Monoclonal antibody therapy in COVID-19.

Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causes coronavirus disease-2019 (COVID-19) which is associated with inflammation, thrombosis edema, hemorrhage, intra-alveolar fibrin deposition, and vascular and pulmonary damage. In COVID-19, the coronavirus activates macrophages by inducing the generation of pro-inflammatory cytokines [interleukin (IL)-1, IL-6, IL-18 and TNF] that can damage endothelial cells, activate platelets and neutrophils to produce thromboxane A2 (TxA2), and mediate thrombus generation. In severe cases, all these phenomena can lead to patient death. The binding of SARS-CoV-2 to the Toll Like Receptor (TLR) results in the release of pro-IL-1ß that is cleaved by caspase-1, followed by the production of active mature IL-1ß which is the most important cytokine in causing fever and inflammation. Its activation in COVID-19 can cause a "cytokine storm" with serious biological and clinical consequences. Blockade of IL-1 with inhibitory and anti-inflammatory cytokines represents a new therapeutic strategy also for COVID-19. Recently, very rare allergic reactions to vaccines have been reported, with phenomena of pulmonary thrombosis. These side effects have raised substantial concern in the population. Highly allergic subjects should therefore be vaccinated under strict medical supervision. COVID-19 has accelerated vaccine therapy but also the use of drugs and monoclonal antibodies (mABs) which have been used in COVID-19 therapy. They are primarily adopted to treat high-risk mild-to-moderate non-hospitalized patients, and it has been noted that the administration of two mABs gave better results. mABs, other than polyclonal plasma antibodies from infected subjects with SARS-CoV-2, are produced in the laboratory and are intended to fight SARS-CoV-2. They bind specifically to the antigenic determinant of the spike protein, inhibiting the pathogenicity of the virus. The most suitable individuals for mAB therapy are people at particular risk, such as the elderly and those with serious chronic diseases including diabetics, hypertension and obesity, including subjects suffering from cardiovascular diseases. These antibodies have a well-predetermined target, they bind mainly to the protein S (formed by the S1A, B, C and D subtypes), located on the viral surface, and to the S2 protein that acts as a fuser between the virus and the cell membrane. Since mABs are derived from a single splenic immune cell, they are identical and form a cell clone which can neutralize SARS-CoV-2 by binding to the epitope of the virus. However, this COVID-19 therapy may cause several side effects such as mild pain, bleeding, bruising of the skin, soreness, swelling, thrombotic-type episodes, arterial hypertension, changes in heart activity, slowed bone marrow activity, impaired renal function, diarrhea, fatigue, nausea, vomiting, allergic reaction, fever, and possible subsequent infection may occur at the site of injection. In conclusion, the studies promoting mAB therapy in COVID-19 are very promising but the results are not yet definitive and more investigations are needed to certify both their good neutralizing effects of SARS-CoV-2, and to eliminate, or at least mitigate, the harmful side effects.

