Reactivation Of Latent Infection Research Articles

VARICELLA-ZOSTER VIRUS INFECTION IN A PATIENT 12 DAYS POST RITUXIMAB: UNUSUAL CO-PRESENTATION OF SHINGLES AND CHICKENPOX

Rituximab, an anti CD20 monoclonal antibody, is used in the management of lymphoproliferative and autoimmune conditions such as pemphigus. As an immunosuppressor, it exposes patients to an increased risk of infection. Two cases of varicella-zoster virus infection post Rituximab were been reported in literature. The coexistence of chickenpox (primary infection) and shingles (reactivation of latent infection) in the same patient has never been reported in the literature, especially after rituximab treatment. Herein we present the first case of association of these 2 manifestations in a patient 12 days after rituximab therapy for pemphigus.

Long COVID or Post-COVID-19 Condition: Past, Present and Future Research Directions.

The presence of symptoms after an acute SARS-CoV-2 infection (long-COVID) has become a worldwide healthcare emergency but remains underestimated and undertreated due to a lack of recognition of the condition and knowledge of the underlying mechanisms. In fact, the prevalence of post-COVID symptoms ranges from 50% during the first months after the infection up to 20% two-years after. This perspective review aimed to map the existing literature on post-COVID symptoms and to identify gaps in the literature to guide the global effort toward an improved understanding of long-COVID and suggest future research directions. There is a plethora of symptomatology that can be due to COVID-19; however, today, there is no clear classification and definition of this condition, termed long-COVID or post-COVID-19 condition. The heterogeneity in the symptomatology has led to the presence of groups/clusters of patients, which could exhibit different risk factors and different mechanisms. Viral persistence, long-lasting inflammation, immune dysregulation, autoimmune reactions, reactivation of latent infections, endothelial dysfunction and alteration in gut microbiota have been proposed as potential mechanisms explaining the complexity of long-COVID. In such an equation, viral biology (e.g., re-infections, SARS-CoV-2 variants), host biology (e.g., genetics, epigenetics) and external factors (e.g., vaccination) should be also considered. These various factors will be discussed in the current perspective review and future directions suggested.

The essential role of intestinal microbiota in cytomegalovirus reactivation.

Human cytomegalovirus (HCMV) is a member of Herpesviridae. It has been reported that HCMV is reactivated in the breast milk of HCMV-seropositive lactating women. As we have reported various aspects of the roles of indigenous microbiota, its role in the murine CMV (MCMV) reactivation was examined in this study. MCMV was latently infected in the salivary gland, mammary tissues, and colon in the pregnant mice. When the salivary gland, mammary tissues, and colon were removed 5 days after delivery, MCMV reactivation of latent infection in each organ was confirmed by the detection of MCMV IE1 mRNA using reverse transcription-quantitative PCR. MCMV reactivation was observed in 100% of the mice during pregnancy. Next, for the elimination of intestinal microbiota, the pregnant mice were treated with low-dose or high-dose non-absorbable antibiotics. Although the numbers of aerobe/anaerobe in cecal content in low-dose antibiotic-treated mice were comparable to those in untreated controls, high-dose antibiotic treatment decreased the number of aerobe/anaerobe microbes from ca.9.0 Log10 to ca.3.0 Log10 (cfu/g). However, it could not be confirmed in 16S rRNA analysis that specific bacterial phylum or genus was eliminated by this high-dose treatment. Interestingly, MCMV reactivation was also observed in 100% of low-dose antibiotic-treated mice, whereas, in high-dose antibiotic-treated mice, MCMV reactivation was not observed in the salivary gland or colon. MCMV IE1 mRNA was detected only in 33% of the mammary tissues of those high-dose-treated mice. These results suggest that the indigenous microbiota played a crucial role in the reactivation of latent infection. IMPORTANCE Human cytomegalovirus (HCMV) infection via breast milk is a serious problem for very preterm infants such as developing a sepsis-like syndrome, cholestasis, or bronchopulmonary dysplasia, among others. It has been reported that HCMV is reactivated in the breast milk of HCMV-seropositive lactating women. In this study, the roles of indigenous microbiota in the murine CMV (MCMV) reactivation were examined using a mouse model. In MCMV latently infected mice, MCMV reactivation was observed in 100% of the mice during pregnancy. For the elimination of intestinal microbiota, MCMV-latent mice were treated with non-absorbable antibiotics. After delivery, MCMV reactivation was not observed in antibiotic-treated mice. This result suggested that the indigenous microbiota played a crucial role in the reactivation of latent infection.

