Protection and Waning of Natural and Hybrid Immunity to SARS-CoV-2.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides natural immunity against reinfection. Recent studies have shown waning of the immunity provided by the BNT162b2 vaccine. The time course of natural and hybrid immunity is unknown. METHODS: Using the Israeli Ministry of Health database, we extracted data for August and September 2021, when the B.1.617.2 (delta) variant was predominant, on all persons who had been previously infected with SARS-CoV-2 or who had received coronavirus 2019 vaccine. We used Poisson regression with adjustment for confounding factors to compare the rates of infection as a function of time since the last immunity-conferring event. RESULTS: The number of cases of SARS-CoV-2 infection per 100,000 person-days at risk (adjusted rate) increased with the time that had elapsed since vaccination with BNT162b2 or since previous infection. Among unvaccinated persons who had recovered from infection, this rate increased from 10.5 among those who had been infected 4 to less than 6 months previously to 30.2 among those who had been infected 1 year or more previously. Among persons who had received a single dose of vaccine after previous infection, the adjusted rate was low (3.7) among those who had been vaccinated less than 2 months previously but increased to 11.6 among those who had been vaccinated at least 6 months previously. Among previously uninfected persons who had received two doses of vaccine, the adjusted rate increased from 21.1 among those who had been vaccinated less than 2 months previously to 88.9 among those who had been vaccinated at least 6 months previously. CONCLUSIONS: Among persons who had been previously infected with SARS-CoV-2 (regardless of whether they had received any dose of vaccine or whether they had received one dose before or after infection), protection against reinfection decreased as the time increased since the last immunity-conferring event; however, this protection was higher than that conferred after the same time had elapsed since receipt of a second dose of vaccine among previously uninfected persons. A single dose of vaccine after infection reinforced protection against reinfection.

Breakthrough infection and reinfection in patients with mpox.

Recently, patients with Mpox breakthrough infection or reinfection were constantly reported. However, the induction, risk factors, and important clinical symptoms of breakthrough infection and reinfection of Mpox virus (MPXV), as well as the factors affecting the effectiveness of Mpox vaccine are not characterized. Herein, a literature review was preformed to summarize the risk factors and important clinical symptoms of patients with Mpox breakthrough infection or reinfection, as well as the factors affecting the effectiveness of smallpox vaccine against Mpox. Results showed that MSM sexual behavior, condomless sexual behavior, multiple sexual partners, close contact, HIV infection, and the presence of comorbidity are important risk factors for Mpox breakthrough infection and reinfection. Genital ulcers, proctitis, and lymphadenopathy are the important clinical symptoms of Mpox breakthrough infection and reinfection. The effectiveness of emergent vaccination of smallpox vaccine for post-exposure of MPXV is associated with smallpox vaccination history, interval between exposure and vaccination, and history of HIV infection. This review provides a better understanding for the risk factors and important clinical symptoms of Mpox breakthrough infection and reinfection, as well as the formulation of Mpox vaccine vaccination strategies.

One dose versus two doses of COVID-19 vaccine for the prevention of breakthrough infections among people previously infected with SARS-Cov-2.

Studies have suggested the effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 reinfection among those previously infected. However, it is not yet clear if one dose of the vaccine is enough to prevent breakthrough infections compared to two doses. Using data from Optum deidentified COVID-19 Electronic Health Record (EHR) data set, we assessed breakthrough infection risks in individuals previously infected, comparing those with one vaccine dose to those with two doses. Propensity scores were applied to mitigate confounding factors. Follow-up spanned 6 months, beginning 2 weeks postvaccination. Among 213 845 individuals, those receiving one vaccine dose had a significantly higher breakthrough infection risk than the two-dose group (HR 1.69, 95% CI 1.54-1.85). This pattern was observed across genders, racial/ethnic groups, age categories, and vaccine types. This study reveals a substantial disparity in the risk of breakthrough infections between individuals receiving one versus two doses of the COVID-19 vaccine, suggesting that a single dose may not provide adequate protection against reinfection.

Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2018.

