ROME. Covid research is leading the international scientific community to learn about the hitherto unknown mechanisms of the virus. The articles selected in this fifth week report results, in the various research areas, which allow some original food for thought. As part of virological research, a retrospective study conducted in 1683 patients (Mizrahi B and others) suggests a possible new application of the molecular swab in addition to the one already in place to detect / confirm SARS-Cov-2 infection. In this regard, the association between the result of a second molecular examination, carried out within 2-7 days from the first positive result, and the severity of the disease was evaluated. The study found that if a second examination is negative, this is associated with the lower risk of a severe clinical form. In case there is further confirmation of this initial report, this approach could provide useful prognosis elements in hospitalized patients since the negativity of the second swab could indicate the reduction or even the disappearance of the virus from the upper respiratory tract.
Reference standard
A prospective study (Winkel B et al.) Evaluated the sensitivity and specificity of a new antigen test for SARS-CoV-2 (compared to the reference standard) applied to asymptomatic subjects represented, in this case, by American football players and by club staff members. The results obtained on 824 subjects analyzed indicated a good sensitivity of the test (80-86.6%) and excellent specificity (99.5-100%). What emerges from this survey is extremely interesting because it indicates an excellent sensitivity and specificity of the new test even if the study was conducted in a selected population of individuals. A study on the neutralizing capacity of the virus by antibodies to SARS-CoV-2 (Cristiano A and others) correlated the concentration of neutralizing anti-spike antibodies and the titer of the viral neutralization test in paucisymptomatic, symptomatic and vaccinated subjects. . The conclusion reached by this study – and which I feel I can share – is that it is not possible to establish a threshold value (cut-off) capable of predicting protection from viral infection, since other mechanisms may exist, besides to those examined, which could intervene to confer protection, such as cellular immunity.
Intensive care
As part of the intensive care studies, I point out a multicentre research conducted from August 2020 to May 2021 in 26 hospitals in Europe and India which involved 1000 COVID-19 patients who needed oxygen therapy or mechanical ventilation (The COVID STEROID 2 trail group). The goal of the study was to investigate whether early use of higher or lower steroid doses in COVID-19 patients improved prognosis. The result obtained indicated that, even in the presence of similar complications in the two groups considered on the basis of the dosage, there was no difference as regards a better outcome of the disease between the two cortisone dosages used. For this reason, pending further evidence, even if the population sample included in the study was large, a lower dosage might be preferred. Protein requirements in a small number of 22 COVID-19 patients admitted to the ICU and undergoing mechanical ventilation were also studied (Buckley CT et al). In the study it was confirmed that even COVID-19 patients, like all critically ill patients admitted to intensive care, need a sustained and adequate protein intake in the enteral diet, although there may be individual variations whose definition derives from a careful diagnostic estimation of needs.
Sos heart
As part of the studies of forensic medicine and pathological anatomy (Brauininger H and others) the autopsy samples of 95 COVID-19 patients who died, in the vast majority of cases, from pneumonia were analyzed and this in order to evaluate any cardiac involvement . In about half of the cases the virus was not found in the heart tissue while, in the remaining part, a large viral load was detected in the tissue analyzed. The study also shows that cardiac tissue infection induced gene alterations that led to an increased expression of pro-inflammatory genes which, however, was not followed by an increased infiltration of immunocompetent cells at the tissue level. The conclusion reached by the article is that heart damage does not depend on direct viral damage but is the consequence of induced gene alterations that can stimulate an inflammatory response. All this further strengthens the usefulness of the use, in the most serious and beautiful patients, in the most advanced stages of therapy, of anti-inflammatory therapy, steroids but not only.
