Modern aspects of COVID-19 in HIV-positive patients (literature review)

The article is devoted to the global problems of modern medicine - HIV infection and the COVID-19 pandemic. The review of the literature highlights current ideas about the pathogenesis and course of COVID-19 in patients with HIV infection, and also touches upon the problems of concomitant pathology and mental health of patients with HIV in the setting of the COVID-19 pandemic. It has been shown that HIV-positive patients are a risk group for the severe course of COVID-19, in particular, individuals with severe immunodeficiency (CD4+ T lymphocytes 200 cells/l) due to the development of synergetic lung damage by SARS-CoV-2 and secondary infectious agents such as cytomegalovirus and Pneumocystis carinii. It has been proven that one of the targets of the SARS-CoV-2 virus is CD4+ T cells, which in COVID-19 leads to a more rapid progression of immunodeficiency in patients with HIV infection and, thus, significantly increases the risk of secondary diseases and death. Particular attention should be paid to middle-aged and elderly people living with HIV, who, compared with HIV-negative patients, are more likely to have concomitant pathology - arterial hypertension, cardiomyopathy and diabetes mellitus, which are the risk factors for severe COVID-19. The results of studies on the effect of antiretroviral drugs on the course of COVID-19 showed that HIV-infected patients receiving tenofovir + emtricitabine have a lower risk of severe COVID-19 and associated hospitalization than patients receiving other HIV treatment regimens. Clinical and preclinical data support the potential use of tenofovir in the treatment of novel coronavirus infection.

Early switch from cladribine to alemtuzumab in highly-active relapsing-remitting multiple sclerosis: A case report

Background Management of patients with multiple sclerosis (MS) and evidence of disease activity during treatment with cladribine tablets represents a challenging point. Objectives To report a patient with highly active multiple sclerosis (HAMS) who has been early switched from cladribine to alemtuzumab owing to tumultuous clinical and radiological activity Methods A single retrospective case report. Results. Treatment with alemtuzumab has led to a complete suppression of disease activity without any evidence of infections or acquired autoimmune diseases. Conclusion Our report suggests that an early switch from cladribine to alemtuzumab, may be safe and efficacious in selected HAMS cases.Copyright © 2022 The Authors

Pneumocystis pneumonia in COVID-19 patients: A comprehensive review.

The admitted patients of intensive care units with coronavirus disease 2019 (COVID-19) meet the challenges of subsequent infections. Opportunistic fungal infections such as Pneumocystis pneumonia (PCP) are among the important factors in the context of COVID-19 patients affecting illness severity and mortality. We reviewed the literature on COVID-19 patients with PCP to identify features of this infection. Although studies confirmed at least the presence of one immunosuppressive condition in half of PCP patients, this disease can also occur in immunocompetent patients who developed the immunosuppressive condition during Covid-19 treatment. The major risk factors associated with COVID-19 patients with PCP can be considered low lymphocyte counts and corticosteroid therapy. Diagnostic and treatment options are complicated by the overlapping clinical and radiologic characteristics of PCP and COVID-19 pneumonia. Therefore, physicians should comprehensively evaluate high-risk patients for PCP prophylaxis.

Invasive Fungal Infections in Hospitalized Patients with COVID-19: A Non-Intensive Care Single-Centre Experience during the First Pandemic Waves.

Invasive fungal infections (IFIs) represent a severe complication of COVID-19, yet they are under-estimated. We conducted a retrospective analysis including all the COVID-19 patients admitted to the Infectious Diseases Unit of the Federico II University Hospital of Naples until the 1 July 2021. Among 409 patients, we reported seven cases of IFIs by Candida spp., seven of Pneumocystis jirovecii pneumonia, three of invasive pulmonary aspergillosis, and one of Trichosporon asahii. None of the cases presented underlying predisposing conditions, excluding one oncohematological patient treated with rituximab. Ten cases showed lymphopenia with high rates of CD4+ < 200/µL. All cases received high-dose steroid therapy (mean duration 33 days, mean cumulative dosage 1015 mg of prednisone equivalent), and seven cases had severe COVID-19 disease (OSCI ≥ 5) prior to IFI diagnosis. The cases showed a higher overall duration of hospitalization (63 vs 24 days) and higher mortality rate (23% vs. 7%) compared with the COVID-19 patients who did not developed IFIs. Cases showed a higher prevalence of high-dose steroid therapy and lymphopenia with CD4+ < 200/µL, primarily due to SARS-CoV-2 infection and not related to underlying comorbidities. IFIs strongly impact the overall length of hospitalization and mortality. Therefore, clinicians should maintain a high degree of suspicion of IFIs, especially in severe COVID-19 patients.

