Uptake of COVID-19 vaccines among healthcare workers and the effect of nudging interventions: A mixed methods study.

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, vaccination of healthcare workers (HCWs) has a critical role because of their high-risk exposure and being a role model. Therefore, we aimed to investigate vaccine hesitancy and the role of mandatory polymerase chain reaction (PCR) testing and education for vaccine uptake. METHODS: We conducted an explanatory sequential designed observational mixed-methods study, including quantitative and qualitative sections consecutively in two different pandemic hospitals between 15 September 2021 and 1 April 2022. The characteristics of vaccinated and unvaccinated HCWs were compared. The vaccine hesitancy scales were applied, and the effect of nudging, such as mandatory PCR and education, were evaluated. In-depth interviews were performed to investigate the COVID-19 vaccine hesitancy among HCWs according to Health Belief Model. RESULTS: In total, 3940 HCWs were included. Vaccine hesitancy was more common among males than females, the ancillary workers than other health professions, and nonmedical departments than other departments. After the mandatory weekly PCR request nudge, 83.33 % (130/156) vaccine-hesitant HCWs were vaccinated, and 8.3 % (13/156) after the small group seminars and mandatory PCR every two days. The rate of COVID-19 vaccination was raised from 95.5 % to 99.67  % (3927/3940). At the end of in-depth interviews (n = 13), the vaccine hesitancy determinants were distrust, fear of uncertainty, immune confidence and spirituality, the media effect, social pressure, and obstinacy. CONCLUSIONS: The nudging interventions such as mandatory PCR testing and small group seminars helped raise the rate of COVID-19 vaccination; the most effective one is mandatory PCR.

Effectiveness of tocilizumab in non-intubated cases with COVID-19: a systematic review and meta-analysis.

PURPOSE: Tocilizumab, a monoclonal IL-6 receptor blocker, is an effective agent for severe-to-critical cases of COVID-19; however, its target patients for the optimum use need to be detailed. We performed a systematic review and meta-analysis to define its effect among severely ill but non-intubated cases with COVID-19. METHODS: We searched PubMed, Scopus, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Medrxiv, and Biorxiv until February 13, 2022, for non-intubated cases, and included randomized-controlled trials (RCT) based on bias assessment. The primary outcomes were the requirement of invasive mechanical ventilation and mortality. Random effect and fixed-effect models were used. The heterogeneity was measured using the χ2 and I2 statistics, with χ2 p ≤ 0.05 and I2 ≥ 50% indicating the presence of significant heterogeneity. We registered the study to the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number CRD42021232575. RESULTS: Among 261 articles, 11 RCTs were included. The pooled analysis of the 11 RCTs demonstrated that the rate of mortality was significantly lower in the tocilizumab group than in the control group (20.0% and 24.2%, OR: 0.84, 95% CI 0.73-0.96, and heterogeneity I2 = 0%. p = 0.82.). The mechanical ventilation rate was lower in the tocilizumab group than the control group (27% vs 35.2%, OR: 0.76, 95% CI 0.67-0.86, and heterogeneity I2 = 6%. p = 0.39). CONCLUSION: Among non-intubated severe COVID-19 cases, tocilizumab reduces the risk of invasive mechanical ventilation and mortality compared to standard-of-care treatment.

Vaccines and therapeutics for immunocompromised patients with COVID-19.

The COVID-19 pandemic has disproportionately impacted immunocompromised patients. This diverse group is at increased risk for impaired vaccine responses, progression to severe disease, prolonged hospitalizations and deaths. At particular risk are people with deficiencies in lymphocyte number or function such as transplant recipients and those with hematologic malignancies. Such patients' immune responses to vaccination and infection are frequently impaired leaving them more vulnerable to prolonged high viral loads and severe complications of COVID-19. Those in turn, have implications for disease progression and persistence, development of immune escape variants and transmission of infection. Data to guide vaccination and treatment approaches in immunocompromised people are generally lacking and extrapolated from other populations. The large clinical trials leading to authorisation and approval of SARS-CoV-2 vaccines and therapeutics included very few immunocompromised participants. While experience is accumulating, studies focused on the special circumstances of immunocompromised patients are needed to inform prevention and treatment approaches.

COVID-19-associated mucormycosis: a systematic review and meta-analysis of 958 cases.

