SARS-CoV-2 Reinfection in a Healthcare Worker Despite the Presence of Detectable Neutralizing Antibodies

So far, only a few reports about reinfections with SARS-CoV-2 have been published, and they often lack detailed immunological and virological data. We report about a SARS-CoV-2 reinfection with a genetically distinct SARS-CoV-2 variant in an immunocompetent female healthcare worker that has led to a mild disease course. No obvious viral escape mutations were observed in the second virus variant. The infectious virus was shed from the patient during the second infection episode despite the presence of neutralizing antibodies in her blood. Our data indicate that a moderate immune response after the first infection, but not a viral escape, did allow for reinfection and live virus shedding.

THE FIRST REPORT OF A POSSIBLE SARS-CoV-2 REINFECTION IN NEPAL

Since August 2020, a growing number of confirmed SARS-CoV-2 cases, after approximately three months, in most of them, again presented a new infection episode, which has been defined as reinfection. So far, no cases have been reported in Nepal, and still there is limited the number of them, especially of those fully confirmed. Here, we report a case and discuss its multiple implications in the ongoing COVID-19 pandemic.

Clinical complications in patients with primary and recurrent Clostridioides difficile infection: A real-world data analysis

Objective: Clostridioides difficile infection and recurrent C. difficile infection result in substantial economic burden and healthcare resource use. Sepsis and bowel surgery are known to be serious complications of C. difficile infection. This study evaluated clinical complications in patients with C. difficile infection and recurrent C. difficile infection during a 12-month period following the primary C. difficile infection. Methods: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus™ database was conducted for patients aged 18–64 years with an index C. difficile infection episode requiring inpatient stay or an outpatient visit for C. difficile infection followed by a C. difficile infection treatment. Each C. difficile infection episode ended after a 14-day C. difficile infection-claim-free period was observed. Recurrent C. difficile infection was defined as a further C. difficile infection episode within an 8-week window following the claim-free period. Clinical complications were documented over 12 months of follow-up and stratified by the number of recurrent C. difficile infection episodes (0 rCDI, 1 rCDI, 2 rCDI, and 3+ rCDI). Results: In total, 46,571 patients with index C. difficile infection episode were included. During the 6-month pre-index, the mean (standard deviation) baseline Charlson comorbidity index score, by increasing the recurrent C. difficile infection group, was 1.2 (1.9), 1.5 (2.2), 1.8 (2.3), and 2.3 (2.5). During the 12-month follow-up, sepsis occurred in 16.5%, 27.3%, 33.1%, and 43.3% of patients, and subtotal colectomy or diverting loop ileostomy was performed in 4.6%, 7.3%, 8.9%, and 10.5% of patients, respectively, by increasing the recurrent C. difficile infection group. Conclusions: Reduction in recurrent C. difficile infection is an important step to reduce the burden of serious clinical complications, and new treatments are needed to reduce C. difficile infection recurrence.

SUN-502 Graves’Disease and Autoimmune Hepatitis: Management Challenges

Graves’ disease (GD) is the most common etiology of hyperthyroidism and may be associated with other autoimmune disorders. Case report: A.J.M.N., 27 years old, previously healthy, presented with abdominal discomfort, nausea and headache. She used paracetamol 750mg t.i.d for seven days. After that, she noticed jaundice and sought medical care. On admission, patient was icteric, oriented, afebrile, without signs of heart failure or alterations in the intestinal habit. Admission laboratory tests: AST 1287 U/L (RR<46), ALT 1090 U/L (RR < 50), total bilirubin (TB) 45.66mg/dL (RR<1.3), direct bilirubin 42.22mg/dL (RR<0.8), TSH 0.04 mcUI/ml, FT4 > 6.99 ng/dL (RR< 2.19). Serology for infectious diseases (A, B and C viral hepatitis; cytomegalovirus; Epstein-Bar Virus, syphilis; Dengue virus) were negative. Available antibodies for autoimmune hepatitis (anti-LKM1, anti-mitochondria, anti-smooth muscle, anti-SSB, anti-SSA, anti-Rnp / Sm, anti-DNA) were non-reactive. Ceruloplasmin and serum copper were normal. TRAB 3 IU/L (RR<1.75 IU /L); Thyroid scintigraphy showed homogeneous distribution of parenchymal contrast and regular contours of the gland; 15-minute uptake was 9.19% (RR: 1%-6%). Propranolol (40mg q.i.d) was prescribed. Burch and Wartofsky score was 30 (possible previous infection episode as precipitation factor = 10 points and unexplained jaundice = 20 points). Since the patient did not have diagnostic criteria for thyroid storm and since liver function was greatly altered, we opted to treat the thyroid disease with 12mCi of radioiodine, instead of antithyroid drugs (ATD). Differential diagnosis of the liver disease, whether due to autoimmunity or due to hyperthyroidism itself or both, were considered. Corticosteroid therapy (prednisone 40mg) was added due to the possibility of the coexistence of GD and autoimmune hepatitis previously reported as been 1.8% of the autoimmune hepatitis cases. Liver biopsy was performed 4 days later, and the findings were compatible with this condition. Ten days after prednisone and 20 days after radioiodine, we noticed a drop in TB (45 to 20mg/dL) and liver enzymes (AST= 69 and ALT 106) and she was discharged with normal FT4. Autoimmune hepatitis and GD presents a management challenge because sometimes it is not possible to confirm the etiology before treatment. The abnormalities could have been due to hyperthyroidism itself, since all autoantibodies to autoimmune hepatitis have been ruled out, but liver biopsy was very suggestive of the autoimmune cause. Initiating ATD for rapid improvement of hyperthyroidism could represent a risk due to hepatotoxicity of these drugs. On the other hand, withholding the treatment in cases of hepatic insufficiency due to hyperthyroidism, can have disastrous consequences. The option with beta-blocker, radioiodine and corticosteroid was successful and might be considered in similar cases.

