The impact of COVID-19 on TB in Iran: an illustrative study

The COVID-19 pandemic has caused significant disruptions in TB services across the globe. Like many other countries, TB case notifications decreased during the pandemic in Iran. In this paper, we describe two cases of concomitant COVID-19 and TB infection whose diagnosis of pulmonary TB was delayed amid the pandemic. We depict how atypical imaging findings may guide physicians to pulmonary TB diagnosis and discuss strategies to maximize TB case detection.

Factors Associated with Medication Adherence in Elderly Individuals with Tuberculosis: A Qualitative Study.

Methods: This qualitative study was conducted in two phases, using an integrative literature review and individual interviews. Studies were gathered without time restriction from MEDLINE databases, Institute for Scientific Information (ISI), Google Scholar, Scopus, and EMBASE, as well as national databases, including Scientific Information Database and Magiran. The findings of 38 studies that met the inclusion criteria were analyzed through the conventional content analysis method based on the ecological approach. After reviewing and forming the data matrix, purposive sampling was performed among healthcare professionals, elderly tuberculosis patients aged 60 and over, and family caregivers of elderly patients to conduct individual interviews. Data obtained from 20 interviews were analyzed using the directed content analysis method. After coding, the data from individual interviews were entered based on similarity and difference in the categories of data matrix obtained from the literature review. Results: In general, the aforementioned codes were placed in four main categories, including individual factors (i.e., biological factors, affective-emotional factors, behavioral factors, cognitive factors, tuberculosis-related factors, and economic factors), interpersonal factors (i.e., patient's relationship with treatment team and family-related factors), factors related to healthcare service provider centers (i.e., medical centers' facilities and capacity building in healthcare service provider), and extraorganizational factors (i.e., social factors and health policymaking). Conclusion: The results of this study showed that medication adherence in elderly patients with tuberculosis was a complex and multidimensional phenomenon. Therefore, society, policymakers, and healthcare providers should scrutinize the factors affecting medication adherence in this group of patients to plan and implement more effective interventions.

The impact of COVID-19 on TB in Iran: An illustrative study.

The COVID-19 pandemic has caused significant disruptions in TB services across the globe. Like many other countries, TB case notifications decreased during the pandemic in Iran. In this paper, we describe two cases of concomitant COVID-19 and TB infection whose diagnosis of pulmonary TB was delayed amid the pandemic. We depict how atypical imaging findings may guide physicians to pulmonary TB diagnosis and discuss strategies to maximize TB case detection.

Changes in PD-1- and CTLA-4-bearing blood lymphocytes in ICU COVID-19 patients treated with Favipiravir/Kaletra or Dexamethasone/Remdesivir: a pilot study.

COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.e., severe) or infection ward (i.e., moderate) and after 7 days of antiviral therapy. COVID-19 patients were treated with either favipiravir or Kaletra (FK group, 11 severe and 11 moderate) or dexamethasone plus remdesivir (DR group, 7 severe and 10 moderate) for 7 days in a pilot study. Eight healthy control subjects were also enrolled. The frequency of PD-1+ and CTLA-4+ lymphocytes in whole blood was evaluated by flow cytometry. Patients on DR therapy had shorter hospital stays than those on FK therapy. The frequency of PD-1+ lymphocytes in the FK group at baseline differed between COVID-19 patients and healthy controls, while the frequency of both PD-1+ and CTLA-4+ cells increased significantly 7 days of FK therapy. The response was similar in both moderate and severe patients. In contrast, the frequency of PD-1+ and CTLA-4+ lymphocytes varied significantly between patients and healthy controls before DR treatment. DR therapy enhanced PD-1+ but not the CTLA-4+ frequency of these cells after 7 days. We show that the frequency of PD-1 and CTAL-4-bearing lymphocytes during hospitalization was increased in Iranian ICU COVID-19 patients who received FK treatment, but that the frequency of CTLA-4+ cells was higher at baseline and did not increase in patients who received DR. The effectiveness of DR treatment may reflect differences in T-cell activation or exhaustion status, particularly in CTLA-4-expressing cells.

Diminution of STING Expression in the Blood of Patients with Severe or Critical COVID-19 Pneumonia.

