Spontaneous Hemoptysis in a Patient With COVID-19.

CASE PRESENTATION: A 65-year-old man presented with shortness of breath, gradually worsening for the previous 2 weeks, associated with dry cough, sore throat, and diarrhea. He denied fever, chills, chest pain, abdominal pain, nausea, or vomiting. He did not have any sick contacts or travel history outside of Michigan. His medical history included hypertension, diabetes mellitus, chronic kidney disease, morbid obesity, paroxysmal atrial fibrillation, and tobacco use. He was taking amiodarone, carvedilol, furosemide, pregabalin, and insulin. The patient appeared to be in mild respiratory distress. He was afebrile and had saturation at 93% on 3 L of oxygen, heart rate of 105 beats/min, BP of 145/99 mm Hg, and respiratory rate of 18 breaths/min. On auscultation, there were crackles on bilateral lung bases and chronic bilateral leg swelling with hyperpigmented changes. His WBC count was 6.0 K/cumm (3.5 to 10.6 K/cumm) with absolute lymphocyte count 0.7 K/cumm (1.0 to 3.8 K/cumm); serum creatinine was 2.81 mg/dL (0.7 to 1.3 mg/dL). He had elevated inflammatory markers (serum ferritin, C-reactive protein, lactate dehydrogenase, D-dimer, and creatinine phosphokinase). Chest radiography showed bilateral pulmonary opacities that were suggestive of multifocal pneumonia (Fig 1). Nasopharyngeal swab for SARS-CoV-2 was positive. Therapy was started with ceftriaxone, doxycycline, hydroxychloroquine, and methylprednisolone 1 mg/kg IV for 3 days. By day 3 of hospitalization, he required endotracheal intubation, vasopressor support, and continuous renal replacement. Blood cultures were negative; respiratory cultures revealed only normal oral flora, so antibiotic therapy was discontinued. On day 10, WBC count increased to 28 K/cumm, and chest radiography showed persistent bilateral opacities with left lower lobe consolidation. Repeat respiratory cultures grew Pseudomonas aeruginosa (Table 1). Antibiotic therapy with IV meropenem was started. His condition steadily improved; eventually by day 20, he was off vasopressors and was extubated. However, on day 23, he experienced significant hemoptysis that required reintubation and vasopressor support.

A 28-Year-Old Pregnant Woman With a Lung Abscess and Complicated Pleural Effusion.

CASE PRESENTATION: A 28-year-old woman G1P0 at 22 weeks of gestation and with no significant medical history presented to the ED complaining of worsening dyspnea and right-sided pleuritic chest pain. Symptoms started 2 weeks before presentation, with minimal productive cough and dyspnea on exertion. One week after the initial symptoms, the patient started noticing right-sided chest and shoulder pain along with subjective fevers and night sweats. She denied hemoptysis, weight loss, abdominal pain, diarrhea, nausea, vomiting, arthralgia, or rash. Her pregnancy had so far been uncomplicated. The patient did not use tobacco, alcohol, or recreational drugs. She worked at a daycare center but denied any particular sick contacts. She moved to the United States 7 years ago from Sudan and denied any recent travel.

Clinical analysis of patients suffering from chronic hepatitis B superinfected with other hepadnaviruses.

To compare the clinical manifestations, laboratory examinations, and prognoses of patients with chronic hepatitis B (CHB) who were superinfected with hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV), or hepatitis E virus (HEV). Two hundred and eleven patients with confirmed CHB in our hospital, a tertiary teaching hospital in China, between 2005 and 2014 were analyzed retrospectively. Among 211 patients with CHB, 35 were superinfected with HAV, 31 were superinfected with HCV, 22 were superinfected with HDV, and 53 were superinfected with HEV. We analyzed and compared the clinical features of the five groups. The tested biochemical indices and markers of liver function included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), prothrombin activity (PTA), serum albumin (Alb), and the serum levels of HBV DNA. The peak values of ALT, AST, and TBil were significantly higher in all of the superinfected groups. Lower peak Alb concentration and PTA were also observed in the superinfected patients, with the exception of patients in the CHB + HAV group. The CHB + HCV, and CHB + HEV groups had higher death rates than the CHB monoinfected group, and the difference was statistically significant. Further analysis of the liver failure groups showed that the level of HBV DNA was not correlated with prognosis. The comparison of clinical outcomes revealed that CHB patients superinfected with HCV, HDV, and HEV compared with CHB monoinfection had statistically greater incidences of exacerbation of the condition and poor prognosis, whereas the patients superinfected with HAV generally had better outcomes.