BACKGROUND: Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic. OBJECTIVES: To provide a comprehensive insight into the characteristics of COVID-19-associated mucormycosis, through a systematic review and meta-analysis. METHODS OF DATA SYNTHESIS: Demographic information and clinical features were documented for each patient. Logistic regression analysis was used to predict the risk of mortality. DATA SOURCES: PubMed, Scopus, Web of Science, Cochrane, CINAHL, Ovid MEDLINE, and FungiSCOPE. STUDY ELIGIBILITY CRITERIA: Studies reporting individual-level information in patients with adult COVID-19-associated mucormycosis (CAM) between 1 January 2020 and 28 December 2022. PARTICIPANTS: Adults who developed mucormycosis during or after COVID-19. INTERVENTIONS: Patients with and without individual clinical variables were compared. ASSESSMENT OF RISK OF BIAS: Quality assessment was performed based on the National Institutes of Health quality assessment tool for case series studies. RESULTS: Nine hundred fifty-eight individual cases reported from 45 countries were eligible. 88.1% (844/958) were reported from low- or middle-income countries. Corticosteroid use for COVID-19 (78.5%, 619/789) and diabetes (77.9%, 738/948) were common. Diabetic ketoacidosis (p < 0.001), history of malignancy (p < 0.001), underlying pulmonary (p 0.017), or renal disease (p < 0.001), obesity (p < 0.001), hypertension (p 0.040), age (>65 years) (p 0.001), Aspergillus coinfection (p 0.037), and tocilizumab use during COVID-19 (p 0.018) increased the mortality. CAM occurred on an average of 22 days after COVID-19 and 8 days after hospitalization. Diagnosis of mucormycosis in patients with Aspergillus coinfection and pulmonary mucormycosis was made on average 15.4 days (range, 0-35 days) and 14.0 days (range, 0-53 days) after hospitalization, respectively. Cutaneous mucormycosis accounted for <1% of the cases. The overall mortality rate was 38.9% (303/780). CONCLUSION: Mortality of CAM was high, and most reports were from low- or middle-income countries. We detected novel risk factors for CAM, such as older age, specific comorbidities, Aspergillus coinfection, and tocilizumab use, in addition to the previously identified factors.

Plasma proteomics identify potential severity biomarkers from COVID-19 associated network.

PURPOSE: Coronavirus disease 2019 (COVID-19) continues to threaten public health globally. Severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection-dependent alterations in the host cell signaling network may unveil potential target proteins and pathways for therapeutic strategies. In this study, we aim to define early severity biomarkers and monitor altered pathways in the course of SARS-CoV-2 infection. EXPERIMENTAL DESIGN: We systematically analyzed plasma proteomes of COVID-19 patients from Turkey by using mass spectrometry. Different severity grades (moderate, severe, and critical) and periods of disease (early, inflammatory, and recovery) are monitored. Significant alterations in protein expressions are used to reconstruct the COVID-19 associated network that was further extended to connect viral and host proteins. RESULTS: Across all COVID-19 patients, 111 differentially expressed proteins were found, of which 28 proteins were unique to our study mainly enriching in immunoglobulin production. By monitoring different severity grades and periods of disease, CLEC3B, MST1, and ITIH2 were identified as potential early predictors of COVID-19 severity. Most importantly, we extended the COVID-19 associated network with viral proteins and showed the connectedness of viral proteins with human proteins. The most connected viral protein ORF8, which has a role in immune evasion, targets many host proteins tightly connected to the deregulated human plasma proteins. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma proteomes from critical patients are intrinsically clustered in a distinct group than severe and moderate patients. Importantly, we did not recover any grouping based on the infection period, suggesting their distinct proteome even in the recovery phase. The new potential early severity markers can be further studied for their value in the clinics to monitor COVID-19 prognosis. Beyond the list of plasma proteins, our disease-associated network unravels altered pathways, and the possible therapeutic targets in SARS-CoV-2 infection by connecting human and viral proteins. Follow-up studies on the disease associated network that we propose here will be useful to determine molecular details of viral perturbation and to address how the infection affects human physiology.

Alterations in vaginal microbiota among pregnant women with COVID-19.