Trends in the Epidemiology of Pneumocystis Pneumonia in Immunocompromised Patients without HIV Infection.

The increasing morbidity and mortality of life-threatening Pneumocystis pneumonia (PCP) in immunocompromised people poses a global concern, prompting the World Health Organization to list it as one of the 19 priority invasive fungal diseases, calling for increased research and public health action. In response to this initiative, we provide this review on the epidemiology of PCP in non-HIV patients with various immunodeficient conditions, including the use of immunosuppressive agents, cancer therapies, solid organ and stem cell transplantation, autoimmune and inflammatory diseases, inherited or primary immunodeficiencies, and COVID-19. Special attention is given to the molecular epidemiology of PCP outbreaks in solid organ transplant recipients; the risk of PCP associated with the increasing use of immunodepleting monoclonal antibodies and a wide range of genetic defects causing primary immunodeficiency; the trend of concurrent infection of PCP in COVID-19; the prevalence of colonization; and the rising evidence supporting de novo infection rather than reactivation of latent infection in the pathogenesis of PCP. Additionally, we provide a concise discussion of the varying effects of different immunodeficient conditions on distinct components of the immune system. The objective of this review is to increase awareness and knowledge of PCP in non-HIV patients, thereby improving the early identification and treatment of patients susceptible to PCP.

Treatment Options for Epstein-Barr Virus-Related Disorders of the Central Nervous System.

Epstein-Barr virus (EBV), a causative agent for several types of lymphomas and mucosal cancers, is a human lymphotropic herpesvirus with the capacity to establish lifelong latent infection. More than 90% of the human population worldwide is infected. The primary infection is usually asymptomatic in childhood, whereas infectious mononucleosis (IM) is common when the infection occurs in adolescence. Primary EBV infection, with or without IM, or reactivation of latent infection in immunocompromised individuals have been associated with a wide range of neurologic conditions, such as encephalitis, meningitis, acute disseminated encephalomyelitis, and cerebellitis. EBV is also involved in malignant lymphomas in the brain. An increasing number of reports on EBV-related disorders of the central nervous system (CNS) including the convincing association with multiple sclerosis (MS) have put in focus EBV-related conditions beyond its established link to malignancies. In this review, we present the clinical manifestations of EBV-related CNS-disorders, put them in the context of known EBV biology and focus on available treatment options and future therapeutic approaches.

Another tool against cytomegalovirus after allogeneic hematopoietic cell transplantation.

Cytomegalovirus (CMV) viremia from reactivation of latent infection is a common complication after allogeneic hematopoietic cell transplantation (HCT). Untreated, CMV viremia can progress to affect other organs, resulting in organ dysfunction with high morbidity and mortality. In this issue of the JCI, Prockop and authors demonstrate that third-party donor T cells sensitized ex vivo to CMV pp65-derived overlapping pentadecapeptides are safe and effective for the treatment of CMV reactivation or CMV disease refractory to first-line pharmacotherapies occurring after HCT. They also provide insight into the biological differences between responders and nonresponders. This work confirms the utility of third-party CMV pp65 VSTs and suggests strategies for further improving the efficacy of this cell-therapy approach.

Case Report] Challenging Detection of Latent Tuberculosis in a Patient Undergoing High-Dose Corticosteroid Therapy for Acute Hemolytic Anemia and Rhupus Arthropathy

Acute autoimmune hemolytic anemia requires rapid stabilization, typically through the administration of high-dose corticosteroids. However, it is important to consider reactivation of latent infection and how immune suppression can interfere with molecular screening tools. In this case report, we present a patient with Rheumatoid Arthritis/Systemic Lupus Erythematosus experiencing severe autoimmune hemolytic anemia complicated by an unknown latent tuberculosis infection.

