Tuberculosis and Hiv Infection - So Many Questions Pending

Since the early days of HIV infection, back in the eighties, TB - particularly extrapulmonary TB emerged as one of the opportunistic infections affecting these patients, specifically as a reactivation of latent TB infections. A diagnosis of TB in the context of HIV infection was then considered as an 'AIDS defining condition' according to classification systems used at that time. It has been recognized for a long time that there are many interactions between HIV and Mycobacterium tuberculosis, which lead to further immune deterioration and to worsening of both conditions due to complex biological and mechanistic interactions between these two agents. Many methods and techniques have been proposed in order to improve diagnosis of TB in HIV-infected subjects, knowing that TB is the most frequent opportunistic infection;and, if not treated in a timely fashion, it may easily take the lives of affected patients. It is not easy to have a diagnosis of TB in HIV-infected subjects, because of the difficulties for obtaining adequate sputum samples, or because of lack of adequate facilities for making a timely diagnosis, particularly in the so-called developing world. On the other hand, extrapulmonary TB is most frequently found in HIV-infected individuals compared to non-infected subjects, and its diagnosis poses significant difficulties, since so many times invasive procedures must be performed in order to obtain an adequate tissue sample and then be able to identify the pathological characteristics of tuberculous disease. In the first days of HIV infection when no antiretroviral therapy was available, a diagnosis of TB was made on clinical grounds, considering a history of contact or some characteristics of the disease, and those of us who are old (or experienced) enough offered antituberculosis therapy for these subjects, obtaining an adequate response many times, but in all cases, the natural history of HIV infection took place, and ultimately these patients died because of the occurrence of another opportunistic infection (or malignancy). With the advent of antiretroviral therapy in the late nineties, another problem occurred. The possibility of drug-drug interactions, taking into account hepatic metabolism of rifampin and the alterations of antiretroviral drug blood - or tissue - concentrations. On top of this, the occurrence of IRIS became another problem, and strategies and protocols have been designed in order to establish the adequate timing of antituberculosis therapy and sometime later antiretroviral therapy. A last point to be considered is the COVID-19 pandemic. The question to be asked is what the influence of the pandemic has been for affecting TB and HIV diagnosis and therapy strategies and programs, particularly in the developing world, knowing that health systems in these countries have many limitations, and that - scant - resources had to be dedicated for the fight against the pandemic.Copyright © 2023

Impact of Hiv Infection on Mpox-Related Hospitalizations in Brazil

Background: Late presentation to care remains a major public health problem in Brazil, despite the countrys longstanding commitment to universal access to ART to all PLWH. The COVID-19 pandemic severely hit the country and further impacted the HIV care continuum, with worse disparities observed by gender and sexual orientation. By December 28th 2022, Brazil reported 10,493 and 14 mpox cases and deaths ranking second globall. Although mpox lethality is low, HIV-related immunosuppression may negatively impact mpox outcomes, increasing hospitalizations and fatalities. We aim to describe mpox hospitalization rates and explore the impact of HIV-infection on mpox-related hospitalizations and clinical outcomes. Method(s): Prospective, observational cohort study of individuals with confirmed mpox infection followed at the major mpox referral center in Rio de Janeiro, Brazil. Demographic and clinical data including reasons for hospitalization were systematically collected. Chi-squared or Fisher's exact tests for qualitative variables and the Moods median test for quantitative variables were used. Result(s): From June 12 to December 12, 2022, 402 participants had a laboratory-confirmed mpox diagnosis. Median age was 34 years, 365 (91%) were cisgender men, and 197 (49%) were PLWH. Overall, 39 (10%) participants were hospitalized due to mpox-related causes;20 (51%) were PLWH. All PLWH with CD4 counts< 200 cells/mm3 required hospitalization. Compared to nonhospitalized PLWH, a higher proportion of hospitalized PLWH had concomitant opportunistic infections (4/20 [20%] vs. 1/177 [0.6%];p< 0.001), were not virologically suppressed (7/20 [35.0%] vs. 22/177 [15.3%];p=0.1) and were not on ART (4/20 [20%] vs. 15/177 [7.6%];p=0.03). Among all hospitalized participants, PLWH were more frequently hospitalized due to severe proctitis than HIV-negative participants (12/20 [60%] vs. 5/19 [26.3%];p=0.03), with no differences regarding hospitalizations for pain control (Table). PLWH accounted for all cases of hospitalized individuals who required intensive care support (n=4), had deep tissue involvement (n=3) and had a mpox related death (n=2). Conclusion(s): Our findings suggest an association between worse outcomes in the HIV care continuum and mpox-related hospitalizations. Advanced immunosuppression (CD4< 200) contributed to more severe clinical presentations and death. Public health strategies to mitigate HIV late presentation and the negative impact of the COVID-19 pandemic to the HIV care continuum are urgently needed. Sociodemographic and clinical characteristics of mpox cases according to HIV and hospitalization status.

