaccine remains elusive, particularly on a regional level, because (a) infection counts suffer from under-reporting, and (b) the overlap between the vaccinated and recovered subpopulations is unknown. Since previous infection, vaccination, or especially a combination of both reduce the risk of severe disease, a high share of individuals with SARS-CoV-2 immunity lowers the probability of severe outbreaks that could potentially overburden the public health system once again, given that emerging variants do not escape this reduction in susceptibility. Here, we estimate the share of immunologically naive individuals by age group for each of the 16 German federal states by integrating an infectious disease model based on weekly incidences of SARS-CoV-2 infections in the national surveillance system and vaccine uptake, as well as assumptions regarding under-ascertainment. We estimate a median share of 7.0% of individuals in the German population have neither been in contact with vaccine nor any variant as of March 31, 2022 (quartile range [3.6%- 9.8%]). For the adult population at higher risk of severe disease, this figure is reduced to 3.5% [1.3%-5.5%] for ages 18-59 and 4.3% [2.7%-5.8%] for ages 60 and above. However, estimates vary between German states mostly due to heterogeneous vaccine uptake. Excluding Omicron infections from the analysis, 16.1% [14.0%-17.8%] of the population in Germany, across all ages, are estimated to be immunologically naive, highlighting the large impact the Omicron wave had until the beginning of spring in 2022.
Subject(s)
COVID-19 , Severe Acute Respiratory Syndrome , Communicable Diseases , InfectionsABSTRACT
In March 2021 several cases of cerebral venous sinus thrombosis (CVST) accompanied by thrombocytopenia were reported that occurred within two weeks after immunization with a viral vector-based COVID-19 vaccine. This study aimed to assess the background incidence of CVST and CVST with concurrent thrombocytopenia in adults using anonymized claims data from 2015-2019 in Germany. The average annual CVST incidence was 1.9 per 100,000 individuals (95%-CI 1.4-2.3). It was higher in women aged 18 to 59 years as compared to same-aged men. In contrast to the currently reported immunization-related cases, CVST was rarely associated with concurrent thrombocytopenia or death.
Subject(s)
COVID-19ABSTRACT
Background: This umbrella review summarises the global evidence on the risk of severe COVID-19 outcomes in patients with pre-existing health conditions. Methods: Systematic reviews (SRs) were identified in PubMed, Embase/Medline, and seven pre-print servers until December 11, 2020. Risk estimates (odds ratio (OR), hazard ratio (HR), relative risk (RR)) for hospitalisation, intensive care unit admission, intubation, and death were extracted from primary studies. Meta-analyses were performed stratified by regions of the World Health Organisation. The evidence certainty was assessed using GRADE. Registration number CRD42020215846.Findings: 160 primary studies from 120 SRs contributed 464 estimates for 42 pre-existing conditions. Most studies were conducted in North America, European, and Western Pacific regions. Evidence from Africa, South/Latin America, and Eastern Mediterranean region was scarce. No evidence was available from South-East Asia region. Diabetes (HR 1∙2-2∙0 (1∙1-2∙8)), obesity (OR 1∙5-1∙75 (1∙1-2∙3)), heart failure (HR 1∙3-3∙3(0∙9-8∙2)), COPD (HR 1∙12-2∙2 (1∙1-3∙2)), and dementia (HR 1∙4-7.7 (1∙2-39∙6)) were associated with fatal COVID-19 in different regions, although the estimates varied. Evidence from Europe and North America showed that liver cirrhosis (OR 3∙2-5∙9 (0∙9-27∙7)) and active cancer (OR 1∙6-4∙7 (0∙5-14∙9)) were also associated with increased risk of death. Association between HIV and severe COVID-19 showed regional heterogeneity, with an increased risk of death in Africa (HR 1∙7 (1∙3-2∙2)). GRADE certainty was moderate to high for most associations.Interpretation: Risk of severe COVID-19 is consistently increased in certain patient subgroups across geographical regions, showing high variability in others. The results can be used to inform COVID-19 vaccine prioritisation or other intervention strategies.Funding Statement: Project ImVaCov – German Federal Ministry of HealthDeclaration of Interests: Authors declare no conflicts of interest.