Steroid-induced secondary immune deficiency.

Despite their widespread clinical use, oral corticosteroids (OCSs) are well known to be associated with a myriad of adverse effects, including immunosuppression. By inhibiting transcription factors and affecting leukocyte function, prolonged OCS use leads to significant CD4 lymphopenia and often a decrease in serum immunoglobulin (Ig)G. Conversely, OCS use has minimal impact on circulating B cell, serum IgM, or serum IgA levels. Although there is a paucity of literature, individuals treated with prolonged OCS seem to typically maintain humoral response to various vaccinations despite hypogammaglobinemia, but this area warrants additional research, especially in the setting of the coronavirus disease 2019 pandemic. Individuals treated with prolonged OCS use are most at risk for opportunistic infections, especially those with underlying malignancy and history of bone marrow transplant. Risk mitigation strategies to decrease infectious complication with OCS use include limiting the dose and duration of therapy, appropriately completing a full vaccination series, consideration for passive immunization, and prophylaxis against opportunistic infections.

A 64-Year-Old Man Hospitalized for COVID-19 Pneumonia and Treated with Tocilizumab Who Developed Chronic Cavitary Pulmonary Aspergillosis.

BACKGROUND The management of (Coronavirus disease 2019) COVID-19 pneumonia is ever-evolving. Tocilizumab, a monoclonal antibody against interleukin-6 (IL-6) receptor, have known mortality benefit in severe COVID-19 pneumonia, but data are limited regarding safety. Attributable to the immunomodulatory nature of this medication, patients may be at risk for opportunistic infections, including chronic cavitary pulmonary aspergillosis (CPPA), a slowly progressive disease characterized pulmonary infiltrates and often a newly-formed cavity. However, current guidelines do not emphasize post-treatment surveillance of patients for opportunistic infections, including CPPA. CASE REPORT We present a particular case of a 64-year-old man treated for COVID-19 pneumonia with Tocilizumab and dexamethasone who developed cavitary pulmonary aspergillosis. He presented to the emergency department with hemoptysis, associated with worsening productive cough, shortness of breath, and weight loss. Computed tomography (CT) of the chest showed areas of focal consolidation and a cavitary lung lesion within the left upper lobe. Sputum culture was positive for Aspergillus niger. The patient received a long course of oral triazole therapy for CPPA, with clinical improvement. CT scan of the chest at 9 months showed that the Itraconazole therapy was effective in resolving the extensive airspace disease and decreasing the size of the upper-lobe cavity and fungal ball. CONCLUSIONS This article illustrates the possibility of a serious infection such as CCPA as an adverse effect of Tocilizumab treatment, especially with concurrent immunosuppressive therapy. Furthermore, this case highlights the importance of regular monitoring of patients who have received Tocilizumab therapy to ensure that early signs of opportunistic infections such as CPPA are detected and treated promptly to prevent permanent lung damage.

COVID-19-Associated Mucormycosis: An Opportunistic Fungal Infection. A Case Series and Review.

BACKGROUND: A surge in COVID-19-associated mucormycosis cases has been observed during the second wave of COVID-19 in summer of 2021. Most cases were reported from India. The Delta variant (B.1.617.2) was the most common variant circulating at that time. Mucormycosis is an opportunistic angioinvasive fungal infection with high morbidity and mortality. METHODS: We present 10 cases of COVID-19-associated rhino-orbital and rhino-orbital-cerebral mucormycosis managed in a secondary hospital in Oman. RESULTS: The median time for developing mucormycosis was two weeks after COVID-19 diagnosis. All patients were newly diagnosed or already known to have poorly controlled diabetes mellitus. Five patients received corticosteroid therapy for COVID-19. Three patients had severe COVID-19 and died of severe acute respiratory distress syndrome and septic shock. Another three patients died of advanced mucormycosis and cerebral involvement. Despite aggressive medical and surgical intervention, the mortality rate was 60% (6/10). CONCLUSION: Mucormycosis is an aggressive opportunistic infection with high morbidity and mortality that requires prompt recognition and urgent intervention. Uncontrolled blood sugar, the use of corticosteroids, and immune dysfunction due to COVID-19 are all important risk factors for development of mucormycosis. Worse outcomes are associated with poor glycemic control despite aggressive medical and surgical interventions.

Phototherapies for COVID-19-associated opportunistic oral infections.

