SARS-CoV-2 in the Middle Ear. CovEar: A Prospective Pilot Study (preprint)

In post mortem analyses, SARS-CoV-2 was found in the middle ear of some, but not all patients with COVID-19 disease. It is not clear whether SARS-CoV-2 penetrated the ear passively post mortem, or existed in the middle ear of living patients during, and perhaps also after infection. This study investigates whether SARS-CoV-2 can be found in the middle ear of living patients during ear surgery. Swabs from the nasopharynx, the filter connected to the tracheal tube and secretion from the middle ear were collected during middle ear surgery. All samples were tested for the presence of SARS-CoV-2 with PCR. History of vaccination, COVID-19 and contact with SARS-CoV-2-positive individuals were recorded preoperatively. Postoperative SARS-CoV-2 infection was noted at the follow-up visit. Overall 63 participants (62%) were children and 39 (38%) were adults. SARS-CoV-2 was found in the middle ear and in the nasopharynx of two and four CovEar Study participants, respectively. The filter connected to the tracheal tube was sterile in all cases. Cycle threshold (ct) values of the PCR test were between 25.94 and 37.06. SARS-CoV-2 penetrates into the middle ear of living patients and can be found in asymptomatic patients. The presence of SARS-CoV-2 in the middle ear may have implications for ear surgery and can pose a risk of infection for operating room staff. It may also directly affect the audio-vestibular system.

COVID-19 outbreak and rural household food security in the Western Democratic Republic of the Congo.

Although global assessments of the initial impacts of the coronavirus disease (COVID-19) have focused on income, jobs, and health conditions, this study constitutes one of the first studies that assessed the impact of COVID-19 on food security in DRC and established the short-term implications of the COVID-19 outbreak on rural households' food security in DRC. In addition, the study recommendations contributed to shaping government interventions toward the pandemic in the Country. The study used data from four western provinces of the country on 1339 households. Our results show that 80 % of households experienced an increase in food prices, 61 % a noticeable decrease in the availability of food, and 54 % a decrease in their dietary diversity. Due to changes in food availability, dietary diversity, and food accessibility imposed by the COVID-19 outbreak, >70 % of households experienced either a decrease in the consumption of meat, milk, fish, and cereals or an increase in their consumption of traditional vegetables. In addition, COVID-19 significantly affected food security dimensions in larger households, households with a greater number of members aged 35 years and above, households headed by women, households where members participate in associations or cooperatives, households that depend on crop sales as the major source of income, and in poorer households. These findings highlight the significant implications of the COVID-19 outbreak on household food security in western DRC and underscore the need for emergency interventions to strengthen the resilience of rural people and accelerate their recovery and other long-term measures toward sustainable and inclusive development.

Kidney Transplant Recipients and Omicron: Outcomes, effect of vaccines and the efficacy and safety of novel treatments (preprint)

We aimed to describe the outcomes of Omicron infection in kidney transplant recipients (KTR), compare the efficacy of the community therapeutic interventions and report the safety profile of molnupiravir. From 142 KTRs diagnosed with COVID-19 infection after Omicron had become the dominant variant in the UK, 116 (78.9%) cases were diagnosed in the community; 47 receiving sotrovimab, 21 molnupiravir and 48 no treatment. 10 (20.8%) non-treated patients were hospitalised following infection, which was significantly higher than the sotrovimab group (2.1%), p=0.0048, but not the molnupiravir treated group (14.3%), p=0.47. The only admission following sotrovimab occurred in a patient infected with BA.2. One patient from the molnupiravir and no-treatment groups required ICU support, and both subsequently died, with one other death in the no-treatment group. No patient receiving sotrovimab died. 6/116 (5.2%) patients required dialysis following their diagnosis; 2 (9.5%) patients receiving molnupiravir and 4 (8.3%) no-treatment. This requirement was significantly higher in the molnupiravir group compared with the sotrovimab treated patients, in whom no patient required dialysis, p=0.035. Both molnupiravir treated patients requiring dialysis had features of systemic thrombotic microangiopathy. Post-vaccination serostatus was available in 110 patients. Seropositive patients were less likely to require hospital admission compared with seronegative patients, 6 (7.0%) and 6 (25.0%) respectively, p=0.023. Seropositive patients were also less likely to require dialysis therapy, (p=0.016). In conclusion, sotrovimab treatment in the community was associated with superior patient and transplant outcomes; its clinical efficacy against the BA.2 variant requires a rapid review. The treatment benefit of molnupiravir was not evident, and wider safety reporting in transplant patients is needed.