ARE ABO INCOMPATIBLE KIDNEY TRANSPLANT RECIPIENTS AT HIGHER RISK OF INFECTIONS?-A SINGLE CENTER EXPERIENCE

Introduction: Because of the limited donor pool, transplants are being done across the blood group and even HLA incompatibility barriers. But this comes at the cost of increased immunosuppression and the side effects. Effect of this intensified immunosuppression on the incidence of post transplant infections and the type of infection has not been studied extensively. Methods: We retrospectively analysed the incidence of infection in ABO incompatible transplants (ABOi) and compared it with propensity matched cohort of ABO compatible transplants(ABOc) over the same timeframe i.e. 2011 to April 2019. using hospital eHIS record system. Patients were matched with 1:2 ratio (ABOi: ABOc) for age (<60yr, >60yrs),sex, number of previous transplants, pretransplant infections, history of prior immunosuppression, diabetic status, NODAT, and induction agent used. Desensitization protocol for ABO incompatible transplant includes rituximab with double filtration plasmapheresis, plasmapharesis or immunoadsorption to target anti blood group titre of 8. Patient with high immunological risk (e.g.second transplant, HLA incompatible) receive ATG induction while others receive basiliximab induction. Valganciclovir prophylaxis was given only in patients with ATG induction. Results: [Formula presented] [Formula presented] During the study period 89 patients underwent ABOi transplants which were compared with 178 ABOc transplants. (Table1)Mean follow up duration was 50.45months (SD 26.8) in ABOi group and 49.47months (SD28.7) in ABOc group. 17% patients lost to follow up with their last follow up being more than 2 years before. Incidence of overall infections was similar in both the groups (59% (43/89) Vs 44.3% (79/178);p=0.6). (Table2) Incidence of urinary tract infections(UTI)was significantly more in ABOi group vs ABOc group.(23.5% (21/89) vs 11.79% (21/178);p=0.019). Cytomegalovirus infections (CMV) were significantly more in ABOi group 12.3% (11/89) as compared to ABOc group 5% (9/187) (p=0.04). All the patients with CMV infection were CMV IgG positive pretransplant except 2, one from ABOc group who was CMV IgG negative and another from ABOi group who’s pretransplant CMV serology was unavailable. There was no significant difference in incidence of fungal infection, pneumocystis infection, diarrheal infections (other than CMV),pneumonia (other than CMV, PCP, fungal), Herpes, BKV infection. Incidence of post-transplant tuberculosis (3.3% (3/89) Vs 2.8% (5/178);p=1.0) and SARS COV2 infections (12.3% (11/89) vs 9% (16/178);p=0.39 was similar in both the groups. Patient survival was similar in both the groups i.e.95.5% but death censored graft loss was significantly more in ABOi group 0.9% (8/89) as compared ABOc group 0.3% (5/178) p=0.03. Reason of graft loss in all the patients was immunological and not infection. Infection was cause for death in three ABOi patients and four ABOc patients. Conclusions: Overall incidence of infections in ABOi transplants was similar to Abo compatible transplant. Incidence of UTIs and CMV infections were significantly higher in ABOi group. No conflict of interest