INTRODUCTION: Cytokine storm and critical COVID-19 pneumonia are caused in at least 10% of patients by inborn errors of or auto-Abs to type I IFNs. The pathogenesis of life-threatening COVID-19 pneumonia in other patients remains unknown. METHODS: This study was conducted at Masih Daneshvari Hospital, Tehran, Iran. In the period of study, 75 confirmed cases of COVID-19 with presentations ranging from mild upper respiratory tract infection to lower respiratory tract infection, including moderate, severe, and critical disease, were recruited. Expression of STING mRNA was measured in peripheral blood mononuclear cells (PBMCs) and compared between patients with different severity and outcome. RESULTS: There was a significant negative correlation between age and STING expression level (p value = 0.010). Patients with "severe to critical" illness had a 20-fold lower STING expression level compared to the "mild to moderate" group (p value = 0.001). Also, the results showed lower expressions of STING in the patients admitted to the ICU (p value = 0.015). Patients who finally died had lower expression of STING at the time of sampling (p value = 0.041). CONCLUSION: STING mRNA expression in PBMCs was significantly lower in older COVID-19 cases, the patients with more severe illness, who needed intensive care, and who eventually died.

Evaluating the efficacy and safety of SpikoGen®, an Advax-CpG55.2-adjuvanted severe acute respiratory syndrome coronavirus 2 spike protein vaccine: a phase 3 randomized placebo-controlled trial.

OBJECTIVES: We sought to investigate the efficacy and safety of SpikoGen®, a subunit coronavirus disease 2019 (COVID-19) vaccine composed of a recombinant severe acute respiratory syndrome coronavirus 2 spike protein with Advax-CpG55.2™ adjuvant. METHODS: This randomized, placebo-controlled, double-blind, phase 3 trial was conducted on 16 876 participants randomized (3:1) to receive two intramuscular doses of SpikoGen® or a saline placebo 21 days apart. The primary outcome was to assess the efficacy of SpikoGen® in preventing symptomatic COVID-19. Secondary outcomes included safety assessments and evaluation of SpikoGen® vaccine's efficacy in preventing severe COVID-19. The study aimed for 147 COVID-19 symptomatic cases. RESULTS: Overall, 12 657 and 4219 participants were randomized to the SpikoGen® and placebo group and followed for a median of 55 days (interquartile range, 48-60 days) and 51 days (interquartile range, 46-58 days) after 14 days of the second dose, respectively. In the final per-protocol analysis, the number of COVID-19 cases was 247 of 9998 (2.4%) in the SpikoGen® group and 119 of 3069 (3.8%) in the placebo group. This equated to a vaccine efficacy of 43.99% (95% CI, 30.3-55.0%). The efficacy was calculated to be 44.22% (95% CI, 31.13-54.82%) among all participants who received both doses. From 2 weeks after the second dose, 5 of 9998 (0.05%) participants in the SpikoGen® group and 6 of 3069 (0.19%) participants in the placebo group developed severe COVID-19, equating to a vaccine efficacy against severe disease of 77.51% (95% CI, 26.3-93.1%). The SpikoGen® vaccine was well tolerated. DISCUSSION: A 2-dose regimen of SpikoGen® reduced the rate of COVID-19 and severe disease in the wave of the Delta variant.

The role of angiotensin I converting enzyme insertion/deletion polymorphism in the severity and outcomes of COVID-19 patients.

The pandemic of coronavirus disease in 2019 has led to a global crisis. COVID-19 shows distinct clinical manifestations of the severity of symptoms. Numerous patients with no associated risk factors demonstrate acute respiratory distress syndrome (ARDS). The role of genetic factors in determining the severity and outcome of the disease remains unresolved. The purpose of this study was to see if a correlation exists between Angiotensin I Converting Enzyme (ACE) insertion/deletion (I/D) polymorphism and the severity of COVID-19 patients' symptoms. 120 COVID-19 patients admitted to Masih Daneshvari Hospital in Tehran with their consent to participate entered the study. Based on the World Health Organization classification, patients were divided into moderate and severe groups, which were primarily affected by O2 saturation levels. The effects of the patients' ACE insertion/deletion polymorphism, background disease, Angiotensin receptor blocker (ARB) drug consumption, and demographic parameters on the severity risk were calculated statistically. The ACE D allele was associated with an increased risk of disease severity (OR = 6.766, p = 0.012), but had no effect on mortality.

Effect of COVID-19 pandemic on incidence of mycobacterial diseases among suspected tuberculosis pulmonary patients in Tehran, Iran.

