Lipoprotein concentrations over time in the intensive care unit COVID-19 patients: Results from the ApoCOVID study.

INTRODUCTION: Severe acute respiratory syndrome coronavirus2 has caused a global pandemic of coronavirus disease 2019 (COVID-19). High-density lipoproteins (HDLs), particles chiefly known for their reverse cholesterol transport function, also display pleiotropic properties, including anti-inflammatory or antioxidant functions. HDLs and low-density lipoproteins (LDLs) can neutralize lipopolysaccharides and increase bacterial clearance. HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) decrease during bacterial sepsis, and an association has been reported between low lipoprotein levels and poor patient outcomes. The goal of this study was to characterize the lipoprotein profiles of severe ICU patients hospitalized for COVID-19 pneumonia and to assess their changes during bacterial ventilator-associated pneumonia (VAP) superinfection. METHODS: A prospective study was conducted in a university hospital ICU. All consecutive patients admitted for COVID-19 pneumonia were included. Lipoprotein levels were assessed at admission and daily thereafter. The assessed outcomes were survival at 28 days and the incidence of VAP. RESULTS: A total of 48 patients were included. Upon admission, lipoprotein concentrations were low, typically under the reference values ([HDL-C] = 0.7[0.5-0.9] mmol/L; [LDL-C] = 1.8[1.3-2.3] mmol/L). A statistically significant increase in HDL-C and LDL-C over time during the ICU stay was found. There was no relationship between HDL-C and LDL-C concentrations and mortality on day 28 (log-rank p = 0.554 and p = 0.083, respectively). A comparison of alive and dead patients on day 28 did not reveal any differences in HDL-C and LDL-C concentrations over time. Bacterial VAP was frequent (64%). An association was observed between HDL-C and LDL-C concentrations on the day of the first VAP diagnosis and mortality ([HDL-C] = 0.6[0.5-0.9] mmol/L in survivors vs. [HDL-C] = 0.5[0.3-0.6] mmol/L in nonsurvivors, p = 0.036; [LDL-C] = 2.2[1.9-3.0] mmol/L in survivors vs. [LDL-C] = 1.3[0.9-2.0] mmol/L in nonsurvivors, p = 0.006). CONCLUSION: HDL-C and LDL-C concentrations upon ICU admission are low in severe COVID-19 pneumonia patients but are not associated with poor outcomes. However, low lipoprotein concentrations in the case of bacterial superinfection during ICU hospitalization are associated with mortality, which reinforces the potential role of these particles during bacterial sepsis.

HEV superinfection accelerates disease progression in patients with chronic HBV infection and increases mortality in those with cirrhosis.

BACKGROUND & AIMS: Acute HEV infection causes varying degrees of liver damage. Although liver-related death due to HEV infection alone is rare in healthy individuals, it is unclear whether HEV superinfection is associated with worse outcomes in patients with chronic HBV infection. Thus, we explored whether HEV superinfection was associated with increased incidence of liver-related death, cirrhosis, and hepatocellular carcinoma (HCC). METHODS: Serum and data were collected from 2 independent retrospective cohorts of patients with chronic HBV infection, comprising 2,123 patients without cirrhosis and 414 with cirrhosis at baseline, respectively. All the patients were negative for HEV-IgG at enrolment and HEV superinfection was defined by the presence of HEV-IgG seroconversion. RESULTS: In the non-cirrhotic cohort, 46 of 2,123 patients developed HEV superinfection. Though HEV superinfection was only associated with increased incidence of liver-related death in the overall cohort, it was a risk factor for all 3 endpoints (liver-related death, cirrhosis, and HCC) in a subgroup of 723 HBeAg-negative patients with chronic HBV infection. In addition, the 1-year mortality rate after HEV superinfection was higher in 4 patients who developed cirrhosis during the follow-up than in those who did not (50% vs. 2.4%, p = 0.001). To elucidate the perceived relationship between HEV superinfection and risk of mortality, an independent cohort of cirrhotic patients (n = 414) was further analyzed to control for the inherent increase in mortality risk due to cirrhosis. The 10 cirrhotic patients with HEV superinfection had a higher 1-year mortality rate than those without (30% vs. 0%, p <0.001). CONCLUSIONS: In both cohorts of patients with chronic HBV infection, acute HEV superinfection increases the risk of liver-related death, especially in those with cirrhosis. LAY SUMMARY: The mortality caused by acute hepatitis E virus infection is usually low in the healthy population, but it is unclear how it affects patients with chronic hepatitis B virus infection, as they already have compromised liver function. Our data show that the 1-year mortality rate is 35.7% in patients with hepatitis B-related cirrhosis who contract hepatitis E virus. Hepatitis E may accelerate disease progression in patients with chronic hepatitis B.

