Humoral and Cellular Immune Response Elicited by Two Doses of mRNA BNT162b2 Vaccine Against SARS-CoV-2 in People Living with HIV.

At present, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines can elicit robust humoral and cellular immune responses in people living with HIV (PLWH) is still controversial. We assessed humoral and cellular immune response after the administration of the BNT162b2-mRNA-vaccine in seven antiretroviral therapy-treated PLWH patients and in nine HIV-negative health care workers (PWOH) over a 3-month span of time from the first vaccine dose. The neutralizing activity against both the European and the Delta variants declined after 3 months equally in both PLWH and PWOH. The gene expression analysis of factors involved in the antiviral immune response did not show any significant difference between PLWH and PWOH; among circulating cytokines/chemokines, a progressive decline was observed in the mean values of IL-1ß, IL-5, IL-6, IL-13, and IL-15 in both PLWH and PWOH. Conversely, the ratio between naive and terminally differentiated T-CD4+ effector memory showed a reduction trend over time in PLWH. Our findings showed no significant differences in the ability to mount an immune response after the administration of two SARS-CoV-2 mRNA BNT162b2 doses in PLWH and PWOH. However, as BNT162b2 vaccinated PLWH display an early waning immunity in the T cell compartment, the administration of a booster dose may be necessary to maintain a SARS-CoV-2-specific immune response.

The Immunological Profile of SARS-CoV-2 Infection in Children Is Linked to Clinical Severity and Age.

Coronavirus disease 19 (COVID-19) is clinically less severe in children, even if the wide variety and degree of severity of symptoms reported in children pose a still-unresolved challenge for clinicians. We performed an in-depth analysis of the immunological profiles of 18 hospitalized SARS-CoV-2-infected children, whose results were compared to those obtained from 13 age- and sex-matched healthy controls (HC). The patients were categorized as paucisymptomatic/moderate (55.6%) or severe/critical (44.5%) according to established diagnostic criteria and further stratified into the categories of infants (1-12 months), children (1-12 years), and adolescents (>12 years). We assessed SARS-CoV-2-specific RBD antibodies (Ab), neutralizing antibodies (nAb), and circulating cytokines/chemokines in the plasma, and the SARS-CoV-2-specific immune response was measured in PBMCs by gene expression and secretome analyses. Our results showed peculiar circulating cytokine/chemokine profiles among patients sharing a similar clinical phenotype. A cluster of patients consisting of infants with severe symptoms presented hyperinflammatory profiles, together with extremely polarized antibody profiles. In a second cluster consisting of paucisymptomatic patients, a less pronounced increase in the level of inflammatory cytokines, together with an association between the selected cytokines and humoral responses, was observed. A third cluster, again consisting of paucisymptomatic patients, showed a circulating cytokine/chemokine profile which overlapped with that of the HC. The SARS-CoV-2-stimulated production of pro-inflammatory proteins, T lymphocyte activation, and migration-specific proteins, were significantly increased in SARS-CoV-2-infected children compared to the HC. Our findings suggest that immune response activation in the course of SARS-CoV-2 infection in children is directly correlated with clinical severity and, to a lesser extent, age.

No association of a risk variant for severe COVID-19 with HIV protection in three cohorts of highly exposed individuals.

An extended haplotype on chromosome 3 is the major genetic risk factor for severe COVID-19. The risk haplotype, which was inherited from Neanderthals, decreases the expression of several cytokine receptors, including CCR5. Recently, a study based on three general population cohorts indicated that the minor allele of one of the variants in the haplotype (rs17713054) protects against HIV infection. We thus expected this allele to be over-represented in highly exposed individuals who remain uninfected (exposed seronegative individuals, ESN). To perform a meta-analysis, we genotyped rs17713054 in three ESN cohorts of European ancestry exposed to HIV through different routes. No evidence of association was detected in the single cohorts. The meta-analysis also failed to detect any effect of the variant on protection from HIV-1. The same results were obtained in a Cox-regression analysis for the time to seroconversion. An in-vitro infection assay did not detect differences in viral replication as a function of rs17713054 genotype status. We conclude that the rs17713054 minor allele is not associated with the ESN phenotype and does not modulate HIV infection in vitro.

