Bacterial co-infections and secondary infections and their antimicrobial resistance in Covid-19 patients during the second pandemic wave.

Background: COVID-19 pneumonia with an unusual outbreak is considered a new, global public health threat. Microbiological characterization of co-infections in patients with COVID-19 is important, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and the antimicrobial resistance of the causative pathogens. Method: From January to December 2020, we tested 1,301 patients who were COVID-19 positive. We received clinical samples (blood, respiratory and sterile body fluids) of COVID-19 patients who were suspected to have bacterial co-infections. Samples were processed and antimicrobial susceptibility testing was performed based on the CLSI recommendation. Demographic, clinical, laboratory and outcome data of those with positive cultures were collected. Result: A total of 1301 COVID-19 patients (568 from the COVID ward and 733 from ICU) were admitted to the Covid care ward of a tertiary care hospital. 363 samples were sent for culturing and testing antibiotic susceptibility, of which 131 (36%) were found to be culture-positive (90 from ICUs, 41 from wards). Out of the 143 total isolates thus obtained from 131 samples, the majority (62.2%) were Gram-negative bacteria, and most of them were (70.8%) multidrug resistant. Discussion: Bacterial co-infection in patients with COVID-19 is more commonly reported in the severely ill hospitalized individuals (58%), particularly in the ICU (73.3%) setting. In terms of mortality, almost half of co-infected patients died (51.1%). In most of them, the cause of death was found to be sepsis with post-COVID ARDS (58%). Conclusion: Co-infection in COVID-19 patients may affect the outcome in terms of increasing the hospital stay.

Navigating the Diagnostic Challenges of Mycoplasma and Legionella Coinfection Through Serological Testing.

Diagnosing community-acquired pneumonia (CAP) is increasingly challenging, especially with the emergence of atypical pathogens such as Mycoplasma pneumoniae and Legionella pneumophila. This report presents the case of a 60-year-old male exhibiting lethargy and decreased oral intake, with a medical history marked by chronic kidney disease and benign prostate hyperplasia. Despite a positive Legionella urine antigen, the clinical and radiological profile did not align with Legionella pneumonia. Elevated M. pneumoniae IgM antibody titers further complicated the diagnostic scenario. We explore the complexities of distinguishing coinfection from primary infection, highlight the limitations of serological testing, and promote a comprehensive diagnostic strategy customized to individual patient circumstances. This case emphasizes the importance of comprehensive assessment strategies to understand atypical pneumonia presentations, particularly within complex clinical scenarios.

COVID-19 and malaria co-infection: a systematic review of clinical outcomes in endemic areas.

Background: COVID-19 and malaria cause significant morbidity and mortality globally. Co-infection of these diseases can worsen their impact on public health. This review aims to synthesize literature on the clinical outcomes of COVID-19 and malaria co-infection to develop effective prevention and treatment strategies. Methods: A comprehensive literature search was conducted using MeSH terms and keywords from the start of the COVID-19 pandemic to January 2023. The review included original articles on COVID-19 and malaria co-infection, evaluating their methodological quality and certainty of evidence. It was registered in PROSPERO (CRD42023393562). Results: Out of 1,596 screened articles, 19 met the inclusion criteria. These studies involved 2,810 patients, 618 of whom had COVID-19 and malaria co-infection. Plasmodium falciparum and vivax were identified as causative organisms in six studies. Hospital admission ranged from three to 18 days. Nine studies associated co-infection with severe disease, ICU admission, assisted ventilation, and related complications. One study reported 6% ICU admission, and mortality rates of 3%, 9.4%, and 40.4% were observed in four studies. Estimated crude mortality rates were 10.71 and 5.87 per 1,000 person-days for patients with and without concurrent malaria, respectively. Common co-morbidities included Diabetes mellitus, hypertension, cardiovascular diseases, and respiratory disorders. Conclusion: Most patients with COVID-19 and malaria co-infection experienced short-term hospitalization and mild to moderate disease severity. However, at presentation, co-morbidities and severe malaria were significantly associated with higher mortality or worse clinical outcomes. These findings emphasize the importance of early detection, prompt treatment, and close monitoring of patients with COVID-19 and malaria co-infection.

Indirect interaction between an endemic and an invading pathogen: A case study of Plasmodium and Usutu virus dynamics in a shared bird host population.