HIV Superinfection Drives De Novo Antibody Responses and Not Neutralization Breadth.

Eliciting antibodies that neutralize a broad range of circulating HIV strains (broadly neutralizing antibodies [bnAbs]) represents a key priority for vaccine development. HIV superinfection (re-infection with a second strain following an established infection) has been associated with neutralization breadth, and can provide insights into how the immune system responds to sequential exposure to distinct HIV envelope glycoproteins (Env). Characterizing the neutralizing antibody (nAb) responses in four superinfected women revealed that superinfection does not boost memory nAb responses primed by the first infection or promote nAb responses to epitopes conserved in both infecting viruses. While one superinfected individual developed potent bnAbs, superinfection was likely not the driver as the nAb response did not target an epitope conserved in both viruses. Rather, sequential exposure led to nAbs specific to each Env but did not promote bnAb development. Thus, sequential immunization with heterologous Envs may not be sufficient to focus the immune response onto conserved epitopes.

Mediastinitis superinfected by Achromobacter xylosoxidans. A case report.

We describe an extremely rare case of mediastinitis superinfected by emerging Achromobacter xylosoxidans. After mitral and aortic valves replacement, the patient first developed a Staphylococcus aureus mediastinitis, and five days after starting adapted antibiotic therapy, superficial pus analysis revealed the presence of Achromobacter xylosoxidans. This superinfection was considered superficial and focus was made on Staphylococcus aureus mediastinitis. Three weeks later, no more Staphylococcus aureus was found in pus samples and the sepsis seemed under control. Unfortunately, blood cultures were again positive for Achromobacter xylosoxidans three weeks later and the patient died from septic shock.

NGS combined with phylogenetic analysis to detect HIV-1 dual infection in Romanian people who inject drugs.

Dual HIV infections are possible and likely in people who inject drugs (PWID). Thirty-eight newly diagnosed patients, 19 PWID and 19 heterosexually HIV infected were analyzed. V2V3 loop of HIV-1 env gene was sequenced on the NGS platform 454 GSJunior (Roche). HIV-1 dual/multiple infections were identified in five PWID. For three of these patients, the reconstructed variants belonged to pure F1 subtype and CRF14_BG strains according to phylogenetic analysis. New recombinant forms between these parental strains were identified in two PWID samples. NGS data can provide, with the help of phylogenetic analysis, important insights about the intra-host sub-population structure.

[Severe acute hepatitis by delta virus superinfection: diagnostic significance of molecular biology.] / Hepatitis aguda grave por sobreinfección por virus delta: importancia diagnóstica de la biologia molecular.

HDV infection may occur within a primary HBV infection (co-infection) or by sub sequent acquisition ofthe virus in patients with chronic hepatitis B (superinfection). Acute HDV infection is rarely diagnosed. Since cero conversion usually takes place about six weeks after viral infection, early diagnosis requires the use of direct diagnostic techniques, such as antigen HD V (HDAg) detection, or genomic amplification by means of molecular biology methods (RT-PCR). Here were port the case of a patient with chronic HBV infection that develops a severe acute hepatitis due to VHD superinfec- tion only detected by molecular biology.

Acute hepatitis B in a patient with OLT during treatment with peg-interferon and ribavirin for hepatitis C recurrence.

The course and outcome of acute viral hepatitis in liver transplanted patients with hepatitis C recurrence are unknown. Here we describe a patient who presented with acute hepatitis B infection while on treatment with peg-interferon and ribavirin for hepatitis C recurrence after liver transplantation. A nucleoside analogue was added (entecavir) and the patient cleared hepatitis C virus (HCV) infection and seroconverted to anti-HBs. In this case, the acute hepatitis B virus (HBV) infection might have contributed to the clearance of HCV, the concomitant immunosuppression might have lead to the slow clearance of HBV infection, and the combined antiviral therapy has helped in the resolution of both infections. Hepatitis B vaccination should be recommended in susceptible patients waiting for liver transplantation.

