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On 30 January 2020, the World Health Organization (WHO) declared the current novel coronavirus disease 2019 (COVID-19) as a public health emergency of international concern and later characterized it as a pandemic. New data show that excess body mass and vitamin D deficiency might be related to the disease severity and mortality. The aim of this study was to evaluate whether latitude, as a proxy of sunlight exposure and Vitamin D synthesis, and prevalent obesity among European populations, is related to COVID-19 spread and severity. European COVID-19 data (incidence and fatality), including information on the prevalence of obesity, social distancing, and others were obtained by the "Our World in Data" website on 17 April 2021. Adjusted analysis showed that higher COVID-19 incidence and fatality were pictured in countries being in higher latitude, both during the whole period, as well as, during the time period 1 November 2020-31 March 2021. Higher incidence and fatality of COVID-19 were observed where the prevalence of overweight/obesity was higher during the whole time period, whereas during the time period 1 November 2020-31 March 2021, only COVID-19 incidence was higher but not a fatality. The present results provide insights for targeted interventions and preventive strategies against COVID-19.

The aim of our study was to investigate the immunogenicity of the BNT162b2 vaccination according to the age and medical status of vaccinated individuals. A total of 511 individuals were enrolled (median age: 54.0 years, range: 19–105); 509 of these individuals (99.6%) received two doses of BNT162b2 at an interval of 21 days. IgG and IgA responses were evaluated on days 21, 42, 90, and 180 after the first dose with chemiluminescent microparticle and ELISA assays. The cell-mediated immune responses were assessed by an automated interferon-gamma release assay. We demonstrated positive antibody responses after vaccination for the majority of enrolled participants, although waning of IgG and IgA titers was also observed over time. We further observed that the intensity of humoral responses was positively correlated with increased age and prior COVID-19 infection (either before or after the first vaccination). Moreover, we found that only a medical history of autoimmune disease could affect the intensity of IgA and IgG responses (3 weeks after the primary and secondary immunization, respectively), while development of systemic adverse reactions after the second vaccination dose was significantly associated with the height of IgG responses. Finally, we identified a clear correlation between humoral and cellular responses, suggesting that the study of cellular responses is not required as a routine laboratory test after vaccination. Our results provide useful information about the immunogenicity of COVID-19 vaccination with significant implications for public health vaccination strategies. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Several lines of evidence suggest that binding SARS-CoV-2 antibodies such as anti-SARSCoV-2 RBD IgG (anti-RBD) and neutralising antibodies (NA) are correlates of protection against SARS-CoV-2, and the correlation of anti-RBD and NA is very high. The effectiveness (VE) of BNT162b2 in preventing SARS-CoV-2 infection wanes over time, and this reduction is mainly associated with waning immunity, suggesting that the kinetics of antibodies reduction might be of interest to predict VE. In a study of 97 health care workers (HCWs) vaccinated with the BNT162b2 vaccine, we assessed the kinetics of anti-RBD 30–250 days after vaccination using 388 individually matched plasma samples. Anti-RBD levels declined by 85%, 92%, and 95% at the 4th, 6th, and 8th month from the peak, respectively. The kinetics were estimated using the trajectories of anti-RBD by various models. The restricted cubic splines model had a better fit to the observed data. The trajectories of anti-RBD declines were statistically significantly lower for risk factors of severe COVID-19 and the absence of vaccination side effects. Moreover, previous SARS-CoV-2 infection was associated with divergent trajectories consistent with a slower anti-RBD decline over time. These results suggest that anti-RBD may serve as a harbinger for vaccine effectiveness (VE), and it should be explored as a predictor of breakthrough infections and VE. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for ‘long-COVID’ diagnosis. Nevertheless, ‘long-COVID’ is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data. The most frequent neurological manifestations of ‘long-COVID’ encompass fatigue; ‘brain fog’; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of ‘long-COVID’, neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological ‘long-COVID’ sequelae. In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological ‘long-COVID’ sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for ‘long-COVID’ are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological ‘long-COVID’ symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological ‘long-COVID’ sequelae. © The Author(s), 2022.

