Ineffectiveness of international travel restrictions to contain spread of the SARS-CoV-2 Omicron BA.1 variant: a continent-wide laboratory-based observational study from Africa (preprint)

Background: In mid-November 2021, the SARS-CoV-2 Omicron BA.1 variant was detected in Southern Africa, prompting international travel restrictions of unclear effectiveness that exacted a substantial economic toll. Methods: Amidst the BA.1 wave, we tested 13,294 COVID-19 patients in 24 African countries between mid-2021 to early 2022 for BA.1 and Delta variants using real-time reverse transcription-PCR tests. The diagnostic precision of the assays was evaluated by high-throughput sequencing in four countries. The observed BA.1 spread was compared to mobility-based mathematical simulations. Findings: By November-December 2021, BA.1 had replaced the Delta variant in all African sub-regions following a South-North gradient, with a median Rt of 2.4 up to 30 days before BA.1 became predominant. PCR-based South-North spread was in agreement with phylogeographic reconstructions relying on 939 SARS-CoV-2 genomes from GISAID. PCR-based reconstructions of country-level BA.1 predominance correlated significantly in time with the emergence of BA.1 genomic sequences on GISAID (p=0.0035, cor=0.70). First BA.1 detections in affluent settings beyond Africa were predicted adequately in time by mobility-based mathematical simulations (p<0.0001). BA.1-infected inbound travelers departing from five continents were identified in five Western countries and one Northern African country by late November/early December 2021, highlighting fast global BA.1 spread aided by international travel. Interpretation: Unilateral travel bans were poorly effective because by the time they came into effect, BA.1 was already widespread in Africa and beyond. PCR-based variant typing combined with mobility-based mathematical modelling can inform rapidly and cost-efficiently on Rt, spread to inform non-pharmaceutical interventions.

Dynamics of upper respiratory tract infections before, during, and after the COVID-19 pandemic in Germany: a cross-sectional study of 2,167,453 outpatients (preprint)

Background Although the burden of the COVID-19 pandemic on global healthcare systems is declining, long-term sequelae such as long COVID syndrome and other disease dynamics not primarily associated with COVID-19 remain a challenge. Recent data suggest that the incidence of non-COVID upper respiratory tract infections (URTI) is increasing sharply in the post-pandemic period, but there is a lack of real-world data from Germany in this respect.Methods This cross-sectional study evaluated the number of patients with a diagnosis of URTI from the Disease Analyzer database (IQVIA) between January 2019 and December 2022. The number of UTRI diagnoses per practice and the duration of sick leave per patient were compared over time.Results A total of 1,872,935 individuals (1,403,907 patients from general practices (GP) and 469,028 patients from pediatric offices) were included, 48% of whom were female. The number of URTI patients per practice was significantly higher in 2022 than in 2019 (732 vs. 464, 58%, p < 0.001) and this was observed for both women (56%, p < 0.001) and men (60%, p < 0.001). The post-pandemic increase in the number of URTI diagnoses correlated with age and was highest in the age group between 18–30 years (22%, p < 0.001) and lowest in older patients > 70 years (3%). In pediatric patients (< 18 years), the increase was highest in the age group ≤ 5 years (89%). Both the number of patients per practice on sick leave due to URTI (184 vs. 92) and the average duration of sick leave (+ 2 days) increased from 2019 to 2022.Conclusion Our data suggest a dramatic increase in the incidence of URTI among all demographic subgroups in Germany between 2019 and 2022, which was associated with a tremendous impact on socioeconomic variables such as the frequency or duration of sick leave. These data could be of great importance in current pandemic management and the management of future pandemics.

Convalescent Plasma Treatment for SARS-CoV-2 Infected High-risk Patients - a Matched Pair Analysis to the LEOSS Cohort (preprint)

Background: Establishing the optimal treatment for COVID-19 patients remains challenging. Specifically, immunocompromised and pre-diseased patients are at high risk for severe disease course and face limited therapeutic options. Convalescent plasma has been considered as therapeutic approach, but reliable data are lacking, especially for high-risk patients. Methods: We performed a retrospective analysis of 55 hospitalized COVID-19 patients with high risk for disease progression, primarily due to immunosuppression from cancer, solid organ transplantation, autoimmune disease, dialysis. A matched-pairs analysis (1:4) was performed with 220 patients from the Lean European Open Survey on SARS-CoV-2-infected Patients (LEOSS) who were treated or not treated with convalescent plasma. Results: Both cohorts, had high mortality (UKD 41.8%, LEOSS 34.1%). A matched-pairs analysis showed no significant effect on mortality. CP administration before the formation of pulmonary infiltrates showed the lowest mortality in both cohorts (10%), whereas mortality in the complicated phase was 27.8%. CP administration during the critical phase revealed the highest mortality; UKD 60.9%, LEOSS 48.3%. Conclusion: In our cohort of SARS-CoV-2 infected patients with severe comorbidities CP did not significantly reduce mortality in a retrospective matched pairs analysis. However, our data supports the concept that a reduction in mortality is achievable when CP is administered early.