Immune responses following 3rd and 4th doses of heterologous and homologous COVID-19 vaccines in kidney transplant recipients (preprint)

Background Solid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. In this study, we report on immune responses to 3rd- (V3) and 4th- (V4) doses of heterologous and homologous vaccines in a kidney transplant population. Methods 724 kidney transplant recipients were prospectively screened for serological responses following 3 primary doses of a SARS-CoV2 vaccine. 322 patients were sampled post-V4 for anti-spike (anti-S), with 69 undergoing assessment of SARS-CoV-2 T-cell responses. All vaccine doses were received post-transplant, only mRNA vaccines were used for V3 and V4 dosing. All participants had serological testing performed post-V2 and at least once prior to their 1st dose of vaccine. Results 586/724 (80.9%) patients were infection-naive post-V3; 141/2586 (24.1%) remained seronegative at 31 (21-51) days post-V3. Timing of vaccination in relation to transplantation, OR: 0.28 (0.15-0.54), p=0.0001; immunosuppression burden, OR: 0.22 (0.13-0.37), p<0.0001, and a diagnosis of diabetes, OR: 0.49 (0.32-0.75), p=0.001, remained independent risk factors for non-seroconversion. Seropositive patients post-V3 had greater anti-S if primed with BNT162b2 compared with ChAdOx1, p=0.001. Post-V4, 45/239 (18.8%) infection-naive patients remained seronegative. De novo seroconversion post-V4 occurred in 15/60 (25.0%) patients who were seronegative post-V3. There was no difference in anti-S post-V4 by vaccine combination, p=0.50. Anti-S post-V4 were sequentially greater in those seroconverting post V2- compared with V3- , and V3- compared with V4-, at 1561 (567-5211), 379 (101-851) and 19 (9.7-48) BAU/ml respectively. T-cell responses were poor, with only 11/54 (20.4%) infection-naive patients having detectable T-cell responses post-V4, with no difference seen by vaccine type. Conclusion A significant proportion of transplant recipients remain seronegative following 3- and 4- doses of SARS-CoV-2 vaccines, with poor T-cell responses, and are likely to have inadequate protection against infection.

Comparative immunogenicity of heterologous versus homologous 3rd SARS-CoV-2 vaccine doses in kidney transplant recipients (preprint)

Background Solid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. Emerging evidence suggests at least equivalent immunogenicity of heterologous compared with homologous vaccine regimens in the general population. In this study, we report on immune responses to 3rd dose BNT162b2 vaccines in transplant recipients either primed with ChAdOx1 or BNT162b2. Methods 700 kidney transplant recipients were prospectively screened for serological responses (median time of 33 (21-52) days) following 3 primary doses of a SARS-CoV2 vaccine. All vaccine doses were received post-transplant, and all 3rd doses were BNT162b2. All participants had serological testing performed post-2nd vaccination at a median time of 34 (IQR 26-46) days following the 2nd inoculation, and at least once prior to their 1st dose of vaccine. Results 366/700 (52.3%) participants were primed with BNT162b2, whilst 334/700 (47.7) had received ChAdOx1. Overall, 139/700 (19.9%) participants had evidence of prior infection. Of 561 infection-naive participants, 263 (46.9%) had no detectable anti-S following 2-doses of vaccine (V2). 134 (23.9%) participants remained seronegative post 3rd vaccine (V3); 54/291 (18.6%) and 79/270 (29.3%) of participants receiving BNT162b2 and ChAdOx1 respectively, p=0.0029. Median anti-S concentrations were significantly higher post-V3 in patients who had received BNT162b2 compared with ChAdOx1, at 612 (27-234) versus 122 (7.1-1111) BAU/ml respectively, p<0.0001. Cellular responses were investigated in 30 infection-naive participants at a median time of 35 (24-46) days post-V3. Eighteen of 30 (60.0%) participants had undetectable T-cell responses. There were neither qualitative or quantitative differences in T-cell responses between those patients who received BNT162b2 or ChAdOx1 as their first 2-doses, with 10/16 (62.5%) and 8/14 (57.1%) respectively having undetectable T-cell responses, p=0.77. Conclusion A significant proportion of transplant recipients remain seronegative following 3 doses of SARS-CoV-2 vaccines, with anti-S concentrations lower in patients receiving heterologous versus homologous vaccinations.

