No abstract

Purpose COVID-19 displays a variety of clinical manifestations; in pauci-symptomatic patients olfactory (OD) and gustatory dysfunctions (GD) may represent the first or only symptom. This topic is currently arousing great interest, and a growing number of papers are being published. Aim of this study is to investigate the timing of recovery from OD and GD in a reallife population hospitalized for COVID-19. Methods We followed up by a phone interview the first 100 patients discharged a month earlier from three Italian nonintensive care wards. Results All 100 patients were Caucasian, mean age was 65 years, 60% were males. Forty-two patients (mean age 63 years) experienced subjective chemosensory dysfunctions (29 OD and 41 GD): the male/female ratio was 2:1; 83% reported a complete or near complete recovery at follow-up. The recovery rate was not significantly different between males and females. The mean duration of OD and GD was 18 and 16 days, respectively. The mean recovery time from OD or GD resulted significantly longer for females than for males (26 vs 14 days, P = 0.009). Among the 42 symptomatic, the mean age of males was significantly higher than that of females (66 vs 57 years, P = 0.04), while the opposite was observed in the 58 asymptomatic patients (60 vs 73 years, P = 0.0018). Conclusions Recovery from OD or GD was rapid, occurring within 4 weeks in most patients. Chemosensory dysfunctions in women was less frequent, but longer lasting. The value of our study is its focus on a population of hospitalized patients significantly older than those previously described, and the additional data on gender differences.

A life-threatening respiratory illness (COVID-19) due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus was first described in December 2019 in Wuhan (China), rapidly evolving into a pandemic. In the first phase, when the viral replication plays a pivotal pathogenetic role, antiviral drugs could be crucial in limiting viral-induced organ damage. Unfortunately, there are no specific antivirals of proven efficacy for COVID-19, and several drugs have been repurposed to face this dramatic pandemic. In this paper we review the studies evaluating lopinavir/ritonavir association (LPV/r) use in COVID-19, and previously in SARS and Middle East respiratory syndrome (MERS). We searched PubMed to identify all relevant clinical and laboratory studies published up to 15 May 2020; the guidelines on the use of LPV/r in COVID-19 were further directly searched on the website of the main international scientific societies and agencies. Available evidence is currently scarce and of low quality. The recommendations issued for COVID-19 vary from positions clearly against the use of LPV/r to other positions that are more favorable. In our opinion, despite the controversial results of an important randomized clinical trial, and some recommendations, clinicians should not abandon the use of LPV/r for the treatment of COVID-19, possibly using this drug inside a prospective randomized trial, waiting for the results of the numerous ongoing trials evaluating its efficacy.

To date the pathophysiology of COVID-19 remains unclear: this represents a factor determining the current lack of effective treatments. In this paper, we hypothesized a complex host response to SARS-CoV-2, with the Contact System (CS) playing a pivotal role in innate immune response. CS is linked with different proteolytic defense systems operating in human vasculature: the Kallikrein-Kinin (KKS), the Coagulation/Fibrinolysis and the Renin-Angiotensin (RAS) Systems. We investigated the role of the mediators involved. CS consists of Factor XII (FXII) and plasma prekallikrein (complexed to highmolecular-weight kininogen-HK). Autoactivation of FXII by contact with SARS-CoV-2 could lead to activation of intrinsic coagulation, with fibrin formation (microthrombosis), and fibrinolysis, resulting in increased D-dimer levels. Activation of kallikrein by activated FXII leads to production of bradykinin (BK) from HK. BK binds to B2-receptors, mediating vascular permeability, vasodilation and edema. B1-receptors, binding the metabolite [des-Arg 9 ]-BK (DABK), are up-regulated during infections and mediate lung inflammatory responses. BK could play a relevant role in COVID-19 as already described for other viral models. Angiotensin-Converting-Enzyme (ACE) 2 displays lung protective effects: it inactivates DABK and converts Angiotensin II (Ang II) into Angiotensin-(1-7) and Angiotensin I into Angiotensin-(1-9). SARS-CoV-2 binds to ACE2 for cell entry, downregulating it: an impaired DABK inactivation could lead to an enhanced activity of B1-receptors, and the accumulation of Ang II, through a negative feedback loop, may result in decreased ACE activity, with consequent increase of BK. Therapies targeting the CS, the KKS and action of BK could be effective for the treatment of COVID-19.

Pending conclusive evidence, use of probiotics should be considered with caution in case of active severe inflammatory bowel diseases with mucosal disruption.