During the COVID-19 pandemic, wastewater-based epidemiology (WBE) has been engaged to complement medical surveillance and in some cases to also act as an early diagnosis indicator of viral spreading in the community. Most efforts worldwide by the scientific community and commercial companies focus on the formulation of protocols for SARS-CoV-2 analysis in wastewater and approaches addressing the quantitative relationship between WBE and medical surveillance are lacking. In the present study, a mathematical model is developed which uses as input the number of daily positive medical tests together with the highly non-linear shedding rate curve of individuals to estimate the evolution of global virus shedding rate in wastewater along calendar days. A comprehensive parametric study by the model using as input actual medical surveillance and WBE data for the city of Thessaloniki (similar to 700,000 inhabitants, North Greece) during the outbreak of November 2020 reveals the conditions under which WBE can be used as an early warning tool for predicting pandemic outbreaks. It is shown that early warning capacity is different along the days of an outbreak and depends strongly on the number of days apart between the day of maximum shedding rate of infected individuals in their disease cycle and the day of their medical testing. The present data indicate for Thessaloniki an average early warning capacity of around 2 days. Moreover, the data imply that there exists a proportion between unreported cases (asymptomatic persons with mild symptoms that do not seek medical advice) and reported cases. The proportion increases with the number of reported cases. The early detection capacity of WBE improves substantially in the presence of an increasing number of unreported cases. For Thessaloniki at the peak of the pandemic in mid-November 2020, the number of unreported cases reached a maximum around 4 times the number of reported cases. (C) 2021 The Authors. Published by Elsevier B.V.

In this Article, the surname of author Christos Hadjichristodoulou surname was incorrectly spelled ‘Hadjicristodoulou’. The original Article has been corrected online. © 2022, The Author(s), under exclusive licence to Springer Nature Limited.

Coronavirus disease 2019 (COVID-19) has resulted in approximately 5 million deaths around the world with unprecedented consequences in people’s daily routines and in the global economy. Despite vast increases in time and money spent on COVID-19-related research, there is still limited information about the factors at the country level that affected COVID-19 transmission and fatality in EU. The paper focuses on the identification of these risk factors using a machine learning (ML) predictive pipeline and an associated explainability analysis. To achieve this, a hybrid dataset was created employing publicly available sources comprising heterogeneous parameters from the majority of EU countries, e.g., mobility measures, policy responses, vaccinations, and demographics/generic country-level parameters. Data pre-processing and data exploration techniques were initially applied to normalize the available data and decrease the feature dimensionality of the data problem considered. Then, a linear ε-Support Vector Machine (ε-SVM) model was employed to implement the regression task of predicting the number of deaths for each one of the three first pandemic waves (with mean square error of 0.027 for wave 1 and less than 0.02 for waves 2 and 3). Post hoc explainability analysis was finally applied to uncover the rationale behind the decision-making mechanisms of the ML pipeline and thus enhance our understanding with respect to the contribution of the selected country-level parameters to the prediction of COVID-19 deaths in EU. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Health-Care-Workers (HCWs) are considered at high risk for SARS-CoV-2 infection. We sought to compare rates and severity of Coronavirus disease 2019 (COVID-19) among vaccinated and unvaccinated HCWs conducting a retrospective cohort study in two tertiary Academic Hos-pitals, namely Laiko and Attikon, in Athens, Greece. Vaccinated by BNT162b2 Pfizer-BioNTech COVID-19 mRNA vaccine and unvaccinated HCWs were included and data were collected between 1 January 2021 and 15 September 2021. Overall, 2921 of 3219 HCWs without a history of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection were fully vaccinated during the study period (90.7% at each Hospital). Demographic characteristics were comparable between 102/2921 (3.5%) vaccinated and 88/298 (29.5%) unvaccinated HCWs with COVID-19, although age and occupa-tion differed significantly. None were in need of hospital admission in the vaccinated Group, whereas in the unvaccinated Group 4/88 (4.5%) were hospitalized and one (1.1%) died. Multivariable logistic regression analysis revealed that lack of vaccination was an independent risk factor for COVID-19 with an odds ratio 11.54 (95% CI: 10.75–12.40). Vaccination hesitancy among HCWs resulted to highly increased COVID-19 rates; almost one in three unvaccinated HCWs was SARS-CoV-2 infected during the 9-month period. The absolute need of vaccination of HCWs, including boosting dose, is highlighted. Evidence should be used appropriately to overcome any hesitancy. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Background: Understanding the factors that affect the transmissibility of SARS-CoV-2 remains important to keep transmission low and maximize the health benefits of vaccination. We assessed the factors associated with the transmissibility of SARS-CoV-2 based on contact tracing data. Methods: From 1 October to 9 December 2020, 29,385 laboratory-confirmed SARS-CoV-2 cases (index cases, i.e. the first identified laboratory-confirmed cases or with the earliest symptom onset in a setting) and 64,608 traced contacts were identified in Greece. We assessed the prevalence of symptoms in cases, calculated secondary attack rates and assessed factors associated with infectivity and susceptibility to infection. Results: There were 11,232 contacts secondarily infected (secondary attack rate: 17.4%, 95% CI:17.0–17.8). Contacts aged 0–11 and 12–17 years were less susceptible to infection than adults 65 years or older (odds ratio (OR) [95% CI]: 0.28 [0.26–0.32] and 0.44 [0.40–0.49], respectively). Index cases aged 65 years or older were more likely to infect their contacts than other adults or children/adolescents. The odds of infection [95% CI] were higher in contacts exposed within the household (1.71 [1.59–1.85] vs. other) and in cases with cough (1.17 [1.11–1.25] vs. no cough). There was an interaction between the age of the index and the age of the contact with contacts 65 years or older having a higher probability of infection when exposed to cases of similar age than to children. Conclusions: Our findings highlight the role of age and age mixing in infectivity and susceptibility to SARS-CoV-2 infection. Precautions are necessary for individuals 65 or older as they have higher infectivity and susceptibility in contact with their peers. © 2021 Society for Scandinavian Journal of Infectious Diseases.