The British variant of the new coronavirus-19 (Sars-Cov-2) should not create a vaccine problem.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious virus that infects humans and a number of animal species causing coronavirus disease-19 (COVID-19), a respiratory distress syndrome which has provoked a global pandemic and a serious health crisis in most countries across our planet. COVID-19 inflammation is mediated by IL-1, a disease that can cause symptoms such as fever, cough, lung inflammation, thrombosis, stroke, renal failure and headache, to name a few. Strategies that inhibit IL-1 are certainly helpful in COVID-19 and can represent one of the therapeutic options. However, until now, COVID-19 therapy has been scarce and, in many cases, ineffective, since there are no specific drugs other than the vaccine that can solve this serious health problem. Messenger RNA (mRNA) vaccines which are the newest approach, are already available and will certainly meet the many expectations that the population is waiting for. mRNA vaccines, coated with protected soft fatty lipids, use genetic mRNA (plus various inactive excipients) to make a piece of the coronavirus spike protein, which will instruct the immune system to produce specific antibodies. The soft fatty lipids allow the entry of mRNA into cells where it is absorbed into the cytoplasm and initiates the synthesis of the spike protein. In addition, vaccination also activates T cells that help the immune system respond to further exposure to the coronavirus. mRNA induces the synthesis of antigens of SARS-CoV-2 virus which stimulate the antibody response of the vaccinated person with the production of neutralizing antibodies. The new variant of the coronavirus-19 has been detected in the UK where, at the moment, the London government has imposed a lockdown with restrictions on international movements. The virus variant had already infected 1/4 of the total cases and in December 2020, it reached 2/3 of those infected in the UK. It has been noted that the spreading rate of the British variant could be greater than 70% of cases compared to the normal SARS-CoV-2 virus, with an R index growth of 0.4. Recent studies suggest that coronavirus-19 variation occurs at the level N501Y of the spike protein and involves 23 separate mutations on the spike, 17 of which are linked to the virus proteins, thus giving specific characteristics to the virus. In general, coronaviruses undergo many mutations that are often not decisive for their biological behavior and does not significantly alter the structure and the components of the virus. This phenomenon also occurs in SARS-CoV-2. It is highly probable that the variants recently described in the UK will not hinder vaccine-induced immunity. In fact, the variant will not break the vaccine although it may have some chance of making it a little less effective. Therefore, it is pertinent to think that the vaccine will work against the SARS-CoV-2 variant as well. In today's pandemic, the D614G mutation of the amino acid of corronavirus-19, which emerged in Europe in February 2020 is the most frequent form and causes high viral growth. The previously infrequent D614G mutation is now globally dominant. This variant, which is being tested by many international laboratories, is rapidly spreading across the countries and a series of vaccinated subjects are testing to see if their antibodies can neutralize the new variant of SARS-CoV-2. This variant has a very high viral growth and is less detectable with the RT-PCR technique in the laboratory. It has been reported that the British variant that increases viral load does not cause more severe effects in the respiratory tract and lung disease, therefore, it is certain that the variant is growing rapidly and must be kept under control; for this reason, laboratory data is expected impatiently. The study on the many variants that coronavirus-19 presents is very interesting and complete and clearer data on this topic will be ready in the near future. In addition, it is still unclear whether the different variants discovered in many countries, including Africa, share the same spike protein mutation and therefore, this is another study to elaborate on. In order to be certain and to not have unexpected surprises, we need to reduce the spread and the transmission speed of viral variants that could appear around the world, creating new pandemics. For this reason, the scientific community is on the alert since laboratory tests on serum antibodies from COVID-19 survivors have been reported to be less effective in attacking the variant. In light of the above, the scientific community must be on the alert as larger variants of the spike protein could escape vaccine-induced antibodies, which for now are of great help to the community and can save millions of lives. Deepening the study of spike protein mutations will help to better understand how to combat coronavirus-19 and its variants.

Presence of Legionella spp. in human dental plaque.

AIMS: The aim of this research is to verify the presence of Legionella in human dental plaque. METHODS: 65 adult patients not treated with systemic or local antibiotics at least 2 months before the time of sample collection were enrolled for plaque collection between September 2015 and December 2016. A brief questionnaire about lifestyle and health risks was administered. Legionella spp. detection has been executed by semi- nested PCR. RESULTS: 8 out of 65 plaque samples (12.3%) were positive for Legionella spp. As regards health risks and lifestyle aspects, no relevant difference was observed between patients involved in our study, except for two positive patients who have reported a COPD ongoing and a pneumonia in the past. CONCLUSIONS: This study represents a step forward in the knowledge of reservoirs of the microorganism and richness of oral microbiota.

Oral features in five adult patients with Wolf-Hirschhorn syndrome.

The Wolf-Hirschhorn syndrome (WHS) is a rare genetic condition presenting with severe mental disability, growth retardation, muscular hypotonia, seizures, craniofacial abnormalities and defects in the cardiovascular, genitourinary and digestive apparata. To date, few data about oral status of afflicted patients were reported, and this syndrome is still unfamiliar among dental and maxillofacial professionals. Aim of the present case series was to provide oral data from five patients with WHS (3 women and 2 men) aged 19-41 years. All patients entered in a long-stay Institution with an inner dental service in 1998 and underwent regular dental examination and hygiene treatment. Neither tooth agenesis or dental size and shape anomalies were found in the analyzed subjects except for one man showing multiple cone-shaped teeth. At the beginning, bad dental and periodontal conditions with gingival signs and recurrent mucosal inflammation were found in all patients. After motivation of their tutors, dental and periodontal parameters were recorded during periodic assessments and a large decrease in the gingival index was found over time. These data could aware dentists about the therapeutic modalities to improve oral health of WHS patients.