Infectious disease agents can influence each other's dynamics in shared host populations. We consider such influence for two mosquito-borne infections where one pathogen is endemic at the time that a second pathogen invades. We regard a setting where the vector has a bias towards biting host individuals infected with the endemic pathogen and where there is a cost to co-infected hosts. As a motivating case study, we regard Plasmodium spp., that cause avian malaria, as the endemic pathogen, and Usutu virus (USUV) as the invading pathogen. Hosts with malaria attract more mosquitoes compared to susceptible hosts, a phenomenon named vector bias. The possible trade-off between the vector-bias effect and the co-infection mortality is studied using a compartmental epidemic model. We focus first on the basic reproduction number R0 for Usutu virus invading into a malaria-endemic population, and then explore the long-term dynamics of both pathogens once Usutu virus has become established. We find that the vector bias facilitates the introduction of malaria into a susceptible population, as well as the introduction of Usutu in a malaria-endemic population. In the long term, however, both a vector bias and co-infection mortality lead to a decrease in the number of individuals infected with either pathogen, suggesting that avian malaria is unlikely to be a promoter of Usutu invasion. This proposed approach is general and allows for new insights into other negative associations between endemic and invading vector-borne pathogens.

Theoretical and mathematical codynamics of nonlinear tuberculosis and COVID-19 model pertaining to fractional calculus and probabilistic approach.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus known as coronavirus 2 (SARS-CoV-2) that affects the pulmonary structure and results in the coronavirus illness 2019 (COVID-19). Tuberculosis (TB) and COVID-19 codynamics have been documented in numerous nations. Understanding the complexities of codynamics is now critically necessary as a consequence. The aim of this research is to construct a co-infection model of TB and COVID-19 in the context of fractional calculus operators, white noise and probability density functions, employing a rigorous biological investigation. By exhibiting that the system possesses non-negative and bounded global outcomes, it is shown that the approach is both mathematically and biologically practicable. The required conditions are derived, guaranteeing the eradication of the infection. Sensitivity analysis and bifurcation of the submodel are also investigated with system parameters. Furthermore, existence and uniqueness results are established, and the configuration is tested for the existence of an ergodic stationary distribution. For discovering the system's long-term behavior, a deterministic-probabilistic technique for modeling is designed and operated in MATLAB. By employing an extensive review, we hope that the previously mentioned approach improves and leads to mitigating the two diseases and their co-infections by examining a variety of behavioral trends, such as transitions to unpredictable procedures. In addition, the piecewise differential strategies are being outlined as having promising potential for scholars in a range of contexts because they empower them to include particular characteristics across multiple time frame phases. Such formulas can be strengthened via classical technique, power-law, exponential decay, generalized Mittag-Leffler kernels, probability density functions and random procedures. Furthermore, we get an accurate description of the probability density function encircling a quasi-equilibrium point if the effect of TB and COVID-19 minimizes the propagation of the codynamics. Consequently, scholars can obtain better outcomes when analyzing facts using random perturbations by implementing these strategies for challenging issues. Random perturbations in TB and COVID-19 co-infection are crucial in controlling the spread of an epidemic whenever the suggested circulation is steady and the amount of infection eliminated is closely correlated with the random perturbation level.

A story of viral co-infection, co-transmission and co-feeding in ticks: how to compute an invasion reproduction number.

With a single circulating vector-borne virus, the basic reproduction number incorporates contributions from tick-to-tick (co-feeding), tick-to-host and host-to-tick transmission routes. With two different circulating vector-borne viral strains, resident and invasive, and under the assumption that co-feeding is the only transmission route in a tick population, the invasion reproduction number depends on whether the model system of ordinary differential equations possesses the property of neutrality. We show that a simple model, with two populations of ticks infected with one strain, resident or invasive, and one population of co-infected ticks, does not have Alizon's neutrality property. We present model alternatives that are capable of representing the invasion potential of a novel strain by including populations of ticks dually infected with the same strain. The invasion reproduction number is analysed with the next-generation method and via numerical simulations.

The characteristics of microbiome in the upper respiratory tract of COVID-19 patients.