Recurrent severe hypoglycaemia: Think about antibiotic choice

A 64 year-old Caucasian woman was admitted profoundly unwell with lethargy and generalised weakness. She had rheumatoid arthritis, with no history of diabetes or long-term steroid-use. Blood tests revealed pancytopaenia secondary to methotrexate (stopped on admission), acute kidney injury and severe metabolic acidosis. CT demonstrated lung base ground-glass changes. The patient had been double-vaccinated for covid-19 and all covid swabs were negative. Despite receiving Tazocin, respiratory symptoms worsened. High-dose co-trimoxazole was commenced to treat potential Pneumocystis infection from being immunocompromised. Subsequently she developed new confusion. Random blood glucose at midday was 1.2mmol/l. After treatment, hypoglycaemia recurred and persisted despite repeated intravenous dextrose boluses and glucagon injection. Blood glucose only improved with continuous 10% dextrose infusion. Causes were explored -a recent CT scan showed no pancreatic or intra-abdominal pathology;morning cortisol was normal. Literature review revealed very rarely Co-trimoxazole causes hypoglycaemia;hence this was stopped. Hypoglycaemia resolved within 48 hours;confusion improved. When serum glucose was 3.3mmol/l, c-peptide measured was inappropriately high (5175pmol/L). Co-trimoxazole is biochemically similar to sulfonylureas, mimicking their action on pancreatic beta-cells. Endogenous insulin hypersecretion raises c-peptide levels during hypoglycaemia. As Co-trimoxazole is renally excreted, when renal function is impaired it accumulates, with exacerbation of side effects such as protracted hypoglycaemia, especially at higher doses, as in our case. Hypoglycaemia will likely resolve after a 24-48h washout period, especially if renal function improves back to baseline. We recommend awareness of hypoglycaemia risk with co-trimoxazole treatment and blood glucose monitoring for inpatients taking high doses, especially in the setting of renal impairment.

Invasive Respiratory Fungal Infections in COVID-19 Critically Ill Patients.

Patients with coronavirus disease 19 (COVID-19) admitted to the intensive care unit (ICU) often develop respiratory fungal infections. The most frequent diseases are the COVID-19 associated pulmonary aspergillosis (CAPA), COVID-19 associated pulmonary mucormycosis (CAPM) and the Pneumocystis jirovecii pneumonia (PCP), the latter mostly found in patients with both COVID-19 and underlying HIV infection. Furthermore, co-infections due to less common mold pathogens have been also described. Respiratory fungal infections in critically ill patients are promoted by multiple risk factors, including epithelial damage caused by COVID-19 infection, mechanical ventilation and immunosuppression, mainly induced by corticosteroids and immunomodulators. In COVID-19 patients, a correct discrimination between fungal colonization and infection is challenging, further hampered by sampling difficulties and by the low reliability of diagnostic approaches, frequently needing an integration of clinical, radiological and microbiological features. Several antifungal drugs are currently available, but the development of new molecules with reduced toxicity, less drug-interactions and potentially active on difficult to treat strains, is highly warranted. Finally, the role of prophylaxis in certain COVID-19 populations is still controversial and must be further investigated.

Antimicrobial prophylaxis in adults and children undergoing hematopoietic cell transplantation: 2021 Polish recommendations

Infections are still one of the most common causes of death after hematopoietic cell transplantation (HCT). Antimicrobial prophylaxis plays a crucial role in decreasing non-relapse mortality after HCT. The objective of this guideline paper was the presentation of current recommendations of antimicrobial prophylaxis for children and adults after hematopoietic cell transplantation, prepared in cooperation with Polish scientific hematological societies. Recommendations were prepared by the working group and finally approved by all 23 Polish transplant centers for children and adults. Existing (European Conference on Infections in Leukemia (ECIL) and European Society of Blood and Marrow Transplantation (EBMT) guidelines, as well as the results of a survey performed among all Polish transplant centers, were the background material for the working group. Recommendations are presented in sections dedicated to antibacterial prophylaxis, antifungal prophylaxis, antiviral prophylaxis, as well as prophylaxis of toxoplasmosis and infections with Pneumocystis jiroveci. Recommendations on the principles of vaccination against COVID-19 are provided based on the state of knowledge in September 2021. A section on guidelines of environmental prophylaxis is also presented.

