Fulminant varicella infection complicated by disseminated intravascular coagulation following influenza-A case report

Objectives: Varicella is common infectious disease mainly in childhood, usually is a mild, self-limited illness and complications are usually rare. The incubation period for this disease is generally 14- 16 days but may vary from 7 to 21 days. Varicella in the adults with comorbidities or immunosuppressed children may be severe and prolonged with complications. Method(s): A case report of a 6-year-old girl hospitalized for new-onset manifestations of disseminated vesicular exanthema, the manifestations of which occurred mainly on the chest, back, capillitium, oral cavity, and genital area. The child was suffering from abdominal, knee and lumbosacral pain at that time. The patient's history revealed that 10 days prior to the cutaneous manifestations, she had influenza with bronchopneumonia requiring oxygen therapy, steroids and antibiotics. Result(s): The condition progressed within 48 h, complicated by the development of multi-organ failure, coagulopathy with the development of disseminated intravascular coagulopathy over the course of antiviral, antibiotic and antifungal therapy. Laboratory parameters included high elevation of C-reactive protein, il-6, leukocytosis, neutrophilia and highly elevated liver enzymes. Varicella infection was confirmed by detection of herpes zoster virus - polymerase chain reaction (PCR) from vesicles. The patient received intravenous immunoglobulin therapy at a dose of 2 g/L and fresh frozen plasma, thrombocyte concentrate. The girl was intubated with analogization. Laboratory parameters subsequently revealed high anti CoV-2 positivity, high CoV-2 IgG positivity and negative CoV-2 IgM. The patient's condition did not preclude the course of multisystem inflammatory syndrome in children (MIS-C) corticosteroids were added to the treatment at a dose of 1 mg/kg weight. Patient's condition stabilized after 1 month. Discussion(s): Our case report presents an example of fulminant complicated life-threatening course of varicella. Even in common respiratory infections, we must think about the risk and consequences of coinfections and post-infectious complications such as in our case especially influenza and COVID-19.

Case study from Kosovo - repetitive COVID-19 infection and pregnancy

A 25-year-old woman, gravida 2, with no medical history of cardiovascular nor other chronic diseases, came to the gynaecologist and described symptoms of a flu-like disease, including very high fever. The gyneacologist prescribed her antibiotics and paracetamol to calm down the fever. At 37 week of gestation she was admitted to the provincial COVID-19 treatment center for isolation and health care in University Clinical Center of Kosovo in Gynecology/Obstetrics department. All bacteriological tests, including hemocultures and cultures of urines were negative. She received antipyretics (acetaminophen), antispasmodics trimethylphloroglucinol and antibiotics (oral azithromycin for 5 days and intravenous ceftriaxone). Despite this treatments, fever and uterine contractions persisted therefor the commission of doctors decided to deliver the baby via ceserean section. The peritoneal cavity and uterus were found to be very inflamed. Fetal appendages as well as the bladder were strewn with eruptive, vesicular lesions bleeding on contact. After few hours after the delivery her temperature (36.5 degreeC) and blood pressure (120/60 mmHg) were normal. The baby was healthy and tested negative on the COVD-19 tests performed. The patients after 2 weeks of treatment and a negative COVID-19 result she was released to go home and was counselled to eat healthy and prescribed multivitamins for her immune system and regular follow ups with the gynecologist. In a period of 8 months the patient became pregnant again and got infected with the COVID-19 again at 25 weeks pregnant. This time the symptoms were not severe and she was followed up at home. The delivery was planned with cesarean section and the baby was in healthy conditions. The patient got vaccinated with Astra Zeneca COVID-19 vaccine after the delivery. Because of their changed physiology, susceptibility to infections, and weakened mechanical and immunological processes, pregnant women are a particularly vulnerable group in any infectious disease outbreak. The requirement to protect the fetus adds to the difficulty of controlling their health. Keywords: COVID-19, pregnant women, cesarean section, Kosovo, astra-zeneca vaccineCopyright © 2023

Monkeypox (mpox) is a new problem on a global scale for humanity.