High Mortality in Hospitalised Virally Suppressed Adults with Hiv in South Africa

Background: Mortality in PWH has been markedly improved by antiretroviral therapy (ART) but there are few reports describing this in the ~5 million virally suppressed (VS) PWH in South Africa(SA). We describe cause of death(CoD) in adults admitted to hospital with suspected pneumonia in SA. Method(s): We enrolled patients from June 2019-October 2021 at four hospitals and then followed them up for >=1 year. Eligibility included: Age >18 years, >=2 signs/symptoms of pneumonia, < 48 hrs since admission. Medical records were reviewed. All had HIV status ascertained and sputum sent for Xpert Ultra and mycobacterial culture. In PWH CD4 count, viral load (VL) and urine lipoarabinomannan were assessed. For those who died, CoD were ed from medical charts and interview of family. We categorised deaths as early: while admitted or to < 30 days after discharge;or late: >=30 days after discharge. We report mortality and CoD in VSPWH (VL<=50 copies/ml), unsuppressed and HIV uninfected(HUI) adults. Result(s): Of 1999 adults, 54% were PWH;61.2% reported receiving ART of whom 43.1% were VS;55.5% were women. Overall median age of VS was 48 years (IQR: 40-55) at entry;34.3% had comorbidities: hypertension (70.1%, obesity 41.3%, diabetes 28.9%) . Only 11.3% were diagnosed with HIV in the past year, 35.0%, had prior TB. Median CD4 count of VS patients was 289 cells/ mm3 (IQR:133-490) and Hb, 12.5g/dL (IQR:10.5-14.0);53.0% had CRP >100mg/ dL and 69.6% had oxygen saturation < 93% on room air;14.8% had >=1 assay positive for TB;and 42.9% were SARS-CoV-2 positive. Overall 25.4% VSPWH died compared to 31.2% and 22.9% of unsuppressed and HUI, respectively;median ages at death were 49 (IQR:43-59), 38 (IQR: 32-47) and 62 (IQR: 53-69) years respectively. Overall median times to early and late death was 8 (IQR: 4-16) and 104 (IQR: 75-254) days, respectively. The leading CoD in VSPWH were: COVID-19 (22.9%), chronic lung disease(CLD) (17.1%),malignancy (12.9%),sepsis, (12.9%) and TB (8.7%);in HIV unsuppressed, CoD were: advanced HIV and opportunistic infections-(TB,PJP)(55.5%), sepsis(9.6%), COVID-19(8.6%);and in HUI: COVID- 19(43.0%), cardiovascular disease (9.0%), TB(9.0%), malignancy (8.5%). Conclusion(s): Mortality in VSPWH admitted with suspected pneumonia was higher than in HUI and occurred 12 years earlier. The challenge for clinicians is to screen for diseases that disproportionately affect VSPWH and to try to prevent recurrent lung infections thereby increasing their comorbidity-free years and reduce mortality gaps.

