Clinical and Epidemiological Characteristics of COVID-19 in Persons Living with HIV Complicated by Tuberculosis

Relevance. At present, three infections – HIV infection, tuberculosis, and COVID-19-are spreading simultaneously in the world. Of great practical importance is the assessment of clinical and epidemiological features of COVID-19 in HIV-infected patients with tuberculosis, COVID-19. Aim. To study the risk of COVID-19 disease and identify clinical and epidemiological features in and population of patients with HIV infection complicated by tuberculosis in comparison with patients with HIV infection and the population without these diseases. Materials and methods. Since 13.03.2020 by 31.12.2021 in the Kemerovo Region-Kuzbass, a continuous prospective analytical epidemiological study of the case-control type was performed. Of those with COVID-19, two observation groups were formed: group I (HIV +), group II (HIV/TB) and comparison group III (persons without either HIV or tuberculosis). All patients underwent: determination of SARS-CoV-2 RNA, standard examination methods in accordance with the temporary methodological recommendations «Prevention, diagnosis and treatment of a new coronavirus infection (COVID-19)», relevant at the time of treatment. Results. The incidence of COVID-19 among patients with HIV infection complicated by tuberculosis exceeded the incidence of COVID-19 among HIV-infected by 14%. There were no gender differences between patients I (HIV +) and II (HIV/TB) groups. In the comparison group, the incidence of COVID-19 was 1.26 times higher in women compared to men. COVID-19 disease in patients with co-infection (HIV/TB) was predominantly mild. Viral pneumonia developed 1.86 times less often, oxygenotherapy was required only in 18.75% of cases, which is 2.5 times lower than in group I (HIV +) and 2.47 times less than in the comparison group (III). In labeled pairs, clinical symptoms of COVID-19 in all groups occurred with the same frequency. Metabolic disorders were evident in all groups. Co-infected patients (HIV/TB) had higher levels of D-dimer, ESR, total bilirubin. Conclusion. Active tuberculosis in HIV-infected people is a factor that increases the risk of COVID-19 disease without affecting the severity of the infectious process. © 2023, Numikom. All rights reserved.

SARS-CoV-2 Co-Infections and Recombinations Identified by Long-Read Single-Molecule Real-Time Sequencing.

Co-infection with at least 2 strains of virus is the prerequisite for recombination, one of the means of genetic diversification. Little is known about the prevalence of these events in SARS-CoV-2, partly because it is difficult to detect them. We used long-read PacBio single-molecule real-time (SMRT) sequencing technology to sequence whole genomes and targeted regions for haplotyping. We identified 17 co-infections with SARS-CoV-2 strains belonging to different clades in 6829 samples sequenced between January and October, 2022 (prevalence 0.25%). There were 3 Delta/Omicron co-infections and 14 Omicron/Omicron co-infections (4 cases of 21K/21L, 1 case of 21L/22A, 2 cases of 21L/22B, 4 cases of 22A/22B, 2 cases of 22B/22C and 1 case of 22B/22E). Four of these patients (24%) also harbored recombinant minor haplotypes, including one with a recombinant virus that was selected in the viral quasispecies over the course of his chronic infection. While co-infections remain rare among SARS-CoV-2-infected individuals, long-read SMRT sequencing is a useful tool for detecting them as well as recombinant events, providing the basis for assessing their clinical impact, and a precise indicator of epidemic evolution. IMPORTANCE SARS-CoV-2 variants have been responsible for the successive waves of infection over the 3 years of pandemic. While co-infection followed by recombination is one driver of virus evolution, there have been few reports of co-infections, mainly between Delta and Omicron variants or between the first 2 Omicron variants 21K_BA.1 and 21L_BA.2. The 17 co-infections we detected during 2022 included cases with the recent clades of Omicron 22A, 22B, 22C, and 22E; 24% harbored recombinant variants. This study shows that long-read SMRT sequencing is well suited to SARS-CoV-2 genomic surveillance.