Purpose - to draw attention to an infection that was little known, but has now become a global problem for society;to familiarize readers with the peculiarities of the 2022 monkeypox outbreak and to increase the level of alertness of doctors to this disease. Monkeypox is a global problem because the disease is spreading rapidly, covering 111 countries. Three cases were diagnosed in Ukraine. It is predominantly a self-limited infection, but there are severe and deadly complications. The lethality of this disease ranges from 0% to 11%. The course of the disease is more severe in children and people with reduced immunity. Vertical transmission of the virus from mother to child is possible, resulting in congenital monkeypox. Monkeypox is a zoonotic disease and its natural reservoir is not exactly known, but rodents are most likely to act. In most cases, person-to-person transmission of the virus occurs through close skin to skin contact, often during sexual intercourse. At the beginning of the outbreak 98% of cases of disease were was diagnosed in homo- and bisexuals. Airborne transmission is also possible. Infection is possible through close contact with infectious skin lesions. Clinically, the initial period resembles influenza, but lymphadenopathy is characteristic, which is considered a pathognomonic symptom of mpox. The rash is similar to that of chickenpox, but with more prevalent location on palms and soles than in chickenpox. In the presence of a vesicular rash in a patient, it is necessary to exclude monkeypox. PCR diagnostics of the virus in samples of vesicles or crusts has the greatest diagnostic value. Hygienic skin care is important. Antiviral drugs (tecovirimat, brincidofovir) are recommended only in severe cases. To reduce the spread of infection, international rules apply as for other infections, such as COVID-19. The monkeypox virus vaccine is recommended primarily for groups at risk of infection, including medical personnel who may come into contact with the patient or samples for laboratory testing. Being aware for this infection, following international health regulations, it is possible to prevent the further spread of monkeypox.Copyright © 2023 Tomsk State University. All rights reserved.

Prospects of lassa fever candidate vaccines

Background: Lassa fever is an acute viral haemorrhagic disease caused by the Lassa virus (LASV). It is endemic in West Africa and infects about 300,000 people each year, leading to approximately 5000 deaths annually. The development of the LASV vaccine has been listed as a priority by the World Health Organization since 2018. Considering the accelerated development and availability of vaccines against COVID-19, we set out to assess the prospects of LASV vaccines and the progress made so far. Materials and Methods: We reviewed the progress made on twenty-six vaccine candidates listed by Salami et al. (2019) and searched for new vaccine candidates through Google Scholar, PubMed, and DOAJ from June to July 2021. We searched the articles published in English using keywords that included "vaccine" AND "Lassa fever" OR "Lassa virus" in the title/. Results: Thirty-four candidate vaccines were identified - 26 already listed in the review by Salami et al. and an additional 8, which were developed over the last seven years. 30 vaccines are still in the pre-clinical stage while 4 of them are currently undergoing clinical trials. The most promising candidates in 2019 were vesicular stomatitis virus-vectored vaccine and live-attenuated MV/LASV vaccine;both had progressed to clinical trials. Conclusions: Despite the focus on COVID-19 vaccines since 2020, LASV vaccine is under development and continues to make impressive progress, hence more emphasis should be put into exploring further clinical studies related to the most promising types of vaccines identified.

Dermatological Manifestations in COVID-19 and Post COVID-19 Patients: An Observational Study