From Covid to Bovid to Ovid: A Case of Disseminated Cryptococcus Neoformans

Case Report: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus, with C. neoformans and C. gattii being the most common species to cause human disease. Immunocompromised individuals are predisposed to infections with C. neoformans, which has known predilection to CNS and pulmonary lymph nodes. We present a unique case of disseminated cryptococcosis in the setting of end-stage renal disease (ESRD), cirrhosis, tumor necrosis factor inhibitor use and steroid use for COVID19. Method(s): A single-patient case report was conducted after IRB approval. Case Presentation: A 55-year-old woman with uncontrolled diabetes, lupus, rheumatoid arthritis on adalimumab, hepatitis C status post boceprevir, cirrhosis, former IV drug use, and ESRD on hemodialysis via bovine arterial-venous fistula graft presented with worsening dyspnea, cough, and altered mental status. Three months prior, patient was admitted to an outside hospital for COVID19, complicated by pulmonary embolism status post anticoagulation therapy. Patient was treated with an unknown steroid regimen, which was continued by a second outside facility when symptoms failed to improve. Patient then presented to our facility 24 hours after discharge due to continued symptoms. On admission, patient was noted to have altered mentation and hypoxia with pulmonary edema on chest x-ray and was urgently hemodialyzed. Further work-up was obtained due to non-resolving symptoms, including blood and sputum cultures, cocci serology and QuantiFERON gold. CT chest revealed bilateral consolidations. Patient was started on antibiotics for presumed hospital-acquired pneumonia. During the hospital stay, preliminarily blood cultures grew yeast and patient was started on Micafungin. However, Micafungin was changed to Liposomal Amphotericin B as ovoid structures seen on gram stain could not confirm nor rule out cryptococcus. Subsequent bronchial wash and bronchoalveolar lavage cultures, as well as final blood cultures resulted Cryptococcus neoformans. Serum cryptococcus antigen returned reactive, titer 1:512. Antibiotics were discontinued and Isavuconazonium was started with Liposomal Amphotericin B. Due to recurrent headaches, lumbar puncture was obtained and revealed lymphocytic pleocytosis without cryptococcal antigenicity. Patient completed 14 days of Liposomal Amphotericin B and Isavuconazole with continuation of Isavuconazole upon discharge. Conclusion(s): Disseminated cryptococcosis in non-HIV patients is rare in the modern HIV era. Clinicians should be aware and include it in their differential of any patient with multiple risk factors for opportunistic infection. In patients with cirrhosis and ESRD, treatment is limited given altered pharmacokinetics. Studies have shown improved survival with the addition of Isavuconazole in patients with disseminated cryptococcosis with CNS involvement in the setting of chronic liver disease and ESRD.

Anaphylaxis to Cyclophosphamide Metabolites during Lymphodepletion for CAR-T Therapy

Background: Cyclophosphamide (Cy) is used in hematopoietic stem cell transplant (HSCT) preparative regimens and lymphodepletion for chimeric antigen receptor T-cell (CAR-T) therapy. We describe a case of cyclophosphamide hypersensitivity in a pediatric patient during CAR-T therapy. Case description: A 13 year old boy was diagnosed with very high risk ALL in 2015 and had 2 isolated CNS relapses treated with intensified chemotherapy (chemo) and cranial radiation (1st relapse) and Blinatumomab with intrathecal (IT) chemo followed by sibling donor HSCT (2nd relapse). At age 19, and 18 months after HSCT, he had a 3rd CNS relapse treated with IT chemo and referral for CAR-T therapy. At our center, leukapheresis and CAR-T production (Novartis) were performed. Later, during lymphodepletion with fludarabine (Flu) and Cy, physiologic replacement hydrocortisone (HC) was briefly held to prevent interference with CAR-T function. After 3 days of Flu/Cy, he developed fever and hypotension requiring inotropic support. Hypotension and fever resolved with stress dose HC and antibiotics and was attributed to culture-negative sepsis and adrenal crisis. CAR-T infusion was subsequently delayed by skin GVHD requiring glucocorticoids and COVID-19 infection treated with convalescent plasma and nirmatrelvir/ritonavir. Physiologic HC replacement was continued when he was re-admitted for CAR-T therapy, but he again developed fever, diffuse erythema and shock in hours following the first dose of Cy necessitating stress dose HC, antibiotics, inotropes, and mechanical ventilation. Negative blood cultures and ongoing physiologic HC replacement suggested an alternative explanation for shock. Case reports of anaphylaxis to Cy metabolites implicated Cy as the causative agent so it was discontinued. After recovery, CAR-T cells were infused without complications. In the following weeks, he had no evidence of recurrent leukemia but was persistently pancytopenic. A sibling donor stem cell boost was proposed but the patient accepted only palliative care. He had several opportunistic infections before succumbing to E. coli sepsis. Discussion(s): The first episode of shock was initially attributed to adrenal crisis and sepsis, although no organism was identified. The second episode appeared anaphylactic in timing and clinical presentation with adequate HC replacement and negative cultures, suggesting Type I hypersensitivity. The patient previously received Cy uneventfully before HSCT, suggesting that the donor-derived immune system was the source of new Cy hypersensitivity. Onset of anaphylaxis within hours rather than minutes after Cy administration supports hypersensitivity to Cy metabolites rather than to the drug itself. This case highlights the importance of consideration of sensitivity to Cy metabolites as well as acquired donor-specific allergy even when alternative explanations are likely.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Cellular immunity in COVID-19 and other infections in Common variable immunodeficiency.

