Several biomarkers have been evaluated as predictors of severity or in directing the treatment of COVID-19, however there are no conclusive results with prediction of the pathobiology of the infection. In this study, we evaluated serum levels of cytokines, chemokines, and cell growth factors in association with the pathobiology of mild to moderate SARS-CoV-2 infection. Those markers may act as immuno-inflammatory biomarkers in adults with mild to moderate flu syndrome who sought care at health units. Serum levels of SARS-CoV-2 infected patients (n=113) and flu symptoms individuals negative for SARS-CoV-2 (n=58), tested by the RT-qPCR test - nasal swab were compared to healthy controls (n=53). Participants who were symptomatic but negative for SARS-CoV-2 were tested for Influenza A/B and Respiratory Syncytial Virus (RSV). Results showed that the pro-inflammatory cytokines IL-1β, MCP-3, TNF-α and G-CSF were increased in symptomatic patients and the cytokines IL-6 and IL-10 were associated with patients positive for SARS-CoV-2 when compared to healthy controls. Symptoms associated with COVID-19 were fever, anosmia, ageusia and myalgia. For patients without SARS-CoV-2 infection their major symptom was sore throat. Five percent (4/83) of SARS-CoV-2 negative patients were positive for RSV. The pathobiology of mild to moderate SARS-CoV-2 infection was associated with increasing pro-inflammatory cytokines and also a pleiotropic IL-6 and anti-inflammatory IL-10 cytokines compared to healthy controls.

As the Coronavirus Disease 2019 (COVID-19) outbreak spread, evidence has emerged that gender and race would bear a disproportionate impact on the morbimortality of COVID-19. Here, we conducted a retrospective observational study using the TabNet/DATASUS platform of the city of São Paulo. COVID-19 records from March 2020 thru December 2021 were included, and we evaluated the temporal trends of confirmed cases and case fatality rate by gender and ethnicity. Statistical analysis was performed using the R-software and the BioEstat-software, considering p<0.05 significant. From March/2020 to December/2021, 1,315,160 COVID-19 confirmed cases were recorded (57.1% females), and 2,973 deaths were due to COVID-19. Males presented higher median mortality (0.44% vs 0.23%; p<0.05) and ICU admission rates (0.34% vs 0.20%; p<0.05). Men were also associated with a higher risk of death (RR=1.28; p<0.05) and a higher chance of requiring ICU care (RR=1.29; p<0.05). The black ethnicity was associated with a higher risk of death (RR=1.19; p<0.05). White patients were more likely to require ICU admission (RR=1.13; p<0.05), whereas browns were associated with a protective effect (RR=0.86; p<0.05). Further, men presented a higher chance of death than women across the three major ethnic groups: whites (RR=1.33; p<0.05), blacks (RR=1.24; p<0.05), and browns (RR=1.35; p<0.05). In this study of COVID-19 in São Paulo, men were associated with worse outcomes, including in the three major ethnicities in the population. Blacks exhibited a higher risk of death, whites were more likely to require intensive care, and browns were at protection from ICU hospitalization.

Postnatal cytomegalovirus (HCMV) infection is well characterized in preterm infants, where it can lead to severe symptomatic infection. We analyzed the rate and route of transmission of postnatal HCMV infections in full-term babies during the first year of life. A cohort of 120 HCMV seropositive mothers and their 122 newborns were tested after delivery for HCMV DNA shedding in different bodily fluids. Postnatal HCMV infection was defined as the detection of >2.5×10 2 HCMV-DNA copies/mL in infants’ saliva swabs. Maternal neutralizing antibody serum titer, HCMV specific T-cell response, and HCMV glycoprotein B (gB) IgG on breastmilk were analyzed. HCMV shedding was detected in 67 of 120 mothers (55.8%), and 20 of 122 infants (16.4%) developed HCMV infection within the first three months of life. Six additional infants were infected during the first year, for a postnatal infection rate of 21.3%. Viral shedding was more frequent in breastmilk than saliva, urine and vaginal secretions, and the mothers of infected infants showed higher levels of HCMV-DNA in milk. No association was found between the antibody levels in serum or milk and maternal viral shedding, whereas a slightly lower frequency of HCMV-specific CD4 + T-cells with long-term memory phenotype was observed in women with HCM-DNA-positive milk. About one out of five infants develop HCMV infection within the first year of life. Breastmilk appears the major route of transmission of the infection, maternal saliva have a minor role whereas the role of vaginal secretions is negligible.

