Initial Viral Load Research Articles

Evolution of spray and aerosol from respiratory releases: theoretical estimates for insight on viral transmission.

By modelling the evaporation and settling of droplets emitted during respiratory releases and using previous measurements of droplet size distributions and SARS-CoV-2 viral load, estimates of the evolution of the liquid mass and the number of viral copies suspended were performed as a function of time from the release. The settling times of a droplet cloud and its suspended viral dose are significantly affected by the droplet composition. The aerosol (defined as droplets smaller than 5 μm) resulting from 30 s of continued speech has O(1 h) settling time and a viable viral dose an order-of-magnitude higher than in a short cough. The time-of-flight to reach 2 m is only a few seconds resulting in a viral dose above the minimum required for infection, implying that physical distancing in the absence of ventilation is not sufficient to provide safety for long exposure times. The suspended aerosol emitted by continuous speaking for 1 h in a poorly ventilated room gives 0.1–11% infection risk for initial viral loads of , respectively, decreasing to 0.03–3% for 10 air changes per hour by ventilation. The present results provide quantitative estimates useful for the development of physical distancing and ventilation controls.

Viral Hepatitis B under Tenofovir in Ouagadougou (Burkina Faso)

Introduction: The treatment of viral hepatitis B is based on nucleotide analogs(s). In Burkina Faso, tenofovir is the most widely used because of its effectiveness and cost. The aim of this study was to describe viral hepatitis B under tenofovir in Ouagadougou. Material and Method: This was a longitudinal study, carried out in the outpatient department of the University Hospital of Tengandogo from May 1, 2013 to September 31, 2020, i.e. a period of seven (07) years and five (05) months. All patients with chronic hepatitis B virus who had been taking tenofovir for at least one year were included in the study. Cases of hepatocellular carcinoma and co-infections with hepatitis D, C and human immunodeficiency viruses were excluded from the study. Results: Of 321 patients with hepatitis B, 120 were on tenofovir and 34 were included in our study. These were 24 men and 10 women with an average age of 39 years. Hepatitis B was most often discovered following systematic or voluntary screening (44.1%) or pain in the right hypochondrium (23.5%). The mean initial viral load was 7.9 log. Ten patients had moderate compliance and four were non-compliant. No side effects were reported in 91.3% of cases. The virologic response was complete in 72.7% of patients after six months. Nine out of ten patients showed a biochemical response after 16 months. A histological response was observed in 19/27 patients within a mean of 26.7 months. HBs seroconversion was found in 2/24 patients. Conclusion: Tenofovir is effective in the treatment of viral hepatitis B, but HBs seroconversion is rarely achieved.

Association of initial viral load of SARS-CoV-2 with clinical progression and mortality in hospitalized patients with COVID-19

Association of initial viral load of SARS-CoV-2 with clinical progression and mortality in hospitalized patients with COVID-19

Lack of Association of Initial Viral Load in SARS-CoV-2 Patients with In-Hospital Mortality.

.Controversy exists in the literature regarding the possible prognostic implications of the nasopharyngeal SARS-CoV-2 viral load. We carried out a retrospective observational study of 169 patients, 96 (58.9%) of whom had a high viral load and the remaining had a low viral load. Compared with patients with a low viral load, patients with a high viral load did not exhibit differences regarding preexisting cardiovascular risk factors or comorbidities. There were no differences in symptoms, vital signs, or laboratory tests in either group, except for the maximum cardiac troponin I (cTnI), which was higher in the group with a higher viral load (24 [interquartile range 9.5–58.5] versus 8.5 [interquartile range 3–22.5] ng/L, P = 0.007). There were no differences in the need for hospital admission, admission to the intensive care unit, or the need for mechanical ventilation in clinical management. In-hospital mortality was greater in patients who had a higher viral load than in those with low viral load (24% versus 10.4%, P = 0.029). High viral loads were associated with in-hospital mortality in the binary logistic regression analysis (odds ratio: 2.701, 95% Charlson Index (CI): 1.084–6.725, P = 0.033). However, in an analysis adjusted for age, gender, CI, and cTnI, viral load was no longer a predictor of mortality. In conclusion, an elevated nasopharyngeal viral load was not a determinant of in-hospital mortality in patients with COVID-19, as much as age, comorbidity, and myocardial damage determined by elevated cTnI are.