BACKGROUND: Co-infection with other pathogens in coronavirus disease 2019 (COVID-19) patients exacerbates disease severity and impacts patient prognosis. Clarifying the exact pathogens co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is premise of the precise treatment for COVID-19 patients. METHODS: Sputum samples were collected from 17 patients in the COVID-19 positive group and 18 patients in the COVID-19 negative group. DNA extraction was performed to obtain the total DNA. Sequencing analysis using 16S and ITS rRNA gene was carried out to analyze the composition of bacterial and fungal communities. Meanwhile, all the samples were inoculated for culture. RESULTS: We did not observe significant differences in bacterial composition between the COVID-19 positive and negative groups. However, a significantly higher abundance of Candida albicans was observed in the upper respiratory tract samples from the COVID-19 positive group compared to the COVID-19 negative group. Moreover, the Candida albicans strains isolated from COVID-19 positive group exhibited impaired secretion of aspartyl proteinases. CONCLUSION: COVID-19 positive patients demonstrate a notable increase in the abundance of Candida albicans, along with a decrease in the levels of aspartyl proteinases, indicating the alteration of microbiota composition of upper respiratory tract.

Clinical and immunologic features of co-infection in COVID-19 patients, along with potential traditional Chinese medicine treatments.

Objectives: With the increasing number of people worldwide infected with SARS-CoV-2, the likelihood of co-infection and/or comorbidities is rising. The impact of these co-infections on the patient's immune system remains unclear. This study aims to investigate the immunological characteristics of secondary infections in hospitalized COVID-19 patients, and preliminarily predict potential therapeutic effects of traditional Chinese medicine and their derivatives for the treatment of co-infections. Methods: In this retrospective cohort study, we included 131 hospitalized patients with laboratory-confirmed COVID-19, of whom there were 64 mild and 67 severe cases. We analyzed clinical characteristics and immunologic data, including circulating immune cell numbers, levels of inflammatory factors and viral load, comparing COVID-19 patients with and without co-infection. Results: Among 131 hospitalized COVID-19 patients, 41 (31.3%) were co-infection positive, with 33 (80.5%) having severe disease and 14 (34.1%) of them resulting in fatalities. Co-infected patients exhibited significantly higher severity and mortality rates compared to non-co-infected counterparts. Co-infected patients had significantly lower absolute counts of lymphocytes, total T lymphocytes, CD4+ T cells, CD8+ T cells and B lymphocytes, while levels of hs-CRP, PCT and IL-6 were significantly elevated compared to non-co-infected patients. Additionally, the viral load of co-infected patients was significantly higher than non-co-infected patients. Conclusion: Co-infection emerges as a dangerous factor for COVID-19 patients, elevating the risk of severe pneumonia and mortality. Co-infection suppresses the host's immune response by reducing the number of lymphocytes and increasing inflammation, thereby diminishing the antiviral and anti-infective effects of the immune system, which promotes the severity of the disease. Therefore, it is crucial to implement infection prevention measures to minimize the spread of co-infections among COVID-19 hospitalized patients. Additionally, changes in these biomarkers provide a theoretical basis for the effective treatment of co-infections with traditional Chinese medicine.

CO-INFECTION OF DENGUE AND HEPATITIS A VIRUSES: A RARE CASE REPORT.

Dengue fever and hepatitis A are endemic infections caused by viruses that mostly affect developing countries (Volchkova et al., 2016). Co-infection is rare, and represents a diagnostic challenge due to their overlapping symptoms (Yakoob et al., 2009). The febrile syndrome accompanied by abdominal pain and vomiting are the common clinical manifestations of both pathologies. However, confirmation of diagnosis depends on laboratory tests ( Khetarpal and Khanna, 2016; Abutaleb and Kottilil, 2020). We report a case of a young female with dengue and hepatitis A co-infection.

Tick-borne pathogens Ehrlichia, Hepatozoon, and Babesia co-infection in owned dogs in Central Thailand.

Tick-borne pathogens are transmitted by a wide range of tick species and affect both human and animal health. Understanding the diversity of these pathogens and their co-infection rates in domesticated animals in urban areas is crucial for effective disease management and prevention. In this study, a total of 565 owned dogs in the central region of Thailand were investigated for the infection rate of three genera of Ehrlichia, Hepatozoon, and Babesia infection using multiplex PCR. The results revealed an overall infection rate of 19.1%, with Ehrlichia having the highest infection rate (12.2%), followed by Babesia (2.5%) and Hepatozoon (1.4%). The rate of co-infection was 3%, with mixed infections involving two or three genera. Male dogs exhibited a slightly higher infection rate compared to females, although not statistically significant. Young adult dogs (1-3 years) showed the highest infection rate of both single infections and co-infections. Monthly infection rate indicated variations throughout the year, with co-infection rate significantly associated with overall infection rate. Clinical manifestations in three genera of infected dogs included thrombocytopenia and eosinopenia. The results of this study are useful to design strategies for the management and prevention of tick-borne diseases in the study area.