SARS-CoV-2 causes COVID-19 pandemic and continues to pose a threat to global public health through genetic mutation. In this study, we have found that an ACE2-specific monoclonal antibody at low concentration was able to greatly enhance SARS-CoV-2 infection and growth in cell culture. Strikingly, it promotes SARS-CoV-2 plaque formation, resulting in accurate titration of different SARS-CoV-2 variants, particularly the newly emerged Omicron variants, which otherwise cannot be determined by standard plaque assays. Quantification of infectious titers of the newly emerged variants will facilitate the development and evaluation of vaccines and antiviral drugs against SARS-CoV-2.

Early in the 2022 Mpox (MPX) global outbreak, caseloads in the New York Metropolitan area climbed rapidly before other US urban areas. This case series summarizes the authors’ clinical experience detecting and treating MPX, during a quickly evolving outbreak. Clinical outcomes were recorded with a focus on varied clinical presentation and outcomes such as complications and response to experimental tecovirimat therapy. A focal or multifocal rash was the most common presenting symptom in 91% of patients. Almost two thirds (62%) of patients had anogenital involvement. Proctitis was one of the most painful presentations with 75% requiring antiviral treatment and 3 patients needing hospitalization for pain management. Most patients responded promptly to antiviral treatment with tecovirimat. Five out of 10 patients treated with tecovirimat reported symptom resolution within 48 – 72 hours of therapy and another 3 saw resolution within first 96 hours. Two patients had poor response to tecovirimat. This series includes the only reported case of an HIV positive, immunocompetent patient who experienced recurrent anal ulcers due to Mpox and required a second course of tecovirimat. Other unique presentations included urethritis, abscess formation and MPX infection post-vaccination. Control of this current Mpox outbreak was possible due to timely diagnosis and the availability of both a licensed vaccine and an investigational drug.

A group of viruses, collectively known as Pteropine orthoreoviruses (PRVs), have recently been found in fruit bats and humans in Southeast Asia, Australia, and some African countries. This article intends to briefly discuss what is known about these viruses and their potential significance in public health and to advocate for increased surveillance of these zoonotic viruses to prevent potential future disease outbreaks, as well as to highlight a recent publication on this topic that was selected as an editor’s choice article in the Journal of Medical Virology 1.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to diverse clinical manifestations and pathologies that involve multiple organs. Even though the disease severity is manifested mainly in the respiratory tract, which is the primary target of SARS-CoV-2 infection, acute kidney injury in the form of acute tubular necrosis has also been noted in some COVID-19 cases. It is not entirely clear whether renal cells can be infected by the virus that might be involved in acute kidney disorder. In a recent publication by Radovic and colleagues (1) that has been selected as the editor’s choice paper published in the Journal of Medical Virology, the authors provided strong histopathological and immunofluorescence evidence of SARS-CoV-2 infection and tissue injury of renal parenchymal and tubular epithelial cells, which strongly suggest an active viral replication in the kidney of some severe and fatal COVID-19 cases, and to a lesser extent, a potential role for innate immune cells in viral infection and renal disease pathogenesis.