Reducing Aerosol Transmission of SARS-CoV-2 in Craniomaxillofacial Osteosynthesis.

INTRODUCTION The current COVID-19 pandemic, accompanied by a wave of medical emergencies across the globe, has caused an unprecedented healthcare crisis, putting both health care providers and their patients at a high risk.1 Aerosol-generating procedures, especially from the aerodigestive tract, carry a serious risk of infection and calls for a better understanding of these procedures to mitigate the associated risks.2,3 Maxillofacial surgical procedures are known to generate significant amounts of aerosols and require specific measures beyond the conventional personal protective equipment to reduce exposure.4 The new norms, guidelines, and safety recommendations from governing/professional bodies of oral and maxillofacial surgery in India are comprehensive in their length and breadth, and they allow elective procedures. However, the concerns regarding the safety of many routine aerosol-generating procedures have not yet been addressed. Evidence suggests that inoculation with a high initial viral load may result in more severe patterns of infection,3 calling for innovative aerosol reduction methods during these procedures. In the maxillofacial practice, osteosynthesis is one of the most commonly undertaken procedures. Considering the high aerosol generation during osteosynthesis, it is recommended that an intermaxillary fixation be performed under local anesthesia. However, in most cases, intermaxillary fixation becomes infeasible due to poor patient compliance, thereby triggering unfavorable outcomes.4 An innovative method of drill activation has recently been proposed. The drill tip, if completely immersed in saline, is known to considerably reduce aerosol generation.4 The method suggests operative fields be fully submerged in saline before drill activation, and the saline be suctioned away before screw placement. However, this method has certain limitations. Firstly, effective submersion of saline is possible only in lower and upper muco-buccal pouch, thereby limiting its utility or mandible fracture fixation and occasionally anterior maxilla. Secondly, the submersion technique risks endanger adjacent vital structures (mental nerve, facial artery, etc) due to poor control and visibility. TECHNICAL NOTE One of the challenges during maxillofacial osteosynthesis is the aerosolization through the use of drills that create aerosols; the splatters that are ejected from the operating site in a ballistic trajectory contaminate the operator and the operating cubicle, thereby increasing the risk of virus exposure.5 Furthermore, in some patients, drilling alongside the nerve and posterior part of the oral cavity becomes a key challenge. We suggest, as an alternative, using the cannula or the trocar sleeve of a transbuccal set as a “drill sleeve” to efficiently reduce the aerosol production and yet protect the vital structures and improve the control over drill (Figs. 1, 2). (See Video [online], which demonstrates aerosol production with and without drill sleeve.) The trocar sleeve is ergonomically designed to be used by the surgeon’s non-operating hand and allows safe drilling even in the non-accessible bony surfaces in the oral cavity. If used, the drill sleeve with saline immersion technique can efficiently reduce aerosolization. Additionally, it can be easily used for fractures in the head and neck regions and also on the bony surfaces with vital structures in its close proximity. The guide helps in decreasing the use of other retractors, and thereby reducing traction on the adjacent soft tissue.5 Further, when used with saline immersion method, safe drilling is ensured even with an obscure view. {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video 1.","caption":"Demonstration of aerosol production with and without drill sleeve","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_38q12sch"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} Fig. 1.: Osteosynthesis on fibula flap without cannula showing aerosol production.Fig. 2.: Osteosynthesis on fibula flap with cannula showing less aerosol production.CONCLUSIONS We have found that the use of the drill sleeve (cannula) is a simple, cost-effective, and reliable method to minimize aerosol generation during surgical procedures. The drill sleeve method can be used in conjunction with the saline submerged drilling technique to further reduce the aerosol generation. Although the described method is not being prescribed as a surrogate to proper protective measures, nor does it condone the need for further studies to conclusively prove its efficacy, it can be considered as a potent alternative to reduce the aerosol production, especially given the severity of the Covid-19 crisis, which affects us on a day-to-day basis.