[5-year surveillance for Legionella pneumophila and comparison of disinfection methods in two hospitals of Milan]. / Sorveglianza ambientale di Legionella pneumophila e meto- di di bonifica a confronto in strutture sanitarie di Milano (risultati di un quinquennio).

We performed an environmental monitoring in an hospital to estimate the level of contamination from Legionella spp., in connection with several treatments of reclamation. In period 2002-2006 we executed 238 samplings in 21 units hospitals (from hot water, biofilm, filter of the conditioning system, instrument for the assisted respiration) for the detection of Legionella spp. The contaminated points have been subordinates to reclamation (hyperchlorination, maintenance of boilers/tanks, taps' and showers' substitution, increased temperature, elimination of dead points of the system and chlorine dioxide) and subsequently we sampled to verify the efficiency of the disinfection. Environmental investigation found 58% of the cases positive for Legionella spp. (139/238), with maximum count in order of the 10(4) UFC/L, demonstrating colonization of Legionella pneumophila (132/139, 70% Serogroup 2-14, 19% Serogroup 1, 11% both). The used treatments were effective, in different ways, in the short period, but not in the medium-term, because progressive recolonization happened approximately after a month; only the use of chlorine dioxide brought to counts less than 100 UFC/L until now. Chlorine dioxide seems to maintain a mainly protecting effect, however this effectiveness will have to be demonstrated also for longer periods.

Immunogenicity and safety of three commercial influenza vaccines in institutionalized elderly.

Influenza is a leading cause of morbidity and mortality in elderly people. This prospective, observed-blind, randomized, multicenter trial compares the immunogenicity and safety of three influenza vaccines in a sample of 635 elderly residents of four nursing homes in Milano (Italy). All vaccines were well tolerated: no serious adverse events were recorded, and a small number (9 subjects) of local and systemic reactions were observed. Twenty-nine oropharyngeal swabs were taken during the season from ILI (influenza-like illness) patients, none of whom was positive for influenza and other respiratory viruses. Immunogenicity was evaluated in a subgroup of 111 subjects with blood samples obtained just before vaccination and after 4 and 12 weeks. The adjuvanted vaccines, subunit vaccine with MF59 (a-SUV) and virosome subunit vaccine (v-SUV), induced a higher antibody response than whole virus vaccine (WVV). There was no significant difference between groups that received a-SUV and v-SUV, but the a-SUV group had higher values of geometric mean titres than the v-SUV group for H1N1 and B influenza strains. These findings suggest that influenza vaccination is effective, and they underscore the importance of vaccination programs for institutionalized elderly. Further studies are needed to compare other adjuvanted vaccines in order to define their different properties.

Oral health profile in an institutionalized population of Italian adults with mental retardation.

The oral health of 219 residents with mental retardation living in a long-term-care institution near Milan was assessed. The dental and periodontal status, daily habits, oral hygiene, and oral mucosal status were evaluated. Of the sample, 179 (81.7%) were males. The mean age of the residents was 61.3 years, and the degree of cooperation was evaluated as good for 131 subjects (59.8%), fair for 79 (36.1%), and poor for nine (4.1%). The percentage of residents who were edentulous was 21.5% (47 subjects), of whom 28 subjects (59.6%) were without dentures. Evaluation showed an overall DMFT of 23.1, and the average number of missing teeth was 20.5. All subjects had periodontal disease: Forty-five subjects had calculus and/or shallow pockets (4-5 mm); 61 had deep pockets (> or = 6 mm). The most common mucosal lesion was oral stomatitis (49.3%). These findings underline the need for special programs aimed at institutionalized subjects with mental retardation.