Superinfection and the coevolution of parasite virulence and host recovery.

Parasite strategies of host exploitation may be affected by host defence strategies and multiple infections. In particular, within-host competition between multiple parasite strains has been shown to select for higher virulence. However, little is known on how multiple infections could affect the coevolution between host recovery and parasite virulence. Here, we extend a coevolutionary model introduced by van Baalen (Proc. R. Soc. B, 265, 1998, 317) to account for superinfection. When the susceptibility to superinfection is low, we recover van Baalen's results and show that there are two potential evolutionary endpoints: one with avirulent parasites and poorly defended hosts, and another one with high virulence and high recovery. However, when the susceptibility to superinfection is above a threshold, the only possible evolutionary outcome is one with high virulence and high investment into defence. We also show that within-host competition may select for lower host recovery, as a consequence of selection for more virulent strains. We discuss how different parasite and host strategies (superinfection facilitation, competitive exclusion) as well as demographic and environmental parameters, such as host fecundity or various costs of defence, may affect the interplay between multiple infections and host-parasite coevolution. Our model shows the interplay between coevolutionary dynamics and multiple infections may be affected by crucial mechanistic or ecological details.

The role of virulence in in vivo superinfection fitness of the vertebrate RNA virus infectious hematopoietic necrosis virus.

We have developed a novel in vivo superinfection fitness assay to examine superinfection dynamics and the role of virulence in superinfection fitness. This assay involves controlled, sequential infections of a natural vertebrate host, Oncorhynchus mykiss (rainbow trout), with variants of a coevolved viral pathogen, infectious hematopoietic necrosis virus (IHNV). Intervals between infections ranged from 12 h to 7 days, and both frequency of superinfection and viral replication levels were examined. Using virus genotype pairs of equal and unequal virulence, we observed that superinfection generally occurred with decreasing frequency as the interval between exposures to each genotype increased. For both the equal-virulence and unequal-virulence genotype pairs, the frequency of superinfection in most cases was the same regardless of which genotype was used in the primary exposure. The ability to replicate in the context of superinfection also did not differ between the genotypes of equal or unequal virulence tested here. For both genotype pairs, the mean viral load of the secondary virus was significantly reduced in superinfection while primary virus replication was unaffected. Our results demonstrate, for the two genotype pairs examined, that superinfection restriction does occur for IHNV and that higher virulence did not correlate with a significant difference in superinfection fitness. To our knowledge, this is the first assay to examine the role of virulence of an RNA virus in determining superinfection fitness dynamics within a natural vertebrate host.

Plausibility of HIV-1 Infection of Oral Mucosal Epithelial Cells.

The AIDS pandemic continues. Little is understood about how HIV gains access to permissive cells across mucosal surfaces, yet such knowledge is crucial to the development of successful topical anti-HIV-1 agents and mucosal vaccines. HIV-1 rapidly internalizes and integrates into the mucosal keratinocyte genome, and integrated copies of HIV-1 persist upon cell passage. The virus does not appear to replicate, and the infection may become latent. Interactions between HIV-1 and oral keratinocytes have been modeled in the context of key environmental factors, including putative copathogens and saliva. In keratinocytes, HIV-1 internalizes within minutes; in saliva, an infectious fraction escapes inactivation and is harbored and transferable to permissive target cells for up to 48 hours. When incubated with the common oral pathogen Porphyromonas gingivalis, CCR5- oral keratinocytes signal through protease-activated receptors and Toll-like receptors to induce expression of CCR5, which increases selective uptake of infectious R5-tropic HIV-1 into oral keratinocytes and transfer to permissive cells. Hence, oral keratinocytes-like squamous keratinocytes of other tissues-may be targets for low-level HIV-1 internalization and subsequent dissemination by transfer to permissive cells.

Coinfections associated with human immunodeficiency virus infection: workshop 1A.

The importance of opportunistic pathogens in HIV disease has been demonstrated from the onset of the epidemic. This workshop aimed to review the evidence for the role of oral microorganisms in HIV-related periodontal disease and HIV transmission and the effect of HIV therapy on periodontal disease. Despite being a common copathogen, tuberculosis seems to have limited oral presentation. The oral manifestations seem to have little impact on the individual and, once diagnosed, are responsive to chemotherapy. The participants debated the available evidence on the role of microorganisms and whether further research was warranted and justified. Although the effects of lipodystrophy on facial aesthetics may be profound and may markedly affect quality of life, there is no evidence to suggest a direct effect on the oral cavity. Though of interest to oral health care workers, lipodystrophy and associated metabolic syndromes were thought to be further investigated by other, more appropriate groups.