Leading Pathogens Involved in Co-Infection and Super-Infection with COVID-19: Forensic Medicine Considerations after a Systematic Review and Meta-Analysis.

The COVID-19 pandemic raised concerns about the potential for co-infection or over-infection with other respiratory infections, as they can complicate the diagnosis, treatment and prognosis of the disease. This is also a challenge for forensic pathologists, who may come across cases where the presence of co-infection or over-infection is suspected or confirmed, and it is important that they take this into account when determining the cause of death. The aim of this systematic review is to analyse the prevalence of each specific pathogen co-infecting or over-infecting patients with SARS-CoV-2 infection. In total, 575 studies were selected from the Scopus and Pub-Med online databases and 8 studies were included in a meta-analysis. Male gender, advanced age and nursing home care are risk factors associated with the development of co-infection, whereas age, tachypnoea, hypoxaemia and bacterial infection are predictors of mortality. Overall, however, having a SARS-CoV-2 infection does not represent a real risk for the development of co-infections/super-infections.

A clinico-epidemiological profile, coinfections and outcome of patients with Influenza Like Illnesses (ILI) presenting to the emergency department during the COVID-19 pandemic.

Background: During the COVID-19 pandemic, many patients presented to the emergency department (ED) with features of Influenza-like illnesses (ILI) and with other atypical presentations. This study was done to determine the etiology, co-infections, and clinical profile of patients with ILI. Methods: This prospective observational study included all patients presenting to the ED with fever and/or cough, breathing difficulty, sore throat, myalgia, gastrointestinal complaints (abdominal pain/vomiting/diarrhea), loss of taste and altered sensorium or asymptomatic patients who resided in or travelled from containment zones, or those who had contact with COVID-19 positive patients during the first wave of the pandemic between April and August 2020. Respiratory virus screening was done on a subset of COVID-19 patients to determine co-infection. Results: During the study period, we recruited 1462 patients with ILI and 857 patients with the non-ILI presentation of confirmed COVID-19 infection. The mean age group of our patient population was 51.4 (SD: 14.9) years with a male predominance (n-1593; 68.7%). The average duration of symptoms was 4.1 (SD: 2.9) days. A sub-analysis to determine an alternate viral etiology was done in 293 (16.4%) ILI patients, where 54 (19.4%) patients had COVID 19 and co-infection with other viruses, of which Adenovirus (n-39; 14.0%) was the most common. The most common symptoms in the ILI-COVID-19 positive group (other than fever and/or cough and/or breathing difficulty) were loss of taste (n-385; 26.3%) and diarrhea (n- 123; 8.4%). Respiratory rate (27.5 (SD: 8.1)/minute: p-value < 0.001) and oxygen saturation (92.1% (SD: 11.2) on room air; p-value < 0.001) in the ILI group were statistically significant. Age more than 60 years (adjusted odds ratio (OR): 4.826 (3.348-6.956); p-value: <0.001), sequential organ function assessment score more than or equal to four (adjusted OR: 5.619 (3.526-8.957); p-value: <0.001), and WHO critical severity score (Adjusted OR: 13.812 (9.656-19.756); p-value: <0.001) were independent predictors of mortality. Conclusion: COVID-19 patients were more likely to present with ILI than atypical features. Co-infection with Adenovirus was most common. Age more than 60 years, SOFA score more than or equal to four and WHO critical severity score were independent predictors of mortality.

Co-dynamics of COVID-19 and TB with COVID-19 vaccination and exogenous reinfection for TB: An optimal control application.