Background: Recent pandemic of coronavirus SARS-CoV-2 (COVID-19) caused limitations in the country's strategies to fight against mycobacterial infections. The aim of this study was to compare the suspected tuberculosis (TB) pulmonary patients before and during the COVID-19 pandemic (January 2018-December 2021) who were referred to the National Reference TB Laboratory (NRL TB), Tehran, Iran. The mycobacterial isolated strains were identified and compared with previous data. Methods: A total of 16,899 clinical samples collected from 7041 suspected pulmonary TB patients were received from 2018 to 2021. Primary isolation of Mycobacterium isolates was done on Löwenstein-Jensen medium. Then, the DNA was extracted from acid-fast bacillus culture-positive samples and identification was performed by IS6110, Hsp65, and 16S-23S rRNA genes using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and nested PCR methods. Results: A total of 11679 specimens (69.1%) from 4866 suspected TB patients were collected in 2018-2019 and 5220 specimens (30.8%; from 2175 patients) in 2020-2021. Out of 11679 specimens, 2046 samples that belong to 852 patients were infected with Mycobacterium tuberculosis, and the remaining were non-TB Mycobacterium (NTM) species (n = 244) isolated from 102 patients. The cultures for 12894 specimens were either negative (76.3%) or contaminated (845/16899; 5%). A comparison of the total number of patients who were referred for diagnosis and treatment (954/666 patients, P > 0.05) showed a 30.1% reduction during the COVID-19 pandemic. Although, with these low number of patients, the significant increases of NTM species (P < 0.05) among suspected TB pulmonary patients were observed. Besides, new species of NTM, for example, Mycobacterium peregrinum and Mycobacterium montefiorense, were detected. For the past 20 years, these two species were not reported from pulmonary patients in Iran. Conclusions: During the pandemic of COVID-19, the TB diagnosis network became irregular, as a consequence, many patients could not reach the treatment center, and this could increase the circulation of mycobacterial diseases (TB and NTM). The study shows the emergence of new opportunistic NTM species also.

Prevalence of Anti-SARS-CoV-2 Specific Antibodies in Health-Care Workers Compared to General Population during an Early Phase of the Pandemic, Tehran-Iran.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly transmits in general population, mainly between health-care workers (HCWs) who are in close contact with patients. OBJECTIVE: To study the seropositivity of HCWs as a high-risk group compared to general population. METHODS: 72 samples were obtained from HCWs working in Masih Daneshvari hospital as one of the main COVID-19 admission centers in Tehran, during April 4 to 6, 2020. Also we collected 2021 blood samples from general population. The SARS-CoV-2 specific IgM, and IgG antibodies in the collected serum specimens were measured by commercial ELISA kits. RESULTS: Based on the clinical manifestations, 25.0%, 47.2%, and 27.8% of HCWs were categorized as symptomatic with typical symptoms, symptomatic with atypical symptoms, and asymptomatic, respectively. Symptomatic individuals with typical and atypical symptoms were 63.2% and 36.8% positive in RT-PCR test, respectively. Anti-SARS-CoV-2 IgM and IgG antibodies were detected in 15.3% and 27.8% of HCWs samples, respectively. Antibody testing in the general population indicated that SARS-CoV-2 specific IgM and IgG were found in (162/2021) 8%, and (290/2021) 14.4%, respectively. The frequency of positive cases of IgM and IgG were significantly increased in HCWs compared to general population (p= 0.028 for IgM and p= 0.002 for IgG). CONCLUSION: The frequency of SARS-CoV-2 specific antibodies in HCWs was higher than general population indicating a higher viral transmission via close exposure with COVID-19 patients.

Antibiotic use during the first 6 months of COVID-19 pandemic in Iran: A large-scale multi-centre study.

WHAT IS KNOWN AND OBJECTIVE: Although antibiotics are ineffective against viral infections, epidemiological studies have revealed that the COVID-19 pandemic resulted in the overuse of antibiotics and disruption of antimicrobial stewardship programmes. We investigated the pattern of antibiotic use during the first 6 months of the COVID-19 pandemic in Iran. METHODS: A multi-centre retrospective study was designed to investigate the use of 16 broad-spectrum antibiotics in 12 medical centres. The rate of antibiotic use was calculated and reported based on the Defined Daily Dose (DDD) per 100 hospital bed-days. The bacterial co-infection rate was also reported. RESULTS AND DISCUSSION: Totally, 43,791 hospitalized COVID-19 patients were recruited in this study. It was found that 121.6 DDD of antibiotics were used per 100 hospital bed-days, which estimated that each patient received approximately 1.21 DDDs of antibiotics every day. However, the bacterial co-infections were detected only in 14.4% of the cases. A direct correlation was observed between the rate of antibiotic use and mortality (r[142] = 0.237, p = 0.004). The rate of antibiotic consumption was not significantly different between the ICU and non-ICU settings (p = 0.15). WHAT IS NEW AND CONCLUSION: In this study, widespread antibiotic use was detected in the absence of the confirmed bacterial coinfection in COVID-19 patients. This over-consumption of broad-spectrum antibiotics may be associated with increased mortality in hospitalized COVID-19 patients, which can be an alarming finding.