A triplex crystal digital PCR for the detection of genotypes I and II African swine fever virus.

African swine fever (ASF) is a highly contagious and lethal viral disease that causes severe hemorrhagic fever in pigs. It keeps spreading around the world, posing a severe socioeconomic risk and endangering biodiversity and domestic food security. ASF first outbroke in China in 2018, and has spread to most provinces nationwide. Genotypes I and II ASF virus (ASFV) as the etiological pathogens have been found in China. In this study, three pairs of specific primers and probes targeting the ASFV B646L gene, F1055L gene, and E183L gene were designed to detect universal, genotype I, and genotype II strains, respectively. A triplex crystal digital PCR (cdPCR) was established on the basis of optimizing various reaction conditions. The assay demonstrated remarkably sensitive with low limits of detection (LODs) of 5.120, 4.218, 4.588 copies/reaction for B646L, F1055L, and E183L gene, respectively; excellent repeatability with 1.24-2.01% intra-assay coefficients of variation (CVs) and 1.32-2.53% inter-assay CVs; good specificity for only detection of genotypes I and II ASFV, without cross-reactivity with PCV2, PRV, SIV, PRRSV, PEDV, FMDV, and CSFV. The triplex cdPCR was used to test 1,275 clinical samples from Guangxi province of China, and the positivity rates were 5.05, 3.22, and 1.02% for genotype I, genotype II, and co-infection of genotypes I and II, respectively. These 1,275 clinical samples were also detected using a reported reference triplex real-time quantitative PCR (qPCR), and the agreements of detection results between these two methods were more than 98.98%. In conclusion, the developed triplex cdPCR could be used as a rapid, sensitive, and accurate method to detect and differentiate genotypes I and II strains of ASFV.

Critically ill children with SARS-COV-2 Omicron infection at a national children medical center, Guangdong, China.

BACKGROUND: SARS-CoV-2 infection is described as asymptomatic, mild, or moderate disease in most children. SARS-CoV-2 infection related death in children and adolescents is rare according to the current reports. COVID-19 cases increased significantly in China during the omicron surge, clinical data regarding pediatric critical patients infected with the omicron variant is limited. In this study, we aim to provide an overview of the clinical characteristics and outcomes of critically ill children admitted to a national children's medical center in Guangdong Province, China, during the outbreak of the omicron variant infection. METHODS: We conducted a retrospective study from November 25, 2022, to February 8, 2023, which included 63 critically ill children, under the age of 18, diagnosed with SARS-CoV-2 infection. The patients were referred from medical institutions of Guangdong province. The medical records of these patients were analyzed and summarized. RESULTS: The median age of patients was 2 years (Interquartile Range, IQR: 1.0-8.0), sex-ratio (male/female) was 1.52. 12 (19%) patients (age ≥ 3 years) were vaccinated. The median length of hospital stay was 14 days (IQR: 6.5-23) in 63 cases, and duration of fever was 5 days (IQR: 3-8.5), pediatric intensive care unit (PICU) stay was 8 days (IQR 4.0-14.0) in 57 cases. 30 (48%) cases had clear contact history with family members who were infected with SARS-CoV-2. Three children who tested positive for SARS-CoV-2 infection did not show any abnormalities on chest imaging examination. Out of the total patients, 33 (52%) had a bacterial co-infection, with Staphylococcus aureus being the most commonly detected bacterial pathogen. Our cohort exhibited respiratory and nervous system involvement as the primary features. Furthermore, fifty (79%) patients required mechanical ventilation, with a median duration of 7 days (IQR 3.75-13.0). Among these patients, 35 (56%) developed respiratory failure, 16 (25%) patients experienced a deteriorating progression of symptoms and ultimately succumbed to the illness, septic shock was the most common condition among these patients (15 cases), followed by multiple organ failure in 12 cases, and encephalopathy identified in 7 cases. CONCLUSION: We present a case series of critically ill children infected with the SARS-CoV-2 omicron variant. While there is evidence suggesting that Omicron may cause less severe symptoms, it is important to continue striving for measures that can minimize the pathogenic impact of SARS-CoV-2 infection in children.

