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Drug resistance mutations emerge in genetic sequences of HIV through drug-selective pressure. Drug resistance can be transmitted. In this review we discuss phylogenetic methods used to study the emergence of drug resistance and the spread of resistant viruses. [ABSTRACT FROM AUTHOR]

We observed an increased frequency of massive perivillous fibrin deposition (MPFD) during the second coronavirus disease 2019 (COVID-19) pandemic wave dominated by the Alpha variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MPFD associated with 100% reverse transcription polymerase chain reaction (RT-PCR) positivity for SARS-CoV-2 and detection by immunohistochemistry. The Alpha variant was identified in all placentas with MPFD that could be sequenced. [ABSTRACT FROM AUTHOR]

The impact of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOCs) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection plus two vaccine doses), S1 antibody, memory B cells, and heterologous neutralization of B.1.351, P.1, and B.1.617.2 plateaued, whereas B.1.1.7 neutralization and spike T cell responses increased. Serology using the Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over the 5 months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines. [ABSTRACT FROM AUTHOR]

The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is of public health concern in case of vaccine escape. Described are 3 patients with advanced human immunodeficiency virus (HIV)-1 and chronic SARS-CoV-2 infection in whom there is evidence of selection and persistence of novel mutations that are associated with increased transmissibility and immune escape. [ABSTRACT FROM AUTHOR]

Background Haemodialysis (HD) patients are extremely vulnerable to coronavirus disease 2019 (COVID-19). Their immune response after infection is unclear. We have found high seroconversion rates in this population, with 95% developing antibodies. It is unclear if and how long these antibodies persist. Here we investigate this with serial antibody (Ab) testing. Methods We identified HD patients who had confirmedsevere acute respiratory syndrome coronavirus 2 between March and May 2020 and measured monthly antibodies (immunoglobulin G/immunoglobulin M) in those who survived. We used a semiquantitative cut-off index to create a qualitative result and plotted optical density (OD) over time. We used linear regression to examine the slope, as well as noting peak OD and time to peak OD. We correlated these against baseline demographics, markers of illness severity and comorbidities. Results A total of 122 patients were analysed. All remained Ab positive during follow-up for a minimum of 148 days. Seventy-one percent had a positive gradient indicating increasing Ab positivity over time. We found that age (P = 0.01), duration of polymerase chain reaction positivity (P = 0.06) and the presence of symptoms (P = 0.05) were associated with a longer time to peak OD. Immunosuppression did not alter peak OD but did lead to a non-significant increase in time to peak OD, and more patients had a subsequent decrease in Ab levels (P = 0.02). Diabetic patients were more likely to have a positive slope (odds ratio 2.26). Conclusions These results indicate that HD patients have a robust and sustained Ab response after confirmed COVID-19 infection with no suggestion that immunosuppression weakens this response. Although it is unclear what protection these antibodies confer, this is encouraging that HD patients should respond to vaccination. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine rollout has coincided with the spread of variants of concern. We investigated whether single-dose vaccination, with or without prior infection, confers cross-protective immunity to variants. We analyzed T and B cell responses after first-dose vaccination with the Pfizer/BioNTech messenger RNA vaccine BNT162b2 in health care workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody-secreting memory B cell response to the spike protein, and neutralizing antibodies effective against variants B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated, or unchanged T cell responses, depending on human leukocyte antigen (HLA) polymorphisms. Single-dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants. [ABSTRACT FROM AUTHOR]

The exponential growth in coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across the UK has been successfully reversed by social distancing and lockdown.[1] RNA testing for prevalent infection is a key part of the exit strategy, but the role of testing for asymptomatic infection remains unclear.[2] Understanding the determinants of asymptomatic or pauci-symptomatic infection will provide new opportunities for personalised risk stratification and reveal much-needed correlates of protective immunity, whether induced by vaccination or natural exposure. Taken together, these data suggest that the rate of asymptomatic infection among HCWs more likely reflects general community transmission than in-hospital exposure. Prospective patients should be reassured that as the overall epidemic wave recedes, asymptomatic infection among HCWs is low and unlikely to be a major source of transmission. [Extracted from the article]

