Inflammation as Prognostic Hallmark of Clinical Outcome in Patients with SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often characterized by a life-threatening interstitial pneumonia requiring hospitalization. The aim of this retrospective cohort study is to identify hallmarks of in-hospital mortality in patients affected by Coronavirus Disease 19 (COVID-19). A total of 150 patients admitted for COVID-19 from March to June 2021 to "F. Perinei" Murgia Hospital in Altamura, Italy, were divided into survivors (n = 100) and non-survivors groups (n = 50). Blood counts, inflammation-related biomarkers and lymphocyte subsets were analyzed into two groups in the first 24 h after admission and compared by Student's t-test. A multivariable logistic analysis was performed to identify independent risk factors associated with in-hospital mortality. Total lymphocyte count and CD3+ and CD4+ CD8+ T lymphocyte subsets were significantly lower in non-survivors. Serum levels of interleukin-6 (IL-6), lactate dehydrogenase (LDH), C-reactive protein (CRP) and procalcitonin (PCT) were significantly higher in non-survivors. Age > 65 years and presence of comorbidities were identified as independent risk factors associated with in-hospital mortality, while IL-6 and LDH showed a borderline significance. According to our results, markers of inflammation and lymphocytopenia predict in-hospital mortality in COVID-19.

Incidence of lower limb deep vein thrombosis in patients with COVID-19 pneumonia through different waves of SARS-CoV-2 pandemic: A multicenter prospective study.

OBJECTIVE: The aim of this study was to evaluate the incidence of deep vein thrombosis (DVT) of the lower limbs in patients hospitalized with COVID-19 pneumonia in a non-ICU setting according to the different waves of the SARS-CoV-2 pandemic. METHODS: Multicenter, prospective study of patients with COVID-19 pneumonia admitted to Internal Medicine units in Italy during the first (March-May 2020) and subsequent waves (November 2020 -April 2021) of the pandemic using a serial compression ultrasound (CUS) surveillance to detect DVT of the lower limbs. RESULTS: Three-hundred-sixty-three consecutive patients were enrolled. The pooled incidence of DVT was 8%: 13.5% in the first wave, and 4.2% in the subsequent waves (p = 0.002). The proportion of patients with early (< 4 days) detection of DVT was higher in patients during the first wave with respect to those of subsequent waves (8.1% vs 1.9%; p = 0.004). Patients enrolled in different waves had similar clinical characteristics, and thrombotic risk profile. Less patients during the first wave received intermediate/high dose anticoagulation with respect to those of the subsequent waves (40.5% vs 54.5%; p = 0.005); there was a significant difference in anticoagulant regimen and initiation of thromboprophylaxis at home (8.1% vs 25.1%; p<0.001). CONCLUSIONS: In acutely ill patients with COVID-19 pneumonia, the incidence of DVT of the lower limbs showed a 3-fold decrease during the first with respect to the subsequent waves of the pandemic. A significant increase in thromboprophylaxis initiation prior to hospitalization, and the increase of the intensity of anticoagulation during hospitalization, likely, played a relevant role to explain this observation.

Diagnosis of SARS-CoV-2 during the Pandemic by Multiplex RT-rPCR hCoV Test: Future Perspectives.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a significant threat to public health. However, among the Coronaviridae family members, there are other viruses that can also cause infections in humans. Among these, severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV) have posed significant threats to human health in the past. Other human pathogenic coronaviruses have been identified, and they are known to cause respiratory diseases with manifestations ranging from mild to severe. In this study, we evaluated the performance of a multiplex RT-rPCR specific to seven human pathogenic coronaviruses in mainly detecting SARS-CoV-2 directly from nasopharyngeal swabs obtained from suspected COVID-19 infected patients, while simultaneously detecting different human pathogenic coronaviruses in case these were also present. We tested 1195 clinical samples suspected of COVID-19 infection. The assay identified that 69% of the samples tested positive for SARS-CoV-2 (1195), which was confirmed using another SARS-CoV-2 RT-PCR kit available in our laboratory. None of these clinical samples were positive for SARS-CoV, MERS-CoV or HCoV. This means that during the endemic phase of COVID-19, infection with other human pathogenic coronaviruses, even the common cold coronavirus (HCoV), is very uncommon. Our study also confirmed that the multiplex RT-rPCR is a sensitive assay for detecting SARS-CoV-2 regardless of differences among the variants. This multiplex RT-rPCR is also time- and cost-saving and very easy to apply in the diagnostic laboratory due to its simple procedure and its stability in storage after preparation. These features make the assay a valuable approach in screening procedures for the rapid detection of SARS-CoV-2 and other human pathogenic coronaviruses that could affect public health.