Background: In December 2019, a new infection termed severe acute respiratory syndrome coronavirus 2 was recognised in Wuhan China. In literature only few studies exist on cutaneous manifestations in COVID-19 and post-COVID-19 phase. Hence the present study is conducted to know the most common cutaneous manifestations. Material(s) and Method(s): The present study included total of 60 patients presented with skin manifestations during COVID-19 and post COVID-19 phase of both in-patients and out-patients from October 2020 to June 2021. The patients aged more than 18yrs, tested positive for SARS CoV2 with dermatological manifestation during the infection and 3wks after testing negative for SARS CoV2 up to 3 months were included. The dermatological manifestations were recorded during the active COVID-19 infection and during post-COVID-19 period. Result(s): Among the 60 patients the common pattern was maculopapular rash in 24 patients (40%), urticaria seen in 8 patients (13.3%), chilblain seen in 4 patients (6.66%) and livedo reticularis seen in 2 patient (3.33%), during post COVID-19 were acneiform eruption seen in 16 patients (26.4%), vesicular lesions seen in 4 patients (6.66%) and lichen plan us observed in 2 patients (3.33%). Conclusion(s): There is significant association of presence of the dermatological manifestations among the patients with COVID-19 and post COVID-19 period. Study of these dermatological manifestations and their pathogenesis and their significance in human health is useful in avoiding misdiagnosis and proper treatment.Copyright © 2023, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Dermatological manifestations associated with the severity of COVID-19 infection: A retrospective cross-sectional observational study in 144 patients

Introduction: COVID-19 infection is a disease caused by the type 2 coronavirus that causes severe acute respiratory syndrome (SARS-CoV-2) that affects the respiratory mucosa and all those organs that present the type 2 angiotensin receptor (ACE2), within them the skin. Several authors have mentioned the importance of reporting and carrying out databases on skin lesions caused by this virus, since it is related to the detection, severity and prognosis of the systemic condition. Material(s) and Method(s): A retrospective cross-sectional observational study was carried out on the cases of patients who presented dermatological manifestations due to COVID-19, registered in the physical database of the National Specialized Hospital of Villa Nueva, Guatemala, from January 1st to December 31, 2021. Result(s): A total of 144 patients presented dermatological manifestations due to COVID-19, which were: acral lesions (42%), rash (21%), subcutaneous emphysema (12%), oral mucosal lesions (7%), necrosis (6%), erythema multiforme (5%), telogen effluvium (2%), vesicular lesions (2%), urticaria (1%), pityriasis rosea Gibert (1%) and livedo-type lesion (1%). A statistically significant association (p = 0,00) was found in patients who presented dermatological manifestations with vasculonecrotic damage as they were more likely to suffer from severe to critical disease (OR 2,91;95% CI 1063-3083). Conclusion(s): Early identification of cutaneous semiology is essential for timely management of complications associated with COVID-19 disease.Copyright © 2022 Elsevier Espana, S.L.U.

A Case Report of Herpes Zoster of the Trigeminal Ganglion after Coronavirus 2019 Vaccination in a 22-year-Old Male

Introduction. Herpes zoster is an acute viral syndrome caused by the reactivation of latent varicella-zoster virus from a previous infection. It is characterized by a painful, unilateral vesicular rash which is distributed over the territory of a dermatome. It is a significant global burden with the incidence very common in the Asia Pacific region. The frequency is closely related with increasing age and is the most common risk factor for reactivation of varicella-zoster virus. Herpes zoster does not often appear after administration of vaccination. But in the advent of increasing vaccinations for COVID-19, there have been reports of herpes zoster following COVID-19 vaccination. Case: This is a case of a 22-year-old healthy male with a previous history of varicella-zoster virus infection during childhood who developed headache, unilateral vesicular rash over the territory of the left trigeminal nerve and left-sided facial pain and numbness. The patient had previously received the COVID-19 vaccine four days prior to the onset of symptoms. The diagnosis of herpes zoster was made on clinical grounds with no need for additional laboratory work-up to confirm the diagnosis. The patient was treated with herpes zoster antiviral therapy and analgesics where improvement of the patient's condition was noted with eventual crusting of the lesions and without development of complications. Conclusion(s): Herpes zoster is a common disease with a benign course in immunocompetent adults. There is a need for further studies to identify risk factors and explain the possible relationship between COVID-19 vaccination and the development of herpes zoster. Due to the increasing COVID-19 vaccination of the population worldwide, there is a possibility of an increase in the number of herpes zoster cases following COVID-19 vaccination.Copyright © 2022, Philippine College of Physicians. All rights reserved.