Airways
In the context of immunological studies, I point out an article (Ravichandran S and others) which confirms that local immunity at the level of the mucous membranes of the upper airways, represents the most important line of defense of the immune system to counteract various pathogens, including SARS-CoV-2, which enter the body through the airways and infect the cells present there. What emerges from this study is not only important for even better defining the natural history of the infection, but can direct the preparation of so-called mucosal vaccines, to be administered by inhalation, through the upper airways. This type of vaccines, some of which are already being tested, can act at the virus entry site and for this, if effective, they could establish a valid protective immune response at the local level and lasting in the long term. Regarding epidemiological studies, an interesting prospective study (Bergwerk M et al.) Evaluated the incidence of infections in 1497 vaccinated healthcare workers in Israel. 39 infections were observed in vaccinated subjects in which the neutralizing antibody titer was significantly lower than that of uninfected controls. The infected subjects, despite the vaccination, however, did not develop any serious form of the disease since all presented either asymptomatic or paucisymptomatic forms.
Third dose
I also report a study that used data from the Official Register of the European Community, relating to 27 countries, which showed that mortality from COVID-19 is significantly increased for men, which underlines that the differences related to sex they may be of some importance in this pandemic. As part of the vaccine studies, the antibody response of 35 vaccinated subjects was evaluated, of which 14 were subsequently infected with SARS-CoV-2 and 21 were not infected (Collier AY and others). This investigation is part of the well-known outbreak of more than 1000 cases of infections that occurred in Provincetown in Massachussets in July 2021 and which was widely reported in the media at the time. In the group of affected subjects, the infections were mild or moderate because the vaccinated, although infected, showed a clear immune response to the virus that remained high for many months. As correctly commented in the report, this article, however not yet published, represents an important element of discussion on which categories, in addition to the immunosuppressed, fragile and super exposed, will have to carry out the so-called third dose of the vaccine in a preliminary manner.
RNA vaccines
A 6-month longitudinal study involving 61 subjects (Goel R and others) conducted at the University of Pennsylvania showed that, even in a situation of progressive fall in the specific antibody titre, vaccinated people still retain valid protection. because it is linked to cellular immunity, especially effective for preventing severe forms of disease. A meta-analysis (Harder T and others) of the studies carried out to evaluate the efficacy of the current vaccines, and in particular of the two RNA vaccines (Pfizer and Moderna) in protecting against infection and disease caused by the Delta variant (formerly Indiana ), was conducted at the Robert Kock Institute in Berlin. The conclusion reached by this meta-analysis is that, even in the presence of a marked heterogeneity of the studies considered, the vaccine protection against the serious disease caused by the Delta (Indian) variant is equal to that against the form caused by the Alpha variant (English ), while the protection against Delta infection is much lower.
Amount of viruses
In the context of clinical studies, a complete and very well-drafted systematic review (Brosseau LM and others) is noted, concerning a topic that has been the subject of interest since the beginning of the pandemic, relative to the role that the presence of a minor or major viruses can play a role in affecting the transmission and severity of the disease. The data at the moment are not yet definitive, even if it is underlined in this article that this is an aspect of no secondary importance both from an epidemiological and a clinical point of view. To better understand the impact in clinical and public health terms, animal models are also recommended that could be used for this purpose. As part of pediatric studies, observational research conducted in the United States (Lael M Yonker et al) has shown that age is not an element that influences viral load and that infectiousness is higher in children in the first 5 days of illness. Furthermore, children, both asymptomatic and symptomatic, can have high viral loads without these correlating to the severity of the disease. In addition to what is well indicated in the comment of the report, it is emphasized, once again, that pediatric populations, especially if not vaccinated, can be the reservoir of a virus that actively replicates with the possibility of developing new cases and favoring the onset. of new variants.
Need for hospitalization
In the context of therapy studies, the study by the RECOVERY Collaborative Group has been reported which demonstrated, through a randomized controlled clinical trial, how the use of colchicine in hospitalized patients with COVID-19, does not determine a significant effect on mortality, duration hospitalization, risks of progression to mechanical ventilation and death. A cohort study conducted in 1179 patients hospitalized for COVID-19, (Memel ZN et al.) Evaluated the association between inpatient statin use and 28-day mortality or the need for ICU admission. The results of the study, in line with a recent meta-analysis, indicated that the use of statins during hospitalization, either as a continuation of an existing home therapy or as a new prescription, was associated with a reduced risk of death or aggravation of the COVID-19 disease.