Predictors of severe hepatotoxicity among retroviral infected adults on HAART regimen in Ilubabor Zone, Southwest Ethiopia.

Nearly half of the deaths among hospitalized human immuno deficiency virus-infected patients in the highly active antiretroviral therapy era have been attributed to liver disease. This may range from an asymptomatic mild increase of liver enzymes to cirrhosis and liver failure. Different works of literature elucidated both retroviral infection and the adverse effects of highly active antiretroviral therapy as a cause of hepatotoxicity. Individual adaptations to medications and environmental exposures, shaped by cultural norms and genetic predispositions, could potentially modulate the risk and progression of liver disease in this population. Therefore, this study aims to assess the predictors of severe hepatotoxicity in retroviral-infected adults receiving highly active antiretroviral therapy regimens within the Ilubabor Zone, Southwest Ethiopia. A facility-based cross-sectional study was conducted among adult retroviral-infected patients in five selected anti-retro virus therapy clinics from May1 to July 30/2022. A systematic sampling technique was used to select 457 study participants and Binary logistic regression statistical data analysis was used, P value < 0.05 was considered statistically significant. The prevalence of severe hepatotoxicity was 21.44% in the study population. CD+4 count < 200 cells/mm3 (AOR = 2.19, 95% CI 1.04-5.22, P = 0.01), human immunodeficiency virus co-infection with tuberculosis (AOR = 2.82, 95% CI 1.01-8.29, P = 0.03) and human immuno deficiency virus co-infection with hepatitis-B/hepatitis C virus (AOR = 5.02, 95% CI 1.82-16.41) were predictors of severe hepatotoxicity. The magnitude of severe hepatotoxicity was high among adult retroviral-infected patients on highly active anti-retroviral drug regimens. Co-infection of human immuno deficiency virus with hepatitis B virus or hepatitis C virus, tuberculosis and CD4+T-cell count below 200 cells/mm3 were predictors of severe hepatotoxicity. Therefore, HIV patients on highly active antiretroviral therapy require close attention and regular monitoring of their liver function.

Co-infection of Helicobacter Pylori and intestinal parasites in children of selected Low-income communities in Lagos State, Nigeria.

Helicobacter pylori and intestinal parasites cause gastrointestinal diseases with a high prevalence in children in resource limited developing countries. There is paucity of information in Nigeria on co-infection of H. pylori and intestinal parasites. The study was conducted to determine the prevalence of H. pylori and parasite co-infection in children from selected low-income communities in Lagos, Nigeria. Fecal samples were collected from 151 healthy children aged ≤11 years across six low-income communities in Lagos. H. pylori was detected using stool antigen test and conventional PCR assay, intestinal parasites were detected using formol-ether concentration and nested PCR assay. Structured questionnaires were administered to parents and legal guardians of the children by an interviewer to collect relevant data on demographic and lifestyle factors. The prevalence of H. pylori was 31.79% (48), with a higher prevalence in children aged 2-3 years. The prevalence of intestinal parasites was 21.19% (32) with the lowest frequency found in children aged 8-9 years. The parasites detected include: A. lumbricoides (10.6%), G. intestinalis (7.3%), hookworm (1.99%), E. histolytica (0.66%), S. mansoni (0.66%). There was co-infection prevalence of 10.6% (16) which was associated with the parasites: G. intestinalis (7.3%) and A. lumbricoides (3.97%). Polyparasitism with G. intestinalis and A. lumbricoides was reported in 2 children infected with H. pylori. This study which is the first reported in Lagos established a low prevalence of H. pylori and intestinal parasite co-infection in children and provides better understanding of the epidemiology of H. pylori infection associated with intestinal parasites in Nigeria.