COVID-19 has shed light on the role of cellular immunity in the absence of humoral response in different patient groups. Common variable immunodeficiency (CVID) is characterized by impaired humoral immunity but also an underlying T-cell dysregulation. The impact of T-cell dysregulation on cellular immunity in CVID is not clear, and this review summarizes available literature on cellular immunity in CVID with a particular focus on COVID-19. Overall mortality of COVID-19 in CVID is difficult to assess, but seems not significantly elevated, and risk factors for severe disease mirrors that of the general population, including lymphopenia. Most CVID patients have a significant T-cell response to COVID-19 disease with possible cross-reactivity to endemic coronaviruses. Several studies find a significant but impaired cellular response to basal COVID-19 mRNA vaccination that is independent of an antibody response. CVID patients with infection only have better cellular responses to vaccine in one study, but there is no clear association to T-cell dysregulation. Cellular response wane over time but responds to a third booster dose of vaccine. Opportunistic infection as a sign of impaired cellular immunity in CVID is rare but is related to the definition of the disease. CVID patients have a cellular response to influenza vaccine that in most studies is comparable to healthy controls, and annual vaccination against seasonal influenza should be recommended. More research is required to clarify the effect of vaccines in CVID with the most immediate issue being when to booster the COVID-19 vaccine.

Infectious complications of chimeric antigen receptor (CAR) T-cell therapies.

CAR T-cells have revolutionized the treatment of many hematological malignancies. Thousands of patients with lymphoma, acute lymphoblastic leukemia, and multiple myeloma have received this "living medicine" and achieved durable remissions. Their place in therapy continues to evolve, and there is ongoing development of new generation CAR constructs, CAR T-cells against solid tumors and CAR T-cells against chronic infections like human immunodeficiency virus and hepatitis B. A significant fraction of CAR T-cell recipients, unfortunately, develop infections. This is in part due to factors intrinsic to the patient, but also to the treatment, which requires lymphodepletion (LD), causes neutropenia and hypogammaglobulinemia and necessarily increases the state of immunosuppression of the patient. The goal of this review is to present the infectious complications of CAR T-cell therapy, explain their temporal course and risk factors, and provide recommendations for their prevention, diagnosis, and management.

Mortality analysis of COVID-19 cases during the second wave and its comparison with the first wave: A hospital-based study.

Objectives: This study was undertaken to determine the characteristics of COVID-19 deaths during the second wave and to compare these characteristics with the mortality during the first wave in a dedicated COVID hospital (DCH). Study Design: It was a hospital record-based descriptive study. Methodology: The study was conducted in a tertiary care COVID hospital, using a standard death audit proforma. The data were analyzed to know various demographic characteristics and factors related to mortality during the second wave from March to June 2021. The findings were compared with the mortality data during the first wave from April to July 2020 at the same hospital. Results: A total of 264 deaths occurred at the center during the study period with a mortality rate of 22.8%. Male cases were more in number, the age group was 21-70 years, the highest number of mortality was seen in the mid of the study period, duration of stay was five days on average and common causes of death were pneumonia alone or with acute respiratory distress syndrome with sepsis. In comparison to the first wave, the mortality rate was four times higher, the age group was younger and opportunistic infections viz. mucormycosis and aspergillosis were present during the second wave. Conclusion: The mortality rate was significantly higher and the younger age groups were involved during the second wave, with opportunistic fungal infections due to the use of immunomodulators.