In the summer of 2021, European governments removed most NPIs after experiencing prolonged second and third waves of the COVID-19 pandemic. Most countries failed to achieve immunization rates high enough to avoid resurgence of the virus. Public health strategies for autumn and winter 2021 have ranged from countries aiming at low incidence by re-introducing NPIs to accepting high incidence levels. However, such high incidence strategies almost certainly lead to the very consequences that they seek to avoid: restrictions that harm people and economies. At high incidence, the important pandemic containment measure ‘test-trace-isolate-support’ becomes inefficient. At that point, the spread of SARS-CoV-2 and its numerous harmful consequences can likely only be controlled through restrictions. We argue that all European countries need to pursue a low incidence strategy in a coordinated manner. Such an endeavour can only be successful if it is built on open communication and trust. © 2021 The Authors

The discovery and facile synthesis of a new class of sartan-like arterial antihypertensive drugs (angiotensin receptor blockers [ARBs]), subsequently referred to as “bisartans” is reported. In vivo results and complementary molecular modelling presented in this communication indicate bisartans may be beneficial for the treatment of not only heart disease, diabetes, renal dysfunction, and related illnesses, but possibly COVID-19. Bisartans are novel bis-alkylated imidazole sartan derivatives bearing dual symmetric anionic biphenyl tetrazole moieties. In silico docking and molecular dynamics studies revealed bisartans exhibited higher binding affinities for the ACE2/spike protein complex (PDB 6LZG) compared to all other known sartans. They also underwent stable docking to the Zn2+ domain of the ACE2 catalytic site as well as the critical interfacial region between ACE2 and the SARS-CoV-2 receptor binding domain. Additionally, semi-stable docking of bisartans at the arginine-rich furin-cleavage site of the SARS-CoV-2 spike protein (residues 681–686) required for virus entry into host cells, suggest bisartans may inhibit furin action thereby retarding viral entry into host cells. Bisartan tetrazole groups surpass nitrile, the pharmacophoric “warhead” of PF-07321332, in its ability to disrupt the cysteine charge relay system of 3CLpro. However, despite the apparent targeting of multifunctional sites, bisartans do not inhibit SARS-CoV-2 infection in bioassays as effectively as PF-07321332 (Paxlovid). © 2022

Background This is an update on the existing evidence regarding a relationship between infection with human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) in order to contribute on the attempt to define the nature and strength of that relationship. Results Study quality was assessed using the criteria proposed by Moore and Wolfson and by the classification criteria used by the Canadian Task Force on the Periodic Health Examination. Studies were categorized both by experimental technique and by quality (high [A], intermediate [B], and low [C]) as determined by the Moore and Wolfson criteria. Overall, 27 (90%) of 30 studies, 18 (86%) of which were classified as A quality, reached a statistically significant result. According to the Canadian Task Force classification, all studies were categorized as evidence of qualityII-1. Limitations of the available experimental techniques and perspectives for future research are discussed. Conclusions The current review continues to emphasize the need for further, objective, evidence-based examination of the relationship between HHV-6 infection and multiple sclerosis.