Clinical Characteristics of HIV-Associated Optic Neuritis.

IntroductionAcute optic neuritis (ON) has been increasingly reported in patients infected with human immunodeficiency virus (HIV). We aimed to describe clinical characteristics of HIV-infected patients with ON.Materials and MethodsThis observational retrospective study was performed from January 2008 to January 2016 in a university hospital in Bangkok, Thailand. Demographic data and clinical manifestations were retrospectively reviewed.ResultsWe included 10 HIV-infected patients and divided them into two groups: infectious and non-infectious ON. There were six patients in the infectious ON group (five males, mean age 33.6 years, median CD4 cell counts during ON episodes 36.5 cells/µL, high viral loads, median initial visual acuity [VA] 1.7, median VA difference [initial VA – follow-up VA] 0). Four patients developed cryptococcal meningitis and 2 developed neuro-syphilis. They were treated with amphotericin B plus fluconazole and penicillin G sodium, respectively. There were four patients in the non-infectious ON group (two males, mean age 44.3 years, median CD4 cell count during acute ON 157.5 cells/µL, undetectable viral loads, median initial VA 1.3, and median VA difference 1.2). They were given corticosteroid treatments. There were no statistically significant differences between the two groups with respect to age, sex, and initial VA. There were statistically significant differences in median VA difference and median CD4 cell counts between the two groups (p=0.02 and 0.03, respectively). There was a significant correlation between CD4 counts and duration in three non-infectious ON patients treated with antiretroviral therapy (ART, p<0.001).DiscussionPatients with infectious ON had low initial CD4 counts and high viral loads. Patients with non-infectious ON had increasing CD4 cell counts and undetectable HIV viral load following ART. The findings are highly suggestive of immune reconstitution inflammatory syndrome. The CD4 cell counts and viral loads may help to identify the type of acute ON in HIV-infected patients and establish proper therapies.

Rapid Antiretroviral Therapy (ART) Initiation at a Community-Based Clinic in Jackson, MS

BackgroundRapid antiretroviral therapy (ART), ideally initiated within twenty-four hours of diagnosis, may be crucial in efforts to increase virologic suppression and reduce HIV transmission. Recent studies, including demonstration projects in large metropolitan areas such as Atlanta, Georgia; New Orleans, Louisiana; San Francisco, California; and Washington D.C., have demonstrated that rapid ART initiation is a novel tool for expediting viral suppression in clinical settings. Here we present an evaluation of the impact of a rapid ART initiation program in a community-based clinic in Jackson, MS.MethodsWe conducted a retrospective chart review of patients who were diagnosed with HIV at Open Arms Healthcare Center or were linked to the clinic for HIV care by the Mississippi State Department of Health Disease Intervention Specialists from January 1, 2016 to December 31, 2018. Initial viral load, CD4+ T cell count, issuance of an electronic prescription (e-script), subsequent viral loads until suppressed and patient demographics were collected for each individual seen in clinic during the review period. Viral suppression was defined as a viral load less than 200 copies/mL. Rapid ART initiation was defined as receiving an e-script for antiretrovirals within seven days of diagnosis.ResultsBetween January 1, 2016 and December 31, 2018, 70 individuals were diagnosed with HIV and presented to Open Arms Healthcare Center, of which 63 (90%) completed an initial HIV counseling visit. Twenty-seven percent of patients were provided with an e-script for ART within 7 days of diagnosis. The median time to linkage to care for this sample was 12 days and 5.5 days for rapid ART starters (p < 0.001). Median time from diagnosis to viral suppression was 55 days for rapid ART starters (p = 0.03), a 22 day decrease from standard time to viral suppression.ConclusionOur results provide a similar level of evidence that rapid ART initiation is effective in decreasing time to viral suppression. Evidence from this evaluation supports the use of rapid ART initiation after an initial HIV diagnosis, including same-day treatment.