Saliva and Plasma Neutralizing Activity Induced by the Administration of a Third bnt162b2 Vaccine Dose.

The BNT162b2 vaccine induces neutralizing activity (NA) in serum, but no data are available on whether a third-dose activates specific-immunity within the oral mucosa, representing the primary route of viral-entry. To carefully address this issue, we investigated if such immunity is boosted by SARS-CoV-2-infection; how long it is maintained over-time; and if it protects against the SARS-CoV-2 lineage B.1 (EU) and the emerging Delta and Omicron variants. NA was measured in plasma and saliva samples from: uninfected SARS-CoV-2-Vaccinated (SV), subjects infected prior to vaccination (SIV), and subjects who were infected after the second (SIV2) or the third (SIV3) vaccine dose. Samples were collected immediately before (T0), 15 days (T1), and 90 days (T2) post third-dose administration (SV and SIV), or 15 days post-infection (SIV2 and SIV3). In all the enrolled groups, NA in plasma and saliva: (i) was higher against EU compared to the other variants at all time-points (SV: T0 and T1, EU vs. both Delta and Omicron p < 0.001; T2 p < 0.01) (SIV: T0, EU vs. Delta p < 0.05; EU vs. Omi p < 0.01; T1 and T2 EU vs. Delta p < 0.01; EU vs. Omi p < 0.001); (ii) was boosted by the administration of the third dose; iii) declined over-time, albeit being detectable in almost all subjects at T2. The monitoring of NA over time will be important in clarifying if different NA levels may influence either acquisition or course of infection to properly plan the timing of a fourth vaccine dose administration.

SARS-CoV-2 vertical transmission during the first trimester of pregnancy in asymptomatic women.

OBJECTIVES: It is now well established that in utero vertical SARS-CoV-2 transmission can occur during the late third trimester. However, little is known about other gestational ages. Recently, an increased risk of early miscarriage was reported in pregnant women who were SARS-CoV-2-positive. The objective of the current study was to evaluate the putative SARS-CoV-2 vertical transmission during the first trimester of pregnancy. DESIGN: This is an observational study on pregnant women who were SARS-CoV-2-positive during the first trimester. Fetal and syncytiotrophoblastic specimens were collected by hysterosuction from 17 pregnant women who were SARS-CoV-2-positive and voluntarily terminated the pregnancy between week 8 and 12. We investigated the viral vertical transmission using SARS-CoV-2 RNA detection in the fetus and syncytiotrophoblast by two different techniques. RESULTS: The results suggest that SARS-CoV-2 vertical transmission is indeed possible during the first trimester in asymptomatic women. Although maternal viremia was never detected, roughly 30% of the fetuses and 17% of the syncytiotrophoblasts were found to be SARS-CoV-2-positive. CONCLUSION: Indeed, SARS-CoV-2 can spread to the fetus through the syncytiotrophoblast. Concerningly, this happens in asymptomatic pregnant women as well. Possible long-term detrimental consequences on fetal development still need to be assessed. This should be taken into consideration in the management of pregnant women by implementing preventive strategies.

Leishmania tarentolae as an Antigen Delivery Platform: Dendritic Cell Maturation after Infection with a Clone Engineered to Express the SARS-CoV-2 Spike Protein.