Low incidence of HIV-1 superinfection even after episodes of unsafe sexual behavior of homosexual men in the Amsterdam Cohort Studies on HIV Infection and AIDS.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) superinfection is infection of an HIV-1 seropositive individual with another HIV-1 strain. The rate at which HIV-1 superinfection occurs might be influenced by sexual behavior. Superinfection might be detected more often by analyzing longitudinal samples collected from time periods of unsafe sexual behavior. METHODS: Envelope C2-C4 and gag sequences were generated from HIV-1 RNA from longitudinal serum samples that were obtained around self-reported sexual risk periods from 15 homosexual therapy-naïve men who participated in the Amsterdam Cohort Studies on HIV Infection and AIDS. Maximum likelihood phylogenetic analysis was used to determine whether HIV-1 superinfection had occurred. RESULTS: We studied a total of 124 serum samples from 15 patients with a median of 8 samples and of 5.8 person-years of follow-up per patient. Phylogenetic analysis on 907 C2-C4 env and 672 gag sequences revealed no case of HIV-1 superinfection, resulting in a superinfection incidence rate of 0 per 100 person-years [95%CI: 0 - -4.2]. CONCLUSIONS: We conclude that HIV-1 superinfection incidence is low in this subgroup of homosexual men who reported unsafe sexual behavior. Additional studies are required to estimate the impact of also other factors, which may determine the risk to acquire HIV-1 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.

Bacterial superinfection in upper respiratory tract infections estimated by increases in CRP values: a diagnostic follow-up in primary care.

OBJECTIVE: The aim of this study was to estimate the rate of bacterial superinfection in patients with URTI by using on-site determination of C-reactive protein (CRP). DESIGN: A prospective cohort study. SETTING: A total of 30 primary care practices. SUBJECTS: Patients with URTI. INTERVENTION: The CRP value was determined at the first consultation and at a follow-up within 3-5 days. CRP values of 30 units (mg) or higher were considered to be an indication of bacterial involvement. MAIN OUTCOME MEASURES: CRP values during follow-up and duration of illness. RESULTS: Among the 506 patients included, 73.1% exhibited a CRP value below the defined limit at their first visit and were considered to suffer from URTI of viral origin. The rate of subsequent bacterial superinfection was 8.1%. Compared with patients suffering from URTI of bacterial or viral origin the duration of illness in patients with bacterial superinfection was significantly longer. CONCLUSION: During follow-up of patients with URTI, the prevalence of bacterial superinfection detected by using a near patient CRP determination is surprisingly low. This result should help to reduce the prescription rate of antibiotics in primary care.

Blood group AB is associated with increased risk for severe dengue disease in secondary infections.

Why certain individuals progress to severe dengue disease is unknown. In this study, blood groups associated with dengue disease were investigated. ABO phenotypes were identified by use of serum from 399 patients with dengue-virus infection who participated in a cohort study. ABO blood-group frequencies were similar in primary versus secondary dengue-virus infections. However, in secondary infection, individuals with blood group AB were likely to have dengue hemorrhagic fever grade 3 than either grades 1 and 2 combined (corrected P value, <.0001; odds ratio, 0.097 [95% confidence interval, 0.03-0.33]) or dengue fever (corrected P value, <.0001; odds ratio, 0.119 [95% confidence interval, 0.04-0.37]). To our knowledge, this is the first report demonstrating an association between ABO blood group and the severity of dengue disease.

Inflammatory/cardiovascular-metabolic responses in a rat model of burn injury with superimposed infection.

Infection remains the major cause of morbidity and mortality in burn patients. Furthermore, the use of antibiotics in such patients has led to the prevalence of antibiotic-resistant microbial infections; one such infection in intensive care unit turns out to be caused by the enterococcal organisms. Our laboratory studies have used a rat model of bum injury and Enterococcus faecalis infection. Sprague-Dawley male rats ( approximately 250 g) were initially given an intragastric gavage of the antibiotic ciprofloxacin for 3 days. This procedure allowed for decontamination of intestine of gram-negative and some gram-positive organisms. The remainders of the gram-positive organisms were, to a large extent, Enterococci. After the decontamination procedure, rats were intra-abdominally inoculated with E. faecalis; inoculation involved preparation of sterilized rat fecal pellets impregnated with E. faecalis (10 colony-forming units) and their implants through a midline abdominal wall incision. Some of the rats that were implanted with the fecal pellets were subject to full-thickness skin bums ( approximately 30% total body surface area; 95 degrees C water for 7 s). Sham abdominal infection rats received a sterile pellet only; sham bum procedure consisted of exposing the skin to room temperature water. All sham and bum and/or E. faecalis infection procedures were carried out on rats under pentobarbital anesthesia. Inflammation and innate host defense-related responses were assessed via measurements of neutrophil effector responses, i.e., oxygen anion free radical (O2)/eIastase production, CD11b/CD18 expression, apoptosis, and tissue infiltration. Determining epithelial lactulose permeability, microvascular albumin leakage, and epithelial tight junction integrity assessed the status of intestinal function/structural derangements. The animals' metabolic and cardiovascular integrity was evaluated determining blood pH, p02, pC02, heart rate, respiratory rate, blood pressure, and cardiac output. Whereas the aforementioned measurements were carried out at 24 to 48 h postbum injury with and without the Enterococcal infection, animal mortality was determined for up to 5 days after the experimental injuries. The results of the studies indicated that whereas bum or E. faecalis infection alone did not produce significant mortality, the dual insult with bum and E. faecalis infection resulted in significant animal death accompanied by relatively more profound metabolic and cardiovascular derangements. Inappropriately heightened neutrophil effector responses were present with bum alone as well as with the dual bum and infection complications. These studies suggest that animal models of bum injury with Enterococcal infection complications simulate the adverse outcomes bum patients infected with Enterococcal organisms.