The effect of temperature on persistence of SARS-CoV-2 on common surfaces

BackgroundThe rate at which COVID-19 has spread throughout the globe has been alarming. While the role of fomite transmission is not yet fully understood, precise data on the environmental stability of SARS-CoV-2 is required to determine the risks of fomite transmission from contaminated surfaces.MethodsThis study measured the survival rates of infectious SARS-CoV-2, suspended in a standard ASTM E2197 matrix, on several common surface types. All experiments were carried out in the dark, to negate any effects of UV light. Inoculated surfaces were incubated at 20 °C, 30 °C and 40 °C and sampled at various time points.ResultsSurvival rates of SARS-CoV-2 were determined at different temperatures and D-values, Z-values and half-life were calculated. We obtained half lives of between 1.7 and 2.7 days at 20 °C, reducing to a few hours when temperature was elevated to 40 °C. With initial viral loads broadly equivalent to the highest titres excreted by infectious patients, viable virus was isolated for up to 28 days at 20 °C from common surfaces such as glass, stainless steel and both paper and polymer banknotes. Conversely, infectious virus survived less than 24 h at 40 °C on some surfaces.ConclusionThese findings demonstrate SARS-CoV-2 can remain infectious for significantly longer time periods than generally considered possible. These results could be used to inform improved risk mitigation procedures to prevent the fomite spread of COVID-19.

High-speed large-scale automated isolation of SARS-CoV-2 from clinical samples using miniaturized co-culture coupled to high-content screening

ObjectivesA novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the current coronavirus disease 2019 global pandemic. Only a few laboratories routinely isolate the virus, which is because the current co-culture strategy is highly time-consuming and requires a biosafety level 3 laboratory. This work aimed to develop a new high-throughput isolation strategy using novel technologies for rapid and automated isolation of SARS-CoV-2. MethodsWe used an automated microscope based on high-content screening (HCS), and we applied specific image analysis algorithms targeting cytopathic effects of SARS-CoV-2 on Vero E6 cells. A randomized panel of 104 samples, including 72 that tested positive by RT-PCR and 32 that tested negative, were processed with our HCS strategy and were compared with the classical isolation procedure. ResultsThe isolation rate was 43% (31/72) with both strategies on RT-PCR-positive samples and was correlated with the initial RNA viral load in the samples, in which we obtained a positivity threshold of 27 Ct. Co-culture delays were shorter with the HCS strategy, where 80% (25/31) of the positive samples were recovered by the third day of co-culture, compared with only 26% (8/30) with the classic strategy. Moreover, only the HCS strategy allowed us to recover all the positive samples (31 with HCS versus 27 with classic strategy) after 1 week of co-culture. ConclusionsThis system allows the rapid and automated screening of clinical samples with minimal operator workload, which reduces the risk of contamination and paves the way for future applications in clinical microbiology, such as large-scale drug susceptibility testing.

Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study.