Varicella is a highly prevalent infectious disease with a similar transmission pathway to coronavirus disease 2019 (COVID-19). In the context of the COVID-19 pandemic, anti-COVID-19 non-pharmaceutical interventions (NPIs) have been implemented to prevent the spread of the infection. This study aims to analyze varicella’s epidemiological characteristics and further investigate the effect of anti-COVID-19 NPIs on varicella in Xi’an, northwestern China. Based on the varicella surveillance data, search engine indices, meteorological factors from 2011 to 2021 in Xi’an, and different levels of emergency response to COVID-19 during the pandemic, we applied Bayesian Structural Time Series models and interrupted time series analysis to predict the counterfactual incidence of varicella and quantify the impact of varying NPIs intensities on varicella. From 2011 to 2021, varicella incidence increased, especially in 2019, with a high incidence of 111.69/100,000. However, there was a sharp decrease of 43.18% in 2020 compared with 2019, and the peak of varicella incidence in 2020 was lower than in previous years from the 21st to the 25th week. In 2021, the seasonality of varicella incidence gradually returned to a seasonal pattern in 2011-2019. The results suggest that anti-COVID-19 NPIs effectively reduce the incidence of varicella, and this reduction has spatiotemporal heterogeneity.

To date (2/5/2023), nearly three years after the official declaration of the COVID-19 pandemic, a total of 754, 018, 841 cases and 6,817,478 deaths have been officially reported to the world health organization (WHO) ([https://covid19.who.int/](https://covid19.who.int/)). During this time, the global populace has witnessed the devastating effects of this pandemic, which can undoubtedly be considered the sanitary event of the century. In my opinion, understanding the mechanisms associated with the evolution of SARS-CoV-2 is the most important aspect of understanding the course of this pandemic. In this respect, the millions of viral sequences generated during the pandemic (1) have significantly aided in the tracking of the pandemic, resulting in the identification of multiple variants of concern.

A method using questionnaire data for estimating the level of under reporting during an outbreak is presented. It is based on rewriting the conditional probabilities for getting tested, being infected, and having symptoms. It shows very good agreement with seroprevalence studies of blood donors. On the one hand, this shows the strength of questionnaires when testing the general population during an outbreak as a means to find the true prevalence. On the other, applying it to covid-19 demonstrates that the asymptomatic cases likely make up around 50% of the infected.

Persistent high-risk human papilloma virus (HR-HPV) infection is the main risk factor for cervical cancer, threatening women’s health. Despite growing prophylactic vaccination, annual cervical cancer cases are still increasing and show a trend of younger onset age. However, therapeutic approaches towards HPV infection are still limited. 25-hydrocholesterol (25HC) has a wide-spectrum inhibitory effect on a variety of viruses. To explore efficient interventions to restrict HPV infection at an early time, we applied different pseudoviruses (PsV) to evaluate anti-HPV efficacy of 25HC. We tested PsV inhibition by 25HC in cervical epithelial-derived HeLa and C-33A cells, using high-risk (HPV16, HPV18, HPV59), possibly carcinogenic (HPV73), and low-risk (HPV6) HPV PsVs. Then we established murine genital HPV PsV infection models and applied IVIS to evaluate anti-HPV efficacy of 25HC in vivo. Next, with the help of confocal imaging, we targeted 25HC activity at filopodia upon HPV exposure. After that, we used RNA-seq and Western blotting to investigate 1) how 25HC disturbs actin cytoskeleton remodeling during HPV infection and 2) how prenylation regulates the cytoskeletal remodeling signaling pathway. Our findings suggest that 25HC perturbs F-actin rearrangement by reducing small GTPase prenylation. In this way, the phenomenon of HPV virion surfing was restricted, leading to failed infection.