IFN-λ4 is associated with increased risk and earlier occurrence of gastrointestinal, respiratory and malarial infections in Malian children

ABSTRACTGenetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with impaired clearance of hepatitis C virus (HCV) infection. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we analyzed episodes of malaria, gastrointestinal and respiratory infections using information for 30,626 clinic visits from birth through up to 5 years of follow-up. Genetic polymorphisms IFNL4-rs368234815 and IFNL3-rs4803217 that functionally affect type III interferons were genotyped with TaqMan assays. For both genetic variants and each infection, we evaluated time-to-first episode and calculated odds ratios (ORs) for the risk of an infection episode during follow-up, controlling for relevant covariates. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), each copy of the rs368234815-dG allele was associated with an earlier first episode of a gastrointestinal infection (p=0.003) and respiratory infection (p=0.045). The risk of experiencing an infection episode during the follow-up was also significantly increased with each copy of the rs368234815-dG allele – for gastrointestinal infections (OR=1.53, 95%CI (1.13-2.07), p=0.005) and malaria (OR=1.30, 95%CI (1.02-1.65), p=0.033). IFNL4-rs368234815 and IFNL3-rs4803217 were in moderate linkage disequilibrium in this population (r2=0.78), and all the associations for rs4803217 were weaker and lost significance after adjusting for rs368234815, implicating IFN-λ4 and not IFN-λ3 as the primary cause of these associations. We conclude that the ability to produce IFN-λ4 may have broad health-related implications by negatively affecting the immune response and clinical outcomes of several common infections.

Quantification and determinants of the amount of respiratory syncytial virus (RSV) shed using real time PCR data from a longitudinal household study

Background: A better understanding of respiratory syncytial virus (RSV) epidemiology requires realistic estimates of RSV shedding patterns, quantities shed, and identification of the related underlying factors. Methods: RSV infection data arise from a cohort study of 47 households with 493 occupants, in coastal Kenya, during the 2009/2010 RSV season. Nasopharyngeal swabs were taken every 3 to 4 days and screened for RSV using a real time polymerase chain reaction (PCR) assay. The amount of virus shed was quantified by calculating the ‘area under the curve’ using the trapezoidal rule applied to rescaled PCR cycle threshold output. Multivariable linear regression was used to identify correlates of amount of virus shed. Results: The median quantity of virus shed per infection episode was 29.4 (95% CI: 15.2, 54.2) log10 ribonucleic acid (RNA) copies * days. Young age (<1 year), presence of upper respiratory symptoms, intra-household acquisition of infection, an individual’s first infection episode in the RSV season, and having a co-infection of RSV group A and B were associated with increased amount of virus shed. Conclusions: The findings provide insight into which groups of individuals have higher potential for transmission, information which may be useful in designing RSV prevention strategies.

Infectious Reactivation of Cytomegalovirus Explaining Age- and Sex-Specific Patterns of Seroprevalence

Human cytomegalovirus is a herpes virus with poorly understood transmission dynamics. We here provide quantitative estimates of the transmissibility of primary infection, reactivation, and re-infection using age-and sex-specific antibody response data. The data are optimally described by three distributions of antibody measurements, i.e. uninfected, infected, and infected after reactivation/re-infection. Estimates of seroprevalence increase gradually with age, such that at 80 years 73% (95%CrI: 64%-78%) of females and 62% (95%CrI: 55%-68%) of males is infected, while 57% (95%CrI: 47%-67%) of females and 37% (95%CrI: 28%-46%) of males has experienced a reactivation or re-infection episode. Merging the statistical analyses with transmission models, we find that infectious reactivation is key to provide a good fit fit to the data. Estimated reactivation rates increase from low values in children to 2%-6% per year older women. The results advance a hypothesis in which adult-to-adult transmission after infectious reactivation is the main driver of infection.

Quantification and determinants of the amount of respiratory syncytial virus (RSV) shed using real time PCR data from a longitudinal household study

Background: A better understanding of respiratory syncytial virus (RSV) epidemiology requires realistic estimates of RSV shedding patterns, quantities shed, and identification of the related underlying factors. Methods: RSV infection data arise from a cohort study of 47 households with 493 occupants, in coastal Kenya, during the 2009/2010 RSV season. Nasopharyngeal swabs were taken every 3 to 4 days and screened for RSV using a real time polymerase chain reaction (PCR) assay. The amount of virus shed was quantified by calculating the ‘area under the curve’ using the trapezoidal rule applied to rescaled PCR cycle threshold output. Multivariable linear regression was used to identify correlates of amount of virus shed. Results: The median quantity of virus shed per infection episode was 29.4 (95% CI: 15.2, 54.2) log10 ribonucleic acid (RNA) copies. Young age (<1 year), presence of upper respiratory symptoms, intra-household acquisition of infection, an individual’s first infection episode in the RSV season, and having a co-infection of RSV group A and B were associated with increased amount of virus shed. Conclusions: The findings provide insight into which groups of individuals have higher potential for transmission, information which may be useful in designing RSV prevention strategies.