COVID-19 and Tuberculosis (TB) are among the major global public health problems and diseases with major socioeconomic impacts. The dynamics of these diseases are spread throughout the world with clinical similarities which makes them difficult to be mitigated. In this study, we formulate and analyze a mathematical model containing several epidemiological characteristics of the co-dynamics of COVID-19 and TB. Sufficient conditions are derived for the stability of both COVID-19 and TB sub-models equilibria. Under certain conditions, the TB sub-model could undergo the phenomenon of backward bifurcation whenever its associated reproduction number is less than one. The equilibria of the full TB-COVID-19 model are locally asymptotically stable, but not globally, due to the possible occurrence of backward bifurcation. The incorporation of exogenous reinfection into our model causes effects by allowing the occurrence of backward bifurcation for the basic reproduction number R0 < 1 and the exogenous reinfection rate greater than a threshold (η > Î·∗). The analytical results show that reducing R0 < 1 may not be sufficient to eliminate the disease from the community. The optimal control strategies were proposed to minimize the disease burden and related costs. The existence of optimal controls and their characterization are established using Pontryagin's Minimum Principle. Moreover, different numerical simulations of the control induced model are carried out to observe the effects of the control strategies. It reveals the usefulness of the optimization strategies in reducing COVID-19 infection and the co-infection of both diseases in the community.

Clinical case of co-infection: COVID19 and invasive meningococcal infection

In light of the current pandemic, doctors need to raise the suspicion of concurrent SARS-CoV-2 infection with Neisseria meningitides infection. In this article we reported a case of invasive meningococcal infection in an adolescent with COVID-19. Severity of the disease depended on septic shock due to invasive meningococcal infection associated with sepsis and meningitis. The differential diagnosis with a multisystem inflammatory syndrome was tricky considering the fever, shock, meningeal symptoms, elevated levels of C-reactive protein and D-dimer, patient age, and a positive test for SARS-CoV-2. The disease outcome was good. Given the risk of invasive forms of meningococcal infection, the possible synergy of SARS-CoV-2 and Neisseria meningitidis, the complexity of differential diagnosis in patients in critical condition, immunization against meningococcal infection should be carried out according to epidemic indications, despite the COVID-19 pandemic.Copyright © 2022 Sorbtsionnye i Khromatograficheskie Protsessy. All rights reserved.

Assessment of Risk Factors and Clinical Outcomes in Hospitalized COVID-19 Patients with Candida spp. Co-infections: Species Distribution and Antifungal Susceptibility Patterns of Isolates.

INTRODUCTION: Fungal co-infections are considered an important complication in hospitalized patients with SARS-CoV-2 that can be attributed to disease aggravation, increased mortality, and poor outcomes. This study was conducted to determine the species distribution and antifungal susceptibility patterns of Candida isolates from hospitalized COVID-19 patients in Shiraz, Iran, in addition to associated risk factors and outcomes of co-infections with Candida species. MATERIALS AND METHODS: In this single-center study, a total of 106 hospitalized COVID-19 patients were evaluated for clinical characteristics and outcomes. Species identification was performed by ITS1-5.8S-ITS2 gene sequencing. Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, amphotericin B, and nystatin was determined according to the M27-A3/S4 CLSI protocol. RESULTS: Candida species were recovered from 48% (51/106) of hospitalized COVID-19 patients. Statistical analysis showed that patients who had heart failure, bacterial co-infection, and were receiving empirical antifungal therapy had a higher risk of developing Candida co-infection. In total, 71 Candida isolates were recovered, of which C. albicans (69%) was the most prevalent isolate. The majority of the Candida isolates were susceptible to all classes of tested antifungal drugs. DISCUSSION: Our results elucidate a high rate of Candida co-infections among hospitalized COVID-19 patients. Comorbidities such as heart failure, HTN, COPD, bacterial infections as well as therapeutic interventions including catheterization, mechanical ventilation, and ICU admission increased the risk of Candida spp. isolation from the bloodstream, respiratory tract and urine samples, which led to a higher in-hospital mortality rate. Additionally, obtained data clarified that empirical antifungal therapy was not as successful as anticipated.

Multi-pathogen based chimeric vaccine to fight against COVID-19 and concomitant coinfections.