Background and Purpose: Cerebral venous sinus thrombosis (CVST) has been reported as a rare adverse event in association with thrombosis-thrombocytopenia syndrome (TTS) following COVID-19 vaccination. Methods: We performed a systematic review and meta-analysis of investigator-initiated registries including confirmed CVST cases, with the aim to calculate (1) the odds ratio of TTS–CVST versus non-TTS–CVST after vector-based vaccines and (2) after non-vector-based vaccines, (3) the in-hospital mortality ratio of TTS–CVST compared to non-TTS–CVST; and (4) the dependency or death at discharge among TTS–CVST compared to non-TTS–CVST cases. Results: Two eligible studies were included in the meta-analysis, comprising a total of 211 patients with CVST associated with COVID-19 vaccination. Vector-based COVID-19 vaccination was associated with a higher likelihood of TTS-associated CVST than with non-TTS–CVST (OR: 52.34, 95% CI 9.58–285.98). TTS–CVST was also associated with higher likelihood of in-hospital mortality (OR: 13.29; 95% CI 3.96–44.60) and death or dependency at discharge compared to non-TTS–CVST (OR: 6.70; 95% CI 3.15–14.26). TTS–CVST was recorded with a shorter interval between vaccination and symptom onset [Mean Difference (MD):-6.54 days; 95% CI − 12.64 to − 0.45], affecting younger patients (MD:-9.00 years; 95% CI − 14.02 to − 3.99) without risk factors for thromboses (OR:2.34; 95% CI 1.26–4.33), and was complicated more frequently with intracerebral hemorrhage (OR:3.60; 95% CI 1.31–9.87) and concomitant thromboses in other sites (OR:11.85; 95% CI 3.51–39.98) compared to non-TTS–CVST cases. Conclusions: TTS–CVST following COVID-19 vaccination has distinct risk factor profile, clinical phenotype and prognosis compared to non-TTS–CVST. Further epidemiological data are required to evaluate the impact of different treatment strategies on outcome of TTS–CVST cases following COVID-19 vaccination. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.

Vaccine hesitancy is a major barrier to achieving large-scale COVID-19 vaccination. We report trends in vaccination intention and associated determinants from surveys in the adult general population in Greece. Four cross-sectional phone surveys were conducted in November 2020 and February, April and May 2021 on nationally representative samples of adults in Greece. Multino-mial logistic regression was used on the combined data of the surveys to evaluate independent predictors of vaccination unwillingness/uncertainty. Vaccination intention increased from 67.6% in November 2020 to 84.8% in May 2021. Individuals aged 65 years or older were more willing to be vaccinated (May 2021: 92.9% vs. 79.5% in 18–39 years, p < 0.001) but between age-groups differences decreased over time. Vaccination intention increased substantially in both men and women, though earlier among men, and was higher in individuals with prograduate education (May 2021: 91.3% vs. 84.0% up to junior high). From multivariable analysis, unwillingness and/or uncertainty to be vaccinated was associated with younger age, female gender (in particular in the April 2021 survey), lower educational level and living with a child ≤12 years old. Among those with vaccine hesitancy, concerns about vaccine effectiveness declined over time (21.6% in November 2020 vs. 9.6% in May 2021, p = 0.014) and were reported more often by men; safety concerns remained stable over time (66.3% in November 2020 vs. 62.1% in May 2021, p = 0.658) and were reported more often by women. In conclusion, vaccination intention increased substantially over time. Tailored communication is needed to address vaccine hesitancy and concerns regarding vaccine safety. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Background: Nation-wide SARS-CoV-2 seroprevalence surveys provide valuable insights into the course of the pandemic, including information often not captured by routine surveillance of reported cases. Methods: A serosurvey of IgG antibodies against SARS-CoV-2 was conducted in Greece between March and December 2020. It was designed as a cross-sectional survey repeated at monthly intervals. The leftover sampling methodology was used and a geographically stratified sampling plan was applied. Results: Of 55,947 serum samples collected, 705 (1.26%) were found positive for anti-SARS-CoV-2 antibodies, with higher seroprevalence (9.09%) observed in December 2020. Highest seropositivity levels were observed in the “0–29” and “30–49” year age groups. Seroprevalence increased with age in the “0–29” age group. Highly populated metropolitan areas were characterized with elevated seroprevalence levels (11.92% in Attica, 12.76% in Thessaloniki) compared to the rest of the country (5.90%). The infection fatality rate (IFR) was estimated at 0.451% (95% CI: 0.382–0.549%) using aggregate data until December 2020, and the ratio of actual to reported cases was 9.59 (7.88–11.33). Conclusions: The evolution of seroprevalence estimates aligned with the course of the pandemic and varied widely by region and age group. Young and middle-aged adults appeared to be drivers of the pandemic during a severe epidemic wave under strict policy measures. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