BACKGROUND: Protozoa of the genus Leishmania are characterized by their capacity to target macrophages and Dendritic Cells (DCs). These microorganisms could thus be exploited for the delivery of antigens to immune cells. Leishmania tarentolae is regarded as a non-pathogenic species; it was previously used as a biofactory for protein production and has been considered as a candidate vaccine or as an antigen delivery platform. However, results on the type of immune polarization determined by L. tarentolae are still inconclusive. METHODS: DCs were derived from human monocytes and exposed to live L. tarentolae, using both the non-engineered P10 strain, and the same strain engineered for expression of the spike protein from SARS-CoV-2. We then determined: (i) parasite internalization in the DCs; and (ii) the capacity of the assayed strains to activate DCs and the type of immune polarization. RESULTS: Protozoan parasites from both strains were effectively engulfed by DCs, which displayed a full pattern of maturation, in terms of MHC class II and costimulatory molecule expression. In addition, after parasite infection, a limited release of Th1 cytokines was observed. CONCLUSIONS: Our results indicate that L. tarentolae could be used as a vehicle for antigen delivery to DCs and to induce the maturation of these cells. The limited cytokine release suggests L. tarentolae as a neutral vaccine vehicle that could be administered in association with appropriate immune-modulating molecules.

Dopamine Reduces SARS-CoV-2 Replication In Vitro through Downregulation of D2 Receptors and Upregulation of Type-I Interferons.

Recent evidence suggests that SARS-CoV-2 hinders immune responses via dopamine (DA)-related mechanisms. Nonetheless, studies addressing the specific role of DA in the frame of SARS-CoV-2 infection are still missing. In the present study, we investigate the role of DA in SARS-CoV-2 replication along with potential links with innate immune pathways in CaLu-3 human epithelial lung cells. We document here for the first time that, besides DA synthetic pathways, SARS-CoV-2 alters the expression of D1 and D2 DA receptors (D1DR, D2DR), while DA administration reduces viral replication. Such an effect occurs at non-toxic, micromolar-range DA doses, which are known to induce receptor desensitization and downregulation. Indeed, the antiviral effects of DA were associated with a robust downregulation of D2DRs both at mRNA and protein levels, while the amount of D1DRs was not significantly affected. While halting SARS-CoV-2 replication, DA, similar to the D2DR agonist quinpirole, upregulates the expression of ISGs and Type-I IFNs, which goes along with the downregulation of various pro-inflammatory mediators. In turn, administration of Type-I IFNs, while dramatically reducing SARS-CoV-2 replication, converges in downregulating D2DRs expression. Besides configuring the CaLu-3 cell line as a suitable model to study SARS-CoV-2-induced alterations at the level of the DA system in the periphery, our findings disclose a previously unappreciated correlation between DA pathways and Type-I IFN response, which may be disrupted by SARS-CoV-2 for host cell invasion and replication.

Natural SARS-CoV-2 Infection Affects Neutralizing Activity in Saliva of Vaccinees.

Background: SARS-CoV-2 transmission mainly occurs through exposure of the upper airway mucosa to infected secretions such as saliva, which are excreted by an infected person. Thus, oral mucosal immunity plays a central role in the prevention of and early defense against SARS-CoV-2 infection. Although virus-specific antibody response has been extensively investigated in blood samples of SARS-CoV-2-infected patients and vaccinees, local humoral immunity in the oral cavity and its relationship to systemic antibody levels needs to be further addressed. Material and Methods: We fine-tuned a virus neutralization assay (vNTA) to measure the neutralizing activity (NA) of plasma and saliva samples from 20 SARS-CoV-2-infected (SI), 40 SARS-CoV-2-vaccinated (SV), and 28 SARS-CoV-2-vaccinated subjects with a history of infection (SIV) using the "wild type" SARS-CoV-2 lineage B.1 (EU) and the Delta (B.1.617.2) strains. To validate the vNTA results, the presence of neutralizing antibodies (NAbs) to the spike receptor binding domain (RBD) was evaluated with an ELISA assay. Results: NA to SARS-CoV-2 lineage B.1 (EU) was present in plasma samples from all the tested subjects, with higher titers in SIV compared to both SI and SV. Conversely, NA was detected in saliva samples from 10.3% SV, 45% SI, and 92.6% SIV, with significantly lower titers in SV compared to both SI and SIV. The detection of NAbs in saliva reflected its reduced NA in SV. Discussion: The difference in NA of plasma vs. saliva was confirmed in a vNTA where the SARS-CoV-2 B.1 and Delta strains were tested head-to-head, which also revealed a reduced NA of both specimens compared to the B.1 variant. Conclusions: The administration of SARS-CoV-2 vaccines was associated with limited virus NA in the oral cavity, as measured in saliva and in comparison to plasma. This difference was more evident in vaccinees without a history of SARS-CoV-2 infection, possibly highlighting the importance of local exposure at the site of virus acquisition to effectively prevent the infection and block its spread. Nevertheless, the presence of immune escape mutations as possibly represented by the SARS-CoV-2 Delta variant negatively affects both local and systemic efficacy of NA associated with vaccination.