BACKGROUND: COVID-19 has proved to be a fatal disease of the year 2020, due to which thousands of people globally have lost their lives, and still, the infection cases are at a high rate. Experimental studies suggested that SARS-CoV-2 interacts with various microorganisms, and this coinfection is accountable for the augmentation of infection severity. METHODS AND RESULTS: In this study, we have designed a multi-pathogen vaccine by involving the immunogenic proteins from S. pneumonia, H. influenza, and M. tuberculosis, as they are dominantly associated with SARS-CoV-2. A total of 8 antigenic protein sequences were selected to predict B-cell, HTL, and CTL epitopes restricted to the most prevalent HLA alleles. The selected epitopes were antigenic, non-allergenic, and non-toxic and were linked with adjuvant and linkers to make the vaccine protein more immunogenic, stable, and flexible. The tertiary structure, Ramachandran plot, and discontinuous B-cell epitopes were predicted. Docking and MD simulation study has shown efficient binding of the chimeric vaccine with the TLR4 receptor. CONCLUSION: The in silico immune simulation analysis has shown a high level of cytokines and IgG after a three-dose injection. Hence, this strategy could be a better way to decrease the disease's severity and could be used as a weapon to prevent this pandemic.

Severe pneumonia due to legionella and SARS-CoV-2 co-infection necessitating medical evacuation from a cargo ship.

Cargo ships are at risk of disease outbreaks like Legionella and SARS-CoV-2 due to their cramped and shared conditions. A case of medical evacuation due to co-infection of Legionella pneumophila with SARS-CoV-2 highlights the need for international infection control guidelines, information networks, and molecular epidemiological approaches for identifying infection routes.

Co-infection of COVID-19 and parasitic diseases: A systematic review.

Co-infection of COVID-19 with other diseases increases the challenges related to its treatment management. COVID-19 co-infection with parasites is studied with low frequency. Here, we systematically reviewed the cases of parasitic disease co-infection with COVID-19. All articles on COVID-19 co-infected with parasites (protozoa, helminths, and ectoparasites), were screened through defined inclusion/exclusion criteria. Of 2190 records, 35 studies remained for data extraction. The majority of studies were about COVID-19 co-infected with malaria, followed by strongyloidiasis, amoebiasis, chagas, filariasis, giardiasis, leishmaniasis, lophomoniasis, myiasis, and toxoplasmosis. No or low manifestation differences were reported between the co-infected cases and naïve COVID-19 or naïve parasitic disease. Although there was a relatively low number of reports on parasitic diseases-COVID-19 co-infection, COVID-19 and some parasitic diseases have overlapping symptoms and also COVID-19 conditions and treatment regimens may cause some parasites re-emergence, relapse, or re-activation. Therefore, more attention should be paid to the on-time diagnosis of COVID-19 and the co-infected parasites.

Optimal control for co-infection with COVID-19-Associated Pulmonary Aspergillosis in ICU patients with environmental contamination.

In this paper, we propose a mathematical model for COVID-19-Associated Pulmonary Aspergillosis (CAPA) co-infection, that enables the study of relationship between prevention and treatment. The next generation matrix is employed to find the reproduction number. We enhanced the co-infection model by incorporating time-dependent controls as interventions based on Pontryagin's maximum principle in obtaining the necessary conditions for optimal control. Finally, we perform numerical experiments with different control groups to assess the elimination of infection. In numerical results, transmission prevention control, treatment controls, and environmental disinfection control provide the best chance of preventing the spread of diseases more rapidly than any other combination of controls.

COVID-19 and Respiratory Virus Co-Infections: A Systematic Review of the Literature.

