Reduced ability to neutralize the Omicron variant among adults after infection and complete vaccination with BNT162b2, ChAdOx1, or CoronaVac and heterologous boosting.

COVID-19 vaccines have dramatically reduced rates of severe infection requiring hospitalization. However, SARS-CoV-2 variants have reduced vaccine effectiveness at preventing any symptomatic infection. This real-world study analyzed binding and neutralizing antibodies generated after complete vaccination and boosting across three vaccine platforms. Binding antibodies decayed most slowly in people under 60 with hybrid immunity. Neutralizing antibodies against Omicron BA.1 were reduced compared to other variants. The anamnestic anti-spike IgG response to the first boost was more pronounced than after the second boost. Monitoring of the effects of SARS-CoV-2 mutations on disease severity and the effectiveness of therapeutics is warranted.

Accuracy of saliva for SARS-CoV-2 detection in outpatients and their household contacts during the circulation of the Omicron variant of concern.

BACKGROUND: While nasopharyngeal (NP) swabs are considered the gold standard for severe acute respiratory coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection, several studies have shown that saliva is an alternative specimen for COVID-19 diagnosis and screening. METHODS: To analyze the utility of saliva for the diagnosis of COVID-19 during the circulation of the Omicron variant, participants were enrolled in an ongoing cohort designed to assess the natural history of SARS-CoV-2 infection in adults and children. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa coefficient were calculated to assess diagnostic performance. RESULTS: Overall, 818 samples were collected from 365 outpatients from January 3 to February 2, 2022. The median age was 32.8 years (range: 3-94 years). RT-PCR for SARS-CoV-2 was confirmed in 97/121 symptomatic patients (80.2%) and 62/244 (25.4%) asymptomatic patients. Substantial agreement between saliva and combined nasopharyngeal/oropharyngeal samples was observed with a Cohen's kappa value of 0.74 [95% confidence interval (CI): 0.67-0.81]. Sensitivity was 77% (95% CI: 70.9-82.2), specificity 95% (95% CI: 91.9-97), PPV 89.8% (95% CI: 83.1-94.4), NPV 87.9% (95% CI: 83.6-91.5), and accuracy 88.5% (95% CI: 85.0-91.4). Sensitivity was higher among samples collected from symptomatic children aged three years and older and adolescents [84% (95% CI: 70.5-92)] with a Cohen's kappa value of 0.63 (95% CI: 0.35-0.91). CONCLUSIONS: Saliva is a reliable fluid for detecting SARS-CoV-2, especially in symptomatic children and adolescents during the circulation of the Omicron variant.

The impact of feedback on laparoscopic skills for surgical residents during COVID-19

Background: We sought to determine how real-time video feedback compares to delayed written feedback on junior resident performance of laparoscopic skills using at-home laparoscopic training boxes. Methods: Junior surgical residents from Memorial University were randomized into 3 groups: a control group (group A), a delayed feedback group (group B), and a live feedback group (group C). Data collection was 5 months in duration. Participants practised prescribed laparoscopic skills biweekly. Intervention groups (B and C) received either delayed or live feedback on weekly practice from an expert. Pre- and post-testing were completed. Results: Twelve residents were recruited;1 was lost to follow-up. After the data collection period, the average number of pegs transferred correctly increased by 2.8 ± 1.7 for group A, 3.0 ± 2.6 for group B, and 2.0 ± 1.4 for group C. There was significant group variance (F2,8 = 5.928, p = 0.026). Post hoc testing resulted in group B outperforming groups A and C. For the intracorporeal knot tying task and number of throws completed, groups B and C both improved;no significant difference was noted between groups. Qualitative data showed an increase in confidence for all groups in completing the tasks and a preference for live compared with delayed feedback. Conclusion: Access to box trainers allowed residents to practise at home, leading to improved skill and confidence. Participants receiving delayed feedback showed a significant improvement in peg transfer. Further studies with larger sample sizes should be conducted on how feedback can affect resident outcomes in laparoscopic surgery skills.