Prevalence of Pneumocystosis in Sub-Saharan Africa and Helminth Immune Modulation.

Sub-Saharan Africa is the region of the world with the highest prevalence of helminth infections. To protect themselves from the defensive mechanisms of their respective hosts, helminths modulate their immune responses. This modulation has relevant clinical and epidemiological consequences, including the inhibition of inflammatory processes that characterize infection by other microorganisms. Severe Pneumocystis pneumonia is characterized by an intense inflammatory reaction that can lead to death. Acquired immunodeficiency syndrome is the main predisposing factor to the development of pneumocystosis. Although the introduction of highly active antiretroviral therapy has led to a notable decline in the incidence of acquired immunodeficiency syndrome-associated complications, pneumocystosis continues to be an important global health problem. Despite the high incidence of human immunodeficiency virus infection in the sub-Saharan region, the prevalence of Pneumocystis pneumonia there has been lower than expected. Several factors, or combinations thereof, may contribute to this evolution. Here, we hypothesize the possible role of helminth immune modulation as an important issue at play. On the other hand, and looking ahead, we believe that the immune modulation achieved by helminths may be an important factor to consider during the design and evaluation processes of vaccines against Pneumocystis jirovecii to be used in Sub-Saharan Africa. The requirements of a balanced triggering of different types of immune responses for controlling the infection produced by this microorganism, as observed during experiments in animal models, support this final consideration.

COVID-19-Associated Pulmonary Aspergillosis, Fungemia, and Pneumocystosis in the Intensive Care Unit: a Retrospective Multicenter Observational Cohort during the First French Pandemic Wave.

The aim of this study was to evaluate diagnostic means, host factors, delay of occurrence, and outcome of patients with COVID-19 pneumonia and fungal coinfections in the intensive care unit (ICU). From 1 February to 31 May 2020, we anonymously recorded COVID-19-associated pulmonary aspergillosis (CAPA), fungemia (CA-fungemia), and pneumocystosis (CA-PCP) from 36 centers, including results on fungal biomarkers in respiratory specimens and serum. We collected data from 154 episodes of CAPA, 81 of CA-fungemia, 17 of CA-PCP, and 5 of other mold infections from 244 patients (male/female [M/F] ratio = 3.5; mean age, 64.7 ± 10.8 years). CA-PCP occurred first after ICU admission (median, 1 day; interquartile range [IQR], 0 to 3 days), followed by CAPA (9 days; IQR, 5 to 13 days), and then CA-fungemia (16 days; IQR, 12 to 23 days) (P < 10-4). For CAPA, the presence of several mycological criteria was associated with death (P < 10-4). Serum galactomannan was rarely positive (<20%). The mortality rates were 76.7% (23/30) in patients with host factors for invasive fungal disease, 45.2% (14/31) in those with a preexisting pulmonary condition, and 36.6% (34/93) in the remaining patients (P = 0.001). Antimold treatment did not alter prognosis (P = 0.370). Candida albicans was responsible for 59.3% of CA-fungemias, with a global mortality of 45.7%. For CA-PCP, 58.8% of the episodes occurred in patients with known host factors of PCP, and the mortality rate was 29.5%. CAPA may be in part hospital acquired and could benefit from antifungal prescription at the first positive biomarker result. CA-fungemia appeared linked to ICU stay without COVID-19 specificity, while CA-PCP may not really be a concern in the ICU. Improved diagnostic strategy for fungal markers in ICU patients with COVID-19 should support these hypotheses. IMPORTANCE To diagnose fungal coinfections in patients with COVID-19 in the intensive care unit, it is necessary to implement the correct treatment and to prevent them if possible. For COVID-19-associated pulmonary aspergillosis (CAPA), respiratory specimens remain the best approach since serum biomarkers are rarely positive. Timing of occurrence suggests that CAPA could be hospital acquired. The associated mortality varies from 36.6% to 76.7% when no host factors or host factors of invasive fungal diseases are present, respectively. Fungemias occurred after 2 weeks in ICUs and are associated with a mortality rate of 45.7%. Candida albicans is the first yeast species recovered, with no specificity linked to COVID-19. Pneumocystosis was mainly found in patients with known immunodepression. The diagnosis occurred at the entry in ICUs and not afterwards, suggesting that if Pneumocystis jirovecii plays a role, it is upstream of the hospitalization in the ICU.