The changing spectrum of neonatal infectious disease.

To understand the changing spectrum of neonatal infectious disease, one must first be familiar with the history, the variety of organisms and the progression of change of neonatal infections over the years. As progressively more immature neonates are surviving, the spectrum of infectious disease has changed in response to current medical practice responsible for this success and to selective pressures on the microorganisms. The surviving very low birth weight infants are at a significant risk for contracting infections from this expanding repertoire of pathogens. Microorganisms once thought seemingly benign and nonpathogenic are now commonly accepted as pathogens and are among the most likely organisms to cause infections in this extremely vulnerable patient population. When considering the possible identity of infecting organisms and attempting to tailor specific therapies to decrease unwanted consequences, one must consider the level of maturity and the age of neonate, as well as the intensity of care necessary for a successful outcome. This brief review focuses primarily on the changing spectrum of bacterial and fungal infections and will not substantially address viral infections.

Inhibition of superinfection and the evolution of viral latency.

Latent viruses generally defend their host cell against superinfection by nonlatent virulent mutants that could destroy the host cell. Superinfection inhibition thus seems to be a prerequisite for the maintenance of viral latency. Yet viral latency can break down when resistance to superinfection inhibition, known as ultravirulence, occurs. To understand the evolution of viral latency, we have developed a model that analyzes the epidemiology of latent infection in the face of ultravirulence. We show that latency can be maintained when superinfection inhibition and resistance against it coevolve in an arms race, which can result in large fluctuations in virulence. An example is the coevolution of the virulence and superinfection repressor protein of phage lambda (cI) and its binding target, the lambda oLoR operator. We show that this repressor/operator coevolution is the driving force for the evolution of superinfection immunity groups. Beyond latent phages, we predict analogous dynamics for any latent virus that uses a single repressor for the simultaneous control of virulence and superinfection.

Evaluation of the relationship between IgE level and skin superinfection in children with atopic dermatitis.

Increased Th2 polarity weakens the innate immune response and predisposes children with atopic dermatitis (AD) to skin superinfection. This study was designed to evaluate the relationship between IgE level and bacterial superinfection in children with AD. A medical chart review was performed on 103 children with AD to assess the association between IgE level and skin superinfection. A multivariable logistic regression model was used to assess the relationship between categorized IgE level and the presence of bacterial superinfection after adjusting for cofounding variables including allergic rhinitis, asthma, and food allergy. A Wilcoxon signed-rank test was used to compare pre- and postskin superinfection median IgE levels in a subset of patients. Compared with children with an IgE level of <300 IU/mL, children with an IgE level of >1001 IU/mL were 66.00 times more likely to have a skin superinfection (p = 0.003) and children with an IgE level between 301 and 1000 IU/mL were 12.38 times more likely to have a skin superinfection (p < 0.001). After controlling for cofounding variables including asthma, allergic rhinitis, and food allergy, children with an IgE level of >1001 IU/mL were 71.89 times more likely to have a skin superinfection (p = 0.018) and children with an IgE level between 301 and 1000 IU/mL were 8.79 times more likely to have a skin superinfection (p < 0.001) when compared with children with an IgE level of <300 IU/mL. There was a significant increase in IgE levels from baseline in 13 children treated for a skin superinfection (p = 0.001). IgE level is associated with Staphylococcus aureus superinfection in children with AD.

Discerning the complexity of community interactions using a Drosophila model of polymicrobial infections.

A number of human infections are characterized by the presence of more than one bacterial species and are defined as polymicrobial diseases. Methods for the analysis of the complex biological interactions in mixed infections with a large number of microorganisms are limited and do not effectively determine the contribution of each bacterial species to the pathogenesis of the polymicrobial community. We have developed a novel Drosophila melanogaster infection model to study microbe-microbe interactions and polymicrobe-host interactions. Using this infection model, we examined the interaction of 40 oropharyngeal isolates with Pseudomonas aeruginosa. We observe three classes of microorganisms, one of which acts synergistically with the principal pathogen, while being avirulent or even beneficial on its own. This synergy involves microbe-microbe interactions that result in the modulation of P. aeruginosa virulence factor gene expression within infected Drosophila. The host innate immune response to these natural-route polymicrobial infections is complex and characterized by additive, suppressive, and synergistic transcriptional activation of antimicrobial peptide genes. The polymicrobial infection model was used to differentiate the bacterial flora in cystic fibrosis (CF) sputum, revealing that a large proportion of the organisms in CF airways has the ability to influence the outcome of an infection when in combination with the principal CF pathogen P. aeruginosa.