Cohort-profile: Household transmission of SARS-CoV-2 in a low-resource community in Rio de Janeiro, Brazil.

PURPOSE: To better understand the household transmission of SARS-COV-2 in a low-resource community in Rio de Janeiro during the COVID-19 pandemic (2020-2022). PARTICIPANTS: This is an open prospective cohort study of children ≤12 years old and their household contacts. During home visits over 24 months, we collected data on sociodemographic characteristics, behavioural data, clinical manifestations of SARS-CoV-2, vaccination status, SARS-CoV-2 (reverse transcription-polymerase chain reaction) RT-PCR and anti-S antibody tests. Among adults, the majority of participants were women (62%). FINDINGS TO DATE: We enrolled 845 families from May 2020 to May 2022. The median number of residents per household was four. The median household density, defined as the number of persons per room, was 0.95. The risk of SARS-CoV-2 occurrence was higher in households with a high number of persons per room. Children were not the principal source of SARS-CoV-2 infections in their households during the first wave of the pandemic. FUTURE PLANS: Future studies will investigate cellular and humoral immune responses to locally circulating SARS-CoV-2 variants, which is relevant for the design of vaccines, antivirals and monoclonal antibodies. We will also engage in outreach to encourage vaccination as a means of limiting the transmission of novel SARS-CoV-2 variants and other emerging pathogens.

Epidemiological and clinical characteristics of children with confirmed COVID-19 infection in a tertiary referral hospital in Manila, Philippines.

BACKGROUND: COVID-19 has challenged the under-resourced health systems of low- and middle-income countries, significantly affecting child health. Available published data on Filipino children with COVID-19 infection are limited. This study aims to describe the epidemiological and clinical characteristics of pediatric patients with confirmed COVID-19 in an infectious disease hospital in Manila, Philippines. MAIN TEXT: This cross-sectional study reviewed data on patients ages 0 to 18 years with confirmed COVID-19 infection, admitted to San Lazaro Hospital from January 25, 2020 to January 25, 2022. Demographic data and clinical characteristics obtained from COVID-19 case investigation forms were summarized and compared between severe and non-severe cases. Risk factors for disease severity and mortality were analyzed. Of 115 patients, 64% were males. There were 87 patients (75.7%) with asymptomatic, mild, or moderate disease, and 28 cases (24.3%) with severe or critical illness. The median age of all patients was 10 years (interquartile range: 4-15 years). The majority of patients (40.9%) were adolescents ages 13 to 18 years. Predominant symptoms were fever (73.9%) and cough (55.7%). Patients with severe or critical illness were more likely to experience difficulty of breathing (55.2% vs 44.8%, p < 0.001), and have a longer hospital stay (11 days vs 8 days, p = 0.043). Among all patients, 48.7% had at least one underlying disease; and common infectious co-morbidities were tuberculosis (17.4%), dengue (12.2%), and HIV (4.3%). Having tuberculosis (p = 0.008) or at least one co-morbidity (p < 0.001) was associated with disease severity. Ten patients (8.7%) died; and mortality was higher among those with severe or critical illness (80% vs 20%, p < 0.001). Sepsis (p = 0.020) or having at least one co-morbidity (p = 0.007) was associated with death. CONCLUSION: Children of all ages remain susceptible to COVID-19 infection, and usually present with mild or moderate symptoms. In this study, many adolescents are affected, highlighting the value of COVID-19 vaccination in this age group. Understanding the clinical features of COVID-19 in Filipino children is essential to identifying and optimally managing those at highest risk of severe disease.

COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection during Delta-dominant and Omicron-dominant periods in Japan: a multi-center prospective case-control study (FASCINATE study).