Case Report] Challenging Detection of Latent Tuberculosis in a Patient Undergoing High-Dose Corticosteroid Therapy for Acute Hemolytic Anemia and Rhupus Arthropathy

Acute autoimmune hemolytic anemia requires rapid stabilization, typically through the administration of high-dose corticosteroids. However, it is important to consider reactivation of latent infection and how immune suppression can interfere with molecular screening tools. In this case report, we present a patient with Rheumatoid Arthritis/Systemic Lupus Erythematosus experiencing severe autoimmune hemolytic anemia complicated by an unknown latent tuberculosis infection.

Cytomegalovirus Infection in Organ Transplant Recipients: Diagnosis, Prevention and Treatment

The most common infectious complication after first month of solid organ transplants is cytomegalovirus (CMV). Both direct such as viral syndrome, hepatitis, pneumonitis, colitis, etc. and indirect consequences such as rejection, infections by other microorganisms and graft dysfunction, are carried on by the virus. Latent infection, active infection, viral syndrome, and invasive disease are the four types of infection that can emerge due to transmission from the transplanted organ, reactivation of latent infection, or after a primary infection in seronegative individuals. Typically, this syndrome appears 30 to 90 days following transplantation. Several antiviral medications, including acyclovir, valacyclovir, ganciclovir, and valganciclovir, are being used for CMV prophylaxis and therapy. Furthermore, these antiviral medications are toxic and have serious adverse effects, including drug resistance, leukopenia, thrombocytopenia, renal failure, and neuropsychiatric symptoms. We attempted to discuss CMV risk factors, laboratory diagnosis, prevention, treatment and therapeutic in this review study with regard to organ transplantation.

Comparison of Herpes Simplex Virus Reactivation Frequency in Acute Idiopathic Cranial Mononeuropathy and Normal Population by Serological Assay

Background: Herpes simplex virus (HSV) is a neurotropic DNA virus with a high prevalence. Following primary infection, HSV remains dormant in the neural ganglia. Secondary infection can emerge after the reactivation of latent infection, presenting as neurological manifestations. Previous studies have demonstrated the relationship between HSV reactivation and selective involvement of cranial nerves. Depending on the affected nerve, cranial mononeuropathies can present with symptoms, including diplopia, blurred vision, vertigo, unilateral facial palsy, speech impairment, swallowing difficulties, and hoarseness. Objectives: This study used a serological assay to compare HSV reactivation frequency between patients with recent idiopathic cranial mononeuropathies and normal individuals. Methods: Plasma samples from 35 idiopathic cranial mononeuropathy cases (57.2% women, mean age 58.37 years) and 35 age and sex-matched healthy controls were analyzed for anti-HSV immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies by enzyme-linked immunosorbent assay (ELISA). Results: Anti-HSV IgG antibody was positive in 91.4% of patients and 88.6% of controls. The mean serum anti-HSV IgG antibody level was significantly higher in patients (146.78 ± 60 RU/mL) than in the controls (130.61 ± 52.99 RU/mL) (P-value = 0.037). Anti-HSV IgM antibody was positive in 37.1% of patients and 14.3% of controls (P = 0.042). Conclusions: The frequency of HSV reactivation was significantly higher in patients with acute idiopathic cranial mononeuropathy than in the healthy controls, indicating the possible role of HSV as an etiology of cranial mononeuropathy.

POS-118 INFECTIONS WITH TUBERCULOSIS AND CYTOMEGALOVIRUS AMONG KIDNEY ALLOGRAFT RECIPIENTS IN A SINGLE CENTRE IN KENYA

The risk of infections in kidney transplant recipients is determined by the interaction between the epidemiological exposures and the net state of patients’ immunosuppression. The infections include Tuberculosis (TB) and Cytomegalovirus (CMV). The diseases can result from reactivations of latent infections or reinfections due to immunosuppressives prescribed after transplant. The current study reported the documented infections with CMV and TB among kidney allograft recipients in the Kenyatta National Hospital in Kenya between 2010 and 2019.