BackgroundThe virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19.MethodsProspective cohort study in patients admitted with COVID-19. Serial nasopharyngeal and plasma samples were measured for SARS-CoV-2 RNA and S-IgG/N-IgG titers, respectively.Findings138 patients with confirmed infection were included; 76 (55%) underwent IL-6 blockade. Median initial SOFA (p = 0•016) and SARS-CoV-2 viral load (p<0•001, Mann-Whitney-Wilcoxon test) were significantly higher among anti-IL-6 users. Patients under IL-6 blockade showed delayed viral clearance in the Kaplan-Meier curves (HR 0•35 [95%CI] [0•15–0•81], log-rank p = 0•014), but an adjusted propensity score matching model did not demonstrate a significant relationship of IL-6 blockade with viral clearance (HR 1•63 [0•35–7•7]). Cox regression showed an inverse association between SARS-CoV-2 RNA clearance and the initial viral load (HR 0•35 [0•11–0•89]). Patients under the IL-6 blocker showed shorter median time to seropositivity, higher peak antibody titers, and higher cumulative proportion of seropositivity in the Kaplan Meier curves (HR 3•1 [1•9–5] for S-IgG; and HR 3•0 [1•9–4•9] for N-IgG; log-rank p<0•001 for both). However, no significant differences between groups were found in either S-IgG (HR 1•56 [0•41–6•0]) nor N-IgG (HR 0•96 [0•26–3•5]) responses in an adjusted propensity score analysis.InterpretationOur results suggest that in patients infected with SARS-CoV-2, IL-6 blockade does not impair the viral specific antibody responses. Although a delayed viral clearance was observed, it was driven by a higher initial viral load. The study supports the safety of this therapy in patients with COVID-19.FundingInstituto de salud Carlos III (Spain).

Association of Initial Viral Load in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Patients with Outcome and Symptoms

The dynamics of viral load (VL) of the severe acute respiratory syndrome coronavirus 2 and its association with different clinical parameters remain poorly characterized in the US patient population. Herein, we investigate associations between VL and parameters, such as severity of symptoms, disposition (admission versus direct discharge), length of hospitalization, admission to the intensive care unit, length of oxygen support, and overall survival in 205 patients from a tertiary care center in New York City. VL was determined using quantitative PCR and log10 transformed for normalization. Associations were tested with univariate and multivariate regression models. Diagnostic VL was significantly lower in hospitalized patients than in patients not hospitalized (log10 VL = 3.3 versus 4.0; P = 0.018) after adjusting for age, sex, race, body mass index, and comorbidities. Higher VL was associated with shorter duration of the symptoms in all patients and hospitalized patients only and shorter hospital stay (coefficient = −2.02, −2.61, and −2.18; P < 0.001, P = 0.002, and P = 0.013, respectively). No significant association was noted between VL, admission to intensive care unit, length of oxygen support, and overall survival. Our findings suggest a higher shedding risk in less symptomatic patients, an important consideration for containment strategies. Furthermore, we identify a novel association between VL and history of cancer. Larger studies are warranted to validate our findings.

Impact of Early Initiation of Direct-Acting Antiviral Therapy in Thoracic Organ Transplantation From Hepatitis C Virus Positive Donors

Thoracic organs from hepatitis C virus (HCV) positive donors are not commonly used for transplantation. The development of direct-acting antivirals (DAA) for HCV treatment has led to renewed interest in using HCV-positive organs. We evaluated HCV transmission rates, viremia clearance, and short-term outcomes in HCV-negative patients who received HCV-positive thoracic organs at our institution. From January 1, 2018 to May 31, 2019, 38 patients underwent HCV-positive thoracic organ transplantation (16 lungs and 22 hearts). Heart recipients were started on glecaprevir/pibrentasvir, a pangenotypic DAA, when they developed HCV viremia. Lung recipients were empirically started on glecaprevir/pibrentasvir within the first 3 post-transplant days. The primary outcome was cure of HCV defined as sustained virologic response at 12 weeks (SVR12). All heart recipients developed HCV viremia with median initial viral load of 64,565 IU/mL (interquartile range: 1660-473,151). The median time from DAA initiation to viremia clearance was 19 days (confidence interval: 15-27 days). Eleven out of 16 (68.8%) lung recipients developed HCV viremia with median initial viral load of 26 IU/mL (interquartile range: 15-143). The median time from DAA initiation to viremia clearance was 10 days (confidence interval: 6-17 days). Five out of 16 (31.3%) lung recipients never became viremic. All patients demonstrated SVR12. Thoracic organ transplantation from HCV viremic donors is safe with excellent short-term survival. Early initiation of HCV treatment results in rapid viremia clearance and SVR12. Long-term outcomes and optimal timing of DAA initiation remains to be determined.