Pregnant Women Develop a Specific Immunological Long-Lived Memory Against SARS-COV-2.

It is well established that pregnancy induces deep changes in the immune system. This is part of the physiological adaptation of the female organism to the pregnancy and the immunological tolerance toward the fetus. Indeed, over the three trimesters, the suppressive T regulatory lymphocytes are progressively more represented, while the expression of co-stimulatory molecules decreases overtime. Such adaptations relate to an increased risk of infections and progression to severe disease in pregnant women, potentially resulting in an altered generation of long-lived specific immunological memory of infection contracted during pregnancy. How potent is the immune response against SARS-CoV-2 in infected pregnant women and how long the specific SARS-CoV-2 immunity might last need to be urgently addressed, especially considering the current vaccinal campaign. To address these questions, we analyzed the long-term immunological response upon SARS-CoV-2 infection in pregnant women from delivery to a six-months follow-up. In particular, we investigated the specific antibody production, T cell memory subsets, and inflammation profile. Results show that 80% developed an anti-SARS-CoV-2-specific IgG response, comparable with the general population. While IgG were present only in 50% of the asymptomatic subjects, the antibody production was elicited by infection in all the mild-to-critical patients. The specific T-cell memory subsets rebalanced over-time, and the pro-inflammatory profile triggered by specific SARS-CoV-2 stimulation faded away. These results shed light on SARS-CoV-2-specific immunity in pregnant women; understanding the immunological dynamics of the immune system in response to SARS-CoV-2 is essential for defining proper obstetric management of pregnant women and fine tune gender-specific vaccinal plans.

UV and violet light can Neutralize SARS-CoV-2 Infectivity.

We performed an in-depth analysis of the virucidal effect of discrete wavelengths: UV-C (278 nm), UV-B (308 nm), UV-A (366 nm) and violet (405 nm) on SARS-CoV-2. By using a highly infectious titer of SARS-CoV-2 we observed that the violet light-dose resulting in a 2-log viral inactivation is only 104 times less efficient than UV-C light. Moreover, by qPCR (quantitative Polymerase chain reaction) and fluorescence in situ hybridization (FISH) approach we verified that the viral titer typically found in the sputum of COVID-19 patients can be completely inactivated by the long UV-wavelengths corresponding to UV-A and UV-B solar irradiation. The comparison of the UV action spectrum on SARS-CoV-2 to previous results obtained on other pathogens suggests that RNA viruses might be particularly sensitive to long UV wavelengths. Our data extend previous results showing that SARS-CoV-2 is highly susceptible to UV light and offer an explanation to the reduced incidence of SARS-CoV-2 infection seen in the summer season.

Anti-Inflammatory Effects of Immunostimulation in Patients with COVID-19 Pneumonia.