Τhe COVID-19 pandemic highly impacted the circulation, seasonality, and morbidity burden of several respiratory viruses. We reviewed published cases of SARS-CoV-2 and respiratory virus co-infections as of 12 April 2022. SARS-CoV-2 and influenza co-infections were reported almost exclusively during the first pandemic wave. It is possible that the overall incidence of SARS-CoV-2 co-infections is higher because of the paucity of co-testing for respiratory viruses during the first pandemic waves when mild cases might have been missed. Animal models indicate severe lung pathology and high fatality; nevertheless, the available literature is largely inconclusive regarding the clinical course and prognosis of co-infected patients. Animal models also indicate the importance of considering the sequence timing of each respiratory virus infection; however, there is no such information in reported human cases. Given the differences between 2020 and 2023 in terms of epidemiology and availability of vaccines and specific treatment against COVID-19, it is rational not to extrapolate these early findings to present times. It is expected that the characteristics of SARS-CoV-2 and respiratory virus co-infections will evolve in the upcoming seasons. Multiplex real-time PCR-based assays have been developed in the past two years and should be used to increase diagnostic and infection control capacity, and also for surveillance purposes. Given that COVID-19 and influenza share the same high-risk groups, it is essential that the latter get vaccinated against both viruses. Further studies are needed to elucidate how SARS-CoV-2 and respiratory virus co-infections will be shaped in the upcoming years, in terms of impact and prognosis.

Viral reactivations and co-infections in COVID-19 patients: a systematic review.

BACKGROUND: Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses. METHODS: Our population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle-Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables. RESULTS: In total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals. CONCLUSION: Overall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients.

A case of Co-infection COVID-19 and influenza with psychotic symptoms.

Coronavirus disease 2019 (COVID-19), is a pandemic disease that has appeared in recent years with different symptoms and manifestations. This disease has Co-infection with other infections and has aggravated the symptoms in patients. This study was conducted with the aim of reporting a case of Co-infection COVID-19 and influenza with psychotic symptoms. In this study, the manifestations of a case of co-infection with COVID-19 and influenza with psychotic symptoms were discussed in Shahroud city in Iran in 2022. Based on this, the patient's laboratory, pathological and therapeutic findings were investigated. The patient, a 16-year-old boy, had symptoms of fever, chills, cough, body pain, and headache with seizures and delirium. Reverse transcription-polymerase chain reaction tests for covid-19 and influenza were positive, but no abnormalities were observed in laboratory variables and graphs. The patient was treated for psychotic disorders for 40 days and then recovered.

Correlation between COVID-19 and hepatitis B: A systematic review.

BACKGROUND: There is growing evidence that patients with coronavirus disease 2019 (COVID-19) frequently present with liver impairment. Hepatitis B virus (HBV) remains a major public health threat in current society. Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HBV can cause liver damage, and current findings on whether HBV infection increases disease severity in COVID-19 patients are inconsistent, and whether SARS-CoV-2 infection accelerates hepatitis B progression or leads to a worse prognosis in hepatitis B patients has not been adequately elucidated. AIM: To explore the complex relationship between COVID-19 and hepatitis B in order to inform the research and management of patients co-infected with SARS-CoV-2 and HBV. METHODS: An experienced information specialist searched the literature in the following online databases: PubMed, China National Knowledge Infrastructure, Google Scholar, Scopus, Wiley, Web of Science, Cochrane, and ScienceDirect. The literature published from December 2019 to September 1, 2022 was included in the search. We also searched medRxiv and bioRxiv for gray literature and manually scanned references of included articles. Articles reporting studies conducted in humans discussing hepatitis B and COVID-19 were included. We excluded duplicate publications. News reports, reports, and other gray literature were included if they contained quantifiable evidence (case reports, findings, and qualitative analysis). Some topics that included HBV or COVID-19 samples but did not have quantitative evidence were excluded from the review. RESULTS: A total of 57 studies were eligible and included in this review. They were from 11 countries, of which 33 (57.9%) were from China. Forty-two of the 57 studies reported abnormalities in liver enzymes, three mainly reported abnormalities in blood parameters, four indicated no significant liver function alterations, and another eight studies did not provide data on changes in liver function. Fifty-seven studies were retrospective and the total number of co-infections was 1932, the largest sample size was 7723, and the largest number of co-infections was 353. Most of the studies suggested an interaction between hepatitis B and COVID-19, while 12 studies clearly indicated no interaction between hepatitis B and COVID-19. Six of the 57 studies clearly reported HBV activation. Six studies were related to liver transplant patients. CONCLUSION: There is some association between COVID-19 and hepatitis B. Future high-quality randomized trials are needed to further elucidate the interaction between COVID-19 and hepatitis B.

