Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2 infected mice (preprint)

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir, an orally available inhibitor of the 3- chymotrypsin-like cysteine protease, has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using a mouse model of SARS-CoV-2 infection, we show that nirmatrelvir administration early after infection blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and to mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals.

Epidemiology and molecular characteristics of respiratory syncytial virus (RSV) among Italian community-dwelling adults, 2021/22 season (preprint)

Background: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections worldwide. While historically RSV research has been focused on children, data on RSV infection in adults are limited. The goal of this study was to establish the prevalence of RSV in Italian adults and analyze its genetic variability during the 2021/22 winter season. Methods: In this cross-sectional study, a random sample of naso-/oropharyngeal specimens from symptomatic adults seeking for SARS-CoV-2 molecular testing between December 2021 and March 2022 were tested for RSV and other respiratory pathogens by means of reverse-transcription polymerase chain reaction. RSV-positive samples were further molecularly characterized by sequence analysis. Results: Of 1,213 samples tested, 1.6% (95% CI: 0.9–2.4%) were positive for RSV and subgroups A (44.4%) and B (55.6%) were identified in similar proportions. The epidemic peak occurred in December 2021, when the RSV prevalence was as high as 4.6% (95% CI: 2.2–8.3%). The prevalence of RSV detection was similar (p = 0.64) to that of influenza virus (1.9%). All RSV A and B strains belonged to the ON1 and BA genotypes, respectively. Most (72.2%) RSV-positive samples were also positive for other pathogens being SARS-CoV-2, Pneumococcus pneumoniae and rhinovirus the most frequent. RSV load was significantly higher among mono-infections than co-infections. Conclusions: During the 2021/22 winter season, characterized by the predominant circulation of SARS-CoV-2 and some non-specific containment measures still in place, a substantial proportion of Italian adults tested positive for genetically diversified strains of both RSV subtypes. In view of the upcoming registration of vaccines, establishment of the National RSV surveillance system is urgently needed.

Broad antiviral effects of Echinacea purpurea against SARS-CoV-2 variants of concern and potential mechanism of action (preprint)

Background SARS-CoV-2 variants of concern (VOC) represent an alarming threat as they show altered biological behavior and may escape vaccination effectiveness. Some exhibit increased pathogenicity and transmissibility compared to the original wild type WUHAN (Hu-1). Broad-spectrum antivirals could complement and further enhance preventive benefits achieved through SARS-CoV-2 vaccination campaigns Methods The anti-coronavirus activity of Echinacea purpurea (Echinaforce® extract, EF) against (i) VOCs B1.1.7 (alpha), B.1.351.1 (beta), P.1 (gamma), B1.617.2 (delta), AV.1 (Scottish) and B1.525 (eta), (ii) SARS-CoV-2 spike (S) protein-pseudotyped viral particles and reference strain OC43 as well as (iii) wild-type SARS-CoV-2 (Hu-1) were analyzed. Molecular dynamics (MD) were applied to study interaction of Echinacea’s phytochemical markers with known pharmacological viral and host cell targets. Results EF extract broadly inhibited propagation of all investigated SARS-CoV-2 VOCs as well as entry of SARS-CoV-2 pseudoparticles at EC50’s ranging from 3.62 to 12.03 µg/ml. Preventive addition of 20 µg/ml EF to epithelial cells significantly reduced sequential infection with SARS-CoV-2 (Hu-1) as well as with the common human strain OC43. MD analyses showed constant binding affinities to Hu-1, B1.1.7, B.1.351, P.1 and B1.617.2-typic S protein variants for alkylamides, caftaric acidand feruoyl-tartaric acid in EF extract. They further indicated that the EF extract could possibly interact with TMPRSS-2, a serine protease required for virus endocytosis. Conclusions EF extract demonstrated stable antiviral activity across 6 tested VOCs, which is likely due to the constant affinity of the contained phytochemical marker substances to all spike variants. A possible interaction of EF with TMPRSS-2 partially would explain cell protective benefits of the extract by inhibition of endocytosis. EF may therefore offer a supportive addition to vaccination endeavors in the control of existing and future SARS-CoV-2 virus mutations.