Antispike Immunoglobulin-G (IgG) Titer Response of SARS-CoV-2 mRNA-Vaccine (BNT162b2): A Monitoring Study on Healthcare Workers.

The secretion of IgG SARS-CoV-2 antispike antibodies after vaccination with BNT162b2 and the protection represent the response of the human organism to the viral vector symptomatic infections. The aim of the present investigation was to evaluate the immune reaction in health workers of the Polyclinic of Bari to identify the relationship of antispike titers with blood type, sex, age, and comorbidities. This prospective observational study (RENAISSANCE) had as its primary endpoint the assessment of serologic response to BNT162b2 at three blood titers: the first at 60 days after the second dose (3 February 2021); the second titer at 75 days after the first titer; and the third titer at 130 days after the second titer. Out of 230 enrolled staff members, all responded excellently to the mRna Pfizer (BNT162b) vaccine. Only one patient, 40 days after the second dose (3 February 2021), was positive on the swab control performed on 15 March 2021, although completely asymptomatic, and was negative on the subsequent molecular swab performed on 30 March 2021. All the patients responded to the mRNA Pfizer (BNT162b) vaccine with an antispike IgG level above 500 BAU/mL at the first antispike protein essay (60 days after the second dose on 3 April 2021); at the second titer (75 days after the first titer on 20 June 2021), 4 (1.7% of 230 enrolled) patients showed an antispike IgG level under 500 BAU/mL; at the third titer (130 days after the second titer on 30 June 2021, which means 9 months after the second dose), 37 (16.1% of 230 enrolled) patients showed an antispike IgG level under 500 BAU/mL. The data analysis demonstrated that patients belonging to blood group 0, regardless of their rhesus factor, showed the strongest level of antibodies compared to the other groups. No dependency was found between low antibodies level and sex or age. Molecular swab controls were performed every 15th of the month continuously. However, the enrolled patients' activity was at high risk because they carried out medical activities such as dental and surgical as well with droplets of water vaporized by the effect of turbines, piezosurgery. The vaccination campaign among health workers of the Policlinico of the University of Bari "Aldo Moro" led to an excellent serological response and the complete absence of COVID-19 incident cases, so the antibody response was excellent. The COVID-19 vaccine booster shot should be administered after 9 months and not without prompt antispike titer detection to assess if any sign of waning immunity is present in that specific patient.

Effectiveness of SARS-CoV-2 Vaccines for Short- and Long-Term Immunity: A General Overview for the Pandemic Contrast.

BACKGROUND: The recent COVID-19 pandemic produced a significant increase in cases and an emergency state was induced worldwide. The current knowledge about the COVID-19 disease concerning diagnoses, patient tracking, the treatment protocol, and vaccines provides a consistent contribution for the primary prevention of the viral infection and decreasing the severity of the SARS-CoV-2 disease. The aim of the present investigation was to produce a general overview about the current findings for the COVID-19 disease, SARS-CoV-2 interaction mechanisms with the host, therapies and vaccines' immunization findings. METHODS: A literature overview was produced in order to evaluate the state-of-art in SARS-CoV-2 diagnoses, prognoses, therapies, and prevention. RESULTS: Concerning to the interaction mechanisms with the host, the virus binds to target with its Spike proteins on its surface and uses it as an anchor. The Spike protein targets the ACE2 cell receptor and enters into the cells by using a special enzyme (TMPRSS2). Once the virion is quietly accommodated, it releases its RNA. Proteins and RNA are used in the Golgi apparatus to produce more viruses that are released. Concerning the therapies, different protocols have been developed in observance of the disease severity and comorbidity with a consistent reduction in the mortality rate. Currently, different vaccines are currently in phase IV but a remarkable difference in efficiency has been detected concerning the more recent SARS-CoV-2 variants. CONCLUSIONS: Among the many questions in this pandemic state, the one that recurs most is knowing why some people become more seriously ill than others who instead contract the infection as if it was a trivial flu. More studies are necessary to investigate the efficiency of the treatment protocols and vaccines for the more recent detected SARS-CoV-2 variant.

Benefits and Implications of Resveratrol Supplementation on Microbiota Modulations: A Systematic Review of the Literature.