Opportunistic infections are widely described in patients with novel coronavirus disease 2019 (COVID-19); however, very few studies have addressed those affecting the oral cavity. Given the lack of information on the clinical presentations and the available treatment options, the present study aimed to show a case in which a combination of antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) was used for the management of two concomitant COVID-19-associated opportunistic oral infections (oral pseudomembranous candidiasis and recurrent herpes labialis). Within 7 days and without any systemic drug administration, all the lesions resolved completely, and the patient no longer reported oral pain or discomfort. According to the current case report and taking into consideration the significant gaps in the knowledge and understanding of COVID-19, this combination of phototherapy modalities seems to be a promising tool for managing viral and fungal opportunistic oral infections.

COVID-19: Overview of rheumatology fellows.

SARS-COV-2 infection has spread worldwide since it originated in December 2019, in Wuhan, China. The pandemic has largely demonstrated the resilience of the world's health systems and is the greatest health emergency since World War II. There is no single therapeutic approach to the treatment of COVID-19 and the associated immune disorder. The lack of randomised clinical trials (RCTs) has led different countries to tackle the disease based on case series, or from results of observational studies with off-label drugs. We as rheumatologists in general, and specifically rheumatology fellows, have been on the front line of the pandemic, modifying our activities and altering our training itinerary. We have attended patients, we have learned about the management of the disease and from our previous experience with drugs for arthritis and giant cell arteritis, we have used these drugs to treat COVID-19.

Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience.

Background: The aim of this study was to assess the drivers of multidrug-resistant (MDR) bacterial infection development in coronavirus disease 2019 (COVID-19) and its impact on patient outcome. Methods: Retrospective analysis on data from 32 consecutive patients with COVID-19, admitted to our intensive care unit (ICU) from March to May 2020. Outcomes considered were MDR infection and ICU mortality. Results: Fifty percent of patients developed an MDR infection during ICU stay after a median time of 8 [4-11] days. Most common MDR pathogens were carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, causing bloodstream infections and pneumonia. MDR infections were linked to a higher length of ICU stay (p = 0.002), steroid therapy (p = 0.011), and associated with a lower ICU mortality (odds ratio: 0.439, 95% confidence interval: 0.251-0.763; p < 0.001). Low-dose aspirin intake was associated with both MDR infection (p = 0.043) and survival (p = 0.015). Among MDR patients, mortality was related with piperacillin-tazobactam use (p = 0.035) and an earlier onset of MDR infection (p = 0.042). Conclusions: MDR infections were a common complication in critically ill COVID-19 patients at our center. MDR risk was higher among those dwelling longer in the ICU and receiving steroids. However, MDR infections were not associated with a worse outcome.

COVID-19-associated opportunistic infections: a snapshot on the current reports.

Treatment of the novel Coronavirus Disease 2019 (COVID-19) remains a complicated challenge, especially among patients with severe disease. In recent studies, immunosuppressive therapy has shown promising results for control of the cytokine storm syndrome (CSS) in severe cases of COVID-19. However, it is well documented that immunosuppressive agents (e.g., corticosteroids and cytokine blockers) increase the risk of opportunistic infections. On the other hand, several opportunistic infections were reported in COVID-19 patients, including Aspergillus spp., Candida spp., Cryptococcus neoformans, Pneumocystis jiroveci (carinii), mucormycosis, Cytomegalovirus (CMV), Herpes simplex virus (HSV), Strongyloides stercoralis, Mycobacterium tuberculosis, and Toxoplasma gondii. This review is a snapshot about the main opportunistic infections that reported among COVID-19 patients. As such, we summarized information about the main immunosuppressive agents that were used in recent clinical trials for COVID-19 patients and the risk of opportunistic infections following these treatments. We also discussed about the main challenges regarding diagnosis and treatment of COVID-19-associated opportunistic infections (CAOIs).

Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review.

Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment.

Conference on retroviruses and opportunistic infections (virtual): March 6-10, 2021.

The Conference on Retroviruses and Opportunistic Infections (CROI) for 2021 was, as with so many other conferences in the past 12 months, held online. CROI provided a forum for basic scientists and clinical researchers to bring together and discuss their work on human retroviruses and associated diseases, with HIV and SARS-CoV-2 being the two viruses most covered this year. Below are some examples of the work presented at the conference, highlighting both the innovative approaches to understanding and treating viral infections but also the breadth of topics covered.

Emerging Fungal Infections.

Various uncommon fungal pathogens have been increasingly identified as causes of disseminated and invasive fungal disease (IFD) worldwide. Growing recognition and clinical knowledge of these emerging fungal pathogens has occurred through improved molecular diagnostics, nucleic sequence databases, and taxonomic reclassification of medically significant fungi. However, emerging fungal diseases carry significant morbidity and mortality and, due to a paucity of published literature, the collective clinical experience with these fungi is often limited. In this review, we focus on unusual emerging fungal pathogens not extensively covered elsewhere in this issue of Infectious Diseases Clinics of North America.