BACKGROUND: The effects of immunomodulators in patients with Coronavirus Disease 2019 (COVID-19) pneumonia are still unknown. We investigated the cellular inflammatory and molecular changes in response to standard-of-care + pidotimod (PDT) and explored the possible association with blood biomarkers of disease severity. METHODS: Clinical characteristics and outcomes, neutrophil-to-lymphocyte ratio (NLR), plasma and cell supernatant chemokines, and gene expression patterns after SARS-CoV-2 and influenza (FLU) virus in vitro stimulation were assessed in 16 patients with mild-moderate COVID-19 pneumonia, treated with standard of care and PDT 800 mg twice daily (PDT group), and measured at admission, 7 (T1), and 12 (T2) days after therapy initiation. Clinical outcomes and NLR were compared with age-matched historical controls not exposed to PDT. RESULTS: Hospital stay, in-hospital mortality, and intubation rate did not differ between groups. At T1, NLR was 2.9 (1.7-4.6) in the PDT group and 5.5 (3.4-7.1) in controls (p = 0.037). In the PDT group, eotaxin and IL-4 plasma concentrations progressively increased (p < 0.05). Upon SARS-CoV-2 and FLU-specific stimulation, IFN-γ was upregulated (p < 0.05), while at genetic transcription level, Pathogen Recognition Receptors (TRLs) were upregulated, especially in FLU-stimulated conditions. CONCLUSIONS: Immunomodulation exerted by PDT and systemic corticosteroids may foster a restoration in the innate response to the viral infection. These results should be confirmed in larger RCTs.

Immunological Characterization of HIV and SARS-CoV-2 Coinfected Young Individuals.

While the risk of SARS-CoV-2 infection and/or COVID-19 disease progression in the general population has been largely assessed, its impact on HIV-positive individuals remains unclear. We present clinical and immunological data collected in a cohort of HIV-infected young individuals during the first wave of COVID-19 pandemic. SARS-CoV-2 RNA, virus-specific antibodies, as well as the expression of factors involved in the anti-viral immune response were analyzed. Moreover, we set up an in vitro coinfection assay to study the mechanisms correlated to the coinfection process. Our results did not show any increased risk of severe COVID-19 in HIV-positive young individuals. In those subjects who contracted SARS-CoV-2 infection, an increase in IL-10 expression and production was observed. Furthermore, in the in vitro coinfection assay, we revealed a reduction in SARS-CoV-2 replication associated to an upregulation of IL-10. We speculate that IL-10 could play a crucial role in the course of SARS-CoV-2 infection in HIV-positive individuals. These results might help defining clinical management of HIV/SARS-CoV-2 co-infected young individuals, or putative indications for vaccination schedules in this population.

PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response.

A substantial proportion of patients who have recovered from coronavirus disease-2019 (COVID-19) experience COVID-19-related symptoms even months after hospital discharge. We extensively immunologically characterized patients who recovered from COVID-19. In these patients, T cells were exhausted, with increased PD-1+ T cells, as compared with healthy controls. Plasma levels of IL-1ß, IL-1RA, and IL-8, among others, were also increased in patients who recovered from COVID-19. This altered immunophenotype was mirrored by a reduced ex vivo T cell response to both nonspecific and specific stimulation, revealing a dysfunctional status of T cells, including a poor response to SARS-CoV-2 antigens. Altered levels of plasma soluble PD-L1, as well as of PD1 promoter methylation and PD1-targeting miR-15-5p, in CD8+ T cells were also observed, suggesting abnormal function of the PD-1/PD-L1 immune checkpoint axis. Notably, ex vivo blockade of PD-1 nearly normalized the aforementioned immunophenotype and restored T cell function, reverting the observed post-COVID-19 immune abnormalities; indeed, we also noted an increased T cell-mediated response to SARS-CoV-2 peptides. Finally, in a neutralization assay, PD-1 blockade did not alter the ability of T cells to neutralize SARS-CoV-2 spike pseudotyped lentivirus infection. Immune checkpoint blockade ameliorates post-COVID-19 immune abnormalities and stimulates an anti-SARS-CoV-2 immune response.

SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes.