A Retrospective Assessment of Sputum Samples and Antimicrobial Resistance in COVID-19 Patients.

Data on bacterial or fungal pathogens and their impact on the mortality rates of Western Romanian COVID-19 patients are scarce. As a result, the purpose of this research was to determine the prevalence of bacterial and fungal co- and superinfections in Western Romanian adults with COVID-19, hospitalized in in-ward settings during the second half of the pandemic, and its distribution according to sociodemographic and clinical conditions. The unicentric retrospective observational study was conducted on 407 eligible patients. Expectorate sputum was selected as the sampling technique followed by routine microbiological investigations. A total of 31.5% of samples tested positive for Pseudomonas aeruginosa, followed by 26.2% having co-infections with Klebsiella pneumoniae among patients admitted with COVID-19. The third most common Pathogenic bacteria identified in the sputum samples was Escherichia coli, followed by Acinetobacter baumannii in 9.3% of samples. Commensal human pathogens caused respiratory infections in 67 patients, the most prevalent being Streptococcus penumoniae, followed by methicillin-sensitive and methicillin-resistant Staphylococcus aureus. A total of 53.4% of sputum samples tested positive for Candida spp., followed by 41.1% of samples with Aspergillus spp. growth. The three groups with positive microbial growth on sputum cultures had an equally proportional distribution of patients admitted to the ICU, with an average of 30%, compared with only 17.3% among hospitalized COVID-19 patients with negative sputum cultures (p = 0.003). More than 80% of all positive samples showed multidrug resistance. The high prevalence of bacterial and fungal co-infections and superinfections in COVID-19 patients mandates for strict and effective antimicrobial stewardship and infection control policies.

A case report of necrotizing fasciitis caused by Haemophilus influenzae co-infection in the setting of COVID-19 pneumonia.

INTRODUCTION AND IMPORTANCE: Necrotizing fasciitis is an aggressive skin and soft tissue infection that is a surgical emergency, and Haemophilus influenzae (H. flu) is a rare cause. We present a case of H. flu co-infection causing necrotizing fasciitis in the setting of COVID-19 pneumonia. CASE PRESENTATION: A 56-year-old male presented with 2 weeks of upper respiratory symptoms. He was unvaccinated against COVID-19 and tested positive for COVID-19 five days prior. He developed respiratory failure requiring intubation, and was treated with dexamethasone, remdesivir, and tocilizumab for COVID-19 pneumonia. On hospital day 2, he was hypotensive with new rapidly evolving erythematous lesions with crepitus of his lower extremities suspicious for necrotizing fasciitis. He underwent wide excision and debridement with significant hemodynamic improvements. H. flu co-infection was identified from blood cultures. Aberrant cells with 94 % lymphocytes were noted and suggested chronic lymphocytic leukemia (CLL) that was not previously known. He developed progressive lesions globally, concerning for purpura fulminans with clinical disseminated intravascular coagulation and neurological decline ultimately leading to withdrawal of care. CLINICAL DISCUSSION: COVID-19 infection is often associated with concomitant opportunistic infections. Our patient was also immunocompromised by CLL, diabetes, chronic steroids, and initial appropriate COVID-19 treatments. Despite appropriate treatments, he could not overcome his medical comorbidities and multiple infections. CONCLUSION: Necrotizing fasciitis caused by H. flu is rare, and we present the first case as a co-infection in the setting of COVID-19 pneumonia. Due to the patient's immunocompromised state with underlying CLL, this proved to be fatal.

COVID-19 associated rhino-orbito-cerebral mucormycosis, risk factors and outcome predictors; a multicentric study.