Profound suppression of chronic hepatitis C following superinfection with hepatitis B virus.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) share similar transmission routes; thus, coinfection is frequent. The consequences of acute HBV infection in patients with chronic hepatitis C are unknown. METHODS: We describe a 47-year-old male with chronic hepatitis C who acquired HBV and then spontaneously and apparently completely cleared HCV but developed chronic hepatitis B. Five serum samples collected over 14 months and lymphoid cells obtained after acquiring HBV were tested for HCV and HBV by both standard assays and ultra-sensitive polymerase chain reaction/nucleic acid hybridization (PCR/NAH) (sensitivity approximately 2 IU/ml). RESULTS: After superinfection with HBV, HBV surface antigen-positive chronic hepatitis developed with readily detectable HBV DNA. All sera collected after acquisition of HBV, which tested negative for HCV RNA by standard laboratory assay, were positive for HCV genomes when analysed by PCR/NAH. Peripheral lymphoid cells carried HBV DNA and covalently closed circular DNA, but were negative for HCV. CONCLUSIONS: This is the first reported case of profound suppression of chronic hepatitis C after superinfection with HBV and establishment of chronic hepatitis B. It is hypothesized that HBV infection precipitated generalized and/or virus-specific cellular immune responses that profoundly suppressed HCV replication and yet failed to inhibit progression to chronic hepatitis B.

Effect of acute self-limited hepatitis C virus (HCV) superinfection on hepatitis B virus (HBV)-related cirrhosis. Virological features of HBV-HCV dual infection.

We investigated the virological impact of acute hepatitis C virus (HCV) superinfection on two patients with hepatitis B virus (HBV)-related cirrhosis. In both patients, chronic HBV-infection persisted while acute HCV infection resolved spontaneously. HBV DNA was transiently suppressed in both patients but increased with HCV resolution. In Case 1 (HBeAg-positive; wild type of basic core promoter [BCP] and precore [PreC]), fluctuations of HBV DNA and HBeAg state were accompanied by mutations of the BCP and PreC. In Case 2 (HBeAg-negative; mutant type of the BCP and PreC), changes in HBV DNA levels were associated with mutations of PreC. In both cases, mutant PreC changed to the wild type upon HCV resolution, and no nucleotide A insertion at position 193 of the HCV 5'-untranslated region, which influences HCV spontaneous clearance, was detected. The putative DNA-binding motif in the HCV core was SPRG (amino acids 99-102). HCV infection was associated with changes in the nucleotide sequences of the binding site for the nuclear receptor family in HBV enhancer 2 (Enh2) including the BCP rather than Enh1. Our results suggest that the impact of acute HCV infection on chronic HBV infection varies according to HBV virological state.

Hepatitis E superinfection produces severe decompensation in patients with chronic liver disease.

BACKGROUND AND AIMS: The adverse effect of acute hepatitis A in chronic liver disease is well known. The outcome of acute hepatitis E in chronic liver disease has not been extensively studied. The present study aimed to examine the clinical profile and outcome of patients with chronic liver disease and hepatitis E virus (HEV) superinfection, and the seroprevalence of hepatitis A and E infections in patients with chronic liver disease and controls in India. METHODS: A retrospective study of patients with chronic liver disease and acute icteric hepatitis E was performed. Acute hepatitis E was diagnosed by immunoglobulin (Ig)M ELISA. Seroprevalence studies were carried out using IgG ELISA in 100 patients with chronic liver disease and 79 age- and sex-matched controls. RESULTS: From June 2001 to December 2002, nine patients with chronic liver disease were found to have superinfection with HEV. Out of these, six patients died of advanced liver failure. The etiology of liver disease was Wilson's disease in six, hepatitis B virus in one, autoimmune in one and cryptogenic in one case. The seroprevalence of hepatitis A was 99 and 100% and 56 and 21% for HEV in cases and controls, respectively. CONCLUSIONS: Acute HEV in patients with chronic liver disease has a grave prognosis. Wilson's disease was the most common cause of chronic liver disease complicated by acute HEV. Seroprevalence studies showed that 44% of patients with chronic liver disease were at risk of developing hepatitis E. Hepatitis E vaccine, when available, is indicated for use in this group.

HIV-1 co-infection, superinfection and recombination.