The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pediatric lung (MSCs-lung) and CPAM tissues (MSCs-CPAM) in order to elucidate potential pathways involved in SARS-CoV-2 infection in a condition of exacerbated inflammatory response. MSCs-lung and MSCs-CPAM do not express angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TRMPSS2). SARS-CoV-2 appears to be unable to replicate in MSCs-CPAM and MSCs-lung. MSCs-lung and MSCs-CPAM maintained the expression of stemness markers MSCs-lung show an inflammatory response (IL6, IL1B, CXCL8, and CXCL10), and the activation of Notch3 non-canonical pathway; this route appears silent in MSCs-CPAM, and cytokine genes expression is reduced. Decreased value of p21 in MSCs-lung suggested no cell cycle block, and cells did not undergo apoptosis. MSCs-lung appears to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keeps stable or reduce the immunomodulatory receptors expression, but they also reduce their cytokines expression. These data indicated that, independently from their perilesional or cystic origin, the MSCs populations already present in a patient affected with CPAM are not permissive for SARS-CoV-2 entry, and they will not spread the disease in case of infection. Moreover, these MSCs will not undergo apoptosis when they come in contact with SARS-CoV-2; on the contrary, they maintain their staminality profile.

Severity of COVID-19 Patients Predicted by Serum Sphingolipids Signature.

The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient's outcome is poorly understood. The present study targets the sphingolipid profile of twenty-four healthy controls and fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted and targeted mass spectrometry and ELISA. Results indicated a progressive increase in dihydrosphingosine, dihydroceramides, ceramides, sphingosine, and a decrease in sphingosine-1-phosphate. These changes are associated with a serine palmitoyltransferase long chain base subunit 1 (SPTLC1) increase in relation to COVID-19 severity. Severe patients showed a decrease in sphingomyelins and a high level of acid sphingomyelinase (aSMase) that influences monosialodihexosyl ganglioside (GM3) C16:0 levels. Critical patients are characterized by high levels of dihydrosphingosine and dihydroceramide but not of glycosphingolipids. In severe and critical patients, unbalanced lipid metabolism induces lipid raft remodeling, leads to cell apoptosis and immunoescape, suggesting active sphingolipid participation in viral infection. Furthermore, results indicated that the sphingolipid and glycosphingolipid metabolic rewiring promoted by aSMase and GM3 is age-dependent but also characteristic of severe and critical patients influencing prognosis and increasing viral load. AUCs calculated from ROC curves indicated ceramides C16:0, C18:0, C24:1, sphingosine and SPTLC1 as putative biomarkers of disease evolution.

Transcriptomic Analysis of HCN-2 Cells Suggests Connection among Oxidative Stress, Senescence, and Neuron Death after SARS-CoV-2 Infection.

According to the neurological symptoms of SARS-CoV-2 infection, it is known that the nervous system is influenced by the virus. We used pediatric human cerebral cortical cell line HCN-2 as a neuronal model of SARS-CoV-2 infection, and, through transcriptomic analysis, our aim was to evaluate the effect of SARS-CoV-2 in this type of cells. Transcriptome analyses revealed impairment in TXN gene, resulting in deregulation of its antioxidant functions, as well as a decrease in the DNA-repairing mechanism, as indicated by the decrease in KAT5. Western blot analyses of SOD1 and iNOS confirmed the impairment of reduction mechanisms and an increase in oxidative stress. Upregulation of CDKN2A and a decrease in CDK4 and CDK6 point to the blocking of the cell cycle that, according to the deregulation of repairing mechanism, has apoptosis as the outcome. A high level of proapoptotic gene PMAIP1 is indeed coherent with neuronal death, as also supported by increased levels of caspase 3. The upregulation of cell-cycle-blocking genes and apoptosis suggests a sufferance state of neurons after SARS-CoV-2 infection, followed by their inevitable death, which can explain the neurological symptoms reported. Further analyses are required to deeply explain the mechanisms and find potential treatments to protect neurons from oxidative stress and prevent their death.

SARS-CoV-2 Infected Pediatric Cerebral Cortical Neurons: Transcriptomic Analysis and Potential Role of Toll-like Receptors in Pathogenesis.