[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.

[Study on hepatitis G virus infection].

OBJECTIVE: To find out the situation of HGV infection in Shandong Province, and to explore the relations between HGV infection and HCV or HBV infection. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to determine the serum anti-HGV in 1,082 patients with viral hepatitis, 77 patients with non A-E hepatitis and 361 blood donors. RESULTS: 53 patients whose serum anti-HGVs were positive (positive rate: 3.49%) were noticed. The anti-HGV positive rate (8.93%) in patients with Hepatitis C was remarkably higher than that (3.32%) in patients with Hepatitis B (chi 2 = 8.80, P < 0.01). The anti-HGV positive rate (4.82%) in patients with chronic hepatitis was significantly higher than that (0.79%) in patients with acute hepatitis (chi 2 = 10.79, P < 0.01). The anti-HGV positive rate (8.00%) in patients with severe hepatitis was obviously higher than that in patients with acute hepatitis (chi 2 = 10.23, P < 0.01). CONCLUSION: The manifestations of HGV infection can be expressed as virus-carriers, subclinical infection or various clinical types. Patients with Hepatitis C were more subjective to be overlapped with HGV than the patients with Hepatitis B; moreover, HCV or HBV infection superinfected with HGV is associated with exacerbation of patients' condition and the formation of chronic infection.

In vivo resistance to simian immunodeficiency virus superinfection depends on attenuated virus dose.

Infection of macaques with attenuated simian immunodeficiency virus (SIV) induces potent superinfection resistance that may be applicable to the development of an AIDS vaccine but little information exists concerning the conditions necessary for the induction of this vaccine effect. We report that only a high dose of attenuated SIVmac protected macaques against intravenous challenge with more virulent virus 15 weeks after primary infection. Three of four animals given 2000-20000 TCID50 of SIVmacC8, a molecular clone of SIVmac251(32H) with a 12 bp deletion in the nef gene, essentially resisted superinfection with uncloned SIVmac. In two animals challenge virus was never detected by PCR and in one animal challenge virus was detected on one occasion only. Although animals given 2-200 TCID50 of attenuated virus were superinfected they were spared from the loss of CD4 cells seen in infected naive controls. Protection from superinfection did not correlate with immune responses, including the levels of virus-specific antibodies or virus-neutralizing activity measured on the day of challenge; although, after superinfection challenge, Nef-specific CTL responses were detected only in animals infected with high doses of attenuated SIV. Unexpectedly, cell-associated virus loads 2 weeks after inoculation were significantly lower in animals infected with a high dose of attenuated SIV compared to those in animals infected with a low dose. Our results suggest that the early dynamics of infection with attenuated virus influence superinfection resistance.

Dual infection of rabbits with human T cell lymphotropic virus types I and II.

Attempts were made to generate a rabbit model of dual infection with human T lymphotropic virus (HTLV) types I and II. Four groups (A, B, C, and D) of three rabbits each were used. Group A was inoculated with the RW-1 cell line coinfected with HTLV-I and HTLV-II and group B was transfused from a dually infected rabbit. Polymerase chain reaction (PCR) using primers specific for the pol region of each virus detected both HTLV-I and HTLV-II in all group A and two group B rabbits, but HTLV-II only in the remaining group B rabbit. Groups C and D already infected with HTLV-I and HTLV-II, respectively, were inoculated with an HTLV-II- or HTLV-I-producing cell line. One group C rabbit became PCR-positive for both viruses but the other five resisted superinfection with the respective viruses. During prolonged observation, three of the six dually infected rabbits converted to single (HTLV-I or HTLV-II) infection. The in vivo dual infection was confirmed by in vitro establishment of a lymphoid cell line coinfected with HTLV-I and HTLV-II. It was also possible to establish coinfected lymphoid cell lines from HTLV-I-infected rabbits by coculture with lethally irradiated HTLV-II-producing cells and vice versa. The mechanism of viral elimination in dually infected rabbits, as well as that of protective immunity against superinfection, remains to be elucidated.