POS-106 PROFILE OF CRYPTOCOCCAL INFECTIONS IN RENAL TRANSPLANT RECIPIENTS IN A TERTIARY CARE HOSPITAL IN NORTH INDIA

Cryptococcosis is a life-threatening opportunistic fungal infection, being the third most common cause of invasive fungal infections in solid organ transplant (SOT) recipients, primarily caused by C. neoformans and C. gattii. The incidence in SOT recipients is 0.2-5%, associated with high morbidity and mortality of up to 30-50% in the acute setting. It is primarily considered to be reactivation of latent infection, occurring usually in the late post-transplantation period (>6 months after transplantation).

AGE, AUTOIMMUNITY, AND INFLAMMATION: THE CURIOUS CASE OF IMMUNOSENESCENCE AND INFLAMM-AGING

An ever-aging population has caused an increase in the prevalence of diseases which occur in the elderly like diabetes and cancer; and autoimmune disease like rheumatoid arthritis (RA). On the other hand, ageing also causes an increased susceptibility to infections, reactivation of latent infections and a poorer vaccine response. Together, this ageing-related decline in immunity is called immunosenescence and the associated ageing-related inflammation is called inflamm-aging.
 In this brief review, we describe the changes seen with ageing in innate and adaptive immunity and how these lead to the various peculiarities associated with ageing in the immune system. TEMRA cells, Senescence associated secretory phenotype (SASP) and exhausted T cells are the main changes that occur in ageing T cells. Age-associated B cells (ABCs) contribute to changes associated with autoimmunity in elderly. In the innate arm, the macrophages-led inflamm-aging cause an overall net pro-inflammatory state. However, the macrophages have reduced phagocytosis leading to accumulation of necrotic and apoptotic debris.
 We also attempt to explain how immunosenescence and inflamm-aging cause defective vaccine responses and an increased predisposition to autoimmune diseases. As the average life expectancy of the world continues to increase, this is not just a curiosity to study at whim, but an indispensable part of medicine in the near-future.

CMV Infection Following mRNA SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients.

CMV Infection Following mRNA SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients.

Association Between Depression or Anxiety and the Risk of Hepatitis B Flares: A Nationwide Population-Based Cohort Study.

PurposeDepression and anxiety have been reported to increase the risk of infectious diseases and reactivation of latent infection. We conducted a nationwide population-based retrospective cohort study to determine the relationship between hepatitis B flares and depression or anxiety, utilizing outpatient and inpatient data from the Taiwan National Health Insurance Research database collected from 2000 to 2015.Patients and MethodsA total of 12,992 patients with chronic hepatitis B and newly diagnosed anxiety/depression, without advanced liver disease, were propensity score-matched for age, sex, and comorbidities in a 1:4 ratio to 51,968 controls with chronic hepatitis B without depression/anxiety or advanced liver disease. Both groups were followed-up until December 31, 2015. Cox proportional hazards regression was used to determine the risk factors for hepatitis B flares. The Log rank test and Kaplan-Meier analysis were performed to assess differences in the cumulative incidence of hepatitis B flares according to anxiety/depression status.ResultsThe incidence of hepatitis B flares was higher in the depression/anxiety cohort than in the control cohort (log-rank; p < 0.001). Patients with depression/anxiety had a significantly higher incidence rate of hepatitis B flares than those without depression/anxiety (3017 per 105 person-years versus 2042 per 105 person-years, p = 0.003). After adjusting for age and comorbidities, anxiety/depression was independently associated with an increased risk of hepatitis B flares (hazard ratio, 1.173; 95% confidence interval, 1.033–1.277; p = 0.003).ConclusionThis analysis suggests that in patients with chronic hepatitis B without advanced liver disease, those with concomitant depression or anxiety may be at higher risk of hepatitis B flares.