Immune response to third SARS-CoV-2 vaccination in seronegative kidney transplant recipients: possible improvement by mycophenolate mofetil reduction (preprint)

BackgroundModification of vaccination strategies is needed to improve the immune response to SARS-CoV-2 vaccination in kidney transplant recipients (KTRs). MethodsThis multicenter observational study aimed to determine antibody kinetics among 60 seropositive KTRs and analyzed the effects of the third vaccination against SARS-CoV-2 in 174 previously seronegative KTRs. We investigated whether mycophenolate mofetil (MMF) dose reduction by 25-50% prior the third vaccination influences vaccination success. Results18 of 60 (30%) seropositive KTRs became seronegative in the serological assay within six months. Loss of antibodies was predicted by low initial antibody levels ([≤]206.8 BAU/ml), older age, and impaired graft function. A third vaccination in previously seronegative KTRs induced seroconversion in 56 of 174 (32.1%) KTRs with median antibody levels 119 (76-353) BAU/ml and median neutralizing capacity titer of 1:10 (0- 1:40). Multivariate logistic regression revealed that initial antibody levels (OR 1.39, 95% CI 1.09-1.76), graft function (OR 0.05, 95% CI 0.01-0.39), time after transplantation (OR 1.04, 95% CI 1.02-1.07) and MMF trough levels (OR 0.43, 95% CI 0.21-0.88) correlated with seroconversion, p<0.05. After controlling for these confounders, the effect of MMF dose reduction was calculated using propensity score matching. KTRs in the MMF reduction group had significantly lower MMF serum concentrations prior to the third vaccination and were more likely to develop antibody levels [≥]35.2 BAU/ml than their matched KTRs (p=0.02). ConclusionsTemporary reduction in MMF dose might be a promising approach to improve the immune response in KTRs.

Acute cardiac side effects after COVID-19 mRNA vaccination, a case series (preprint)

Background: Since development and approval of the world´s first mRNA vaccines, created under pressure of the global pandemic caused by SARS-CoV-2, potential side effects have naturally been a much-debated topic. Vaccination may be one, if not the only way out of the pandemic claiming more than 4 million deaths worldwide to date. Potential side effects from vaccination have long been controversial, and case reports of fatal side effects have been published. Therefore, data are needed to identify persons being at high risk for potential side effects. Until September 30, 2021, 1.243 cases of myocarditis after vaccination with BNT162b2 Comirnaty© in young adults were registered by the Paul-Ehrlich-Institute in Germany alone. The exact pathophysiology and the risk factors for myocarditis following vaccination remain unclear. We present a case series of eight patients with cardiac symptom shortly after SARS-CoV-2 mRNA vaccination (BNT162b6, Biontech, Comirnaty© or mRNA-1237 Moderna, Spikevax©).Patients and Methods: Eight patients between 13-56 years of age, vaccinated with mRNA vaccine either BNT162b2 or mRNA-1273 between January and August 2021 developed cardiac side effects shortly after either their first or second vaccination. Clinical data were retrieved from the clinical information system and analyzed. To support diagnosis of myocarditis or pericarditis, cardiac magnetic resonance imaging (MRI) was performed shortly after onset of symptoms and investigated further in severe cases. Symptoms were defined as dyspnea, chest pain, cardiac arrhythmia as determined by electrocardiography.Results: Eight patients (five males and three females) developed cardiac symptoms compatible with myocarditis according to CDC criteria shortly after SARS-CoV-2 mRNA vaccination. Three patients (two males, one female) required hospitalization due to severe chest pain and elevated troponin levels. All patients recovered fully within seven days after symptom onsetConclusion: Our data suggest that cardiac adverse events such as myocarditis or pericarditis shortly after SARS-CoV-2 mRNA vaccination are rare but possible and occur particularly in male patients.