Antibiotics daptomycin interacts with S protein of SARS-CoV-2 to promote cell invasion of Omicron (B1.1.529) pseudovirus.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed enormous challenges to global public health. The use of antibiotics has greatly increased during the SARS-CoV-2 epidemic owing to the presence of bacterial co-infection and secondary bacterial infections. The antibiotics daptomycin (DAP) is widely used in the treatment of infectious diseases caused by gram-positive bacteria owing to its highly efficient antibacterial activity. It is pivotal to study the antibiotics usage options for patients of coronavirus infectious disease (COVID-19) with pneumonia those need admission to receive antibiotics treatment for bacterial co-infection in managing COVID-19 disease. Herein, we have revealed the interactions of DAP with the S protein of SARS-CoV-2 and the variant Omicron (B1.1.529) using the molecular docking approach and Omicron (B1.1.529) pseudovirus (PsV) mimic invasion. Molecular docking analysis shows that DAP has a certain degree of binding ability to the S protein of SARS-CoV-2 and several derived virus variants, and co-incubation of 1-100 µM DAP with cells promotes the entry of the PsV into human angiotensin-converting enzyme 2 (hACE2)-expressing HEK-293T cells (HEK-293T-hACE2), and this effect is related to the concentration of extracellular calcium ions (Ca2+). The PsV invasion rate in the HEK-293T-hACE2 cells concurrently with DAP incubation was 1.7 times of PsV infection alone. In general, our findings demonstrate that DAP promotes the infection of PsV into cells, which provides certain reference of antibiotics selection and usage optimization for clinicians to treat bacterial coinfection or secondary infection during SARS-CoV-2 infection.

Epidemiological and Clinical Characteristics of Neonatal Ureaplasma urealyticum Infection.

Purpose: To understand the epidemiology and clinical features of Ureaplasma urealyticum (UU) infection in hospitalized neonates due to vertical transmission from mother to child. Methods: Respiratory secretions were collected from neonates hospitalized in the neonatology department of the Maternal and Child Health Hospital of Hubei Province from July 2020 to June 2022, and PCR was used to detect UU-DNA in respiratory secretions. The neonates were divided into UU-positive and UU-negative groups, the epidemiological and clinical characteristics of two groups, were statistically analyzed. Results: A total of 7257 hospitalized neonates were included in this study, of whom 561 were UU positive and 6696 were UU negative, with a UU detection rate of 7.73%. The detection rate among female neonates was higher than male neonates, and the highest detection rate was found in the period from 1-7 days after birth; the detection rate was highest in spring and fall, and the lowest in winter, but the overall difference was not statistically significant (P>0.05). Compared with the UU-negative group, neonates in the UU-positive group were more likely to be preterm, have a lower birth weight, be delivered vaginally, and have maternal preterm rupture of membranes. In addition, neonates in the UU-positive group were more likely to be co-infected with pathogens and to have complications related to UU infections, which were all statistically significant (P<0.05). Conclusion: Neonatal UU infections are detected more frequently in female infants, with the highest detection rate occurring in 1-7 days after birth, and the most prevalent periods for infection being spring and fall. Vaginal delivery and premature rupture of membranes may lead to an increased risk of vertical UU transmission from mother to child, and UU infection is strongly associated with preterm labor, low birth weight, pathogen co-infection, and related complications.

Ranavirus and helminth parasite co-infection in invasive American bullfrogs in the Atlantic forest, Brazil.

Emerging infectious diseases threaten amphibian species across the globe. In Brazil, the American bullfrog (Aquarana catesbeiana) is a highly invasive species that can potentially transmit parasites and pathogens to native amphibians. This is the first assessment of co-infection of Ranavirus and helminth macroparasites in invasive populations of bullfrogs in South America. We collected, measured, and euthanized 65 specimens of A. catesbeiana sampled from 9 sites across three states of Brazil in the Atlantic Forest biome. We collected and identified helminth macroparasites and sampled host liver tissue to test for the presence and load of Ranavirus with quantitative PCR. We documented patterns of prevalence, parasite load, and co-infection with generalized linear mixed models, generalized logistic regressions, and randomization tests. Most individual bullfrogs did not exhibit clinical signs of infection, but the overall Ranavirus prevalence was 27% (95% confidence interval, [CI 17-38]). Bullfrogs were infected with helminth macroparasites from 5 taxa. Co-infection of helminth macroparasites and Ranavirus was also common (21% CI [12-31]). Bullfrog size was positively correlated with total macroparasite abundance and richness, and the best-fitting model included a significant interaction between bullfrog size and Ranavirus infection status. We observed a negative correlation between Ranavirus viral load and nematode abundance (slope = -0.22, P = 0.03). Invasive bullfrogs (A. catesbeiana) in Brazil were frequently infected with both Ranavirus and helminth macroparasites, so adult bullfrogs could serve as reservoir hosts for both pathogens and parasites. However, many macroparasites collected were encysted and not developing. Coinfection patterns suggest a potential interaction between Ranavirus and macroparasites because helminth abundance increased with bullfrog size but was lower in Ranavirus infected individuals. Future studies of bullfrogs in the Atlantic Forest should investigate their potential role in pathogen and parasite transmission to native anurans.