Resveratrol is a polyphenol that has been shown to possess many applications in different fields of medicine. This systematic review has drawn attention to the axis between resveratrol and human microbiota, which plays a key role in maintaining an adequate immune response that can lead to different diseases when compromised. Resveratrol can also be an asset in new technologies, such as gene therapy. PubMed, Cochrane Library, Scopus, Web of Science, and Google Scholar were searched to find papers that matched our topic dating from 1 January 2017 up to 18 January 2022, with English-language restriction using the following Boolean keywords: ("resveratrol" AND "microbio*"). Eighteen studies were included as relevant papers matching the purpose of our investigation. Immune response, prevention of thrombotic complications, microbiota, gene therapy, and bone regeneration were retrieved as the main topics. The analyzed studies mostly involved resveratrol supplementation and its effects on human microbiota by trials in vitro, in vivo, and ex vivo. The beneficial activity of resveratrol is evident by analyzing the changes in the host's genetic expression and the gastrointestinal microbial community with its administration. The possibility of identifying individual microbial families may allow to tailor therapeutic plans with targeted polyphenolic diets when associated with microbial dysbiosis, such as inflammatory diseases of the gastrointestinal tract, degenerative diseases, tumors, obesity, diabetes, bone tissue regeneration, and metabolic syndrome.

COVID-19 Infection in Children and Infants: Current Status on Therapies and Vaccines.

Since the beginning in December 2019, the SARS-CoV-2 outbreak appeared to affect mostly the adult population, sparing the vast majority of children who only showed mild symptoms. The purpose of this investigation is to assess the status on the mechanisms that give children and infants this variation in epidemiology compared to the adult population and its impact on therapies and vaccines that are aimed towards them. A literature review, including in vitro studies, reviews, published guidelines and clinical trials was performed. Clinical trials concerned topics that allowed a descriptive synthesis to be produced. Four underlying mechanisms were found that may play a key role in providing COVID-19 protection in babies. No guidelines are available yet for therapy due to insufficient data; support therapy remains the most used. Only two vaccines are approved by the World Health Organization to be used in children from 12 years of age, and there are currently no efficacy or safety data for children below the age of 12 years. The COVID-19 clinical frame infection is milder in children and adolescents. This section of the population can act as vectors and reservoirs and play a key role in the transmission of the infection; therefore, vaccines are paramount. More evidence is required to guide safely the vaccination campaign.

COVID-19 Infection in Children, Infants and Pregnant Subjects: An Overview of Recent Insights and Therapies.

BACKGROUND: The SARS-CoV-2 pandemic has involved a severe increase of cases worldwide in a wide range of populations. The aim of the present investigation was to evaluate recent insights about COVID-19 infection in children, infants and pregnant subjects. METHODS: a literature overview was performed including clinical trials, in vitro studies, reviews and published guidelines regarding the present paper topic. A descriptive synthesis was performed to evaluate recent insights and the effectiveness of therapies for SARS-CoV-2 infection in children, infants and pregnant subjects. RESULTS: Insufficient data are available regarding the relationship between COVID-19 and the clinical risk of spontaneous abortion and premature foetus death. A decrease in the incidence of COVID-19 could be correlated to a minor expression of ACE2 in childrens' lungs. At present, a modulation of the dose-effect posology for children and infants is necessary. CONCLUSIONS: Pregnant vertical transmission has been hypothesised for SARS-CoV-2 infection. Vaccines are necessary to achieve mass immunity for children and also pregnant subjects.

The Vitamin D, IL-6 and the eGFR Markers a Possible Way to Elucidate the Lung-Heart-Kidney Cross-Talk in COVID-19 Disease: A Foregone Conclusion.

BACKGROUND: Based on recent findings, we speculated the existence of the lung, heart, and kidney axis as the main pathway for the COVID-19 disease progression. METHODS: This paper reports on an observational study conducted by a team of researchers and doctors of the 118-Pre-Hospital and Emergency Department of SG Moscati of Taranto City in Italy. The study was conducted on a totality of 185 participants that were divided into three groups. The study group included COVID-19 affected patients (PP n = 80), the first control group included patients with different pathologies (non-COVID-19 NNp n = 62) of the SG Moscati Hospital, and the second control group included healthy individuals (NNh n = 43). The core of the current trial was focused on assessing the level of the vitamin D (serum 25(OH) D concentration), IL-6, and the renal glomerular filtrate (eGFR) in COVID-19 disease and non-COVID-19 patients in both groups. RESULTS: It was observed that the majority of COVID-19-infected patients showed a progressive multi-organ involvement, especially in regard to the lung, kidney, and heart. The majority of the COVID-19 patients exhibited preexisting comorbidities which include cardiovascular, respiratory, and renal disorders accompanied by a severely low level of vitamin D, extremely high level of IL-6, and low glomerular filtration rate (eGFR). The significant overall damages exerted by the immune-mediated responses under the hyper-expression of proinflammatory cytokines and interleukins, such as IL-6, may be facilitated by either a decreased level of vitamin D or the ageing process. The reduced presence of vitamin D was often found together with a reduced functionality of renal activity, as revealed by the low eGFR, and both were seen to be concomitant with an increased mortality risk in patients with lung disorders and heart failure (HF), whether it is showed at baseline or it develops during manifestation of COVID-19. Therefore, the documentation of the modifiable risk factors related to SARS-CoV-2 and lung impairment in older patients with kidney and heart disease may help the clinician to better manage the situation. CONCLUSIONS: This paper addresses how a low level of vitamin D and older age may be indicative of systemic worsening in patients with COVID-19, with a goal of providing a broader context in which to view a better therapeutic approach.

