Background. Several drugs which are easy to administer in outpatient settings have been authorized and endorsed for high-risk COVID-19 patients with mild–moderate disease to prevent hospital admission and death, complementing COVID-19 vaccines. However, the evidence on the efficacy of COVID-19 antivirals during the Omicron wave is scanty or conflicting. Methods. This retrospective controlled study investigated the efficacy of Molnupiravir or Nirmatrelvir/Ritonavir (Paxlovid®) or Sotrovimab against standard of care (controls) on three different endpoints among 386 high-risk COVID-19 outpatients: hospital admission at 30 days; death at 30 days; and time between COVID-19 diagnosis and first negative swab test result. Multinomial logistic regression was employed to investigate the determinants of hospitalization due to COVID-19-associated pneumonia, whereas time to first negative swab test result was investigated by means of multinomial logistic analysis as well as Cox regression analysis. Results. Only 11 patients (overall rate of 2.8%) developed severe COVID-19-associated pneumonia requiring admission to hospital: 8 controls (7.2%); 2 patients on Nirmatrelvir/Ritonavir (2.0%); and 1 on Sotrovimab (1.8%). No patient on Molnupiravir was institutionalized. Compared to controls, hospitalization was less likely for patients on Nirmatrelvir/Ritonavir (aOR = 0.16; 95% CI: 0.03; 0.89) or Molnupiravir (omitted estimate); drug efficacy was 84% for Nirmatrelvir/Ritonavir against 100% for Molnupiravir. Only two patients died of COVID-19 (rate of 0.5%), both were controls, one (a woman aged 96 years) was unvaccinated and the other (a woman aged 72 years) had adequate vaccination status. At Cox regression analysis, the negativization rate was significantly higher in patients treated with both antivirals—Nirmatrelvir/Ritonavir (aHR = 1.68; 95% CI: 1.25; 2.26) or Molnupiravir (aHR = 1.45; 95% CI: 1.08; 1.94). However, COVID-19 vaccination with three (aHR = 2.03; 95% CI: 1.51; 2.73) or four (aHR = 2.48; 95% CI: 1.32; 4.68) doses had a slightly stronger effect size on viral clearance. In contrast, the negativization rate reduced significantly in patients who were immune-depressed (aHR = 0.70; 95% CI: 0.52; 0.93) or those with a Charlson index ≥5 (aHR = 0.63; 0.41; 0.95) or those who had started the respective treatment course 3+ days after COVID-19 diagnosis (aOR = 0.56; 95% CI: 0.38; 0.82). Likewise, at internal analysis (excluding patients on standard of care), patients on Molnupiravir (aHR = 1.74; 95% CI: 1.21; 2.50) or Nirmatrelvir/Ritonavir (aHR = 1.96; 95% CI: 1.32; 2.93) were more likely to turn negative earlier than those on Sotrovimab (reference category). Nonetheless, three (aHR = 1.91; 95% CI: 1.33; 2.74) or four (aHR = 2.20; 95% CI: 1.06; 4.59) doses of COVID-19 vaccine were again associated with a faster negativization rate. Again, the negativization rate was significantly lower if treatment started 3+ days after COVID-19 diagnosis (aHR = 0.54; 95% CI: 0.32; 0.92). Conclusions. Molnupiravir, Nirmatrelvir/Ritonavir, and Sotrovimab were all effective in preventing hospital admission and/or mortality attributable to COVID-19. However, hospitalizations also decreased with higher number of doses of COVID-19 vaccines. Although they are effective against severe disease and mortality, the prescription of COVID-19 antivirals should be carefully scrutinized by double opinion, not only to contain health care costs but also to reduce the risk of generating resistant SARS-CoV-2 strains. Only 64.7% of patients were in fact immunized with 3+ doses of COVID-19 vaccines in the present study. High-risk patients should prioritize COVID-19 vaccination, which is a more cost-effective approach than antivirals against severe SARS-CoV-2 pneumonia. Likewise, although both antivirals, especially Nirmatrelvir/Ritonavir, were more likely than standard of care and Sotrovimab to reduce viral shedding time (VST) in high-risk SARS-CoV-2 patients, vaccination had an independent and stronger effect on viral clearance. However, the effect of antivirals or COVID-19 vaccination on VST should be considered a secondary benefit. Indeed, recommending Nirmatrelvir/Ritonavir in order to control VST in high-risk COVID-19 patients is rather questionable since other cheap, large spectrum and harmless nasal disinfectants such as hypertonic saline solutions are available on the market with proven efficacy in containing VST.