Multiple Sclerosis and the Risk of Infection: A Consensus Guideline

Multiple sclerosis (MS) is an inflammatory condition affecting the central nervous system. Infection is a major consideration in the MS population due to its relevance to several stages of the disease process: (i) it has been suggested that infective processes may be 'triggering' or aetiological factors for MS, (ii) concurrent infection is known to exacerbate symptoms in MS, (iii) people with MS are at higher risk of infection when compared to the general population, and this risk is exaggerated in those receiving disease modifying therapies (DMTs). This guidance document was developed by specialists in the field of MS, Immunology, Infectious Disease and Pharmacy. A modified Delphi approach was used to develop clinically relevant, evidence-based consensus guidelines to help physicians navigate the complex interaction between DMTs and infectious diseases. We focus on specific risks predisposing people with MS to infection and how to manage these risks. We also provide recommendations on how to screen for, prevent, and manage infection in this population, in particular tuberculosis, progressive multifocal leukoencephalopathy, hepatitis B, human papillomavirus, herpetic and other opportunistic infections. We also discuss vaccination and the COVID-19 pandemic in people on DMTs.

Etrasimod for the treatment of ulcerative colitis: analysis of infection rates from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 clinical trials

Background: Infections are an important safety concern in patients with IBD and may be due to its therapies, such as corticosteroids. Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 (S1P1,4,5) modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). The biologic effect of etrasimod leads to selective and reversible lymphocyte retention in lymph nodes with a decrease in peripheral lymphocyte count. We report the infection events from the phase 3 ELEVATE programme. Method(s): Infection events were evaluated in the pivotal UC pooled safety analyses set comprising two phase 3 studies: ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369). Subjects (16- 80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo (PBO). We report the n (%) and exposure-adjusted incidence rate (EAIR) of infections including serious infections, severe infections, opportunistic infections (including tuberculosis), and herpes infections. Infections were considered adverse events of special interest (AESI) if they were severe (>= CTCAE Grade 3), were opportunistic infections, or were herpes zoster or herpes simplex infections. Result(s): From the pooled ELEVATE UC 12 and ELEVATE UC 52 trials, 527 subjects received >=1 dose of etrasimod 2 mg (265.6 subject-years of exposure) and 260 subjects were randomised to PBO (103.0 subjectyears of exposure). Infections were similar between treatment groups (etrasimod: 99 [18.8%], EAIR=0.41;PBO: 46 [17.7%], EAIR=0.52). The most frequent infections in both groups were COVID-19, urinary tract infections, and nasopharyngitis (Table 1). Serious infections occurred in 3 (0.6%) subjects in the etrasimod arm (EAIR=0.01) and 5 (1.9%) in PBO arm (EAIR=0.05). Two cases of herpes zoster were reported in each treatment group (etrasimod: 0.4%, EAIR<0.01;PBO: 0.8%, EAIR=0.02);these were localised and nonserious. One opportunistic infection was reported in each arm (etrasimod: Subject withdrew from the study on day 20, the AE of Cytomegalovirus infection [Grade 2] was reported on day 36;PBO: Tuberculosis [Grade 2]). Overall, 3 cases of infection led to discontinuation: 2 in the etrasimod arm (both mild) and 1 in the PBO arm (Table 2). No subject with an absolute lymphocyte count <0.2x109/L subsequently reported a serious/ severe or opportunistic infection. There were no deaths. Downloaded from https://academic.oup.com/ecco-jcc/article/17/Supplement-1/i689/7010119 by guest on 04 February 2023 Sample output to test PDF Combine only i690 Poster presentations In these trials, etrasimod-treated subjects reported no in-crease in infections relative to PBO. Serious infections and herpes zoster were more commonly reported in the PBO-treated group. Longer-term follow-up data from the ongoing 5-year open-label extension will fur-ther characterize the etrasimod safety profile.