Background: The lung-brain-axis is an emerging biological pathway that is being investigated in relation to microbiome medicine. Increasing evidence suggest that pulmonary viral infections can lead to distinct pathological imprints in the brain, thereby the need to explore and understand this mechanism and find possible interventions.  Objective:  This study used RSV infection in mice as a model to establish the potential lung-brain axis phenomenon. We hypothesized that RSV infection could disrupt the lung microbiota, thereby compromising the immune barriers and thus induces significant shift in microglia phenotype.  Methods: Mice were randomized into the Control, Ampicillin, RSV, and RSV+Ampicillin treated groups (n = 6 each). Ampicillin was given intratracheal instillation and seven days after the respective treatments, the mice were anesthetized. Hematoxylin-eosin (HE) staining of lung tissue to detect histopathology. Immunofluorescence label of specific target antigens in both the lung and brain tissues, namely, Malondialdehyde (MDA) and Superoxide dismutase (SOD) were used as markers of cellular damage. RT-qPCR was used to detect viral RNA in both tissues,  ELISA to measure IL-1β, iNOS, IL-10 and Arg1 in the supernatant and 16s DNA technology were used to detect the lung microflora.  Results: We found out that RSV infection induces elevated oxidative stress, reduced anti-oxidant and caused significant dysbacteriosis in the lungs of the mice. Pulmonary microbes were found affecting Th1-type immunoreactivity induced by RSV infection and eventually, microbiota in lung induced microglia phenotype shift in the brain of the mice.  Conclusion. This study was able to establish that RSV infection can disrupt the pulmonary microbiome and immune barriers to induce microglia phenotype shift. Thus, we recommend a large sample size study with robust data analysis for the long-term effects of antibiotics and RSV infection on brain physiology.

Rotavirus A (RVA) is an important cause of acute gastroenteritis (AGE) in children. This study aims to investigate the molecular epidemiology of RVA children hospitalized with AGE in Chiang Rai, Thailand in 2018-2020 by RT-PCR. Of 302 samples, RVA was detected in 11.6% (35 samples): 11.3% (19/168) in 2018-2019 and 11.9% (16/134) in 2019-2020. Surprisingly, G8P[8] was detected as the predominant genotype at 68.4% in 2018-2019 and 81.2% in 2019-2020. In addition, other genotypes were also detected, including G1P[8] (15.8%), G2P[4] (5.3%), G3P[8] (10.5%) in 2018-2019 and G9P[8] (18.8%) in 2019-2020. Analysis of genomic constellation of G8P[8] strains, represented by RVA/Human-wt/ THA/5CR11/2019/G8P[8], revealed a DS-1-like genetic backbone: G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis of the VP7 gene showed that the DS-1-like G8P[8] strains clustered in a distinct sublineage A together with 13 G8P[8] strains reported from Thailand and China, and these sublineage A G8P[8] strains contained unique amino acid substitutions in two positions (A125S and N147D) on the VP7 antigenic epitopes. Homology modeling of the VP7 capsid protein confirmed that these two amino acid changes were located on the surface exposed area of the virion. Phylogenetic trees of the VP1, VP6, NSP2, NSP3, and NSP4 genes have demonstrated that DS-1-like G8P[8] strains in the present study and 51 DS-1-like G8P[8] reference strains published formerly clustered in separate lineages. To the best of our knowledge, this is the first report of the emergence of novel DS-1-like G8P[8] strains that might have evolved genetically through reassortment events with locally or globally circulating genotypes.

Monkeypox infections in the US and across the world have been rising in the past few months. Most of these infections have been found to be transmitted among men who have sex with men (MSM). Our case report discusses the rare presentation of a patient with monkeypox along with multiple comorbidities, including AIDS, late latent syphilis, acute hepatitis C, and asymptomatic and scrotal and penile cellulitis secondary to MRSA. Further, our case report raises discussion on the need for further research to identify the effect of monkeypox vaccine on symptomatic patients who are immunocompromised.

1. A survey on the recent COVID-19 epidemic in China was conducted. 2. The epidemic likely made over 85% of people in China sick in December 2022. 3. The epidemic likely ended in early January 2023. 4. The epidemic had the features of spreading more rapidly and widely and having a higher symptomatic rate than previously thought. 5. The above features could lead to many severe cases and deaths due to the shortages of medical resources. 6. The above features greatly enhanced the population immunity in China, which will accelerate the end of the COVID-19 pandemic and reduce the emergence of risky variants of SARS-CoV-2 in China.