An antibiotic stewardship program targeted to limit the consumption of extended-spectrum cephalosporins and fluoroquinolones in favor of amoxicillin/clavulanate and piperacillin/tazobactam correlates with a decreasing rate of MRSA and ESBL-positive Enterobacteriaceae. The analysis of correlations between antibiotic consumption and bacterial resistance rates is a useful tool to orient antimicrobial stewardship policies at local level.

Studies suggest that the incidence of coinfections in patients with the coronavirus disease 2019 (COVID-19) is low, but a large number of patients receive antimicrobials during hospitalisation. This may fuel a rise in antimicrobial resistance (AMR). We conducted a multicentre point-prevalence survey in seven tertiary university hospitals (in medical wards and intensive care units) in Croatia, Italy, Serbia and Slovenia. Of 988 COVID-19 patients, 521 were receiving antibiotics and/or antifungals (52.7%; range across hospitals: 32.9–85.6%) on the day of the study. Differences between hospitals were statistically significant (χ2 (6, N = 988) = 192.57, p < 0.001). The majority of patients received antibiotics and/or antifungals within 48 h of admission (323/521, 62%; range across hospitals: 17.4–100%), their most common use was empirical (79.4% of prescriptions), and pneumonia was the main indication for starting the treatment (three-quarters of prescriptions). The majority of antibiotics prescribed (69.9%) belonged to the “Watch” group of the World Health Organization AWaRe classification. The pattern of antimicrobial use differed across hospitals. The data show that early empiric use of broad-spectrum antibiotics is common in COVID-19 patients, and that the pattern of antimicrobial use varies across hospitals. Judicious use of antimicrobials is warranted to prevent an increase in AMR.

Summary The intrusion of infectious diseases in everyday life forces humans to reassess their attitudes. Indeed, pandemics are able catalyze rapid transitions in scientific knowledge, politics, social behaviors, culture and arts. The current Coronavirus diesease-19 (COVID-19) outbreak has driven an unprecedented interest toward the influenza pandemic of 1918. The issue is whether history can shed light on the best preventive response and future scenarios. The aim of this review is to highlight the parallelism between the two pandemics. Starting from epidemiology and clinical features, but further focusing on social and cultural issues, it is possible to unreveal great similarities. Their outbreak pattern lead to hypothesize a similar duration and death burden in absence of effective vaccines or innovative treatments for COVID-19. Thus, then as now, preventive medicine represents the first and most effective tool to contain the course of the pandemic; being treatments available only supportive. At the same time,both pandemics shared the same pattern of narration (e.g. scapegoating) and the same impact on minorities in high-income countries. Furthermore, visual art responded to pandemic issues in 2020 in the form of Graffiti art, while similar role was ruled by Expressionism movement during the Spanish flu. Photography also was capable to document both catastrophic scenarios. Thus, it is possible to find a lot of clinical and social similarities between the two pandemics. Nevertheless, if the Spanish flu was not unforseen, COVID-19 spillover was partially predictable and its global impact will hopefully not be overshadowed by a major crisis such as World War I.

Post-coronavirus disease 2019 (post-COVID-19) condition, previously referred to as long COVID, includes a post-acute syndrome defined by the presence of non-specific symptoms occurring usually 3 months from the onset of the acute phase and lasting at least 2 months. Patients with chronic lymphocytic leukemia (CLL) represent a high-risk population for COVID-19. Moreover, the response to SARS-CoV-2 vaccination is often absent or inadequate. The introduction of monoclonal antibodies (mAbs) in the treatment landscape of COVID-19 allowed to reduce hospitalization and mortality in mild–moderate SARS-CoV-2 infection, but limited data are available in hematological patients. We here report the effective use of casirivimab/imdevimab (CI) in the treatment of two CLL patients with persistent infection and post-COVID-19 condition. Full genome sequencing of viral RNA from nasopharyngeal swabs was performed at the time of COVID-19 diagnosis and before the administration of CI. Both patients experienced persistent SARS-CoV-2 infection with no seroconversion for 8 and 7 months, respectively, associated with COVID symptoms. In both cases after the infusion of CI, we observed a rapid negativization of the nasal swabs, the resolution of post-COVID-19 condition, and the development of both the IgG against the trimeric spike protein and the receptor-binding domain (RBD) of the spike protein. The analysis of the viral genome in the period elapsed from the time of COVID-19 diagnosis and the administration of mAbs showed the development of new mutations, especially in the S gene. The genome variations observed during the time suggest a role of persistent SARS-CoV-2 infection as a possible source for the development of viral variants. The effects observed in these two patients appeared strongly related to passive immunity conferred by CI treatment permitting SARS-CoV-2 clearance and resolution of post-COVID-19 condition. On these grounds, passive anti-SARS-CoV-2 antibody treatment may represent as a possible therapeutic option in some patients with persistent SARS-CoV-2 infection.