Cerebral Cryptococcosis Associated with CD4+ T-lymphocytopenia in Non-HIV Patients after SARS-CoV-2 Infection: Case Series in a Specialized Institute in Lima, Peru.

Cases of cryptococcosis have been reported in patients with COVID-19. The majority are in patients with severe symptoms or who received immunosuppressants. However, there is still no clear association between COVID-19 and cryptococcosis. We report eight cases of cerebral cryptococcosis associated with CD4+ T lymphocytopenia in non-HIV patients after SARS-CoV-2 infection. The median age was 57 years and 5/8 were male. In addition, 2/8 of patients had diabetes, and 8/8 had a history of mild COVID-19, with a median of 75 days before diagnosis of cerebral cryptococcosis. All patients denied having received prior immunosuppressive therapy. The most frequent symptoms were confusion (8/8), headache (7/8), vomiting (6/8), and nausea (6/8) All patients were diagnosed by isolating Cryptococcus in cerebrospinal fluid. The median CD4+ and CD8+ T lymphocytes were 247 and 173.5, respectively. Other causes of immunosuppression, such as HIV or HTLV infection, were excluded in all patients. Finally, three patients died, and one presented long-term visual and auditory sequelae. The CD4+/CD8+ T lymphocyte count normalized during follow-up in those patients who survived. We hypothesize that CD4+ T lymphocytopenia in the patients in this case series could increase the risk of cryptococcosis after SARS-CoV-2 infection.

Multidisciplinary Management of COVID-Associated Mucormycosis Syndemic in India.

The study aimed to determine clinical presentation, contributing factors, medical and surgical management, and outcome of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). A cross-sectional, single-center study was conducted on patients receiving multidisciplinary treatment for mucormycosis following the second wave of COVID-19 pandemic from April to June 2021 in India. Clinicoepidemiological factors were analyzed, 30-day overall survival and disease-specific survival were determined, and t-test was used to determine the statistical significance. A total of 215 patients were included in the study, the cases were stratified into sino-nasal 95 (44.2%), sino-naso-orbital 32 (14.9%), sino-naso-palatal 55 (25.6%), sino-naso-cerebral 12 (5.6%), sino-naso-orbito-cerebral 16 (7.4%), and sino-naso-orbito-palato-cerebral 5 (2.3%) based on their presentation. A multidisciplinary team treated patients by surgical wound debridement and medical therapy with broad-spectrum antibiotics and amphotericin B. Across all disease stages, cumulative 30-day disease-specific survival is 94% (p < 0.001, intergroup comparison, Breslow (generalized Wilcoxon) CI 95%) and overall 30-day survival is 87.9% (p < 0.001, intergroup comparison, Breslow (generalized Wilcoxon) CI 95%) (censored). Early identification, triaging, and proper multidisciplinary team management with systemic antifungals, surgical debridement, and control of comorbidities lead to desirable outcomes in COVID-associated mucormycosis. The patients with intracranial involvement have a higher chance of mortality compared to the other group. Supplementary Information: The online version contains supplementary material available at 10.1007/s12262-021-03134-0.

Opportunistic non-communicable diseases in times of COVID-19

We previously proposed the term ‘opportunistic non-communicable diseases (NCDs)' to raise awareness of how NCDs thrive in societies with inadequate healthcare services. However, we did not anticipate that within the next year the new coronavirus disease (COVID-19) would sweep the globe. Lockdowns became the primary strategy for mitigation in most countries. However, the extensive restrictions and allocation of resources towards the containment of the pandemic have likely served as a catalyst of NCDs, especially in populations, societies and individuals already at high risk. We are presenting evidence to qualify two primary factors responsible for the potential impact on the development of NCDs during the COVID-19 pandemic. The first is disrupted healthcare services including avoidance and postponement of healthcare visits. The second is effects of changing lifestyle and living conditions including isolation, loss of job and income. The accumulated effect of these factors will likely further accelerate the development of NCDs and impair their management, especially in low- and middle-income countries. Insufficient vaccination coverage due to inequality in vaccine distribution and vaccine hesitancy left room for the incubation of immune-evasive variants that threatened to sustain or reinitiate the pandemic. We believe the concept of opportunistic NCDs and the potential catalytic effect that pandemics may have on the development of NCDs and their management, should be used as further arguments to secure equal vaccine distribution, promote global vaccine acceptance and to speed up and increase investments in primary health care in low- and middle-income countries to cope with the already existing NCD crisis and to prepare for future epidemics. © 2022 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.