Different mechanisms were proposed as responsible for COVID-19 neurological symptoms but a clear one has not been established yet. In this work we aimed to study SARS-CoV-2 capacity to infect pediatric human cortical neuronal HCN-2 cells, studying the changes in the transcriptomic profile by next generation sequencing. SARS-CoV-2 was able to replicate in HCN-2 cells, that did not express ACE2, confirmed also with Western blot, and TMPRSS2. Looking for pattern recognition receptor expression, we found the deregulation of scavenger receptors, such as SR-B1, and the downregulation of genes encoding for Nod-like receptors. On the other hand, TLR1, TLR4 and TLR6 encoding for Toll-like receptors (TLRs) were upregulated. We also found the upregulation of genes encoding for ERK, JNK, NF-κB and Caspase 8 in our transcriptomic analysis. Regarding the expression of known receptors for viral RNA, only RIG-1 showed an increased expression; downstream RIG-1, the genes encoding for TRAF3, IKKε and IRF3 were downregulated. We also found the upregulation of genes encoding for chemokines and accordingly we found an increase in cytokine/chemokine levels in the medium. According to our results, it is possible to speculate that additionally to ACE2 and TMPRSS2, also other receptors may interact with SARS-CoV-2 proteins and mediate its entry or pathogenesis in pediatric cortical neurons infected with SARS-CoV-2. In particular, TLRs signaling could be crucial for the neurological involvement related to SARS-CoV-2 infection.

Unlikely SARS-CoV-2 Transmission During Vaginal Delivery.

Pregnant women display a higher risk of progression to disease and higher viral loads during infections due to their more permissive, tolerogenic immune system. However, only few studies have focused on SARS-CoV-2 intrapartum vertical transmission via vaginal secretions or faeces. The aim of this study was to investigate the presence of the virus in vaginal, rectal and blood specimens from pregnant women characterized by different COVID-19 disease severity. We enrolled 56 SARS-CoV-2-positive pregnant women, of which 46 (82%) were in the third trimester of pregnancy, 6 (10%) in the second and 4 (7%) in the first. QPCR was performed to detect the virus in vaginal and rectal swabs and in plasma samples. SARS-CoV-2 was detected in 27% of rectal swabs of pregnant women in the third trimester, while no virus particles were detected in vaginal swabs of the same patients. Furthermore, only 4% plasma samples tested positive to SARS-CoV-2. No virus was detected in newborn's nasopharyngeal swabs. Despite the low number of subjects enrolled, our data suggest that, while theoretically possible, intrapartum vaginal or orofecal SARS-CoV-2 transmission seems to be unlikely.

Solar UV-B/A radiation is highly effective in inactivating SARS-CoV-2.

Solar UV-C photons do not reach Earth's surface, but are known to be endowed with germicidal properties that are also effective on viruses. The effect of softer UV-B and UV-A photons, which copiously reach the Earth's surface, on viruses are instead little studied, particularly on single-stranded RNA viruses. Here we combine our measurements of the action spectrum of Covid-19 in response to UV light, Solar irradiation measurements on Earth during the SARS-CoV-2 pandemics, worldwide recorded Covid-19 mortality data and our "Solar-Pump" diffusive model of epidemics to show that (a) UV-B/A photons have a powerful virucidal effect on the single-stranded RNA virus Covid-19 and that (b) the Solar radiation that reaches temperate regions of the Earth at noon during summers, is sufficient to inactivate 63% of virions in open-space concentrations (1.5 × 103 TCID50/mL, higher than typical aerosol) in less than 2 min. We conclude that the characteristic seasonality imprint displayed world-wide by the SARS-Cov-2 mortality time-series throughout the diffusion of the outbreak (with temperate regions showing clear seasonal trends and equatorial regions suffering, on average, a systematically lower mortality), might have been efficiently set by the different intensity of UV-B/A Solar radiation hitting different Earth's locations at different times of the year. Our results suggest that Solar UV-B/A play an important role in planning strategies of confinement of the epidemics, which should be worked out and set up during spring/summer months and fully implemented during low-solar-irradiation periods.