To identify differences in perception on multi-drug-resistant (MDR) organisms and their management at intensive care units (ICU). A cross-sectional survey was conducted. A proposal addressing a pathogen priority list (PPL) for ICU, arising from the TOTEM study, was compared with a sample of global experts in infections in critically ill patients. The survey was responded by 129 experts. Globally, ESBL Enterobacteriaceae, followed by carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Klebsiella pneumoniae, were the main concerns. Some differences in opinion were identified between 63 (49%) ICU physicians (ICU/anesthesiology) and 43 (33%) infectious disease consultants (ID physicians/microbiologists). The pathogens most concerning in the ICU for intensivists were ESBL Enterobacteriaceae (38%) versus carbapenem-resistant A. baumannii (48.3%) for ID consultants, (p 0.05). Increasing number of ID consultants over intensivists (26% vs 14%) reported difficulty in choosing initial therapy for carbapenem-resistant A. baumannii. For intensivists, the urgent measures to limit development of antibiotic resistance were headed by cohort measures (26.3%) versus increasing nurse/patient ratio (32.5%) for ID consultants, (p 0.05). Regarding effectiveness to prevent MDR development and spread, education programs (42.4%) were the priority for intensivists versus external consultation (35.7%) for ID consultants. Finally, both groups agreed that carbapenem resistance was the most pressing concern ( 70%) regarding emerging resistance. Differences in priorities regarding organisms, infection control practices, and educational priorities were visualized between ID/clinical microbiologists and ICU/anesthesiologists. Multi-disciplinary collaboration is required to achieve best care for ICU patients with severe infections.

Severe COVID-19 pneumonia has been associated with the development of intense inflammatory responses during the course of infections with SARS-CoV-2. Given that human endogenous retroviruses (HERVs) are known to be activated during and participate in inflammatory processes, we examined whether HERV dysregulation signatures are present in COVID-19 patients. By comparing transcriptomes of bronchoalveolar lavage fluid (BALF) of COVID-19 patients and healthy controls, and peripheral blood monocytes (PBMCs) from patients and controls, we have shown that HERVs are intensely dysregulated in BALF of COVID-19 patients compared to those in BALF of healthy control patients but not in PBMCs. In particular, upregulation in the expression of specific HERV families was detected in BALF samples of COVID-19 patients, with HERV-FRD being the most highly upregulated family among the families analyzed. In addition, we compared the expression of HERVs in human bronchial epithelial cells (HBECs) without and after senescence induction in an oncogene-induced senescence model in order to quantitatively measure changes in the expression of HERVs in bronchial cells during the process of cellular senescence. This apparent difference of HERV dysregulation between PBMCs and BALF warrants further studies in the involvement of HERVs in inflammatory pathogenetic mechanisms as well as exploration of HERVs as potential biomarkers for disease progression. Furthermore, the increase in the expression of HERVs in senescent HBECs in comparison to that in noninduced HBECs provides a potential link for increased COVID-19 severity and mortality in aged populations. © 2021 American Society for Microbiology. All rights reserved.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Chains of infections starting from various countries worldwide seeded the outbreak of COVID-19 in Athens, capital city of Greece. A full-genome analysis of isolates from Athens' hospitals and other healthcare providers revealed the variety of SARS-CoV-2 that initiated the pandemic before lockdown and passenger flight restrictions. A dominant variant, encompassing the G614D amino acid substitution, spread through a major virus dispersal event, and sporadic introductions of rare variants characterized the local initiation of the epidemic. Mutations within the genome highlighted the genetic drift of the virus as rare variants emerged. An important variant contained a premature stop codon in orf7a leading to the truncation of a possibly important for viral pathogenesis domain. This study may serve as a reference for resolving future lines of infection in the area, especially after resumption of passenger flight connections to Athens and Greece during summer of 2020. © 2021 Wiley Periodicals LLC