Development of an Integrated Continuous Manufacturing Process for the rVSV-Vectored SARS-CoV-2 Candidate Vaccine.

The administration of viral vectored vaccines remains one of the most effective ways to respond to the ongoing novel coronavirus disease 2019 (COVID-19) pandemic. However, pre-existing immunity to the viral vector hinders its potency, resulting in a limited choice of viral vectors. Moreover, the basic batch mode of manufacturing vectored vaccines does not allow one to cost-effectively meet the global demand for billions of doses per year. To date, the exposure of humans to VSV infection has been limited. Therefore, a recombinant vesicular stomatitis virus (rVSV), which expresses the spike protein of SARS-CoV-2, was selected as the vector. To determine the operating upstream process conditions for the most effective production of an rVSV-SARS-CoV-2 candidate vaccine, a set of critical process parameters was evaluated in an Ambr 250 modular system, whereas in the downstream process, a streamlined process that included DNase treatment, clarification, and a membrane-based anion exchange chromatography was developed. The design of the experiment was performed with the aim to obtain the optimal conditions for the chromatography step. Additionally, a continuous mode manufacturing process integrating upstream and downstream steps was evaluated. rVSV-SARS-CoV-2 was continuously harvested from the perfusion bioreactor and purified by membrane chromatography in three columns that were operated sequentially under a counter-current mode. Compared with the batch mode, the continuous mode of operation had a 2.55-fold increase in space-time yield and a reduction in the processing time by half. The integrated continuous manufacturing process provides a reference for the efficient production of other viral vectored vaccines.

Recent Developments in Oral Delivery of Vaccines Using Nanocarriers.

As oral administration of vaccines is the preferred route due to its high patient compliance and ability to stimulate both cellular and humoral immune responses, it is also associated with several challenges that include denaturation of vaccine components in the acidic environment of the stomach, degradation from proteolytic enzymes, and poor absorption through the intestinal membrane. To achieve effective delivery of such biomolecules, there is a need to investigate novel strategies of formulation development that can overcome the barriers associated with conventional vaccine delivery systems. Nanoparticles are advanced drug delivery carriers that provide target-oriented delivery by encapsulating vaccine components within them, thus making them stable against unfavorable conditions. This review provides a detailed overview of the different types of nanocarriers and various approaches that can enhance oral vaccine delivery.

Cellular and humoral responses to an HIV DNA prime by electroporation boosted with recombinant vesicular stomatitis virus expressing HIV subtype C Env in a randomized controlled clinical trial.

BACKGROUND: HIV subtypes B and C together account for around 60% of HIV-1 cases worldwide. We evaluated the safety and immunogenicity of a subtype B DNA vaccine prime followed by a subtype C viral vector boost. METHODS: Fourteen healthy adults received DNA plasmid encoding HIV-1 subtype B nef/tat/vif and env (n = 11) or placebo (n = 3) intramuscularly (IM) via electroporation (EP) at 0, 1, and 3 months, followed by IM injection of recombinant vesicular stomatitis virus encoding subtype C Env or placebo at 6 and 9 months. Participants were assessed for safety, tolerability of EP, and Env-specific T-cell and antibody responses. RESULTS: EP was generally well tolerated, although some device-related adverse events did occur, and vaccine reactogenicity was mild to moderate. The vaccine stimulated Env-specific CD4 + T-cell responses in greater than 80% of recipients, and CD8 + T-cell responses in 30%. Subtype C Env-specific IgG binding antibodies (bAb) were elicited in all vaccine recipients, and antibody-dependent cell-mediated cytotoxicity (ADCC) responses to vaccine-matched subtype C targets in 80%. Negligible V1/V2 and neutralizing antibody (nAb) responses were detected. CONCLUSIONS: This prime/boost regimen was safe and tolerable, with some device-related events, and immunogenic. Although immunogenicity missed targets for an HIV vaccine, the DNA/rVSV platform may be useful for other applications. CLINICALTRIALS: gov: NCT02654080.