BACKGROUND: Since the onset of the Covid-19 pandemic, an increase in mucormycosis cases has been observed in many countries, including Iran. However, the role of covid-19 and associated risk factors have not been thoroughly investigated. OBJECTIVE: This study is designed to identify epidemiologic characteristics, risk factors, and outcome predictors of Covid-19-Associated Rhino-Orbito-Cerebral Mucormycosis (C-ROCM). METHODS: Data of pathology proven Covid Associated ROCM cases were retrospectively obtained from 7 tertiary care centers throughout Iran from February 20, 2021, to July 22, 2021. Univariate and multivariate analyses were performed using binary logistic regression to assess the effects of various factors on the outcome. RESULTS: A total of 132 patients with C-ROCM were included in the study. The mean age of patients was 61.6 ± 13.9 (60.6% male). In 12 patients (9.1%), both eyes were involved. Diabetes was the most common comorbidity (94.7%). The mortality rate was 9.1%, higher in males (12.5%) than females (3.8%). Severe vision impairment was seen in 58 patients (43.9%). Main factors that had a negative impact on the outcome in the univariate analysis include older age (P < 0.001), higher steroid dosage (P < 0.001), higher HbA1c level (P < 0.001), Covid-19 severity (P < 0.001), and brain involvement (P < 0.001). However, in the multivariate analysis, the effects of age (P = 0.062), steroid dosage (P = 0.226), and Covid-19 intensity (P = 0.084) decreased, and the difference was no longer statistically significant. CRAO was a predictor of mortality in the univariate analysis (P = 0.008, OR = 4.50), but in the multivariate analysis, this effect decreased and was no longer significant (P = 0.125). CONCLUSION: The risk of C-ROCM and its complications may increase in patients with more severe Covid-19, steroid over-prescription, ICU admission due to Covid-19, and poor glycemic control during and after Covid-19 treatment.

Tuberculosis and HIV responses threatened by nCOVID-19: A situation prompting an in silico investigation of reported MbtA inhibitors for combined inhibition of SARS-CoV-2 and HIV-TB co-infection

The menace of infectious diseases has constantly been a reason of concern for humankind since time immemorial. As evident by the name, infectious diseases can infect a huge population within a short period, leading to an eruption of pandemics and epidemics. The present human era is fortunate enough to have a wide array of readily available drugs that help cure and prevent various diseases. Moreover, the scientific community has always responded to the needs of society through its drug discovery and development programs. The co-existence of multiple diseases calls forth the scientific community to design and develop drugs that could have a broad spectrum of activity. In this perspective, our goal was to investigate the potential of reported MbtA inhibitors (antitubercular molecules) in inhibiting HIV-1 RT and nCovid-19-RdRp and eventually leading to the identification of a multi-targeted ligand (triple co-infection inhibitor). In this study, the primary success was attained by capitalizing on the structure-based virtual screening drug discovery approach. Results were quite promising. Molecular docking results showed that GV17 interacted strongly with the active site residues of both the target proteins (HIV-1 RT and nCOVID-19-RdRp). Moreover, the docking score of GV17 was more than that of the internal ligands of both the target proteins, which indicates a firm binding. Molecular dynamics further validated these results as identical amino acid residues were observed in the protein's docked pose with the ligand. The detailed atomic interactions of ligand GV17 with the protein residues have been discussed. Overall, the protein–ligand complexes remained stable throughout the simulation, and the system's backbone fluctuations were modest. MM-GBSA analysis revealed free binding energy of − 72.30 ± 7.85 kcal/mol and − 65.40 ± 7.25 kcal/mol for 1RT2 and 7BV2, respectively. The more negative binding energy indicates a stronger affinity of GV17 with both the receptors. GV17 also gave satisfactory predictive in silico ADMET results. Overall, this computational study identified GV17 as a potential HIT molecule and findings can open up a new avenue to explore and develop inhibitors against nCOVID-19-HIV-TB triple-infections.