The maintenance of vaginal microbiota is an important factor to achieve optimum pregnancy outcomes. The study aims to describe the alterations in the composition of vaginal microbiota in pregnant women with coronavirus disease 2019 (COVID-19). This was a prospective case-control study. Vaginal swabs were collected from uninfected pregnant women (n = 28) and pregnant women with COVID-19 (n = 19) during the active phase of infection and within a month after recovering from infection. The vaginal microbiota on the swabs was examined by 16S rRNA gene sequencing. Shannon index indicates that alpha diversity is significantly higher in women with COVID-19 (p = 0.012). There was a significant decrease in Firmicutes (p = 0.014) with an increase in Bacteroidota (p = 0.018) phyla and a decrease in Lactobacillus (p = 0.007) genus in women with COVID-19 than those of uninfected pregnant women. The relative abundance of L. crispatus, L. iners, L. gasseri, and L. jensenii were lower in the COVID-19 group than in uninfected pregnant women. In subgroup analysis, the amount of Ureaplasma spp. was higher in women with moderate/severe than those of asymptomatic/mild disease (p = 0.036). The study revealed that vaginal dysbiosis with low abundance of Lactobacillus species occurred in pregnant women infected with severe acute respiratory syndrome coronavirus-2. These findings may lead to new studies to elucidate the risk of pregnancy adverse outcomes related to COVID-19.

The association between Acinetobacter baumannii infections and the COVID-19 pandemic in an intensive care unit.

We aimed to describe the increased rate of Acinetobacter baumannii infections during the COVID-19 pandemic and define its significance within the last five years. This study was performed in a tertiary hospital with 280 beds and included all patients infected with A. baumannii in the intensive care unit between January 1, 2018, and June 30, 2022. A. baumannii-infected patients in the intensive care unit 27 months before the pandemic and 27 months during the pandemic were included. Pulsed-field gel electrophoresis was performed to assess clonal relatedness. The infection control measures were specified based on the findings and targeted elimination. In total, 5718 patients were admitted to the intensive care unit from January 1st, 2018, to June 30th, 2022. A. baumannii infection was detected in 81 patients. Compared to the pre-pandemic era, the rate of A. baumannii infection during the pandemic was 1.90 times higher (OR: 1.90, 95% CI: [1.197, 3.033]). Clonality assessment of multidrug-resistant A. baumannii samples revealed eight clusters with one main cluster comprising 14/27 isolates between 2021 and 2022. The case fatality rate of the pre-pandemic and pandemic era was not different statistically (83.33% vs. 81.48%, p = 0.835). Univariate analysis revealed the association of mechanical ventilation (p = 0.002) and bacterial growth in tracheal aspirate (p = 0.001) with fatality. During the COVID-19 pandemic, potential deficits in infection control measures may lead to persistent nosocomial outbreaks. In this study, the introduction of enhanced and customized infection control measures has resulted in the containment of an A. baumannii outbreak.

[Consensus Report from Turkish Society of Cardiology: COVID-19 and Cardiovascular Diseases. What cardiologists should know. (25th March 2020)]. / Türk Kardiyoloji Dernegi Uzlasi Raporu: COVID-19 Pandemisi ve Kardiyovasküler Hastaliklar Konusunda Bilinmesi Gerekenler (25 Mart 2020).

In December 2019, in the city of Wuhan, in the Hubei province of China, treatment-resistant cases of pneumonia emerged and spread rapidly for reasons unknown. A new strain of coronavirus (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) was identified and caused the first pandemic of the 21st century. The virus was officially detected in our country on March 11, 2020, and the number of cases increased rapidly; the virus was isolated in 670 patients within 10 days. The rapid increase in the number of patients has required our physicians to learn to protect both the public and themselves when treating patients with this highly infectious disease. The group most affected by the outbreak and with the highest mortality rate is elderly patients with known cardiovascular disease. Therefore, it is necessary for cardiology specialists to take an active role in combating the epidemic. The aim of this article is to make a brief assessment of current information regarding the management of cardiovascular patients affected by COVID-19 and to provide practical suggestions to cardiology specialists about problems and questions they have frequently encountered.

[Turkish Cardiology Association Consensus Report: COVID-19 Pandemic and Cardiovascular Diseases (May 13, 2020)]. / Türk Kardiyoloji Dernegi Uzlasi Raporu: COVID-19 Pandemisi ve Kardiyovasküler Hastaliklar Konusunda Bilinmesi Gerekenler (13 Mayis 2020).

In December 2019, in the city of Wuhan, in the Hubei province of China, treatment-resistant cases of pneumonia emerged and spread rapidly for reasons unknown. A new strain of coronavirus (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) was identified and caused the first pandemic of the 21st century. The virus was officially detected in our country on March 11, 2020, and the number of cases increased rapidly; the virus was isolated in 670 patients within 10 days. The rapid increase in the number of patients has required our physicians to learn to protect both the public and themselves when treating patients with this highly infectious disease. The group most affected by the outbreak and with the highest mortality rate is elderly patients with known cardiovascular disease. Therefore, it is necessary for cardiology specialists to take an active role in combating the epidemic. The aim of this article is to make a brief assessment of current information regarding the management of cardiovascular patients affected by COVID-19 and to provide practical suggestions to cardiology specialists about problems and questions they have frequently encountered.