Rapid Protection from COVID-19 in Nonhuman Primates Vaccinated Intramuscularly but Not Intranasally with a Single Dose of a Vesicular Stomatitis Virus-Based Vaccine.

The ongoing pandemic of coronavirus (CoV) disease 2019 (COVID-19) continues to exert a significant burden on health care systems worldwide. With limited treatments available, vaccination remains an effective strategy to counter transmission of severe acute respiratory syndrome CoV 2 (SARS-CoV-2). Recent discussions concerning vaccination strategies have focused on identifying vaccine platforms, number of doses, route of administration, and time to reach peak immunity against SARS-CoV-2. Here, we generated a single-dose, fast-acting vesicular stomatitis virus (VSV)-based vaccine derived from the licensed Ebola virus (EBOV) vaccine rVSV-ZEBOV, expressing the SARS-CoV-2 spike protein and the EBOV glycoprotein (VSV-SARS2-EBOV). Rhesus macaques vaccinated intramuscularly (i.m.) with a single dose of VSV-SARS2-EBOV were protected within 10 days and did not show signs of COVID-19 pneumonia. In contrast, intranasal (i.n.) vaccination resulted in limited immunogenicity and enhanced COVID-19 pneumonia compared to results for control animals. While both i.m. and i.n. vaccination induced neutralizing antibody titers, only i.m. vaccination resulted in a significant cellular immune response. RNA sequencing data bolstered these results by revealing robust activation of the innate and adaptive immune transcriptional signatures in the lungs of i.m. vaccinated animals only. Overall, the data demonstrate that VSV-SARS2-EBOV is a potent single-dose COVID-19 vaccine candidate that offers rapid protection based on the protective efficacy observed in our study. IMPORTANCE The vesicular stomatitis virus (VSV) vaccine platform rose to fame in 2019, when a VSV-based Ebola virus (EBOV) vaccine was approved by the European Medicines Agency and the U.S. Food and Drug Administration for human use against the deadly disease. Here, we demonstrate the protective efficacy of a VSV-EBOV-based COVID-19 vaccine against challenge in nonhuman primates (NHPs). When a single dose of the VSV-SARS2-EBOV vaccine was administered intramuscularly (i.m.), the NHPs were protected from COVID-19 within 10 days. In contrast, if the vaccine was administered intranasally, there was no benefit from the vaccine and the NHPs developed pneumonia. The i.m. vaccinated NHPs quickly developed antigen-specific IgG, including neutralizing antibodies. Transcriptional analysis highlighted the development of protective innate and adaptive immune responses in the i.m. vaccination group only.

Budesonide-Loaded Bilosomes as a Targeted Delivery Therapeutic Approach Against Acute Lung Injury in Rats.

Budesonide (BUD), a glucocorticoids drug, inhibits all steps in the inflammatory response. It can reduce and treat inflammation and other symptoms associated with acute lung injury such as COVID-19. Loading BUD into bilosomes could boost its therapeutic activity, and lessen its frequent administration and side effects. Different bilosomal formulations were prepared where the independent variables were lipid type (Cholesterol, Phospholipon 80H, L-alpha phosphatidylcholine, and Lipoid S45), bile salt type (Na cholate and Na deoxycholate), and drug concentration (10, 20 mg). The measured responses were: vesicle size, entrapment efficiency, and release efficiency. One optimum formulation (composed of cholesterol, Na cholate, and 10 mg of BUD) was selected and investigated for its anti-inflammatory efficacy in vivo using Wistar albino male rats. Randomly allocated rats were distributed into four groups: The first: normal control group and received intranasal saline, the second one acted as the acute lung injury model received intranasal single dose of 2 mg/kg potassium dichromate (PD). Whereas the third and fourth groups received the market product (Pulmicort® nebulising suspension 0.5 mg/ml) and the optimized formulation (0.5 mg/kg; intranasal) for 7 days after PD instillation, respectively. Results showed that the optimized formulation decreased the pro-inflammatory cytokines TNF-α, and TGF-ß contents as well as reduced PKC content in lung. These findings suggest the potentiality of BUD-loaded bilosomes for the treatment of acute lung injury with the ability of inhibiting the pro-inflammatory cytokines induced COVID-19.