Comparison of vaccine effectiveness against the Omicron (B.1.1.529) variant in patients receiving haemodialysis (preprint)

Background Emerging data suggest a reduction in SARS-CoV-2 vaccine effectiveness against Omicron SARS-CoV-2 infection. There is also evidence to show that Omicron is less pathogenic than previous variants. For clinically vulnerable populations, a less pathogenic variant may still have significant impact on morbidity and mortality. Herein we assess the clinical impact of Omicron infection, and vaccine effectiveness, in an in-centre haemodialysis (IC-HD) population. Methods One thousand, one hundred and twenty-one IC-HD patients were included in the analysis, all patients underwent weekly screening for SARS-CoV-2 infection via RT-PCR testing between 1 st December 2021 and 16 th January 2022. Screening for infection via weekly RT-PCR testing and 3-monthly serological assessment started prior to the vaccine roll out in 2020. Results Omicron infection was diagnosed in 145/1121 (12.9%) patients over the study period, equating to an infection rate of 3.1 per 1000 patient days. Vaccine effectiveness (VE) against Omicron infection in patients who had received a booster vaccine was 58 (23-75)%, p=0.002; VE was seen in patients who received either ChAdOx1, VE of 47(2-70)%, p=0.034, or BNT162b2, VE of 66 (36-81)%, p=0.0005, as their first two doses. No protection against infection was seen in patients who were partially vaccinated (2-doses), p=0.83. Prior infection was associated with reduced likelihood of Omicron infection, HR 0.69 (0.50-0.96), p=0.0289. Four (2.8%) patients died within 28 days of infection diagnosis, with no excess mortality was seen in patients with infection. Conclusion 3-doses of SARS-CoV-2 vaccines are required in ICHD to provide protection against Omicron infection.

Coronary artery calcification on low-dose chest CT is an early predictor of severe progression of COVID-19-A multi-center, multi-vendor study.

PURPOSE: Cardiovascular comorbidity anticipates severe progression of COVID-19 and becomes evident by coronary artery calcification (CAC) on low-dose chest computed tomography (LDCT). The purpose of this study was to predict a patient's obligation of intensive care treatment by evaluating the coronary calcium burden on the initial diagnostic LDCT. METHODS: Eighty-nine consecutive patients with parallel LDCT and positive RT-PCR for SARS-CoV-2 were included from three centers. The primary endpoint was admission to ICU, tracheal intubation, or death in the 22-day follow-up period. CAC burden was represented by the Agatston score. Multivariate logistic regression was modeled for prediction of the primary endpoint by the independent variables "Agatston score > 0", as well as the CT lung involvement score, patient sex, age, clinical predictors of severe COVID-19 progression (history of hypertension, diabetes, prior cardiovascular event, active smoking, or hyperlipidemia), and laboratory parameters (creatinine, C-reactive protein, leucocyte, as well as thrombocyte counts, relative lymphocyte count, d-dimer, and lactate dehydrogenase levels). RESULTS: After excluding multicollinearity, "Agatston score >0" was an independent regressor within multivariate analysis for prediction of the primary endpoint (p<0.01). Further independent regressors were creatinine (p = 0.02) and leucocyte count (p = 0.04). The Agatston score was significantly higher for COVID-19 cases which completed the primary endpoint (64.2 [interquartile range 1.7-409.4] vs. 0 [interquartile range 0-0]). CONCLUSION: CAC scoring on LDCT might help to predict future obligation of intensive care treatment at the day of patient admission to the hospital.

Comparison of humoral and cellular responses in kidney transplant recipients receiving BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines (preprint)

Background Attenuated immune responses to mRNA SARS-CoV-2 vaccines have been reported in solid organ transplant recipients. Most studies have assessed serological responses alone, and there is limited immunological data on vector-based vaccines in this population. This study compares the immunogenicity of BNT162b2 with ChAdOx1 in kidney transplant patients, assessing both serological and cellular responses. Methods 920 patients were screened for spike protein antibodies (anti-S) following 2 doses of either BNT162b2 (n=490) or ChAdOx1 (n=430). 106 patients underwent assessment with T-cell ELISpot assays. 65 health care workers were used as a control group. Results Anti-S was detected in 569 (61.8%) patients. Seroconversion rates in infection-naive patients who received BNT162b2 were higher compared with ChAdOx1, at 269/410 (65.6%) and 156/358 (43.6%) respectively, p<0.0001. Anti-S concentrations were higher following BNT162b, 58(7.1-722) BAU/ml, compared with ChAdOx1, 7.1(7.1-39) BAU/ml, p<0.0001. Calcineurin inhibitor monotherapy, vaccination occurring >1st year post-transplant and receiving BNT162b2 was associated with seroconversion. Only 28/106 (26.4%) of patients had detectable T-cell responses. There was no difference in detection between infection-naive patients who received BNT162b2, 7/40 (17.5%), versus ChAdOx1, 2/39 (5.1%), p=0.15. There was also no difference in patients with prior infection who received BNT162b2, 8/11 (72.7%), compared with ChAdOx1, 11/16 (68.8%), p=0.83. Conclusions. Enhanced humoral responses were seen with BNT162b2 compared with ChAdOx1 in kidney transplant patients. T-cell responses to both vaccines were markedly attenuated. Clinical efficacy data is still required but immunogenicity data suggests weakened responses to both vaccines in transplant patients, with ChAdOx1 less immunogenic compared with BNT162b2.