As the human immunodeficiency virus (HIV) pandemic progresses, an increasing number of recombinant viruses have been identified and in many geographical regions they are now the predominating strain. These recombinants are formed when an individual has acquired a co-infection or superinfection with more than one HIV-1 strain or subtype. Thus, dually infected individuals provide opportunities for studying HIV recombinants and viral interactions between infecting strains in vivo. The possible epidemiological, clinical and therapeutic implications of dual infections and recombination are many. Recombination may result in the emergence of more pathogenic and virulent HIV strains with altered fitness, tropism, and resistance to multiple drugs, and may hamper the development of subtype-based vaccines. This review is aimed at providing a more thorough understanding of dual infections (both co-infection and super-infection) and the possible consequences of the emergence of recombinant HIV-1 strains.

[The effects of hepatitis E virus superinfection on patients with chronic hepatitis B: a clinico-pathological study].

OBJECTIVE: To observe the effect of hepatitis E virus (HEV) superinfection on hepatic lesion and hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB). METHODS: Totally 122 patients with CHB were enrolled in this study. They were tested for anti-HEV IgM and IgG in serum, amount of HBV DNA in serum and liver tissue obtained by liver biopsy and HBcAg expression in liver tissue. Other parameters such as ALT, total bilirubin (TBil), albumin (A) and globulin (G), gamma-electrophoretic protein (gamma-EP), prothrombin activity (PTA) were also measured. 21 of the 122 patients (17.2%) were found to have HEV superinfection and the remaining 101 were not. Repeat liver biopsy was performed after 1 year in 7 patients with HEV superinfection and 14 patients without. Moreover, HBV DNA amount in serum from 8 HBeAg negative patients with HEV superinfection were tested dynamically in acute and recovery stage of HEV infection. RESULTS: Comparison of the data from the 21 patients with HEV superinfection and 101 without showed that there was no significant difference in the level of A/G ratio (1.74 +/- 0.50 vs. 1.83 +/- 0.37) and gamma-EP [(24.18 +/- 6.36)% vs. (22.27 +/- 4.59)%, P > 0.05]. However, the level of ALT [(244.61 +/- 81.07) U/L vs. (143.87 +/- 47.69) U/L] and TBil [(88.24 +/- 28.54) micro mol/L vs. (46.16 +/- 17.13) micro mol/L] was significantly higher (P < 0.05), but that of PTA lower in the group with HEV superinfection than in the group without superinfection [(58.57 +/- 17.44)% vs. (72.52 +/- 12.25)%, P < 0.05]. So were the amount of HBV DNA in serum [(5.45 +/- 1.86) copies/ml vs. (6.59 +/- 1.28) copies/ml, P < 0.05] and liver tissue [(6.96 +/- 2.52) copies/g vs. (8.47 +/- 1.79) copies/g, P < 0.05] as well as HBeAg and HBcAg positive rates (8/21 vs. 64/101; 9/21 vs. 67/101, P < 0.05). Pathologically, the hepatic inflammatory activity was more severer in patients with HEV superinfection, but the severity of fibrosis was not significantly different. There was no difference in the severity of inflammatory activity and stage of fibrosis between the 7 patients with HEV superinfection and the 14 patients without as well as before and after 1 year of treatment. The amount of HBV DNA and HBeAg positive rate in serum from recovery stage of HEV infection were higher than those of acute stage. CONCLUSIONS: HEV superinfection leads to activation of hepatic pathological changes and worsens the inflammatory activity. Moreover, HEV superinfection inhibits HBV replication, but it may not be long-lasting.

Brain resistance to HSV-1 encephalitis in a mouse model.

Brain resistance to intracerebral superinfections develops after a peripheral inoculation of neurovirulent viruses. Superinfection resistance combines specificity, toward the virus used for the peripheral inoculum, and short-term duration after the inoculum. In order to study this unusual combination, neurovirulent superinfections were made on albino Swiss mice previously infected with a nasal inoculum. A herpesvirus strain SC16, or a homologue recombinant virus carrying the reporter lac Z gene or a vesicular stomatitis virus (VSV) (a virus taxonomically unrelated to Herpesviridae) were used. The mice underwent a neurological examination and their survival rate was recorded. The brains superinfected with the reporter virus were stained for the beta-galactosidase reaction to trace the virus spread and the inflammatory infiltrates were characterized immunocytochemically. The results confirm and extend previous observations about virus specificity and short-term duration of superinfection resistance. They show, moreover, an enhanced brain inflammation with T-cells and macrophages infiltrating the tissue around microvessels, at a time when both neurovirulence and the spread of herpesvirus in the brain are reduced. The results suggest that the immune response to superinfection in the nervous tissue is enhanced by blood-brain barrier mechanisms that promote the timely extravasation of immune cells.