BACKGROUND: The use of artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan Africa (SSA), including mainland Tanzania, where it was introduced in December 2006. The WHO recommends regular assessment to monitor the efficacy of the first-line treatment specifically considering that artemisinin partial resistance was reported in Greater Mekong sub-region and has been confirmed in East Africa (Rwanda and Uganda). The main aim of this study was to assess the efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in mainland Tanzania. METHODS: A single-arm prospective anti-malarial drug efficacy trial was conducted in Kibaha, Mlimba, Mkuzi, and Ujiji (in Pwani, Morogoro, Tanga, and Kigoma regions, respectively) in 2018. The sample size of 88 patients per site was determined based on WHO 2009 standard protocol. Participants were febrile patients (documented axillary temperature ≥ 37.5 °C and/or history of fever during the past 24 h) aged 6 months to 10 years. Patients received a 6-dose AL regimen by weight twice a day for 3 days. Clinical and parasitological parameters were monitored during 28 days of follow-up to evaluate the drug efficacy and safety. RESULTS: A total of 653 children were screened for uncomplicated malaria and 349 (53.7%) were enrolled between April and August 2018. Of the enrolled children, 345 (98.9%) completed the 28 days of follow-up or attained the treatment outcomes. There were no early treatment failures, but recurrent infections were higher in Mkuzi (35.2%) and Ujiji (23%). By Kaplan-Meier analysis of polymerase chain reaction (PCR) uncorrected adequate clinical and parasitological response (ACPR) ranged from 63.4% in Mkuzi to 85.9% in Mlimba, while PCR-corrected ACPR on day 28 varied from 97.6% in Ujiji to 100% in Mlimba. The drug was well tolerated; the commonly reported adverse events were cough, runny nose, and abdominal pain. No serious adverse event was reported. CONCLUSION: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria. The high number of recurrent infections were mainly due to new infections, indicating the necessity of utilizing alternative artemisinin-based combinations, such as artesunate amodiaquine, which provide a significantly longer post-treatment prophylactic effect.

Exploring group differences in the response to a sexual risk reduction intervention to prevent hepatitis C virus reinfection in HIV-infected MSM: a mixed-methods study.

To prevent hepatitis C virus (HCV) reinfection, within the Swiss HCVree Trial, a preventive risk reduction intervention was implemented alongside curative treatment. Formative qualitative research identified three response patterns to the intervention. This mixed-methods study's aim was to cross-validate group differences in (a) the content of sexual risk reduction goals set during intervention and (b) the extent of their behavioural change in condomless anal intercourse with non-steady partners (nsCAI), sexualised and intravenous drug use at start and six-month post-intervention. Qualitative thematic analysis was used to summarise goal setting domains. Quantitative descriptive analysis was used to evaluate group differences based on assumptions of the group descriptions. Results largely confirmed assumptions on inter-group response differences in goal setting and behaviour: as expected group 1 Avoid risks showed the lowest HCV risk profile with changes in nsCAI. Group 2 Minimize-risks and Group 3 Accept-risks showed unchanged nsCAI. Group 3 had the highest HCV risk profile. Differences in their goal preferences (1: condom use; 2 reduction blood exposure; 3 safer dating) highlight diversity in attitudes to behavioural change. Our results improve understanding of variability in intervention responses such as changes in attitudes and behaviour. This provides evidence for intervention tailoring and outcome measurement.

Vaccine escape, increased breakthrough and reinfection in infliximab-treated patients with IBD during the Omicron wave of the SARS-CoV-2 pandemic.

OBJECTIVE: Antitumour necrosis factor (TNF) drugs impair serological responses following SARS-CoV-2 vaccination. We sought to assess if a third dose of a messenger RNA (mRNA)-based vaccine substantially boosted anti-SARS-CoV-2 antibody responses and protective immunity in infliximab-treated patients with IBD. DESIGN: Third dose vaccine induced anti-SARS-CoV-2 spike (anti-S) receptor-binding domain (RBD) antibody responses, breakthrough SARS-CoV-2 infection, reinfection and persistent oropharyngeal carriage in patients with IBD treated with infliximab were compared with a reference cohort treated with vedolizumab from the impaCt of bioLogic therApy on saRs-cov-2 Infection and immuniTY (CLARITY) IBD study. RESULTS: Geometric mean (SD) anti-S RBD antibody concentrations increased in both groups following a third dose of an mRNA-based vaccine. However, concentrations were lower in patients treated with infliximab than vedolizumab, irrespective of whether their first two primary vaccine doses were ChAdOx1 nCoV-19 (1856 U/mL (5.2) vs 10 728 U/mL (3.1), p<0.0001) or BNT162b2 vaccines (2164 U/mL (4.1) vs 15 116 U/mL (3.4), p<0.0001). However, no differences in anti-S RBD antibody concentrations were seen following third and fourth doses of an mRNA-based vaccine, irrespective of the combination of primary vaccinations received. Post-third dose, anti-S RBD antibody half-life estimates were shorter in infliximab-treated than vedolizumab-treated patients (37.0 days (95% CI 35.6 to 38.6) vs 52.0 days (95% CI 49.0 to 55.4), p<0.0001).Compared with vedolizumab-treated, infliximab-treated patients were more likely to experience SARS-CoV-2 breakthrough infection (HR 2.23 (95% CI 1.46 to 3.38), p=0.00018) and reinfection (HR 2.10 (95% CI 1.31 to 3.35), p=0.0019), but this effect was uncoupled from third vaccine dose anti-S RBD antibody concentrations. Reinfection occurred predominantly during the Omicron wave and was predicted by SARS-CoV-2 antinucleocapsid concentrations after the initial infection. We did not observe persistent oropharyngeal carriage of SARS-CoV-2. Hospitalisations and deaths were uncommon in both groups. CONCLUSIONS: Following a third dose of an mRNA-based vaccine, infliximab was associated with attenuated serological responses and more SARS-CoV-2 breakthrough infection and reinfection which were not predicted by the magnitude of anti-S RBD responses, indicative of vaccine escape by the Omicron variant. TRIAL REGISTRATION NUMBER: ISRCTN45176516.