Inhibition of influenza A virus and SARS-CoV-2 infection or co-infection by griffithsin and griffithsin-based bivalent entry inhibitor.

Outbreaks of acute respiratory viral diseases, such as influenza and COVID-19 caused by influenza A virus (IAV) and SARS-CoV-2, pose a serious threat to global public health, economic security, and social stability. This calls for the development of broad-spectrum antivirals to prevent or treat infection or co-infection of IAV and SARS-CoV-2. Hemagglutinin (HA) on IAV and spike (S) protein on SARS-CoV-2, which contain various types of glycans, play crucial roles in mediating viral entry into host cells. Therefore, they are key targets for the development of carbohydrate-binding protein-based antivirals. This study demonstrated that griffithsin (GRFT) and the GRFT-based bivalent entry inhibitor GL25E (GRFT-L25-EK1) showed broad-spectrum antiviral effects against IAV infection in vitro by binding to HA in a carbohydrate-dependent manner and effectively protected mice from lethal IAV infection. Although both GRFT and GL25E could inhibit infection of SARS-CoV-2 Omicron variants, GL25E proved to be significantly more effective than GRFT and EK1 alone. Furthermore, GL25E effectively inhibited in vitro co-infection of IAV and SARS-CoV-2 and demonstrated good druggability, including favorable safety and stability profiles. These findings suggest that GL25E is a promising candidate for further development as a broad-spectrum antiviral drug for the prevention and treatment of infection or co-infection from IAV and SARS-CoV-2.IMPORTANCEInfluenza and COVID-19 are highly contagious respiratory illnesses caused by the influenza A virus (IAV) and SARS-CoV-2, respectively. IAV and SARS-CoV-2 co-infection exacerbates damage to lung tissue and leads to more severe clinical symptoms, thus calling for the development of broad-spectrum antivirals for combating IAV and SARS-CoV-2 infection or co-infection. Here we found that griffithsin (GRFT), a carbohydrate-binding protein, and GL25E, a recombinant protein consisting of GRFT, a 25 amino acid linker, and EK1, a broad-spectrum coronavirus inhibitor, could effectively inhibit IAV and SARS-CoV-2 infection and co-infection by targeting glycans on HA of IAV and spike (S) protein of SARS-CoV-2. GL25E is more effective than GRFT because GL25E can also interact with the HR1 domain in SARS-CoV-2 S protein. Furthermore, GL25E possesses favorable safety and stability profiles, suggesting that it is a promising candidate for development as a drug to prevent and treat IAV and SARS-CoV-2 infection or co-infection.

Clinical features and outcomes of COVID-19 patients with concomitant herpesvirus co-infection or reactivation: A systematic review.

Background: Since the first case of COVID-19 was diagnosed in Wuhan, China in late 2019, concomitant infections with Herpesviridae were documented that were presented from simple skin manifestations to severe life-threatening conditions that may lead to mortality. In this systematic review, we have included studies conducted in different parts of the world to find out the association of clinical features and outcomes of COVID-19 infection and concomitant Herpesviridae infection. Methods: A comprehensive search was conducted in electronic databases including Medline through PubMed, Cochrane database, Scopus and Web of science (core collection). Two review authors independently screened the articles and extracted data. The Risk of bias assessment was done by using RoBANS tool. Results: A total of 919 studies were retrieved and 19 studies were included having data of 539 patients who were infected with both COVID-19 and Herpesviridae. Herpes Simplex-1, Varicella Zoster, Cytomegalovirus, Epstein-Barr virus and Human Herpes Virus-6 were the detected viruses in the included studies. Cytomegalovirus (CMV) reactivation was the most detected concomitant infection. In case of reactivation with more than one Herpes virus mortality among patients were detected along with single viral infection in some studies. Significant association was noted in dosage and usage of steroid and Herpesviridae reactivation in COVID-19 patients. Blood markers such as D-dimer, CRP along with length of stay in the ICU and usage of invasive mechanical ventilation were found to be the significantly associated markers. Conclusion: Findings from this study will aid clinicians to assess and treat COVID-19 cases with co-infections.