COVID-19 Severity among Healthcare Workers: Overweight Male Physicians at Risk.

We performed a prospective longitudinal cohort study in two healthcare settings. In total, 909 HCWs out of 3982 (23.35%) were diagnosed with COVID-19 before the vaccination era. Eighty-five per cent of COVID-19 positive HCWs (n = 774) were asymptomatic or mild, and 15% were moderate or severe. The mean age of the infected HCWs in the moderate or severe group was higher than the mild or asymptomatic group (35.4 vs. 31.3 years, p < 0.001). Thirty-two per cent of HCWs were male and the rate of male gender was more frequent in the moderate/severe group (p = 0.009). The rate of those who have cardiovascular diseases (p = 0.003) and diabetes mellitus (p = 0.044) were significantly higher among the HCWs with moderate or severe COVID-19. In multivariate analysis, male gender (OR:1.65, CI:1.11-2.46, p = 0.013), BMI > 30 (OR: 1.9, CI: 1.09-3.51, p = 0.024), and being physician (OR: 2.56, CI:1.45-4.52, p = 0.001) were found to be associated with moderate or severe COVID-19.

Effect of BTN162b2 and CoronaVac boosters on humoral and cellular immunity of individuals previously fully vaccinated with CoronaVac against SARS-CoV-2: A longitudinal study.

BACKGROUND: It is essential to know about immune response levels after booster doses of the two different types of vaccines, mRNA, and the inactivated, currently used against COVID-19. For this purpose, we aimed to determine the effects of BNT162b2 (BNT) and CoronaVac (CV) boosters on the humoral and cellular immunity of individuals who had two doses of CV vaccination. METHODS: The study was conducted in three centers (Koc University Hospital, Istanbul University Cerrahpasa Hospital, and Istanbul University, Istanbul Medical School Hospital) in Istanbul, Turkey. Individuals who had been previously immunized with two doses of CV and no history of COVID-19 were included. The baseline blood samples were collected 3-5 months after the second dose of CV. Follow-up blood samples were taken 1 and 3 months after administration of third doses of CV, or one dose of BNT boosters. Neutralizing antibody titers were measured by plaque reduction assay. The CD4+ T cell, CD8+ T cell, effector CD4+CD38+CD69+ T cell, and effector CD8+CD38+CD69+ T cell ratios were determined by flow cytometry. The intracellular IFN-γ and IL-2 responses were measured by ELISpot assay. RESULTS: We found a 3.38-fold increase in neutralizing antibody geometric mean titers (NA GMT, 78.69) 1 month after BNT booster and maintained at the third month (NA GMT, 80). Nevertheless, in the CV booster group, significantly lower NA GMT than BNT after 1 month and 3 months were observed (21.44 and 28.44, respectively) (p < .001). In the ELISpot assay, IL-2 levels after BNT were higher than baseline and CV booster (p < .001) while IFN-γ levels were significantly higher than baseline (p < .001). The CD8+CD38+CD69+ and CD4+CD38+CD69+ T cells were stimulated predominantly in the third month of the BNT boosters. CONCLUSION: The neutralizing antibody levels after 3 months of the BNT booster were higher than the antibody levels after CV in fully vaccinated individuals. On the contrary, ratio of the effector T cells increased along with greater IFN-γ activation after BNT booster. By considering the waning immunity, we suggest a new booster dose with BNT for the countries that already had two doses of primary CV regimens.

Role of institutional, cultural and economic factors in the effectiveness of lockdown measures.

OBJECTIVE: This study considered the role of institutional, cultural and economic factors in the effectivemess of lockdown measures during the coronavirus pandemic. Earlier studies focusing on cross-sectional data found an association between low case numbers and a higher level of cultural tightness. Meanwhile, institutional strength and income levels revealed a puzzling negative relationship with the number of cases and deaths. METHODS: Data available at the end of September 2021 were used to analyse the dynamic impact of these factors on the effectiveness of lockdowns. The cross-sectional dimension of country-level data was combined with the time-series dimension of pandemic-related measures, using econometric techniques dealing with panel data. FINDINGS: Greater stringency of lockdown measures was associated with fewer cases. Institutional strength enhanced this negative relationship. Countries with well-defined and established laws performed better for a given set of lockdown measures compared with countries with weaker institutional structures. Cultural tightness reduced the effectiveness of lockdowns, in contrast to previous findings at cross-sectional level. CONCLUSION: Institutional strength plays a greater role than cultural and economic factors in enhancing the performance of lockdowns. These results underline the importance of strengthening institutions for pandemic control.