Background: Since early May 2022, outbreaks of Monkeypox (Mpox) cases have emerged and become a global concern. Studies exploring the gastrointestinal (GI) and/or liver manifestations of Mpox are still very limited. This systematic review and meta-analysis is the first to summarize the GI manifestations reported by Mpox patients. Methods: We searched for Mpox studies published until October 21, 2022, in MEDLINE, EMBASE, SCOPUS, and organization websites. Mpox studies were observational studies that reported at least one of either GI and/or liver manifestations. Meta-analysis was done to obtain the pooled prevalence of GI manifestations in Mpox patients. The quality of included studies was assessed using the NIH Quality Assessment Tool. Results: Overall, 31 studies that reported GI and/or liver manifestations in Mpox patients were included. The five most commonly reported GI manifestations by studies were abdominal pain, anorexia, diarrhea, nausea and/or vomiting, and proctitis. There is a lack of reporting for liver manifestations. The most prevalent GI manifestations in Mpox patients were anorexia (47%; 95%CI 41-53%), followed by nausea and/or vomiting (12%; 95%CI 11-13%), proctitis (11%; 95%CI 11-12%), abdominal pain (9%; 95%CI 8-10%), and diarrhea (5%; 95%CI 4-6%). Conclusion: Anorexia was the most frequently reported GI manifestation in Mpox patients, followed by nausea and/or vomiting, proctitis, abdominal pain, and diarrhea. The presentation of proctitis during the ongoing Mpox outbreak highly suggests a potential for Mpox diagnosis.

Monkeypox virus (MPXV) is a zoonotic disease endemic in the rain forest countries of Central and West Africa. Understanding the immune response in zoonosis is fundamental to prevent and contrast viral spreading. MPXV is a close relative of the Variola (smallpox) virus and vaccination with vaccinia virus give an 85% protection against MPXV. With the emergence of the recent MPXV outbreak, Jynneos vaccine has been proposed to individuals at high-risk of exposure. Comparative data on MPXV immune response in vaccinated or infected subjects is still scarce. Here we described the differences between a group of infected patients in comparison to smallpox or Jynneos vaccinated subjects. The patients’ response is stronger and faster, while the Jynneos vaccinated controls need more time to develop a good immunity. Interestingly, the historic smallpox-vaccinated controls retain a degree of protection, even after years from vaccination, which is most visible in the T-cellular memory that is comparable to the newly vaccinated subjects.

Background: We assessed whether the association between the risk of cerebrospinal fluid escape (CVE) and specific antiretroviral (ARV) classes, such as protease inhibitors, is due to suboptimal pharmacological profile generated by archived resistance-associated mutations (RAMs). Methods: A retrospective multicentric study on 300 adult people with HIV on antiretroviral therapy (ART) and available historical plasma genotype resistance testing (HGRT) for reverse transcriptase (RT) and protease genes between 2001 and 2021. The odds ratio for demographic, clinic-, and ART-related variables and CVE was estimated by multivariable modelling. HGRT-adjusted central nervous system effectiveness penetration (CPE) score was computed in modelling the risk. Results: Median age, plasma VL, and CD4 count were 49 years, <50 copies/mL, and 310 cells/μL. CVE was detected in 51 participants (17.0%). No difference in CVE prevalence was observed according to ART type, number of ARVs or ARV classes. Participants with CVE had more frequently plasma (52.9% vs 32.1%, p=0.005) and CSF RAMs in RT (n=63, 57.1% vs 28.6%, p=0.029), but not in protease gene. The presence of plasma RAMs in RT associated with increased odds of CVE in adjusted analyses (aOR 3.9, p<0.001) and in models restricted to plasma viral load ≤50 copies/mL (n=202; aOR 4.3 , p=0.003). CVE risk decreased by 40% per each point increase in HGRT-adjusted CPE score in multivariable models (p<0.001). Conclusions: Viruses harboring mutations appear to favor CVE and the impact of single ARV classes or type of ART regimens may lose significance when adjusted for the presence and effect of specific RAMs.