A comprehensive narrative review of the cutaneous manifestations associated with COVID-19.

The systemic and respiratory clinical manifestations of coronavirus disease 2019 (COVID-19) include fever, coughing, sneezing, sore throat, rhinitis, dyspnea, chest pain, malaise, fatigue, anorexia and headache. Moreover, cutaneous manifestations have been reported in 0.2% to 20.4% of cases. Early diagnosis of COVID-19 leads to a better prognosis; knowledge of its cutaneous manifestations is one way that may help fulfil this goal. In this review, PubMed and Medline were searched with the terms "dermatology", "skin" and "cutaneous", each in combination with "SARS-CoV-2" or "COVID-19". All articles, including original articles, case reports, case series and review articles published from the emergence of the disease to the time of submission, were included. In this comprehensive narrative review, we tried to provide an analysis of the cutaneous manifestations associated with COVID-19, including maculopapular rash, urticaria, Chilblain-like, vesicular lesions, livedo reticularis and petechiae in asymptomatic/symptomatic COVID-19 patients that might be the first complication of infection after respiratory symptoms. Immune dysregulation, cytokine storms, side effects of antiviral drugs, environmental conditions and high-dose intravenous immunoglobulin (IVIG) therapy might be involved in the pathogenesis of the cutaneous manifestations in COVID-19 patients. Therefore, knowledge of cutaneous COVID-19 manifestations might be vital in achieving a quick diagnosis in some COVID-19 patients, which would help control the pandemic. Further research is very much warranted to clarify this issue.

Characterization of a Vesicular Stomatitis Virus-Vectored Recombinant Virus Bearing Spike Protein of SARS-CoV-2 Delta Variant.

The frequent emergence of SARS-CoV-2 variants thwarts the prophylactic and therapeutic countermeasures confronting COVID-19. Among them, the Delta variant attracts widespread attention due to its high pathogenicity and fatality rate compared with other variants. However, with the emergence of new variants, studies on Delta variants have been gradually weakened and ignored. In this study, a replication-competent recombinant virus carrying the S protein of the SARS-CoV-2 Delta variant was established based on the vesicular stomatitis virus (VSV), which presented a safe alternative model for studying the Delta variant. The recombinant virus showed a replication advantage in Vero E6 cells, and the viral titers reach 107.3 TCID50/mL at 36 h post-inoculation. In the VSV-vectored recombinant platform, the spike proteins of the Delta variant mediated higher fusion activity and syncytium formation than the wild-type strain. Notably, the recombinant virus was avirulent in BALB/c mice, Syrian hamsters, 3-day ICR suckling mice, and IFNAR/GR-/- mice. It induced protective neutralizing antibodies in rodents, and protected the Syrian hamsters against the SARS-CoV-2 Delta variant infection. Meanwhile, the eGFP reporter of recombinant virus enabled the visual assay of neutralizing antibodies. Therefore, the recombinant virus could be a safe and convenient surrogate tool for authentic SARS-CoV-2. This efficient and reliable model has significant potential for research on viral-host interactions, epidemiological investigation of serum-neutralizing antibodies, and vaccine development.

Long-term passaging of pseudo-typed SARS-CoV-2 reveals the breadth of monoclonal and bispecific antibody cocktails.

The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential. Here, based on a replication competent vesicular stomatitis virus model that incorporates the spike of SARS-CoV-2 (VSV-SARS-CoV-2), we evaluated the breadth of a number of antibody cocktails consisting of monoclonal antibodies and bispecific antibodies by long-term passaging the virus in the presence of the cocktails. Results from over two-month passaging of the virus showed that 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 from these cocktails were highly resistant to random mutation, and there was no breakthrough after 30 rounds of passaging. As a control, antibody REGN10933 was broken through in the third passage. Next generation sequencing was performed and several critical mutations related to viral evasion were identified. These mutations caused a decrease in neutralization efficiency, but the reduced replication rate and ACE2 susceptibility of the mutant virus suggested that they might not have the potential to become epidemic strains. The 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 cocktails that picked from the VSV-SARS-CoV-2 system efficiently neutralized all current variants of concern and variants of interest including the most recent variants Delta and Omicron, as well as SARS-CoV-1. Our results highlight the feasibility of using the VSV-SARS-CoV-2 system to develop SARS-CoV-2 antibody cocktails and provide a reference for the clinical selection of therapeutic strategies to address the mutational escape of SARS-CoV-2.