Comparison of immunogenicity between BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines in a large haemodialysis population (preprint)

Background Limited data exists on the immunogenicity of vector-based SARS-CoV-2 vaccines in patients with kidney disease. Given their use in over 180 countries, such data is of upmost importance to inform policy on optimal vaccination strategies. This study compares the immunogenicity of BNT162b2 with ChAdOx1 in patients receiving haemodialysis. Methods 1021 patients were screened for spike protein antibodies (anti-S) following 2 doses of either BNT162b2 (n=523) or ChAdOx1 (n=498). 191 patients underwent assessment with T-cell ELISpot assays. 65 health care workers were used as a control group. Results Anti-S was detected in 936 (91.2%) of patients post-vaccination. There was no difference in seroconversion rates between infection-naive patients who received BNT162b2, 248/281 (88.3%), compared with ChAdOx1, 227/272 (83.5%), p=0.11. Anti-S concentrations were higher following BNT162b, 462(152-1171) BAU/ml, compared with ChAdOx-1 79(20-213) BAU/ml, p<0.0001. Immunosuppression was associated with failure to seroconvert (p<0.0001); whilst being active on the transplant wait list was a predictor for seroconversion (p=0.02). Only 73 (38.2%) of patients had detectable T-cell responses post-vaccination, with no proportional difference between infection-naive patients who received BNT162b2, 2/19 (10.5%), versus ChAdOx1, 15/75 (20.0%), p=0.34. There were no quantitative differences in T-cell responses in infection-naive patients, with a median 2(0-16) SFU/106 PBMCs and 10(4-28) SFU/106 PBMCs in those receiving BNT162b2 and ChAdOx1 respectively, p=0.35. These responses were significantly weaker compared with healthy controls. Conclusions. Enhanced immunogenicity was seen with BNT162b2 compared with ChAdOx1, driven by superior humoral responses, with attenuated T-cell responses to both vaccines. Comparative data on clinical efficacy is now required.

The mechanistic overview of SARS-CoV-2 using angiotensin-converting enzyme 2 to enter the cell for replication: possible treatment options related to the renin-angiotensin system.

The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be made available as rapidly as possible. This relies on a solid theoretical understanding of the mechanisms of SARS-CoV-2 infection and host responses, which is coupled to the practical experience of clinicians that are treating patients. Because SARS-CoV-2 enters the cell by binding to angiotensin-converting enzyme 2 (ACE2), targeting ACE2 to prevent such binding seems an obvious strategy to combat infection. However, ACE2 performs its functions outside the cell and was found to enter the cell only by angiotensin II type 1 receptor (AT1R)-induced endocytosis, after which ACE2 is destroyed. This means that preventing uptake of ACE2 into the cell by blocking AT1R would be a more logical approach to limit entry of SARS-CoV-2 into the cell. Since ACE2 plays an important protective role in maintaining key biological processes, treatments should not disrupt the functional capacity of ACE2, to counterbalance the negative effects of the infection. Based on known mechanisms and knowledge of the characteristics of SARS-CoV we propose the hypothesis that the immune system facilitates SARS-CoV-2 replication which disrupts immune regulatory mechanisms. The proposed mechanism by which SARS-CoV-2 causes disease immediately suggests a possible treatment, since the AT1R is a key player in this whole process. AT1R antagonists appear to be the ideal candidate for the treatment of SARS-CoV-2 infection. AT1R antagonists counterbalance the negative consequences of angiotesnin II and, in addition, they might even be involved in preventing the cellular uptake of the virus without interfering with ACE2 function. AT1R antagonists are widely available, cheap, and safe. Therefore, we propose to consider using AT1R antagonists in the treatment of SARS-CoV-2.