Effectiveness of a Second Dose of an mRNA Vaccine Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Infection in Individuals Previously Infected by Other Variants.

BACKGROUND: Single-dose vaccination was widely recommended in the pre-Omicron era for persons with previous SARS-CoV-2 infection. The effectiveness of a second vaccine dose in this group in the Omicron era is unknown. METHODS: We linked nationwide population registries in Spain to identify community-dwelling individuals aged 18-64, with a positive SARS-CoV-2 test before single-dose mRNA vaccination (mRNA-1273 or BNT162b2). Every day between 3 January and 6 February 2022 we matched 1:1 individuals receiving a second mRNA vaccine dose and controls on sex, age, province, first dose type and time, month of primary infection, and number of previous tests. We then estimated Kaplan-Meier risks of confirmed SARS-CoV-2 reinfection. We performed a similar analysis in a Delta-dominant period, between 19 July and 30 November 2021. RESULTS: In the Omicron period, estimated effectiveness (95% CI) of a second dose was 62.2% (58.2-66.4%) 7-34 days after administration, similar across groups defined by age, sex, type of first vaccine, and time since the first dose. Estimated effectiveness was 65.4% (61.1-69.9%) for mRNA-1273 and 52.0% (41.8-63.1%) for BNT162b2. Estimated effectiveness was 78.5% (67.4-89.9%), 66.1% (54.9-77.5%), and 60.2% (55.5-64.8%) when primary infection had occurred in the Delta, Alpha, and pre-Alpha periods, respectively. In the Delta period, the estimated effectiveness of a second dose was 8.8% (-55.3% to 81.1%). CONCLUSIONS: Our results suggest that, over 1 month after administration, a second dose of mRNA vaccine increases protection against SARS-CoV-2 reinfection with the Omicron variant among individuals with single-dose vaccination and previously infected with another variant.

Prevention of Thelazia callipaeda Reinfection among Humans.

Thelazia callipaeda is a zoonotic vector-borne nematode that infects and causes eye disease among a wide range of domestic and wild mammals, including humans. We describe an unusual case of reinfection by this nematode in Serbia and call for a focus on preventive measures in endemic areas.

SARS-CoV-2 Reinfection Risk in Persons with HIV, Chicago, Illinois, USA, 2020-2022.

Understanding if persons with HIV (PWH) have a higher risk for SARS-CoV-2 reinfection may help tailor future COVID-19 public health guidance. To determine whether HIV infection was associated with increased risk for SARS-CoV-2 reinfection, we followed adult residents of Chicago, Illinois, USA, with SARS-CoV-2 longitudinally from their first reported infection through May 31, 2022. We matched SARS-CoV-2 laboratory data and COVID-19 vaccine administration data to Chicago's Enhanced HIV/AIDS Reporting System. Among 453,587 Chicago residents with SARS-CoV-2, a total of 5% experienced a SARS-CoV-2 reinfection, including 192/2,886 (7%) PWH and 23,642/450,701 (5%) persons without HIV. We observed higher SARS-CoV-2 reinfection incidence rates among PWH (66 [95% CI 57-77] cases/1,000 person-years) than PWOH (50 [95% CI 49-51] cases/1,000 person-years). PWH had a higher adjusted rate of SARS-CoV-2 reinfection (1.46, 95% CI 1.27-1.68) than those without HIV. PWH should follow the recommended COVID-19 vaccine schedule, including booster doses.