Mucormycosis after Coronavirus disease 2019 infection in a heart transplant recipient - Case report and review of literature.

Mucormycosis is an invasive fungal infection (IFI) due to several species of saprophytic fungi, occurring in patients with underlying co-morbidities (including organ transplantation). During the ongoing Coronavirus disease 2019 (COVID-19) pandemic, there have been increasing reports of bacterial and fungal co-infections occurring in COVID-19 patients, including COVID-19 associated pulmonary aspergillosis (CAPA). We describe a case of mucormycosis occurring after COVID-19, in an individual who received a recent heart transplant for severe heart failure. Two months after heart transplant, our patient developed upper respiratory and systemic symptoms and was diagnosed with COVID-19. He was managed with convalescent plasma therapy and supportive care. Approximately three months after COVID-19 diagnosis, he developed cutaneous mucormycosis at an old intravascular device site. He underwent extensive surgical interventions, combined with broad-spectrum antifungal therapy. Despite the aggressive therapeutic measures, he died after a prolonged hospital stay. In this case report, we also review the prior well-reported cases of mucormycosis occurring in COVID-19 patients and discuss potential mechanisms by which COVID-19 may predispose to IFIs. Similar to CAPA, mucormycosis with COVID-19 may need to be evaluated as an emerging disease association. Clinicians should be vigilant to evaluate for invasive fungal infections such as mucormycosis in patients with COVID-19 infection.

Post COVID-19 opportunistic candida retinitis: A case report.

A 42-year-old male patient presented with profound impairment of vision in both eyes, just as he was recovering from COVID-19. A known diabetic and hypertensive, he suffered from COVID-19 pneumonia further complicated by ARDS, septicaemia and acute kidney injury. His vision on presentation was finger counting close to face bilaterally with multiple, yellowish lesions at the posterior pole. Based on the clinical findings and previous blood culture report, it was diagnosed as candida retinitis and treated with oral and intravitreal anti-fungals. The lesions were regressing at follow-up. This is a post COVID-19 presumed candida retinitis case report.

Recommendations for antibacterial therapy in adults with COVID-19 - an evidence based guideline.

SCOPE: The Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19). METHODS: We performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: We assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic.

Coronavirus Disease 2019 Pneumonia in Immunosuppressed Renal Transplant Recipients: A Summary of 10 Confirmed Cases in Wuhan, China.

BACKGROUND: Previous studies on coronavirus disease 2019 (COVID-19) have focused on populations with normal immunity, but lack data on immunocompromised populations. OBJECTIVE: To evaluate the clinical features and outcomes of COVID-19 pneumonia in kidney transplant recipients. DESIGN, SETTING, AND PARTICIPANTS: A total of 10 renal transplant recipients with laboratory-confirmed COVID-19 pneumonia were enrolled in this retrospective study. In addition, 10 of their family members diagnosed with COVID-19 pneumonia were included in the control group. INTERVENTION: Immunosuppressant reduction and low-dose methylprednisolone therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The clinical outcomes (the severity of pneumonia, recovery rate, time of virus shedding, and length of illness) were compared with the control group by statistical analysis. RESULTS AND LIMITATIONS: The clinical symptomatic, laboratory, and radiological characteristics of COVID-19 pneumonia in the renal transplant recipients were similar to those of severe COVID-19 pneumonia in the general population. The severity of COVID-19 pneumonia was greater in the transplant recipients than in the control group (five severe/three critical cases vs one severe case). Five patients developed transient renal allograft damage. After a longer time of virus shedding (28.4 ± 9.3 vs 12.2 ± 4.6 d in the control group) and a longer course of illness (35.3 ± 8.3 vs 18.8 ± 10.5 d in the control group), nine of the 10 transplant patients recovered successfully after treatment. One patient developed acute renal graft failure and died of progressive respiratory failure. CONCLUSIONS: Kidney transplant recipients had more severe COVID-19 pneumonia than the general population, but most of them recovered after a prolonged clinical course and virus shedding. Findings from this small group of cases may have important implications for the treatment of COVID-19 pneumonia in immunosuppressed populations. PATIENT SUMMARY: Immunosuppressed transplant recipients with coronavirus disease 2019 infection had more severe pneumonia, but most of them still achieved a good prognosis after appropriate treatment.