BACKGROUND: Although several COVID-19 vaccines initially showed high efficacy, there have been concerns due to waning immunity and the emergence of variants with immune escape capacity. METHODS: A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period, compared to unvaccinated individuals. RESULTS: The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received mRNA-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% CI: 82-93) 14 days-3 months after dose 2 and 87% (95% CI: 38-97) 3-6 months after dose 2. During the Omicron-dominant period, VE was 56% (95% CI: 37-70) 14 days-3 months since dose 2, 52% (95% CI: 40-62) 3-6 months after dose 2, 49% (95% CI: 34-61) 6 + months after dose 2, and 74% (95% CI: 62-83) 14 + days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (i.e. mask-wearing/high-risk behaviors) yielded similar estimates, respectively. CONCLUSIONS: In Japan where most are infection-naïve and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level.

High SARS-CoV-2 Seroprevalence after Second COVID-19 Wave (October 2020-April 2021), Democratic Republic of the Congo.

Serologic surveys are important tools for estimating the true burden of COVID-19 in a given population. After the first wave of SARS-CoV-2 infections, a household-based survey conducted in Kinshasa, Democratic Republic of the Congo, estimated >292 infections going undiagnosed for every laboratory-confirmed case. To ascertain the cumulative population exposure in Kinshasa after the second wave of COVID-19, we conducted a prospective population-based cross-sectional study using a highly sensitive and specific ELISA kit. The survey included 2,560 consenting persons from 585 households; 55% were female and 45% male. The overall population-weighted, test kit-adjusted SARS-CoV-2 seroprevalence was 76.5% (95% CI 74.5%-78.5%). The seroprevalence was 4-fold higher than during the first wave, and positivity was associated with age, household average monthly income, and level of education. Evidence generated from this population-based survey can inform COVID-19 response, especially vaccination campaign strategies in the context of vaccine shortages and hesitancy.

Cohort-profile: Household transmission of SARS-CoV-2 in a low-resource community in Rio de Janeiro, Brazil

Purpose To better understand the household transmission of SARS-COV-2 in a low-resource community in Rio de Janeiro during the COVID-19 pandemic (2020–2022). Participants This is an open prospective cohort study of children ≤12 years old and their household contacts. During home visits over 24 months, we collected data on sociodemographic characteristics, behavioural data, clinical manifestations of SARS-CoV-2, vaccination status, SARS-CoV-2 (reverse transcription-polymerase chain reaction) RT-PCR and anti-S antibody tests. Among adults, the majority of participants were women (62%). Findings to date We enrolled 845 families from May 2020 to May 2022. The median number of residents per household was four. The median household density, defined as the number of persons per room, was 0.95. The risk of SARS-CoV-2 occurrence was higher in households with a high number of persons per room. Children were not the principal source of SARS-CoV-2 infections in their households during the first wave of the pandemic. Future plans Future studies will investigate cellular and humoral immune responses to locally circulating SARS-CoV-2 variants, which is relevant for the design of vaccines, antivirals and monoclonal antibodies. We will also engage in outreach to encourage vaccination as a means of limiting the transmission of novel SARS-CoV-2 variants and other emerging pathogens.

SARS-CoV-2 seroprevalence and infection rate in Manila, Philippines prior to national vaccination program implementation: a repeated cross-sectional analysis.