Sexually Transmitted Infections and the Risk of Reinfection Within 12 Months: A Population-Based Cohort.

BACKGROUND: Chlamydia, gonorrhea, and syphilis are common sexually transmitted infections that disproportionately affect specific groups in New Zealand (NZ). Predictors of reinfection are not well studied in NZ but could inform public health strategies to decrease sexually transmitted infection (STI) incidence. METHODS: New Zealand-wide chlamydia, gonorrhea, and syphilis cases during 2019 were identified using nationally collected data. Cases were followed-up to identify reinfection with the same STI within 12 months of initial infections. Logistic regression models were used to identify predictors for each STI reinfection. RESULTS: Determinants identified for increased odds of chlamydia reinfection were age groups 16-19 and 20-24 years, females, Maori and Pacific peoples, cases in the Northern region, and cases with at least one test before the initial infection. Age 40 years and older was associated with lower odds of gonorrhea reinfection, as was being of Asian ethnicity, living in Midland or Southern regions, and reporting heterosexual behavior. Region was the only statistically significant predictor for syphilis reinfection, with higher odds of reinfection for people living in the Central region. CONCLUSIONS: Our findings reflect disproportionate STI rates for some groups in NZ, with younger age groups, Maori and Pacific peoples, men who have sex with men, and people living in the Northern region experiencing higher odds of reinfection. Groups identified with higher odds for reinfection require increased access to culturally responsive health services to treat, understand, and prevent possible reinfection. Changes to current public health strategies could include culturally specific behavioral counseling, and improvements to and adherence to effective contract tracing.

Vaccine perceptions among Black adults with long COVID.

OBJECTIVES: Low uptake of COVID vaccines within Black communities is a concern given the stark racial inequities associated with the pandemic. Prior research details COVID vaccine perceptions within the general population and Black communities specifically. However, Black individuals with long COVID may be more or less receptive to future COVID vaccination than their peers without long COVID. The impact of COVID vaccination on long COVID symptoms is still controversial, since some studies suggest that vaccination can improve long COVID symptoms, whereas other studies report no significant change in symptoms or a worsening of symptoms. In this study, we aimed to characterize the factors influencing perceptions of COVID vaccines among Black adults with long COVID to inform future vaccine-related policies and interventions. DESIGN: We conducted 15 semi-structured, race-concordant interviews over Zoom with adults who reported physical or mental health symptoms that lingered for a month or more after acute COVID infection. We transcribed and anonymized the interviews and implemented inductive, thematic analysis to identify factors influencing COVID vaccine perceptions and the vaccine decision-making process. RESULTS: We identified five themes that influenced vaccine perceptions: (1) Vaccine safety and efficacy; (2) Social implications of vaccination status; (3) Navigating and interpreting vaccine-related information; (4) Possibility of abuse and exploitation by the government and scientific community; and (5) Long COVID status. Safety concerns were amplified by long COVID status and mistrust in social systems due to mistreatment of the Black community. CONCLUSIONS: Among the factors influencing COVID vaccine perceptions, participants reported a desire to avoid reinfection and a negative immune response. As COVID reinfection and long COVID become more common, achieving adequate uptake of COVID vaccines and boosters may require approaches that are tailored in partnership with the long COVID patient community.

[Fecal microbiota transplantation in an older patient with Clostridioides difficile recurrent infection. Report of one case]. / Trasplante de microbiota fecal por colonoscopía en paciente mayor de 65 años con infección recurrente de Clostridioides difficile: aún una estrategia subutilizada.

Clostridioides difficile infection (CDI) is a major public health problem and responsible for significant morbidity and mortality. Eighty percent of CDIs occur in adults older than 65 years of age due to a decreased gastrointestinal microbial diversity, immunosenescence and frailty. Thus, the most reported risk factor for recurrent CDI is older age since nearly 60% of cases occur in individuals aged ≥ 65 years. Fecal microbiota transplantation (FMT) is a highly cost-effective alternative to antibiotic treatment for patients with recurrent CDI. We report a 75-year-old male with recurrent CDI, who received a FMT after several unsuccessful antimicrobial treatments. He had a satisfactory evolution after the procedure and remained without diarrhea during the ensuing five months.

COVID-19 false dichotomies and a comprehensive review of the evidence regarding public health, COVID-19 symptomatology, SARS-CoV-2 transmission, mask wearing, and reinfection.