WhiB4 Is Required for the Reactivation of Persistent Infection of Mycobacterium marinum in Zebrafish

ABSTRACTGranulomas are the pathological hallmark of tuberculosis (TB). In individuals with latent TB infection, Mycobacterium tuberculosis cells reside within granulomas in a nonreplicating dormant state, and a portion of them will develop active TB. Little is known on the bacterial mechanisms/factors involved in this process. In this study, we found that WhiB4, an oxygen sensor and a transcription factor, plays a critical role in disease progression and reactivation of Mycobacterium marinum (M. marinum) infection in zebrafish. We show that the whiB4::Tn mutant of M. marinum caused persistent infection in adult zebrafish, which is characterized by the lower but stable bacterial loads, constant number of nonnecrotized granulomas in fewer organs, and reduced inflammation compared to those of zebrafish infected with the wild-type bacteria or the complemented strain. The mutant bacteria in zebrafish were also less responsive to antibiotic treatments. Moreover, the whiB4::Tn mutant was defective in resuscitation from hypoxia-induced dormancy and the DosR regulon was dysregulated in the mutant. Taken together, our results suggest that WhiB4 is a major driver of reactivation from persistent infection.IMPORTANCE About one-quarter of the world’s population has latent TB infection, and 5 to 10% of those individuals will fall ill with TB. Our finding suggests that WhiB4 is an attractive target for the development of novel therapeutics, which may help to prevent the reactivation of latent infection, thereby reducing the incidences of active TB.

Infectious risk in multiple sclerosis patients treated with disease-modifying therapies: A three-year observational cohort study.

BackgroundThe disease-modifying therapies (DMTs) largely used in multiple sclerosis (MS) may result in higher infectious risk.ObjectiveWe aimed to investigate the infectious risk in DMT-treated MS patients.MethodsMS patients were evaluated for infectious risk before starting, switching or during DMT.ResultsIn this three-year observational cohort study 174 MS patients were enrolled. Among them, 18 patients were anti-HBc + and 19 patients were QuantiFERON®-TB Gold In-Tube (QFT) + . No patients with anti-HBc + showed a detectable HBV-DNA and all started DMT. Among QTB + patients, 17 latent TB infections (LTBIs) and 2 active TB infections (TBIs) were identified. After one month of LTBI prophylaxis or TB treatment, respectively, all patients started DMTs.Overall, 149 started DMTs. During DMTs, one ocrelizumab-treated patient with anti-HBc + developed HBV reactivation and six patients (3 on natalizumab, 2 on ocrelizumab and 1 on IFN-β) showed reactivation of HSV-1, with detectable plasma DNA. Finally, 1 cladribine-treated patient experienced VZV reactivation. All the reactivations of latent infections have been successfully treated.ConclusionScreening of infectious diseases in DMT candidate MS patients helps to mitigate the infectious risk. During DMTs, a regular assessment of infectious risk allows to avoid discontinuing MS therapy and guarantees a higher degree of safety.

The impact of active case finding on transmission dynamics of tuberculosis: A modelling study

BackgroundIn the last decade, active case finding (ACF) strategies for tuberculosis (TB) have been implemented in many diverse settings, with some showing large increases in case detection and reporting at the sub-national level. There have also been several studies which seek to provide evidence for the benefits of ACF to individuals and communities in the broader context. However, there remains no quantification of the impact of ACF with regards to reducing the burden of transmission. We sought to address this knowledge gap and quantify the potential impact of active case finding on reducing transmission of TB at the national scale and further, to determine the intensification of intervention efforts required to bring the reproduction number (R0) below 1 for TB.MethodsWe adopt a dynamic transmission model that incorporates heterogeneity in risk to TB to assess the impact of an ACF programme (IMPACT TB) on reducing TB incidence in Vietnam and Nepal. We fit the models to country-level incidence data using a Bayesian Markov Chain Monte Carlo approach. We assess the impact of ACF using a parameter in our model, which we term the treatment success rate. Using programmatic data, we estimate how much this parameter has increased as a result of IMPACT TB in the implementation districts of Vietnam and Nepal and quantify additional efforts needed to eliminate transmission of TB in these countries by 2035.ResultsExtending the IMPACT TB programme to national coverage would lead to moderate decreases in TB incidence and would not be enough to interrupt transmission by 2035. Decreasing transmission sufficiently to bring the reproduction number (R0) below 1, would require a further intensification of current efforts, even at the sub-national level.ConclusionsActive case finding programmes are effective in reducing TB in the short term. However, interruption of transmission in high-burden countries, like Vietnam and Nepal, will require comprehensive incremental efforts. Complementary measures to reduce progression from infection to disease, and reactivation of latent infection, are needed to meet the WHO End TB incidence targets.