Acute exacerbation and superinfection in patients with chronic viral hepatitis.

Recent studies, particularly those in Orientals, have shown that both acute exacerbation from the reactivation of the original virus and acute superinfection with other viruses occur frequently in patients with chronic viral hepatitis. The clinicopathologic features of acute exacerbation and acute superinfection are similar to those of acute hepatitis caused by a single virus, but acute exacerbation is usually less severe than acute superinfection. Recurrent acute exacerbations result from the host's intermittent but persistant efforts to eliminate the replicating virus by immune-mediated mechanisms, thus killing hepatocytes with viral replication. Severe acute exacerbation or acute superinfection may result in immediate hepatic decompensation, or even mortality, and late disease progression, including liver cirrhosis and hepatocellular carcinoma. Further studies are needed to elucidate the basic mechanisms and provide more effective ways to avoid acute exacerbation and acute superinfection in patients with chronic viral hepatitis.

Natural history of hepatitis D viral superinfection: significance of viremia detected by polymerase chain reaction.

BACKGROUND/AIMS: Polymerase chain reaction (PCR) is very sensitive. The aim of the study was to reevaluate viral replication in hepatitis D virus (HDV) superinfection by PCR. METHODS: HDV and hepatitis B virus (HBV) were detected by PCR in 185 patients. RESULTS: The acute hepatitis group had the highest detection rate of HDV RNA compared with chronic hepatitis, cirrhosis, hepatocellular carcinoma, and remission groups (63 of 64 vs. 35 of 47, 17 of 23, 19 of 30, and 7 of 21) and the highest alanine aminotransferase (ALT) levels (mean, 1741 U/L vs. 266 to 27 U/L; P < 0.05). The detection rate of HBV DNA was the lowest in the acute group (41%) compared with 66%, 70%, 80%, and 57% in the remaining groups (P < 0.02). At the chronic stage, 13%-25% of cases had HDV RNA, and 30%-48% of cases had HBV DNA detected by PCR but not by traditional method. HDV RNA was associated with ALT levels in horizontal and longitudinal analyses. CONCLUSIONS: HDV superinfection may be divided into the following three phases: acute phase, active HDV replication and suppression of HBV with high ALT levels; chronic phase, decreasing HDV and reactivating HBV with moderate ALT levels; and late phase, development of cirrhosis and hepatocellular carcinoma caused by replication of either virus or remission resulting from marked reduction of both viruses.

Superinfection of chimpanzees carrying hepatitis C virus of genotype II/1b with that of genotype III/2a or I/1a.

Three chimpanzees persistently infected with hepatitis C virus of genotype II/1b were challenged with hepatitis C virus of genotype III/2a and 6 wk later with hepatitis C virus of genotype I/1a. They were tested for titers of total and genotype-specific hepatitis C virus RNA, as well as for serum transaminase levels, until 52 wk after the first challenge. One chimpanzee (CH489) with intermittent low hepatitis C virus RNA titers of genotype II/1b in serum was superinfected with hepatitis C virus of genotype III/2a between wk 1 and 7 after the challenge; superinfection was accompanied by fluctuating high transaminase levels. Later, the animal was superinfected with hepatitis C virus of genotype I/1a. Superinfection was accompanied by persistently high transaminase levels immediately after the challenge. Hepatitis C virus of genotype I/1a persisted, whereas hepatitis C virus of genotype II/1b was undetectable 22 wk after the challenge and thereafter. In another chimpanzee (CH353) with intermittent low hepatitis C virus RNA titers of genotype II/1b, hepatitis C virus of genotype III/2a induced fluctuating high levels of serum transaminases without revealing itself in serum. Then, HCV of genotype I/1a superinfected her, induced persistently high transaminase levels and took over HCV of genotype II/1b at 22 wk after the challenge and thereafter. The third chimpanzee (CH451) with persistently high HCV RNA titers of genotype II/1b did not reveal HCV RNA of genotype III/2a in serum after the challenge, although transaminases sharply increased. Low-titered HCV RNA of genotype I/1a was detected at 18 wk after the challenge.(ABSTRACT TRUNCATED AT 250 WORDS)