Insights from the Infection Cycle of VSV-ΔG-Spike Virus.

Fundamental key processes in viral infection cycles generally occur in distinct cellular sites where both viral and host factors accumulate and interact. These sites are usually termed viral replication organelles, or viral factories (VF). The generation of VF is accompanied by the synthesis of viral proteins and genomes and involves the reorganization of cellular structure. Recently, rVSV-ΔG-spike (VSV-S), a recombinant VSV expressing the SARS-CoV-2 spike protein, was developed as a vaccine candidate against SARS-CoV-2. By combining transmission electron microscopy (TEM) tomography studies and immuno-labeling techniques, we investigated the infection cycle of VSV-S in Vero E6 cells. RT-real-time-PCR results show that viral RNA synthesis occurs 3-4 h post infection (PI), and accumulates as the infection proceeds. By 10-24 h PI, TEM electron tomography results show that VSV-S generates VF in multi-lamellar bodies located in the cytoplasm. The VF consists of virus particles with various morphologies. We demonstrate that VSV-S infection is associated with accumulation of cytoplasmatic viral proteins co-localized with dsRNA (marker for RNA replication) but not with ER membranes. Newly formed virus particles released from the multi-lamellar bodies containing VF, concentrate in a vacuole membrane, and the infection ends with the budding of particles after the fusion of the vacuole membrane with the plasma membrane. In summary, the current study describes detailed 3D imaging of key processes during the VSV-S infection cycle.

Cutaneous Eruptions in the Course of COVID-19 Among Geriatric Patients in a Nursing Home in Poland.

Purpose: The aim of this study was to assess the incidence and characteristics of COVID-19 cutaneous manifestations among geriatric patients infected with the SARS-CoV-2 virus. Patients and Methods: Sixty-four nursing home residents in Dobre Miasto, Poland (mean age: 79 years) infected with SARS-CoV-2 were monitored for skin lesions during the epidemic outbreak in 2020. Only five of them presented COVID-19 dermatological manifestation: vesicular (4 cases) and erythematous (1 case) skin lesions, which appeared after the remaining symptoms of the disease had resolved. Results: The average time between COVID-19 onset and cutaneous manifestation was 22 days. Skin lesions persisted in five cases 112, 17, 21,19 and 27 days, respectively, and were often accompanied by pruritus and neuropathic pain. Conclusion: Skin manifestations of SARS-CoV-2 infection might be misdiagnosed or overlooked, particularly among elderly patients with chronic diseases. The recognition of skin lesions due to COVID-19 might improve patients' quality of life by reducing the intensity of symptoms such as pruritus or neuropathic pain.

Rapid Reversible Osmoregulation of Cytoplasmic Biomolecular Condensates of Human Interferon-α-Induced Antiviral MxA GTPase.