Multiple opportunistic infection in a male with systemic lupus erythematosus and concomitant human immunodeficiency virus infection

Background/Purpose: Concomitant systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) infection cases are rare worldwide. It is established that SLE patients have an increased risk of opportunistic infection due to immune dysregulation, as well as in HIV. Method(s): A case of a 25-year- old Filipino man with systemic lupus erythematosus admitted due to a 1-week intermittent fever associated with headache, loss of appetite, and generalized body weakness was reviewed in a tertiary hospital in the Philippines. Result(s): An initial diagnosis was made from the clinical presentation of Raynaud's phenomenon, an elevated antinuclear antibody (1:320;nuclear, speckled), 2+ proteinuria, thrombocytopenia, and nail fold capillaroscopy findings consistent with mixed connective tissue disease. Patient was started on hydroxychloroquine and prednisone. He was admitted as a case of Streptococcus bacteremia with COVID-19 pneumonia after initial diagnosis, presenting as fever, and thrombocytopenia as low as 23.000/mul. Patient presented with a scaly erythematous annular lesion at his left wrist since December 2021 where a skin punch biopsy showed findings consistent with dermatophytosis. Direct immunofluorescence staining showed deposition of granular IgM (+3), C3 (+1), Fibrinogen (+3), and C1q (+1) in the basement membrane zone consistent with Lupus Erythematosus. Additional findings were oral thrush, dermatophytosis, and Pneumocystis pneumonia. Patient was started on antibiotics, remdesivir, and antifungal medications. Being severely immunocompromised, work up for HIV was initiated. Rapid HIV screening was positive, CD4 count revealed 7 (3.14%), and subsequent confirmatory western blot was positive. Additional treatment included hydroxychloroquine, methylprednisolone pulse therapy, and platelet concentrate transfusion. He was referred for CD4 monitoring, and ARV treatment enrollment, however, the patient expired a month after his discharge. Conclusion(s): This case is thereby reported to document a rare case of systemic lupus erythematosus (SLE) male patient with concomitant HIV, SARS-CoV- 2, and opportunistic infections secondary to AIDS. Diagnosis becomes challenging in patients with autoimmune diseases and multiple infectious diseases as clinical presentations tend to overlap and may show similar manifestations. In this setting, skin biopsy utilizing direct immunofluorescence can help establish an accurate diagnosis especially when clinical features and histopathology are overlapping.

Does The Suffering End After Cure From Covid?

Background Multisystem involvement of Covid-19 has been known since beginning of the pandemic. Multisystem after-effects or sequelae of covid-19 have been noted and the term 'long Covid' encompasses these signs and symptoms. This leads to prolonged morbidity which have not been adequately addressed by Covid guidelines.The primary aim of our study was to know the spectrum of different sequelae patients have endured after recovery from acute Covid-19 and study their impact on their quality of life. Methods It was a longitudinal observational study of a cohort of 146 patients who recovered from Covid-19 illness. Patients were enrolled within a week of their onset of Covid symptoms and were followed up monthly for a duration of 6 months with a detailed clinical and investigational pulmonary, cardiac, neurological and psychiatric assessment anda final follow-up after a year. Impact on quality of life was assessed using EQ-5D-3L questionnaire. Those lost to follow up were excluded from the analysis. Results 120/146 patients qualified for final analysis. Pulmonary sequelae (40%) were the majority among the patients, followed by psychiatric (25%), neurological (21.7%) and opportunistic infections (5.8%). 4/120 died within a year. 62/120 patients documented worsening in quality of life. Sequelae like pulmonary fibrosis, PTSD had the worst impact on the quality of life.95% severe, 54.5% moderate and 25% mild Covid patients reported deterioration in QoL score respectively. Conclusion Study indicates health related consequences from Covid-19 extend far beyond acute infection andmake significant impact on their quality of life, regardless of the severity of the disease. Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