BACKGROUND: SARS-CoV-2 seroepidemiological studies are used to guide public health decision making and to prepare for emerging infectious diseases. Disease occurrence estimates are limited in the Philippines, the country with the highest reported number of coronavirus disease-related deaths in the Western Pacific region. We aimed to estimate SARS-CoV-2 seroprevalence and infection rate among outpatient clinic attendees in Metro Manila prior to the implementation of the national coronavirus disease vaccination program. METHODS: We conducted repeated cross-sectional surveys at the animal bite clinic in San Lazaro Hospital, Manila, the Philippines across four periods, 3 months apart, between May 2020 and March 2021. Multivariable logistic regression was used to assess associations between different characteristics and infection status including seropositivity. RESULTS: In total 615 participants were enrolled, ranging from 115 to 174 per period. Seroprevalence quadrupled between the first (11.3%) and second (46.8%) periods and plateaued thereafter (third-46.0%, fourth-44.6%). Among seropositive participants, total antibody concentration was comparable throughout the first to third periods but declined between the third and fourth periods. Infection prevalence was comparable across enrollment periods (range 2.9-9.5%). Post-secondary education [aOR 0.42 (95% CI 0.26, 0.67)] was protective, and frontline work [aOR 1.81 (95% CI 1.18, 2.80)] was associated with increased odds of seropositivity. Frontline work status [aOR 2.27 (95% CI 1.10, 4.75)] and large household size [aOR 2.45 (95% CI 1.18, 5.49)] were associated with increased odds of infection. CONCLUSIONS: The quadrupling of seroprevalence over 3 months between the first and second enrollment periods coincided with the high burden of infection in Metro Manila in early 2020. Our findings suggest a limit to the rise and potential decline of population-level SARS-CoV-2 infection-induced immunity without introduction of vaccines. These results may add to our understanding of how immunity develops against emerging infectious diseases including coronaviruses.

Detection of SARS-CoV-2 and HHV-8 from a large pericardial effusion in an HIV-positive patient with COVID-19 and clinically diagnosed Kaposi sarcoma: a case report.

BACKGROUND: Pericardial effusion is a late manifestation of HIV more commonly observed in individuals with depressed CD4 counts. Although Mycobacterium tuberculosis remains to be one of the most frequently identified pathogens in the pericardial fluid among people living with HIV, less commonly described etiologies include SARS-CoV-2 that causes coronavirus disease and human herpesvirus-8 which is associated with Kaposi sarcoma. Isolation of more than one pathogen in normally sterile sites remains challenging and rare. We report the first documentation of both SARS-CoV-2 and HHV-8 in the pericardial fluid. CASE PRESENTATION: We present the case of a young man in his 20s with a recent history of clinically diagnosed pulmonary tuberculosis who was admitted for progressive dyspnea and cough. He had multiple violaceous cutaneous lesions on the face, neck, and trunk and diffused lymphadenopathies. He tested positive for SARS-CoV-2 on admission. The patient was clinically diagnosed with pneumonia, Kaposi sarcoma, and HIV/AIDS. Empiric broad spectrum antimicrobial regimen was subsequently initiated. HIV with low CD4 count was confirmed during hospitalization. Echocardiography revealed a large pericardial effusion, in impending cardiac tamponade. Frond-like fibrin strands, extending to the parietal pericardium, were also observed. Pericardiostomy yielded hemorrhagic, exudative effusion with lymphocytic predominance. SARS-CoV-2 and HHV-8 were detected in the pericardial fluid, and bacterial, fungal, and tuberculous studies were negative. The patient had clinical improvement after pericardial drainage. However, despite our best clinical care, he developed a nosocomial infection leading to clinical deterioration and death. CONCLUSION: Detection of SARS-CoV-2 and HHV-8 in the pericardial fluid is rare, and interpretation of their significance in clinical care is challenging. However, coronavirus disease and Kaposi sarcoma must be considered and adequately addressed in immunocompromised adults presenting with large pericardial effusion.

Safeguarding equitable HIV service delivery at the health facility-level in a resource-limited setting during the pandemic.

The COVID-19 pandemic had a severe impact on delivering essential health services, including HIV service delivery. Among the challenges encountered and addressed by the HIV and AIDS Department of the San Lazaro Hospital were ensuring continued access to antiretroviral therapy and ensuring continuity of client education and empowerment. Two years into the pandemic, challenges still ensue, such as protecting health care providers from COVID-19 and regular clinical monitoring of clients. This highlights the importance of urgent action to strengthen the resilience of health systems at all its levels, not only to respond to sudden disturbances, but also to transform and evolve to be able to better face future pandemics.