Co-infection of Klebsiella pneumonia, Cytomegalovirus, Aspergillus and Zygomycete in a patient with SARS-CoV-2.

Co-infection between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens has become a serious threat. There are the reports of fungal, bacterial, and viral co-infections with SARS-CoV-2. We report the unusual case of concomitant aspergillosis, mucormycosis, cytomegalovirus pneumonia, and also klebsiella pneumoniae empyema as the complication of SARS-CoV-2.

Immunogenicity and safety of SpikoGen®, an adjuvanted recombinant SARS-CoV-2 spike protein vaccine as a homologous and heterologous booster vaccination: A randomized placebo-controlled trial.

SpikoGen® is a subunit recombinant spike protein vaccine combined with Advax-CpG55.2™ adjuvant. This COVID-19 vaccine was shown to be safe, immunogenic and efficacious in previous clinical trials. This study aimed to assess the safety and immunogenicity of SpikoGen® vaccine as a homologous and heterologous booster vaccination. This double-blind and randomized placebo-controlled (5:1) trial was performed on 300 already vaccinated participants. SpikoGen® or saline placebo was administered as a booster dose to participants who had received a full two-dose COVID-19 vaccination course. Immunogenicity assessments were done 14 days after the booster dose with the primary immunogenicity outcome seroconversion rate of neutralizing antibodies. Safety outcomes included the incidence of solicited adverse events up to 7 days after the booster dose. SpikoGen® vaccine induced a robust humoral response both as a homologous and heterologous booster, when compared to the placebo. At Day 14, seroconversion of neutralizing antibodies was 76% (95% confidence interval [CI]: 69%-82%) in the SpikoGen® group versus 3% (95% CI: 0%-13%) in the placebo group. The most common local and systemic reported adverse events were injection site pain and fatigue. No serious adverse events were reported. The SpikoGen®-booster induced cross-neutralization of other SARS-CoV-2 variants. Irrespective of the primary vaccine course received, SpikoGen® vaccine showed promising effects as both a homologous and heterologous booster dose. This vaccine also had a good safety profile with no vaccine-associated serious adverse events. On the basis of these results, SpikoGen® vaccine has been approved as a booster dose.

National Research Institute of Tuberculosis and Lung Disease (NRITLD) Protocol for the Treatment of Patients with COVID-19.

More than a year after the onset of the coronavirus disease pandemic in 2019, the disease remains a major global health issue. During this time, health organizations worldwide have tried to provide integrated treatment guidelines to control coronavirus disease 2019 (COVID-19) at different levels. However, due to the novel nature of the disease and the emergence of new variants, medical teams' updating medical information and drug prescribing guidelines should be given special attention. This version is an updated instruction of the National Research Institute of Tuberculosis and Lung Disease (NRITLD) in collaboration with a group of specialists from Masih Daneshvari Hospital in Tehran, Iran, which is provided to update the information of caring clinicians for the treatment and care of COVID-19 hospitalized patients.

Blood Purification Techniques, Inflammatory Mediators and Mortality in COVID-19 Patients.

BACKGROUND: Inflammatory mediators are an important component in the pathophysiology of the coronavirus disease 2019 (COVID-19). This study aimed to assess the effects of reducing inflammatory mediators using hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the mortality of patients with COVID-19. MATERIALS AND METHODS: Twelve patients with confirmed diagnosis of COVID-19 were included. All patients had acute respiratory distress syndrome (ARDS). Patients were divided into three groups, namely, HP, CRRT and HP+CRRT. The primary outcome was mortality and the secondary outcomes were oxygenation and reduction in inflammatory mediators at the end of the study. RESULTS: Patients were not different at baseline in demographics, inflammatory cytokine levels, and the level of acute phase reactants. Half of the patients (3 out of 6) in the HP+CRRT group survived along with the survival of one patient (1 out of 2) in the HP group. All four patients in the CRRT group died. Serum creatinine (SCr), Interleukin-1 (IL1), Interleukin-6 (IL6), Interleukin-8 (IL8), partial pressure of oxygen (PaO2), O2 saturation (O2 sat), and hemodynamic parameters improved over time in HP+CRRT and CRRT groups, but no significant difference was observed in the HP group (All Ps > 0.05). CONCLUSION: Combined HP and CRRT demonstrated the best result in terms of mortality, reduction of inflammatory mediators and oxygenation. Further investigations are needed to explore the role of HP+CRRT in COVID-19 patients.