A comparison of coronavirus disease 2019 and seasonal influenza surveillance in five European countries: France, Germany, Italy, Spain and the United Kingdom (preprint)

Background: In response to the coronavirus disease (COVID-19) outbreak that unfolded across Europe in 2020, the World Health Organisation called for repurposing existing influenza surveillance systems to monitor COVID-19. This analysis aimed to compare descriptively the extent to which influenza surveillance systems were adapted and enhanced, and how COVID-19 surveillance could ultimately benefit or disrupt routine influenza surveillance. Methods: We used a previously developed framework in France, Germany, Italy, Spain and the United Kingdom to describe COVID-19 surveillance and its impact on influenza surveillance. The framework divides surveillance systems into 7 sub-systems and 20 comparable outcomes of interest, and uses 5 evaluation criteria based on WHO guidance. Information on influenza and COVID-19 surveillance systems were collected from publicly available resources shared by European and national public health agencies. Results: Overall, non-medically attended, virological, primary care and mortality surveillance were adapted in most countries to monitor COVID-19, whilst community, outbreak, and hospital surveillance were reinforced in all countries. Data granularity improved, with more detailed demographic and medical information recorded. A shift to systematic notification for cases and deaths enhanced both geographic and population representativeness whilst the sampling strategy benefited from the roll out of widespread molecular testing. Data communication was greatly enhanced, contributing to improved public awareness. Conclusions: Well-established influenza surveillance systems are a key component of pandemic preparedness and their upgrade allowed European countries to respond to the COVID-19 pandemic. However, uncertainties remain on how both influenza and COVID-19 surveillance can be jointly and durably implemented.

SARS-CoV-2 RNA in urban wastewater samples to monitor the COVID-19 epidemic in Lombardy, Italy (March - June 2020) (preprint)

Wastewater-based viral surveillance is a promising approach to monitor the circulation of SARS-CoV-2 in the general population. The aim of this study was to develop an analytical method to detect SARS-CoV-2 RNA in urban wastewater, to be implemented in the framework of a surveillance network in the Lombardy region (Northern Italy). This area was the first hotspot of COVID-19 in Europe. Composite 24h samples were collected weekly in eight cities from end-March to mid-June 2020 (first peak of the epidemic). The method developed and optimized, involved virus concentration, using PEG centrifugation, and one-step real-time RT-PCR for analysis. SARS-CoV-2 RNA was identified in 65 (61%) out of 107 samples, and the viral concentrations (up to 2.1 E +05 copies/L) were highest in March-April. By mid-June, wastewater samples tested negative in all the cities. Viral loads were used for inter- city comparison and Brembate, Ranica and Lodi had the highest. The pattern of decrease of SARS-CoV-2 in wastewater was closely comparable to the decline of active COVID-19 cases in the population, reflecting the effect of lock-down. Wastewater surveillance of SARS-CoV-2 can integrate ongoing virological surveillance of COVID-19, providing information from both symptomatic and asymptomatic individuals, and monitoring the effect of health interventions.

Are health indicators able to describe the ability to cope of Health Systems with COVID-19 epidemic? (preprint)

The Coronavirus Disease 19 epidemic is an infectious disease which was declared as a pandemic and hit all the Countries, all over the world, from the beginning of the year 2020. Despite the emergency vigilance plans, in all the Countries, Health Systems experienced a different ratio of lethality, admissions to intensive care units and managing quarantine of positive patients. The aim of this study is to investigate if some health indicators might have been useful to understand the capacity of Italian National Health Service to manage the COVID 19 epidemic. We will compare data in two different Italian regions in the Northern part of Italy (Lombardy and Veneto) with the national data to understand if different health strategies might be significant to explain different patterns of COVID 19 epidemic in Italy. The two regions have two different health policies to face CoViD-2019 epidemic. To face epidemic like this one the answer should be outside hospitals but this means to have general practitioners well-trained and enough healthcare personnel working outside hospitals.