Social and Behavioral Factors Associated with Lack of Intent to Receive COVID-19 Vaccine, Japan.

Persons in Japan who did not intend to receive COVID-19 vaccines after widespread rollout were less likely than others to engage in preventive measures or to be afraid of getting infected or infecting others. They were also not less likely to engage in potentially high-risk behaviors, suggesting similar or higher exposure risks.

Incidence of SARS-CoV-2 over four epidemic waves in a low-resource community in Rio de Janeiro, Brazil: A prospective cohort study.

Background: Incidence rates of SARS-CoV-2 infections in low-resource communities can inform vaccination strategies and non-pharmaceutical interventions (NPIs). Our objective was to estimate incidence over four epidemic waves in a slum in Rio de Janeiro, a proxy for economically deprived areas in the Global South. Methods: Prospective cohort of children and household contacts screened for SARS-CoV-2 by PCR and serology (IgG). The incidence density of PCR positive infections estimated for each wave - the first wave, Zeta, Gamma and Delta - was compared to an index combining NPIs and vaccination coverage. Findings: 718 families and 2501 individuals were enrolled, from May 2020 to November 2021. The incidence density of SARS-CoV-2 infection due to the first wave was 2, 3 times that of the other waves. The incidence among children was lower than that of older participants, except in later waves, when vaccination of the elderly reached 90%. Household agglomeration was significantly associated with incidence only during the first wave. Interpretation: The incidence of infection greatly exceeded rates reported in similar cohorts. The observed reduction in incidence in the elderly during the Delta variant wave, in spite of the rollback of NPIs, can be attributed to increased vaccine coverage. The high incidence in young people reinforces the importance of vaccination in this age group, a policy that has yet to receive the full support of some sectors of society. Funding: UK Medical Research Council, Foundation for the Advancement of Science of the State of Rio de Janeiro, National Council for Scientific and Technological Development.

5-Aminolevulinic acid antiviral efficacy against SARS-CoV-2 omicron variant in vitro.

The coronavirus disease 2019 (COVID 19) pandemic continues to pose a threat to global health. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) has spread rapidly worldwide and became dominant in many countries. A natural 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) has demonstrated antiviral activity in Wuhan, Alpha, Beta, Gamma, and Delta variants of SARS-CoV-2 infections in vitro. In this study, we report antiviral activity of 5-ALA, 5-ALA with SFC led to IC50 of 329 and 765/191, respectively after infection with Omicron variant of SARS-CoV-2 in vitro. Our finding suggests that 5-ALA could be used as antiviral drug candidate to treat Omicron variant infected patients.

Behavioral factors associated with SARS-CoV-2 infection in Japan.

BACKGROUND: The relative burden of COVID-19 has been less severe in Japan. One reason for this may be the uniquely strict restrictions imposed upon bars/restaurants. To assess if this approach was appropriately targeting high-risk individuals, we examined behavioral factors associated with SARS-CoV-2 infection in the community. METHODS: This multicenter case-control study involved individuals receiving SARS-CoV-2 testing in June-August 2021. Behavioral exposures in the past 2 weeks were collected via questionnaire. SARS-CoV-2 PCR-positive individuals were cases, while PCR-negative individuals were controls. RESULTS: The analysis included 778 individuals (266 [34.2%] positives; median age [interquartile range] 33 [27-43] years). Attending three or more social gatherings was associated with SARS-CoV-2 infection (adjusted odds ratio [aOR] 2.00 [95% CI 1.31-3.05]). Attending gatherings with alcohol (aOR 2.29 [1.53-3.42]), at bars/restaurants (aOR 1.55 [1.04-2.30]), outdoors/at parks (aOR 2.87 [1.01-8.13]), at night (aOR 2.07 [1.40-3.04]), five or more people (aOR 1.81 [1.00-3.30]), 2 hours or longer (aOR 1.76 [1.14-2.71]), not wearing a mask during gatherings (aOR 4.18 [2.29-7.64]), and cloth mask use (aOR 1.77 [1.11-2.83]) were associated with infection. Going to karaoke (aOR 2.53 [1.25-5.09]) and to a gym (aOR 1.87 [1.11-3.16]) were also associated with infection. Factors not associated with infection included visiting a cafe with others, ordering takeout, using food delivery services, eating out by oneself, and work/school/travel-related exposures including teleworking. CONCLUSIONS: We identified multiple behavioral factors associated with SARS-CoV-2 infection, many of which were in line with the policy/risk communication implemented in Japan. Rapid assessment of risk factors can inform decision making.