• Serological testing of Hepatitis A (HA) is frequently performed to investigate abnormal liver function tests and interpretation of equivocal and low-level positive anti-hepatitis A virus (HAV) IgM is difficult. This project characterised the association between low-level reactive anti-HAV IgM results and clinical disease. • Acute HA was associated with a mean Architect anti-HAV IgM value of 9.4. • Cases of HA had a mean peak ALT value of 1920. • All confirmed cases of acute HAV were associated with at least one clinical indicator, with 90% having a documented jaundice. • 100% of cases of acute HAV infection had anti-HAV IgM > 4.0. • Where clinical information was available, acute HA was excluded in all 31 patients with equivocal or • low-level reactive anti-HAV IgM results. • An interpretive algorithm is proposed including a clinically significant cut-off value for anti-HAV IgM. Hepatitis A (HA) remains a common infection globally that results in a self-limiting hepatitis with gastrointestinal and systemic symptoms. Direct detection of the virus in blood or stool is often not possible once symptomatic. Serological testing is frequently performed to investigate abnormal liver function tests – and interpretation of equivocal and low-level positive anti-hepatitis A virus (HAV) IgM is difficult even in the context of accurate epidemiological and clinical information. The aim of this project was to characterise the association between low-level reactive anti-HAV IgM results and clinical disease. Anti-HAV serology results recorded over 22 months were analysed. Equivocal and positive Architect anti-HAV IgM results were matched with available clinical and demographical data to identify confirmed and probable cases of acute HAV infection. Reactive anti-HAV IgM results were recorded for 88/7661 (1.15%) samples. Using clinical and laboratory data, 35 patients were confirmed to have acute HAV infection. Acute HA was associated with a mean Architect anti-HAV IgM value of 9.4 (SD 6.8-12.0). Cases of HA had a mean peak ALT value of 1920 (SD 682-3158). All confirmed cases (35/35) of acute HAV were associated with at least one clinical indicator, with 28/31 cases (90%) having a documented jaundice. All 35 (100%) cases of acute HAV infection had anti-HAV IgM > 4.0. A diagnosis other than acute HA was identified in 7/11 (63.6%) of low-level reactive anti-HAV IgM results (clinical data unavailable for further 4/11, 36.3%). Where clinical information was available, acute HA was excluded in all 31 patients with equivocal or low-level reactive anti-HAV IgM results. The accuracy of reports sent out to the clinician showed room for improvement. An interpretive algorithm is proposed including a clinically significant cut-off value for anti-HAV IgM. [ABSTRACT FROM AUTHOR]

A case study of 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, is presented. Topics include Genomes were assembled with reference based assembly and a bioinformatics pipeline; and region of the genome and 50% cut-off for defining single nucleotide polymorphisms (SNPs).

• The Roche Elecsys anti-SARS-CoV-2 and the Abbott SARS-CoV-2 IgG assay both had 100% specificity. • Overall sensitivity of the Roche assay was 92.1% at ≥14 days and 94.8% at ≥21 days, and the overall sensitivity of the Abbott assay was 94.4% at ≥14 days and 98.2% at ≥21 days. • Low rates of seroconversion seen in the immunocompromised (95.2% vs. 81.0% sensitivity at ≥21 days). • Sensitivity in the immunocompromised was numerically higher with the Abbott assay. • After excluding samples from immunocompromised patients sensitivity of both assays appeared excellent (100% for both assays at ≥21 days. • Short-term antibody waning was demonstrated with both assays. • Seroreversion was seen with the Roche assay. Introduction: During the COVID-19 pandemic, widespread introduction of SARS-CoV-2 antibody testing was introduced without a full understanding of the assays performance or the antibody kinetics following infection with SARS-CoV-2. Methods: We performed an evaluation of 2 anti-SARS-CoV-2 antibody assays with a more detailed look into the effect of immune status on antibody sensitivity. Results: Both assays demonstrated 100% specificity. The overall sensitivity of the Roche was 92.1% at ≥14 days and 94.8% at ≥21 days, and the overall sensitivity of the Abbott was 94.4% at ≥14 days and 98.2% at ≥21 days. 7/41 (17%) of patients included in this cohort were immunocompromised. Seroconversion was seen less commonly in the immunocompromised (4/7 [57.1%] seroconverted) and after excluding these patients 100% sensitivity was seen in both assays at ≥21 days. Discussion: Performance of both assays in the immunocompetent appeared excellent after 21 days postsymptom onset. Both assays are highly specific. [ABSTRACT FROM AUTHOR]