Upper Respiratory Tract Viral Ribonucleic Acid Load at Hospital Admission Is Associated With Coronavirus Disease 2019 Disease Severity.

BackgroundThe outbreak of coronavirus disease 2019 (COVID-19) has aroused global public health concerns. Multiple clinical features relating to host profile but not for virus have been identified as the risk factors for illness severity and/or the outcomes in COVID-19.MethodsThe clinical features obtained from a cohort of 195 laboratory-confirmed, nasopharynx-sampled patients with COVID-19 in Guangdong, China from January 13 to February 29, 2020 were enrolled to this study. The differences in clinical features among 4 groups (mild, moderate, severe, and critical) and between 2 groups (severe vs nonsevere) were compared using one-way analysis of variance and Student’s t test, respectively. Principal component analysis and correlation analysis were performed to identify the major factors that account for illness severity.ResultsIn addition to the previously described clinical illness severity-related factors, including older age, underlying diseases, higher level of C-reactive protein, D-dimer and aspartate aminotransferase, longer fever days and higher maximum body temperature, larger number of white blood cells and neutrophils but relative less lymphocytes, and higher ratio of neutrophil to lymphocytes, we found that the initial viral load is an independent factor that accounts for illness severity in COVID-19 patients.ConclusionsThe initial viral load of severe acute respiratory syndrome coronavirus 2 is a novel virological predictor for illness severity of COVID-19.

Assessing the Contributions of Inactivation, Removal, and Transfer of Ebola Virus and Vesicular Stomatitis Virus by Disinfectant Pre-soaked Wipes.

Disinfectant pre-soaked wipes (DPW) containing activated hydrogen peroxide (AHP) or quaternary ammonium compounds (QAC) were tested using ASTM E2967-15 to determine removal, transfer, and inactivation of Ebola virus Makona variant (EBOV/Mak) and vesicular stomatitis virus (VSV) from contaminated stainless steel prototypic environmental surfaces. The infectious virus-contaminated carriers were subjected to wiping in the Wiperator per the standard. Following the use of negative control (J-Cloth)-, AHP-, or QAC-based wipes, recovery of residual infectious virus was assayed. In the case of the J-Cloth wipes (negative control), although removal of virus from inoculated carriers was extensive i.e., ~99% (1.9–3.5 log10) transfer of virus by these wipes to a secondary surface amounted to ≤ 2% (~3.8 log10) of the initial virus load. In the case of each DPW, >6 log10 removal/inactivation of virus was observed, with limited (EBOV/Mak) or no (VSV) virus transfer observed. The efficacy of wipes for decontaminating high-touch environmental surfaces spiked with EBOV/Mak or VSV is discussed. In summary, removal of EBOV/Mak and VSV using wipes was extensive in this study. In the absence of a sufficient concentration and contact time of an appropriate microbicidal active in DPW (such as the AHP- and QAC-based DPW tested), transfer of a low, albeit significant (from an infectious unit/infectious dose perspective), quantity of infectious virus from the inoculated surface to a secondary surface was observed. In the case of Ebola virus, it is essential that a DPW with an appropriate microbicidal active, following the appropriate contact time, be used to prevent unintended transfer of infectious virus to a clean secondary surface (as observed in negative control /J-Cloth). Otherwise, there exists the possibility of dissemination of Ebola virus and the associated risk of transmission of Ebola virus disease.

Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets?

COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described “cytokine storm” and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically.

Routine viral load monitoring and enhanced adherence counselling at a public ART centre in Mumbai, India.