Mucoromycosis: A Double Blow to the Country Amidst the Covid 19 Pandemic

INTRODUCTION: American pathologist R.D. Baker coined the term mucormycosis. Fungal infections are on a rise in the past 2 decades. It is defined as an insidious, broad aseptate ubiquitous fungal infection caused by members of mucorales and zygomcotic species.(1) It is colloquially termed as black fungus, when viewed through microscope it shows dark spherical spores and so the name. Earlier it was also known as zygomycetes, which means primitive fungi with broad, asepta including mucor, rhizopus, absidia and cunninghaemella. It is an opportunistic infection which is widely distributed in nature and predominantly in soil and thrives in dead and decaying substrates. It affects various organs involving the blood vessels causing thrombosis, infarction and necrosis of tissues and organs. As of 26th May 2021, India had noted approximately 12000 cases of mucor along with the Second wave of COVID 19, due to its fatality;it has become a notifiable disease under epidemic act.(2). Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Long-Term Post-COVID-19 Associated Oral Inflammatory Sequelae.

The oral cavity remains an underappreciated site for SARS-CoV-2 infection despite the myriad oral conditions observed in COVID-19 patients. Recently, replicating SARS-CoV-2 was found inside salivary epithelial cells resulting in inflammation and atrophy of salivary glands. Saliva possesses healing properties crucial for maintaining the health of the oral mucosa. Specifically, salivary antimicrobial peptides, most notable, histatin-5 exclusively produced in salivary glands, plays a vital role in innate immunity against colonizing microbial species. The demonstration of SARS-CoV-2 destruction of gland tissue where histatin-5 is produced strongly indicate that histatin-5 production is compromised due to COVID-19. Here we present a case of a patient presenting with unexplained chronic oral dysesthesia and dysgeusia post-recovery from COVID-19. To explore potential physiological mechanisms behind the symptoms, we comparatively analyzed saliva samples from the patient and matched healthy subject for histatin-5 and key cytokines. Findings demonstrated significantly reduced histatin-5 levels in patient's saliva and activation of the Th17 inflammatory pathway. As histatin-5 exhibits potent activity against the opportunistic oral pathogen Candida albicans, we evaluated saliva potency against C. albicans ex vivo. Compared to control, patient saliva exhibited significantly reduced anti-candidal efficacy. Although speculative, based on history and salivary analysis we hypothesize that salivary histatin-5 production may be compromised due to SARS-CoV-2 mediated salivary gland destruction. With the current lack of emphasis on implications of COVID-19 on oral health, this report may provide lacking mechanistic insights that may lead to reassessment of risks for oral opportunistic infections and mucosal inflammatory processes in acutely-ill and recovered COVID-19 patients.

Listerial Meningitis and Brain Abscess With Coexisting COVID-19 Infection in a Young, Immunocompetent Male: A Case Report.

Listeria monocytogenes (LM) is a gram-positive intracellular pathogen that can cause central nervous system infections such as meningitis, meningoencephalitis, rhombencephalitis, or cerebritis. It rarely causes a brain abscess. Listerial meningitis and brain abscess most commonly occur in immunocompromised individuals, neonates, pregnant females, alcoholics, and the elderly. We present a unique case of a young immunocompetent male who presented with listerial meningitis and brain abscess. Coexisting coronavirus disease 2019 (COVID-19) infection was also present. Since LM was not included in the differentials, the standard antibiotic regimen started for the meningitis therapy was ineffective. Remdesivir was administered to treat the coexisting COVID-19 infection. When the lumbar tap polymerase chain reaction pointed out that the causative agent was Listeria, we shifted to ampicillin and gentamicin therapy, to which the patient responded very effectively.LM is an atypical cause of meningitis and brain abscesses. A high index of suspicion is therefore required for early detection and effective treatment of listerial meningitis and brain abscess.