We previously discovered that exogenously expressed GFP-tagged cytoplasmic human myxovirus resistance protein (MxA), a major antiviral effector of Type I and III interferons (IFNs) against several RNA- and DNA-containing viruses, existed in the cytoplasm in phase-separated membraneless biomolecular condensates of varying sizes and shapes with osmotically regulated disassembly and reassembly. In this study we investigated whether cytoplasmic IFN-α-induced endogenous human MxA structures were also biomolecular condensates, displayed hypotonic osmoregulation and the mechanisms involved. Both IFN-α-induced endogenous MxA and exogenously expressed GFP-MxA formed cytoplasmic condensates in A549 lung and Huh7 hepatoma cells which rapidly disassembled within 1-2 min when cells were exposed to 1,6-hexanediol or to hypotonic buffer (~40-50 mOsm). Both reassembled into new structures within 1-2 min of shifting cells to isotonic culture medium (~330 mOsm). Strikingly, MxA condensates in cells continuously exposed to culture medium of moderate hypotonicity (in the range one-fourth, one-third or one-half isotonicity; range 90-175 mOsm) first rapidly disassembled within 1-3 min, and then, in most cells, spontaneously reassembled 7-15 min later into new structures. This spontaneous reassembly was inhibited by 2-deoxyglucose (thus, was ATP-dependent) and by dynasore (thus, required membrane internalization). Indeed, condensate reassembly was preceded by crowding of the cytosolic space by large vacuole-like dilations (VLDs) derived from internalized plasma membrane. Remarkably, the antiviral activity of GFP-MxA against vesicular stomatitis virus survived hypoosmolar disassembly and subsequent reassembly. The data highlight the exquisite osmosensitivity of MxA condensates, and the preservation of antiviral activity in the face of hypotonic stress.

Clinical Conundrums: Differentiating Monkeypox From Similarly Presenting Infections.

Post the coronavirus disease 2019 (COVID-19) pandemic, there arises the concern of a new epidemic as cases of monkeypox are being confirmed, globally. With the initial clinical manifestation of monkeypox resembling that of the common cold or seasonal flu, recognizing alternative differential diagnoses is imperative as a medical health practitioner. The characteristic monkeypox maculopapular rash with the progression to vesicles and pustules before scabbing can be described in several other infections. Understanding the disease progression and distinct clinical presentation of monkeypox in its various stages may allow for a more expedient diagnosis among healthcare providers. Though eradicated, the clinical presentation of smallpox is the most similar to that of monkeypox; however, smallpox is no longer a concern for the general population. Other conditions such as molluscum contagiosum, syphilis, varicella zoster, measles, rickettsialpox, and scabies can present with rashes that may resemble singular or multiple states of the monkeypox rash progression. The ability to correctly diagnose an individual's condition promptly may allow healthcare providers to provide correct supportive therapies or treatments.

Clinical characteristics and outcomes of patients with Herpes Zoster Infection in the context of SARS-CoV-2 infection. A case report and a systematic review.

INTRODUCTION: Severe acute respiratory syndrome-coronavirus 2 (SARSCoV2) pandemic has been an unceasing plight with a wide range of clinical presentations. The direct effects of the virus, increased use of medications, and lifestyle changes have contributed to the vulnerability to co-infections. Fungal and bacterial co-infections led to increased morbidity and mortality during the pandemic. Similarly, the surge of skin signs in conjunction with herpes zoster (HZ) manifestations has been reported. In this study, we pooled the data on the clinical characteristics of SARS-CoV-2 patients co-infected with HZ. METHODOLOGY: Electronic databases including PubMed, Scopus, and Google Scholar were extensively searched to identify the relevant studies on HZ infection among the SARS-CoV-2 patients. RESULTS: A total of 79 patients (from case reports, series, and retrospective studies) were included in the analysis. Fever was the most common constitutional symptom recorded, followed by cough and dyspnea. A systemic rash was reported in 78.5% of cases with mild symptoms of HZ and SARS-CoV-2 in 87% and 76%, respectively. Only 19% of the cases presented during the prodrome period of SARS-CoV-2. HZV polymerase chain reaction (PCR) was positive in 8.9% of the cases, and the remaining were diagnosed clinically. SARS-CoV-2 PCR was reported positive in 65 cases (82.3%). Leukopenia was observed in 7 cases (8.9%) and lymphopenia in 25 (31.6%). All patients recovered through conservative treatment. CONCLUSION: SARS-CoV-2 escalated the incidence of HZ reactivation. Most of the patients were seen with older individuals either simultaneously or a few days after the SARS-CoV-2 infection, but a few cases were reported during the asymptomatic prodrome period of SARS-CoV-2.