BackgroundRoutine viral-load (VL) measurements along with enhanced adherence counselling (EAC) are recommended to achieve virological suppression among people living with HIV/AIDS (PLHA) on anti-retroviral therapy (ART). The Mumbai Districts AIDS Control Society along with Médecins Sans Frontières has provided routine VL measurements and EAC to PLHA on ART at King Edward Memorial (KEM) hospital, Mumbai since October-2016. This study aims to describe the initial VL results and impact of EAC on viral suppression and factors associated with initial viral non-suppression among patients with an initial detectable VL, in a cohort of patients tested between October-2016 and September-2018.MethodsThis is a descriptive study of PLHA on ART who received VL testing and EAC during October-2016 to September-2018. Log-binomial regression was used to identify factors associated with a high VL.ResultsAmong 3849 PLHA who underwent VL testing, 1603(42%) were female and median age was 42 years (IQR:35–48). Majority were referred for routine testing (3432(89%)) and clinical/immunological failure (233(6%)). Overall, 3402(88%) PLHA had suppressed VL at initial testing. Among 3432 tested for routine monitoring, 3141(92%) had VL suppressed. Of 291 with VL>1000c/ml, 253(87%) received EAC and after repeat VL, 70(28%) had VL<1000c/ml. Among 233 referred for clinical/immunological failure, 122(52%) had VL>1000c/ml and 109 have been switched to second-line ART.CD4 count<500 (aOR-5.0[95%CI 3.8–6.5]), on ART for<5 years (aOR-1.5[1.1–2.0]) and age<15 years (aOR-5.2[3.0–8.9]) were associated with an initial VL>1000c/ml. Factors associated with follow-up VL suppression included EAC (p<0.05) and being on second-line ART (p<0.05).ConclusionResults from a routine VL program in public sector in India were encouraging and in line with UNAIDS 90-90-90 targets. Routine VL monitoring along with EAC resulted in early switch to alternative optimised regimens while also preventing unnecessary switches. Along with the vital scale up of routine VL monitoring, implementation of enhanced adherence strategies for patients with detectable viral load should be ensured.

Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Transplantation of viral-positive hepatitis C-positive kidneys into uninfected recipients offers an opportunity to increase organ access.

The advent of direct-acting antivirals (DAAs) has provided the impetus to transplant kidneys from hepatitis C virus-positive donors into uninfected recipients (D+/R-). Thirty D+/R- patients received DAA treatment. Sustained virologic response (SVR12) was defined as an undetectable viral load in 12weeks after treatment. An age-matched cohort of uninfected donor and recipient pairs (D-/R-) transplanted during same time period was used for comparison. The median day of viral detection was postoperative day (POD) 2. The detection of viremia in D+/R- patients was 100%. The initial median viral load was 531 copies/μL (range: 10-1×108 copies/μL) with a median peak viral load of 3.4×105 copies/μL (range: 804-1.0×108 copies/μL). DAAs were initiated on median POD 9 (range: 5-41days). All 30 patients had confirmed SVR12. During a median follow-up of 10months, patient and graft survival was 100%, and acute rejection was 6.6% with no major adverse events related to DAA treatment. Delayed graft function was significantly decreased in D+/R- patients as compared to the age-matched cohort (27% vs 60%; P=.01). D+/R- transplantation offers patients an alternative strategy to increase access.

Diagnosis of SARS-CoV-2 infection based on CT scan vs RT-PCR: reflecting on experience from MERS-CoV

Diagnosis of SARS-CoV-2 infection based on CT scan vs RT-PCR: reflecting on experience from MERS-CoV

Bistable dynamics and Hopf bifurcation in a refined model of early stage HIV infection

Recent clinical studies have shown that HIV disease pathogenesis can depend strongly on many factors at the time of transmission, including the strength of the initial viral load and the local availability of CD4+ T-cells. In this article, a new within-host model of HIV infection that incorporates the homeostatic proliferation of T-cells is formulated and analyzed. Due to the effects of this biological process, the influence of initial conditions on the proliferation of HIV infection is further elucidated. The identifiability of parameters within the model is investigated and a local stability analysis, which displays additional complexity in comparison to previous models, is conducted. The current study extends previous theoretical and computational work on the early stages of the disease and leads to interesting nonlinear dynamics, including a parameter region featuring bistability of infectious and viral clearance equilibria and the appearance of a Hopf bifurcation within biologically relevant parameter regimes.