A COVID-19 outbreak occurred among residents of a Roma settlement in Greece (8 April– 4 June 2020). The aim of this study was to identify factors associated with an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to evaluate the effectiveness of control measures implemented. Data were analyzed from individuals that were tested for SARS-CoV-2 during contact tracing, population screening or hospital visits. RT-PCR was used for the detection of SARS-CoV-2 in oropharyngeal samples. Risk factors for household secondary attack rates (SAR) and hospitalization with COVID-19 were examined using chi-square tests, Fisher’s exact tests and logistic regression analyses. During the outbreak, 142 cases, 20 hospitalizations and 1 death were recorded, with a total of 2273 individuals tested. The risk of hospitalization was associated with age (OR: 1.04, 95% CI: 1.02–1.07) and Cycle threshold (Ct) values (OR for a decrease in Ct values by 1: 1.18, 95% CI: 1.07–1.31). Household SAR was estimated at 38.62% (95% CI: 32.50%– 45.01%). After the designation of an isolation facility for cases, household SAR declined from 74.42% to 31.03%. Household size was associated with the risk of infection (OR: 2.65, 95% CI: 1.00–7.07). The presence of COVID-19 symptoms among index cases was correlated with higher transmission (OR: 23.68, 95% CI 2.21–253.74) in multivariate analysis, while age was found to be associated with SAR only in univariate analysis. Roma communities can be particularly vulnerable to the spread of SARS-CoV-2. In similar settings, symptomatic cases are more important transmitters of SARS-CoV-2. Within these communities, immediate measures should be implemented to mitigate disease spread. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1–2 weeks after vaccination or 15–59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651–5583), 6228 (3254–9203) and 7651 (4479–10,823) AU/mL in 35–44, 45–54, 55–70 yrs, respectively, compared with the 18–34 yrs group. In females, the median levels were higher by 2823 (859–4787), 5024 (3122–6926) in individuals with VSE, and 9971 (5158–14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Background: Nosocomial pneumonia in the critical care setting is associated with increased morbidity, significant crude mortality rates and high health care costs. Ventilator-associated pneumonia represents about 80% of nosocomial pneumonia cases in intensive care units (ICUs). Wide variance in incidence of nosocomial pneumonia and diagnostic techniques used has been reported, while successful treatment remains complex and a matter of debate. Objective: To describe the epidemiology, diagnostic strategies and treatment modalities for nosocomial pneumonia in contemporary ICU settings across multiple countries around the world. Design, setting and patients: PneumoINSPIRE is a large, multinational, prospective cohort study of adult ICU patients diagnosed with nosocomial pneumonia. Participating ICUs from at least 20 countries will collect data on 10 or more consecutive ICU patients with nosocomial pneumonia. Site-specific information, including hospital policies on antibiotic therapy, will be recorded along with patient-specific data. Variables that will be explored include: aetiology and antimicrobial resistance patterns, treatment-related parameters (including time to initiation of antibiotic therapy, and empirical antibiotic choice, dose and escalation or de-escalation), pneumonia resolution, ICU and hospital mortality, and risk factors for unfavourable outcomes. The concordance of ventilator-associated pneumonia diagnosis with accepted definitions will also be assessed. Results and conclusions: PneumoINSPIRE will provide valuable information on current diagnostic and management practices relating to ICU nosocomial pneumonia, and identify research priorities in the field. Trial registration: ClinicalTrials.gov identifier NCT02793141. © 2021, College of Intensive Care Medicine. All rights reserved.

How will the coronavirus disease 2019 (COVID-19) pandemic develop in the coming months and years? Based on an expert survey, we examine key aspects that are likely to influence the COVID-19 pandemic in Europe. The challenges and developments will strongly depend on the progress of national and global vaccination programs, the emergence and spread of variants of concern (VOCs), and public responses to non-pharmaceutical interventions (NPIs). In the short term, many people remain unvaccinated, VOCs continue to emerge and spread, and mobility and population mixing are expected to increase. Therefore, lifting restrictions too much and too early risk another damaging wave. This challenge remains despite the reduced opportunities for transmission given vaccination progress and reduced indoor mixing in summer 2021. In autumn 2021, increased indoor activity might accelerate the spread again, whilst a necessary reintroduction of NPIs might be too slow. The incidence may strongly rise again, possibly filling intensive care units, if vaccination levels are not high enough. A moderate, adaptive level of NPIs will thus remain necessary. These epidemiological aspects combined with economic, social, and health-related consequences provide a more holistic perspective on the future of the COVID-19 pandemic.