ESCMID COVID-19 living guidelines: drug treatment and clinical management.

SCOPE: In January 2021, the ESCMID Executive Committee decided to launch a new initiative to develop ESCMID guidelines on several COVID-19-related issues, including treatment of COVID-19. METHODS: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search with a third panellist involved in case of inconsistent results. Voting was based on the GRADE approach. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: A synthesis of the available evidence and recommendations is provided for each of the 15 PICOs, which cover use of hydroxychloroquine, bamlanivimab alone or in combination with etesevimab, casirivimab combined with imdevimab, ivermectin, azithromycin and empirical antibiotics, colchicine, corticosteroids, convalescent plasma, favipiravir, remdesivir, tocilizumab and interferon ß-1a, as well as the utility of antifungal prophylaxis and enoxaparin. In general, the panel recommended against the use of hydroxychloroquine, ivermectin, azithromycin, colchicine and interferon ß-1a. Conditional recommendations were given for the use of monoclonal antibodies in high-risk outpatients with mild-moderate COVID-19, and remdesivir. There was insufficient evidence to make a recommendation for use of favipiravir and antifungal prophylaxis, and it was recommended that antibiotics should not be routinely prescribed in patients with COVID-19 unless bacterial coinfection or secondary infection is suspected or confirmed. Tocilizumab and corticosteroids were recommended for treatment of severe COVID-19 but not in outpatients with non-severe COVID-19. SCOPE: The aim of the present guidance is to provide evidence-based recommendations for management of adults with coronavirus disease 2019 (COVID-19). More specifically, the goal is to aid clinicians managing patients with COVID-19 at various levels of severity including outpatients, hospitalized patients, and those admitted to intensive care unit. Considering the composition of the panel, mostly clinical microbiologists or infectious disease specialists with no pulmonology or intensive care background, we focus only on pharmacological treatment and do not give recommendations on oxygen supplement/support. Similarly, as no paediatricians were included in the panel; the recommendations are only for adult patients with COVID-19. Considering the current literature, no guidance was given for special populations such as the immunocompromised.

Placental deficiency during maternal SARS-CoV-2 infection.

INTRODUCTION: Maternal anti-SARS-CoV-2 Spike antibodies can cross the placenta during pregnancy, and neonates born to infected mothers have acquired antibodies at birth. Few studies reported data on the histopathological changes of the placenta during infection and placental infection. SARS-CoV-2 infection may cause impaired development of the placenta, thus predisposing maternal and fetal unfavorable outcomes. The prospective study aims to evaluate the risk of vertical transmission of SARS-CoV-2 and placental passage of anti-Spike antibodies as well as the impact of clinical severity on placental structures. METHODS: This is a prospective cohort study on 30 pregnant women infected by SARS-CoV-2 with their neonates. The demographic features and pregnancy outcomes were collected. Gross and microscopic examinations of the placentas were done. Maternal and umbilical cord sera were obtained at the time of delivery. Nasopharyngeal swabs were collected from neonates immediately after birth. RESULTS: The concentrations of total anti-SARS-CoV-2 Spike antibodies were higher in pregnant women with moderate to severe/critical disease. The maternal total anti-SARS-CoV-2 Spike levels were correlated with those of neonatal levels. The rate of placental abnormalities is high in the mothers with severe disease, and those with positive anti-SARS-CoV-2 IgM. All neonates had negative nasopharyngeal swabs for SARS- CoV-2 infections and all placentas were negative in immunohistochemical staining for Spike protein. DISCUSSION: The maternally derived anti-SARS-CoV-2 Spike antibody can transmit to neonates born to infected mothers regardless of gestational age. Our results indicated that the disease severity is associated with ischemic placental pathology which may result in adverse pregnancy outcomes.

Achieving global equity for COVID-19 vaccines: Stronger international partnerships and greater advocacy and solidarity are needed.

Peter Figueroa and co-authors advocate for equity in the worldwide provision of COVID-19 vaccines.