Detection of Pneumocystis jirovecii in Patients with Severe COVID-19: Diagnostic and Therapeutic Challenges.

Cases of Pneumocystis jirovecii pneumonia (PCP) in patients suffering from COVID-19 were described in patients with various comorbidities and outcomes. The diagnosis of PCP in these patients is difficult due to clinical and radiological similarities. We carried out this study in order to better describe potentially at-risk patients and their outcomes. We retrospectively analyzed all patients with a P. jirovecii PCR performed in bronchoalveolar lavage fluid, tracheal aspirate, or sputum within a month after the COVID-19 diagnosis. Fifty-seven patients with COVID-19 infection were tested for P. jirovecii. Among 57 patients with COVID-19, four patients had a concomitant positive P. jirovecii PCR. These four patients were elderly with a mean age of 78. Two patients were immunocompromised, and the two others presented only diabetes mellitus. Three patients presented an ARDS requiring transfer to the ICU and mechanical ventilation. All patients presented lymphocytopenia. Three patients had probable PCP, and one had proven PCP. All patients died within two months after hospital admission. These co-infections are rare but severe, therefore, PCP should be considered in case of worsening of the condition of patients with severe COVID-19.

Epidemiology of Systemic Mycoses in the COVID-19 Pandemic.

The physiopathologic characteristics of COVID-19 (high levels of inflammatory cytokines and T-cell reduction) promote fungal colonization and infection, which can go unnoticed because the symptoms in both diseases are very similar. The objective of this work was to study the current epidemiology of systemic mycosis in COVID-19 times. A literature search on the subject (January 2020-February 2021) was performed in PubMed, Embase, Cochrane Library, and LILACS without language restrictions. Demographic data, etiological agent, risk factors, diagnostic methods, antifungal treatment, and fatality rate were considered. Eighty nine publications were found on co-infection by COVID-19 and pneumocystosis, candidiasis, aspergillosis, mucormycosis, coccidioidomycosis, or histoplasmosis. In general, the co-infections occurred in males over the age of 40 with immunosuppression caused by various conditions. Several species were identified in candidiasis and aspergillosis co-infections. For diagnosis, diverse methods were used, from microbiological to molecular. Most patients received antifungals; however, the fatality rates were 11-100%. The latter may result because the clinical picture is usually attributed exclusively to SARS-CoV-2, preventing a clinical suspicion for mycosis. Diagnostic tests also have limitations beginning with sampling. Therefore, in the remainder of the pandemic, these diagnostic limitations must be overcome to achieve a better patient prognosis.

Fungal co-infection in COVID-19 patients: Should we be concerned?

Critically ill COVID-19 patients have higher pro-inflammatory (IL-1, IL-2, IL-6, tumor necrosis alpha) and anti-inflammatory (IL-4, IL-10) cytokine levels, less CD4 interferon-gamma expression, and fewer CD4 and CD8 cells. This severe clinical situation increases the risk of serious fungal infections, such as invasive pulmonary aspergillosis, invasive candidiasis or Pneumocystis jirovecii pneumonia. However, few studies have investigated fungal coinfections in this population. We describe an update on published reports on fungal coinfections and our personal experience in three Spanish hospitals. We can conclude that despite the serious disease caused by SARS-CoV-2 in many patients, the scarcity of invasive mycoses is probably due to the few bronchoscopies and necropsies performed in these patients because of the high risk in aerosol generation. However, the presence of fungal markers in clinically relevant specimens, with the exception of bronchopulmonary colonization by Candida, should make it advisable to early implement antifungal therapy.