Scientists across disciplines, policymakers, and journalists have voiced frustration at the unprecedented polarization and misinformation around coronavirus disease 2019 (COVID-19) pandemic. Several false dichotomies have been used to polarize debates while oversimplifying complex issues. In this comprehensive narrative review, we deconstruct six common COVID-19 false dichotomies, address the evidence on these topics, identify insights relevant to effective pandemic responses, and highlight knowledge gaps and uncertainties. The topics of this review are: 1) Health and lives vs. economy and livelihoods, 2) Indefinite lockdown vs. unlimited reopening, 3) Symptomatic vs. asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 4) Droplet vs. aerosol transmission of SARS-CoV-2, 5) Masks for all vs. no masking, and 6) SARS-CoV-2 reinfection vs. no reinfection. We discuss the importance of multidisciplinary integration (health, social, and physical sciences), multilayered approaches to reducing risk ("Emmentaler cheese model"), harm reduction, smart masking, relaxation of interventions, and context-sensitive policymaking for COVID-19 response plans. We also address the challenges in understanding the broad clinical presentation of COVID-19, SARS-CoV-2 transmission, and SARS-CoV-2 reinfection. These key issues of science and public health policy have been presented as false dichotomies during the pandemic. However, they are hardly binary, simple, or uniform, and therefore should not be framed as polar extremes. We urge a nuanced understanding of the science and caution against black-or-white messaging, all-or-nothing guidance, and one-size-fits-all approaches. There is a need for meaningful public health communication and science-informed policies that recognize shades of gray, uncertainties, local context, and social determinants of health.

Platelet-Rich Fibrin in Combination with Local Antibiotics Optimizes Wound Healing After Deep Sternal Wound Problems and Prevents Reinfection.

OBJECTIVE: Disturbed wound healing is a significant problem in patients after cardiac surgery. Problems with deep sternal wound healing are rare, but can be quite difficult to treat. Furthermore, the therapy is highly expensive and consumes many of the patient's personal resources. Another major obstacle in this patient group is reinfection after secondary wound closure. We examined how to prevent early reinfection through the use of growth factors in combination with local antibiotics. METHODS: Our study included 232 patients with a deep sternal wound healing problem. After initial vacuum therapy, we planned secondary wound closure. During wound closure, we used only platelet-rich fibrin in a PRF group (109 patients). In another group (123 patients), we covered the wounds intraoperatively with a combination of PRF and local antibiotics (PRF CoDelivery). All patients were observed for 30 days for signs of early surgical site infection. RESULTS: After 30 days, 22 patients (20.2%) in the PRF group showed a persistent problem with wound healing with or without reinfection. In contrast, only 12 patients (9.8%) in the PRF CoDelivery group had this problem (p=0.023 PRF vs. PRF CoDelivery). CONCLUSION: The combination of growth factors and antibiotics was associated with a significantly reduced incidence of early reinfection and thus can be expected to have a positive impact on wound healing in complicated scenarios. Furthermore, the combination of PRF and local antibiotics was easy to use. Further studies are needed to verify these initial findings.

Influenza A Reinfection in Sequential Human Challenge: Implications for Protective Immunity and "Universal" Vaccine Development.

BACKGROUND: Identification of correlates of protection against human influenza A virus infection is important in development of broadly protective ("universal") influenza vaccines. Certain assumptions underlie current vaccine developmental strategies, including that infection with a particular influenza A virus should offer long-term or lifelong protection against that strain, preventing reinfection. In this study we report observations made when 7 volunteers participated in sequential influenza challenge studies where they were challenged intranasally using the identical influenza A(H1N1)pdm09 virus approximately 1 year apart. We evaluate and describe the outcomes of these 7 rechallenge participants and discuss what these results may suggest about correlates of protection and development of more broadly protective influenza vaccines. METHODS: Seven participants were enrolled in 2 viral challenge studies at 7.5- to 18.5-month intervals. Both challenge studies used the identical lot of influenza A (H1N1)pdm09 virus administered intranasally. We evaluated pre- and postchallenge hemagglutination inhibition, neuraminidase inhibition, and stalk antibody titers; peripheral blood leukocyte host gene expression response profiles; daily viral detection via nasal wash; and clinical signs and symptoms. RESULTS: At least 3 of 7 participants demonstrated confirmed laboratory evidence of sequential infection, with 5 of 7 demonstrating clinical evidence. CONCLUSIONS: The data presented in this report demonstrate that sequential infection with the identical influenza A virus can occur and suggest it may not be rare. These data raise questions about immune memory responses in an acute superficial respiratory mucosal infection and their implications in development of broadly protective influenza vaccines. Further investigation of these observations is warranted. CLINICAL TRIALS REGISTRATION: NCT01646138; NCT01971255.