A central paradigm of immunity is that interferon (IFN)-mediated antiviral responses precede pro-inflammatory ones, optimizing host protection and minimizing collateral damage1,2. Here, we report that for coronavirus disease 2019 (COVID-19) this paradigm does not apply. By investigating temporal IFN and inflammatory cytokine patterns in 32 moderate-to-severe patients with COVID-19 hospitalized for pneumonia and longitudinally followed for the development of respiratory failure and death, we reveal that IFN-λ and type I IFN production were both diminished and delayed, induced only in a fraction of patients as they became critically ill. On the contrary, pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-6 and IL-8 were produced before IFNs in all patients and persisted for a prolonged time. This condition was reflected in blood transcriptomes wherein prominent IFN signatures were only seen in critically ill patients who also exhibited augmented inflammation. By comparison, in 16 patients with influenza (flu) hospitalized for pneumonia with similar clinicopathological characteristics to those of COVID-19 and 24 nonhospitalized patients with flu with milder symptoms, IFN-λ and type I IFN were robustly induced earlier, at higher levels and independently of disease severity, whereas pro-inflammatory cytokines were only acutely produced. Notably, higher IFN-λ concentrations in patients with COVID-19 correlated with lower viral load in bronchial aspirates and faster viral clearance and a higher IFN-λ to type I IFN ratio correlated with improved outcome for critically ill patients. Moreover, altered cytokine patterns in patients with COVID-19 correlated with longer hospitalization and higher incidence of critical disease and mortality compared to flu. These data point to an untuned antiviral response in COVID-19, contributing to persistent viral presence, hyperinflammation and respiratory failure. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

An overall long-term strategy for managing the coronavirus disease 2019 (COVID-19) pandemic is presented. This strategy will need to be maintained until herd immunity is achieved, hopefully through vaccination rather than natural infection. We suggest that a pure test-trace-isolate strategy is likely not practicable in most countries, and a degree of social distancing, ranging up to full lockdown, is the main public-health tool to mitigate the COVID-19 pandemic. Guided by reliable surveillance data, distancing should be continuously optimised down to the lowest sustainable level that guarantees a low and stable infection rate in order to balance its wide-ranging negative effects on public health. The qualitative mixture of social-distancing measures also needs to be carefully optimised in order to minimise social costs. © Author(s) 2020.

BACKGROUND AND PURPOSE: We systematically evaluated the impact of the coronavirus 2019 (COVID-19) pandemic on stroke care across the world. METHODS: Observational studies comparing characteristics, acute treatment delivery, or hospitalization outcomes between patients with stroke admitted during the COVID-19 pandemic and those admitted before the pandemic were identified by Medline, Scopus, and Embase databases search. Random-effects meta-analyses were conducted for all outcomes. RESULTS: We identified 46 studies including 129 491 patients. Patients admitted with stroke during the COVID-19 pandemic were found to be younger (mean difference, -1.19 [95% CI, -2.05 to -0.32]; I2=70%) and more frequently male (odds ratio, 1.11 [95% CI, 1.01-1.22]; I2=54%) compared with patients admitted with stroke in the prepandemic era. Patients admitted with stroke during the COVID-19 pandemic, also, had higher baseline National Institutes of Health Stroke Scale scores (mean difference, 0.55 [95% CI, 0.12-0.98]; I2=90%), higher probability for large vessel occlusion presence (odds ratio, 1.63 [95% CI, 1.07-2.48]; I2=49%) and higher risk for in-hospital mortality (odds ratio, 1.26 [95% CI, 1.05-1.52]; I2=55%). Patients with acute ischemic stroke admitted during the COVID-19 pandemic had higher probability of receiving endovascular thrombectomy treatment (odds ratio, 1.24 [95% CI, 1.05-1.47]; I2=40%). No difference in the rates of intravenous thrombolysis administration or difference in time metrics regarding onset to treatment time for intravenous thrombolysis and onset to groin puncture time for endovascular thrombectomy were detected. CONCLUSIONS: The present systematic review and meta-analysis indicates an increased prevalence of younger patients, more severe strokes attributed to large vessel occlusion, and higher endovascular treatment rates during the COVID-19 pandemic. Patients admitted with stroke during the COVID-19 pandemic had higher in-hospital mortality. These findings need to be interpreted with caution in view of discrepant reports and heterogeneity being present across studies. © 2021 Lippincott Williams and Wilkins. All rights reserved.