Safety and immunogenicity of SpikoGen®, an Advax-CpG55.2-adjuvanted SARS-CoV-2 spike protein vaccine: a phase 2 randomized placebo-controlled trial in both seropositive and seronegative populations.

OBJECTIVE: We aimed to investigate the immunogenicity and safety of SpikoGen®, a subunit COVID-19 vaccine composed of a recombinant prefusion-stabilized SARS-CoV-2 spike protein combined with the Advax-CpG55.2™ adjuvant, in seronegative and seropositive populations as primary vaccination. METHODS: This randomized, placebo-controlled, double-blind phase 2 trial was conducted on 400 participants randomized 3:1 to receive two doses of 25 µg of SpikoGen® 3 weeks apart or the placebo. The primary safety outcomes were the incidence of solicited adverse events up to 7 days after each dose and unsolicited adverse events up to 28 days after the second dose. The primary immunogenicity outcomes were seroconversion against the S1 protein and the geometric mean concentration of S1 antibodies by days 21 and 35. RESULTS: The SpikoGen® vaccine was well tolerated and no serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, largely graded as mild and transient. By day 35 (2 weeks post second dose), the seroconversion rate against S1 was 63.55 (95% CI: 57.81-69.01) in the SpikoGen® group versus 7.23 (95% CI: 2.7-15.07) in the placebo group. The geometric mean concentration of S1 antibodies was 29.12 (95% CI: 24.32-34.87) in the SpikoGen® group versus 5.53 (95% CI: 4.39-6.97) in the placebo group. Previously infected seropositive volunteers showed a large SARS-CoV-2 humoral response after a single SpikoGen® dose. DISCUSSION: SpikoGen® had an acceptable safety profile and induced promising humoral and cellular immune responses against SARS-CoV-2.

Assessment of BIV1-CovIran inactivated vaccine-elicited neutralizing antibody against the emerging SARS-CoV-2 variants of concern.

OBJECTIVES: The BIV1-CovIran vaccine is highly effective against COVID-19. The neutralizing potency of all SARS-CoV-2 vaccines seems to be decreased against variants of concern. We assessed the sensitivity of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants to neutralizing antibodies (NAbs) present in sera from individuals who had received the BIV1-CovIran candidate vaccine compared with an original Wuhan-related strain. METHODS: The ability of vaccine serum to neutralize the variants was measured using the conventional virus neutralization test. The correlation of spike (S) protein antibody and anti-receptor binding domain with neutralizing activity was investigated. RESULTS: The current study demonstrated that 29 of 32 (90.6%; 95% CI: 75.0-98.0) of the vaccinees developed NAbs against a Wuhan-related strain. It is noteworthy that 28 (87.50%) and 24 of 32 (75%) of the recipients were able to produce NAbs against Alpha, Beta, and Delta variants, respectively. Serum virus-neutralizing titres for different SARS-CoV-2 strains were weakly correlated with anti-receptor binding domain antibodies (Spearman r = 36-42, p < 0.05), but not S-binding antibodies (p > 0.05). DISCUSSION: Although there was a reduction in neutralization titres against the Alpha, Beta, and Delta variants compared with the Wuhan strain, BIV1-CovIran still exhibited potent neutralizing activity against the SARS-CoV-2 variants of concern.

SARS-CoV-2 Seroprevalence Among Health Care Workers in Major Private and Public Hospitals With COVID-19 Patient's Referral in Tehran, Iran.