DISSEMINATED HISTOPLASMOSIS IN A PATIENT WITH NEWLY DIAGNOSED AIDS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Disseminated Histoplasmosis (DH) is an AIDS-defining illness caused by the dimorphic fungus Histoplasma capsulatum. Outbreaks have been associated with exposure to bird or bat droppings and amongst construction workers. It remains unclear whether DH represents an acute infection or a reactivation of latent infection. We present a case of DH in a newly diagnosed AIDS patient. CASE PRESENTATION: A 50 year old male Hispanic construction worker presented with a month history of persisting fever, chills, diaphoresis, progressive shortness of breath on exertion, non-bloody diarrhea and 15lbs weight loss. HIV screen was positive (new diagnosis) and his CD4+ cell count was 3 per cubic millimeter with a viral load of over 1 million copies/ml. CXR showed diffuse interstitial infiltrates in both lung fields and CT chest showed numerous punctate miliary pattern pulmonary nodules in the lungs with necrotic appearing lymph nodes in the proximal jejunal mesentery. SARS-CoV2 PCR was negative. BAL culture grew Histoplasma capsulatum, Lung biopsy pathology showed broad based budding yeast and urine histoplasma antigen was positive at greater than 23 ng/ml. He was treated with highly active antiretroviral therapy (HAART), IV liposomal amphotericin, and steroid. Empiric anti-TB therapy was stopped with negative quantiferon TB gold, BAL AFB smear and BAL MTB complex PCR. Silver stain for PCP, serum cryptococcal antigen, serum galactomammanan and fungitell assays were all negative. Hospital course was complicated by pneumothorax, septic shock, line related bloodstream infections that resolved with line removal and antimicrobials. Despite appropriate antifungal therapy for 40 days with decrease in his urine histoplasma antigen to 11 ng/ml, and HIV viral load decreasing to 330 copies/ml after 3 weeks of HAART, he remained ventilator dependent, on chest tubes and could not be weaned off sedation. His family made him comfort care only on hospital day 43 and he died peacefully after. DISCUSSION: Histoplasmosis has been recognized as an opportunistic infection in patients with AIDS and typically presents as disseminated disease. DH in conjunction with HIV infection is particularly common among Hispanic persons in the United states. In AIDS patients, DH is associated with a nonspecific clinical presentation—usually unexplained fever and weight loss. Histoplasmosis causes significant morbidity and mortality. Fungal infections deaths in AIDS were estimated at more than 700, 000 deaths (47%) annually. The frequent occurence of histoplasmosis with other opportunistic infections especially tuberculosis requires that tuberculosis be ruled out even if histoplasmosis is diagnosed. CONCLUSIONS: This case highlights the fact that although miliary pattern on CT Chest typically signifies tuberculosis, it can also be seen in histoplasmosis. Also associated morbidity and mortality of DH remains high in AIDS patients not on HAART. REFERENCE #1: Rana A. Hajjeh. Disseminated Histoplasmosis in Persons Infected with Human Immunodeficiency Virus. Clinical Infectious Diseases 1995; 21(Suppl 1):S108 -10. REFERENCE #2: Stuart M. Levitz, and Eugene J. Mark. Case 38-1998 — A 19-Year-Old Man with the Acquired Immunodeficiency Syndrome and Persistent Fever. N Engl J Med 1998; 339:1835-1843. REFERENCE #3: David W. Denning. Minimizing fungal disease deaths will allow the UNAIDS target of reducing annual AIDS deaths below 500 000 by 2020 to be realized. Philos Trans R Soc Lond B Biol Sci. 2016 Dec 5;371(1709). DISCLOSURES: No relevant relationships by Oluwadamilola Adeyemi, source=Web Response No relevant relationships by Ingrid Gils, source=Web Response No relevant relationships by Drew Ludwig, source=Web Response No relevant relationships by Biana Modilevsky, source=Web Response