Sars-CoV-2 Virus Infection May Interfere CD34+ Hematopoietic Stem Cells and Megakaryocyte-Erythroid Progenitors Differentiation Contributing to Platelet Defection towards Insurgence of Thrombocytopenia and Thrombophilia.

To date, several cases of thrombosis have been confirmed to be related to Sars-CoV-2 infection. Multiple attempts detected the prolonged occurrence of Sars-CoV-2 viral RNA (long COVID) in whole blood suggesting that virus byproducts may remain within cells and tissues well over the disease has finished. Patients may develop severe thrombocytopenia, acute anemia of inflammation and, systemic thrombosis with the fatal course of disease, which is suggestive of further interferences of Sars-CoV-2 on hematopoietic stem cells (HSCs) within the differentiation process towards erythroid and megakaryocytic cells. Therefore, we speculated whether Sars-CoV-2 propagates in or compartmentalizes with hematopoietic progenitor, erythroid, and megakaryocytic cells as the main cause of thrombotic events in either COVID-19 patients or vaccinated individuals. Results: The Sars-CoV-2 RNA replication, protein translation and infectious particle formation as the spike proteins in hematopoietic cell lines take place via the angiotensin-converting enzyme 2 (ACE2) entry pathway within primary CD34+ HSCs inducing, ex vivo, the formation of defected erythroid and megakaryocytic cells that eventually become targets of humoral and adaptive immune cells. Conclusions: Viral particles from affected CD34+ HSCs or the cellular component of RBC units and eventually platelets, present the greatest risk for sever thrombosis-transmitted Sars-CoV-2 infections.

Incidence of deep vein thrombosis through an ultrasound surveillance protocol in patients with COVID-19 pneumonia in non-ICU setting: A multicenter prospective study.

OBJECTIVE: The aim of this study was to assess the incidence of deep vein thrombosis (DVT) of the lower limbs, using serial compression ultrasound (CUS) surveillance, in acutely ill patients with COVID-19 pneumonia admitted to a non-ICU setting. METHODS: Multicenter, prospective study of patients with COVID-19 pneumonia admitted to Internal Medicine units. All patients were screened for DVT of the lower limbs with serial CUS. Anticoagulation was defined as: low dose (enoxaparin 20-40 mg/day or fondaparinux 1.5-2.5 mg/day); intermediate dose (enoxaparin 60-80 mg/day); high dose (enoxaparin 120-160 mg or fondaparinux 5-10 mg/day or oral anticoagulation). The primary end-point of the study was the diagnosis of DVT by CUS. RESULTS: Over a two-month period, 227 consecutive patients with moderate-severe COVID-19 pneumonia were enrolled. The incidence of DVT was 13.7% (6.2% proximal, 7.5% distal), mostly asymptomatic. All patients received anticoagulation (enoxaparin 95.6%) at the following doses: low 57.3%, intermediate 22.9%, high 19.8%. Patients with and without DVT had similar characteristics, and no difference in anticoagulant regimen was observed. DVT patients were older (mean 77±9.6 vs 71±13.1 years; p = 0.042) and had higher peak D-dimer levels (5403 vs 1723 ng/mL; p = 0.004). At ROC analysis peak D-dimer level >2000 ng/mL (AUC 0.703; 95% CI 0.572-0.834; p = 0.004) was the most accurate cut-off value able to predict DVT (RR 3.74; 95%CI 1.27-10, p = 0.016). CONCLUSIONS: The incidence of DVT in acutely ill patients with COVID-19 pneumonia is relevant. A surveillance protocol by serial CUS of the lower limbs is useful to timely identify DVT that would go otherwise largely undetected.