Estimating the prevalence of SARS-CoV-2 antibody seropositivity among health care workers (HCWs) is crucial. In this study, the seroprevalence of anti-SARS-CoV-2 antibodies among HCWs of five hospitals of Tehran, Iran with high COVID-19 patient's referrals from April to June, 2020, was assessed. In this cross-sectional study, HCWs from three public and two private hospitals, selected randomly as a pilot, were included. Participants were asked questions on their demographic characteristics, medical history, hospital role, and usage of personal protective equipment (PPE). Iran FDA-approved SARS-CoV-2 ELISA kits were used to detect IgG and IgM antibodies in blood samples. The seroprevalence was estimated on the basis of ELISA test results and adjusted for test performance. Among the 2,065 participants, 1,825 (88.4%) and 240 (11.6%) HCWs were recruited from public and private hospitals, respectively. A total of 340 HCWs were tested positive for SARS-CoV-2-specific IgG or IgM antibodies, and 17.9% of seropositive individuals were asymptomatic. The overall test performance-adjusted seroprevalence estimate among HCWs was 22.6 (95% CI: 20.2-25.1), and PPE usage was significantly higher among HCWs of public vs. private hospitals (66.5 vs. 20.0%). This study found that seroprevalence of SARS-CoV-2 among HCWs was higher in private hospitals (37.0%; 95% CI: 28.6-46.2) than public hospitals (20.7%; 95% CI: 18.2-23.3), and also highest among assistant nurses and nurses, and lowest among janitor or superintendent categories. The PPE usage was especially suboptimal among HCWs in private hospitals. Continued effort in access to adequate PPE and regular screening of hospital staff for detecting asymptomatic personnel, especially during the upcoming wave of infection, are warranted.

Diagnosis of COVID-19 by Serology in Admitted Patients with Negative RT-PCR Assay

Considering the increasing prevalence and burden of coronavirus disease 2019 (COVID-19) disease and false-negative results in routine reverse transcription-polymerase chain reaction (RT-PCR) tests, additional diagnostic methods are needed to diagnose active cases of this disease. This prospective study was conducted on patients, in whom clinical and radiological symptoms/signs were in favor of COVID-19 while their first PCR test was negative. Later on, a second RT-PCR was performed and serological evaluation was carried out and results were compared with each other. Out of 707 patients who had been referred to the hospital and were clinically and radiologically suspicious of disease, 137 patients with negative RT-PCR tests entered the study. RT-PCR assay became positive for the second time in 45 (32.8%). Anti-COVID-19 IgM and IgG antibodies were positive in 83 (60.6%) and 86 (62.8%) patients, respectively. Finally, it was determined that serological test was diagnostic in 73% of patients and the diagnostic yield of serology was significantly higher after the first week of illness (54.8% in the first week and 88% after that). Taking advantage of both serological tests and RT-PCR helps in diagnosing 83.9% of cases. Based on the present study, the serology may be useful as a complementary test and in parallel to RT-PCR assay for diagnosis of COVID-19 among admitted symptomatic cases.

Coinfection by Aspergillus and Mucoraceae Species in Two Cases of Acute Rhinosinusitis as a Complication of COVID-19.

Acute invasive fungal rhinosinusitis (AIFR) is a life-threatening infection often found in immunocompromised patients. In the COVID-19 era, reports of AIFR have emerged, with high mortality and morbidity rate. This paper presents two cases of COVID-19 associated AIFR with the combined proven fungal etiology of Aspergillus flavus and Rhizopus arrhizus in case 1 and Aspergillus fumigatus and Rhizopus arrhizus in case 2. Both patients received liposomal amphotericin B then posaconazole combined with aggressive surgical debridement of necrotic tissues with a favorable clinical outcome. Mixed etiology AIFR can influence the outcome; hence, further studies are required upon this new threat.

Mixed etiology COVID-19 associated acute rhinosinusitis caused by two Aspergillus species.

INTRODUCTION: Acute invasive fungal rhino-sinusitis (AIFR) is a life-threatening infection that is mostly found in immunocompromised patients with serious morbidity and mortality. Recently, reports of AIFR have also emerged among SARS-CoV-2 infected patients. CASE PRESENTATION: A 50-year-old diabetic woman, previously diagnosed with COVID-19 pneumonia, was presented to the hospital with left facial pain on day 12 after discharge. Paranasal sinuses computed tomography was performed and according to the mucosal thickening in both maxillary sinuses and ethmoidal air cells, the patient underwent functional endoscopic sinus surgery (FESS) and necrosis were observed. The histopathologic examination revealed mycelium with septation suspected to Aspergillus and the culture was consistent with Aspergillus flavus and also Aspergillus niger . We reported a case of COVID-19 associated AIFR with two combined Aspergillus species from Iran. The patient received liposomal amphotericin B, which then switched to voriconazole combined with aggressive surgical debridement of necrotic tissues with a clinically favorable outcome. CONCLUSION: Mixed etiology AIFR can influence the outcome. However, further investigation is required upon this new threat.