ATYPICAL PAROTITIS AS A RESULT OF SEVERE COVID-19 INFECTION

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Parotitis occurs in extremes of age and is associated with infections or inflammatory conditions. Typical bacterial parotitis presents with a unilateral, tender enlarged parotid gland and fever whereas inflammatory parotitis presents with bilateral enlargement of the parotids without fever. Here, we present two atypical cases: bilateral parotitis likely secondary to bacterial infection and unilateral parotitis likely due to inflammation. CASE PRESENTATION: We present a 45-year-old male with history of obesity who presented with hypoxia and dyspnea. CT angiogram noted multifocal pneumonia, consistent with COVID-19. He was started on dexamethasone, remdesivir and baricitinib as well as community acquired pneumonia coverage. On day 5, he was placed on high-flow nasal cannula due to progressive hypoxia. Although initially afebrile, he developed a fever on day 12, with tachypnea and tachycardia. Acute swelling of the submandibular space with adjacent erythema and a lactic acid of 3.2 were noted. CT neck demonstrated enlarged parotid glands bilaterally with inflammatory changes indicative of parotitis, no abscess or mass was noted. He was started on vancomycin, with improvement of his erythema and swelling within 3 days. Blood cultures were positive for MSSA. Patient continued to deteriorate, requiring intubation on day 18 and died on day 34.The second case is a 79-year-old-male with history of COPD on 3L and type 2 diabetes mellitus who presented with hypercapnic respiratory failure, found to be COVID-19 positive. The patient required non-invasive ventilation for progressive respiratory failure, despite COVID-19 treatment. He developed a sudden swelling of the right mandibular area on day 7 of admission. CT neck identified an enlarged heterogenous enhancement of the right parotid gland and edema consistent with parotitis. Blood cultures were negative. The patient was started on vancomycin but had worsening oxygen requirements and encephalopathy, was ultimately made DNR and expired on day 9. DISCUSSION: There has been increased incidence of atypical disease presentation and reactivation of latent infections during the COVID-19 pandemic. In the above patients, parotitis occurred secondary to severe viral illness, immune suppression, increased inflammation and/or superimposed bacterial infection. COVID-19 has been shown to cause significant inflammatory response and immunosuppression with lymphopenia, thrombocytopenia and low complement levels. Both patients had elevated inflammatory markers and persistent leukopenia. CONCLUSIONS: The pathophysiology of atypical parotitis and other atypical disease presentations, in the setting of severe COVID-19, should further be investigated. REFERENCE #1: Tian W, Zhang N, Jin R, et al. Immune suppression in the early stage of COVID-19 disease. Nat Commun. 2020;11(1):5859. Published 2020 Nov 17. doi:10.1038/s41467-020-19706-9 REFERENCE #2: Fisher J, Monette DL, Patel KR, Kelley BP, Kennedy M. COVID-19 associated parotitis. Am J Emerg Med. 2021;39:254.e1-254.e3. doi:10.1016/j.ajem.2020.06.059 REFERENCE #3: Wilson M, Pandey S. Parotitis. [Updated 2020 Dec 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560735/ DISCLOSURES: No relevant relationships by Michael Bonk, source=Web Response No relevant relationships by Andrew Marcano, source=Web Response No relevant relationships by Ananya Nanduri, source=Web Response No relevant relationships by TAHMINA SALEEM, source=Web Response