Riesgos, contaminación y prevención frente al COVID-19 en el quehacer odontológico: una revisión

Introducción En abril del 2020, la pandemia del COVID-19 ha causado más de un millón de contagios y 54 600 muertes a nivel mundial. El contagio del SARS-CoV-2 es rápido y su transmisión se da a través de gotas de saliva. De allí su importancia en la odontología. Objetivo Identificar los principales riesgos, vías de transmisión y medidas de prevención frente al COVID-19. Métodos Se realizó una revisión de literatura científica de los últimos dos años sobre el tema, en las bases de datos PubMed, ScienceDirect, Google Scholar y Research Gate. Los descriptores utilizados fueron los siguientes: “coronavirus”, “COVID-19”, “dental”, “dentistry”, “oral”, “stomatology” y “aerosol”. Se encontraron 350 artículos, de lo que se seleccionaron 50 por su actualidad, relación y enfoque. La transmisión del COVID-19 se da principalmente a través de gotas de saliva, aerosoles y fómites. El virus puede subsistir por un tiempo en el ambiente y en las superficies. Los odontólogos son trabajadores de la salud con peligro de contagiarse debido que varios de sus procedimientos liberan aerosoles. La bioseguridad en el ejercicio de esta profesión debe ser estricta y extrema, también la limpieza y desinfección del ambiente y superficies de contacto. Conclusiones En la profesión odontológica el riesgo potencial de contaminación entre operados, asistentes y pacientes es alto. El conocimiento del agente causal y de la enfermedad permitirá reducir la posibilidad de contagio. El odontólogo debe considerar a los pacientes como sospechosos de COVID-19 y aplicar la bioseguridad a todo nivel.Alternate abstract: Introdução: A pandemia de COVID-19 tem causado mais de um milhão de infecções e 54.600 mortes até o momento. A disseminação do SARS-CoV-2 é rápida e sua transmissão ocorre através de gotículas de saliva, daí a sua importância na odontologia. Objetivo: Identificar os principais riscos, rotas de transmissão e medidas de prevenção contra o COVID-19. Métodos: Uma revisão da literatura científica dos últimos dois anos sobre o assunto foi realizada nas bases de dados PubMed, ScienceDirect, Google Scholar e Research Gate. Os descritores utilizados foram: Coronavírus, COVID-19, odontológico, odontológico, oral, estomatológico e aerossol. Foram encontrados 350 artigos, mas 50 foram selecionados por sua atualidade, relacionamento e foco. Análise e integração de informações: A transmissão do COVID-19 é realizada principalmente por meio de gotas de saliva, aerossóis e fomitos. O vírus pode subsistir por um tempo no ambiente e nas superfícies. Dentistas são profissionais de saúde que correm o risco de serem infectados porque vários de seus procedimentos liberam aerossóis. A biossegurança no exercício dessa profissão deve ser rigorosa e extrema, além da limpeza e desinfecção do ambiente e das superfícies de contato. Conclusões: Na profissão odontológica, o risco potencial de contaminação entre os operados, auxiliares e pacientes é alto. Conhecer o agente causador e a doença permitirá reduzir a possibilidade de contágio. O dentista deve considerar os pacientes como suspeitos do COVID-19 e aplicar a biossegurança em todos os níveis.Alternate abstract: Introduction In April 2020 The COVID-19 pandemic caused more than one million infections and 54 600 deaths to date around the world. The spread of SARS-CoV-2 is rapid, and its transmission is through droplets of saliva, hence its importance in dentistry. Objective Identify the main risks, transmission routes and prevention measures against COVID-19. Methods A review of the scientific literature of the last two years on the subject was carried out in the PubMed, ScienceDirect, Google Scholar and Research Gate databases. The descriptors used were: “coronavirus”, “COVID-19”, “dental”, “dentistry”, “oral”, “stomatology”, and “aerosol”. 350 articles were found, but 50 were selected for their topicality, relationship, and focus. The transmission of the COVID-19 is carried out m inly through saliva drops, aerosols and fomites. The virus can subsist for a time on the environment and surfaces. Dentists are health workers who are at risk of contagion because several of their procedures release aerosols. The biosecurity in the exercise of this profession must be strict and extreme, also the cleaning and disinfection of the environment and contact surfaces. Conclusions In the dental profession the potential risk of contamination among operators, assistants and patients is high. Knowing the causative agent and the disease allows you to reduce the possibility of contagion. The dentist must consider patients as suspects to COVID-19 and apply biosecurity at all levels.