Influenza vaccination among the elderly in Italy.

This article surveys the attitudes and perceptions of a random sample of the elderly population in three regions of Italy on the use and efficacy of influenza vaccine. The data were collected by direct interviews using a standard questionnaire. The results show that vaccination coverage against influenza is inadequate (26-48.6%). The major reasons for nonvaccination were lack of faith in the vaccine and disbelief that influenza is a dangerous illness. These data emphasize the need for a systematic education programme targeted at the elderly and the provision of influenza vaccination, with the increased cooperation of general practitioners.

Comparison of RT-PCR with other diagnostic assays for rapid detection of influenza viruses.

To compare the effectiveness of reverse transcription-polymerase chain reaction (RT-PCR), shell vial culture and cytospin assay as laboratory techniques for rapid diagnosis of influenza infections, a retrospective study was carried out on 270 aliquots of oropharyngeal swabs collected from October 1993 to March 1996 and already characterized by standard isolation procedures, and a prospective study in which 65 clinical samples taken from patients with influenza-like syndrome between October 1996 and March 1997 were tested. In the retrospective study, using conventional isolation as the gold standard, the sensitivity of RT-PCR and cytospin assay for virus A was 100% (95% confidence interval (CI), 89.1-100) and for virus B it was 100% (95% CI, 56.1-100) compared with 77.5% (95% CI, 61.1-88.6) and 71.4% (95% CI, 30.3-94.9) for shell vial culture. The specificity of all the three assays was 100% (95% CI, 98.0-100) for virus A and 100% (95% CI, 98.2-100) for virus B. In the prospective study the sensitivity of RT-PCR was greater than that of the other tests considered, both rapid and standard. It is suggested that RT-PCR should be employed in combination with conventional culture techniques in routine diagnosis of influenza infections in order to obtain results more rapidly and to improve virus detection even in circumstances in which standard isolation could be problematic.

Clinical efficacy of a vaccine-immunostimulant combination in the prevention of influenza in patients with chronic obstructive pulmonary disease and chronic asthma.

Influenza is a leading cause of morbidity and mortality in patients with chronic respiratory diseases. This study compares two influenza prevention schemes in patients with chronic obstructive pulmonary disease and chronic asthma. We enrolled 66 patients, distributed as follows: Group A: 32 subjects treated with influenza vaccine; Group B: 34 patients treated with influenza vaccine and bacterial immunostimulant. The rate of influenza episodes was recorded. Hemoagglutination inhibiting antibody titers for vaccine strains H1N1, H3N2, and B were determined at time 0 (prior to vaccination), and on days 30 and 90 following vaccination. We observed a lower rate of influenza episodes in Group B patients (8.82%) compared to Group A (31.25%) (p < 0.05). At day 90 Group B patients presented higher geometric mean antibody titers for strains H1N1 (p = 0.07) and H3N2 (p = 0.08). Bacterial immunostimulants appear as possible adjuvants in the prevention of influenza episodes, and may prolong antibody response to influenza vaccine strains.

Simultaneous influenza and pneumococcal vaccination in elderly individuals.

The study was performed to evaluate the effects of influenza and pneumococcal vaccines administered alone or in combination. 124 elderly subjects living in community were vaccinated either with influenza split vaccine or with pneumococcal 23-valent or with both vaccines at the same time in different sites. Sera were tested for hemoagglutination inhibiting antibodies for influenza and for antibodies against 23-valent vaccine for streptococcus pneumoniae. No side effects were observed in the vaccinated population. Serological results indicated that influenza vaccine increased significantly antibody levels. No difference was observed between the group which received influenza vaccine alone and that which received influenza and pneumococcal vaccines associated, considering either G.M.T or the percentages of protected individuals or the percentages of subjects who seroconverted. When pneumococcal vaccine was administered at the same time with influenza vaccine, there was a not statistically significant reduction in both mean antibody concentration and mean fold increase. It is concluded that the simultaneous administration of influenza and pneumococcal vaccines to elderly individuals, including subjects at risk, is safe, effective and economically advantageous.