Unique Mode of Antiviral Action of a Marine Alkaloid against Ebola Virus and SARS-CoV-2.

Lamellarin α 20-sulfate is a cell-impenetrable marine alkaloid that can suppress infection that is mediated by the envelope glycoprotein of human immunodeficiency virus type 1. We explored the antiviral action and mechanisms of this alkaloid against emerging enveloped RNA viruses that use endocytosis for infection. The alkaloid inhibited the infection of retroviral vectors that had been pseudotyped with the envelope glycoprotein of Ebola virus and SARS-CoV-2. The antiviral effects of lamellarin were independent of the retrovirus Gag-Pol proteins. Interestingly, although heparin and dextran sulfate suppressed the cell attachment of vector particles, lamellarin did not. In silico structural analyses of the trimeric glycoprotein of the Ebola virus disclosed that the principal lamellarin-binding site is confined to a previously unappreciated cavity near the NPC1-binding site and fusion loop, whereas those for heparin and dextran sulfate were dispersed across the attachment and fusion subunits of the glycoproteins. Notably, lamellarin binding to this cavity was augmented under conditions where the pH was 5.0. These results suggest that the final action of the alkaloid against Ebola virus is specific to events following endocytosis, possibly during conformational glycoprotein changes in the acidic environment of endosomes. Our findings highlight the unique biological and physicochemical features of lamellarin α 20-sulfate and should lead to the further use of broadly reactive antivirals to explore the structural mechanisms of virus replication.

Adapting an evidence-based contraceptive behavioural intervention delivered by mobile phone for young people in Zimbabwe.

BACKGROUND: Despite the availability of a range of contraceptive methods, young people around the world still face barriers in accessing and using them. The use of digital technology for the delivery of health interventions has expanded rapidly. Intervention delivery by mobile phone can be a useful way to address young people's needs with regard to sexual and reproductive health, because the information can be digested at a time of the recipients' choosing. This study reports the adaptation of an evidence-based contraceptive behavioural intervention for young people in Zimbabwe. METHODS: Focus group discussions and in depth interviews were used to evaluate the 'fit' of the existing intervention among young people in Harare, Zimbabwe. This involved determining how aligned the content of the existing intervention was to the knowledge and beliefs of young Zimbabweans plus identifying the most appropriate intervention deliver mode. The verbatim transcripts were analysed using a thematic analysis. The existing intervention was then adapted, tested and refined in subsequent focus group discussions and interviews with young people in Harare and Bulawayo. RESULTS: Eleven key themes resulted from the discussions evaluating the fit of the intervention. While there were many similarities to the original study population, key differences were that young people in Zimbabwe had lower levels of personal and smart mobile phone ownership and lower literacy levels. Young people were enthusiastic about receiving information about side effects/side benefits of the methods. The iterative testing and refinement resulted in adapted intervention consisting of 97 messages for female recipients (94 for male), delivered over three months and offered in English, Shona and Ndebele. CONCLUSIONS: Young people in Zimbabwe provided essential information for adapting the existing intervention. There was great support for the adapted intervention among the young people who took part in this study. The adapted intervention is now being implemented within an integrated community-based sexual and reproductive health service in Zimbabwe.