Kawasaki Disease in the Time of COVID-19 and MIS-C - The International Kawasaki Disease Registry.

BACKGROUND: Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics/clinical presentation, management, and outcomes of patients by evidence of prior SARS-CoV-2 infection. METHODS: The International KD Registry (IKDR) enrolled KD and MIS-C patients from sites from North, Central and South America, Europe, Asia and Middle East. Evidence of prior infection was defined as: Positive (+ve household contact or positive PCR/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure). RESULTS: Of 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible 89 (4%), Negative 404 (17%) and Unknown for 311 (13%) patients. Clinical outcomes varied significantly between the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to Intensive Care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, while patients in the Negative and Unknown groups had more severe coronary artery abnormalities. results CONCLUSION: : There appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for prior acute SARS CoV2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C.

SARS-CoV-2 Vaccine Effectiveness against Omicron Variant in Infection-Naive Population, Australia, 2022.

SARS-CoV-2 transmission in Western Australia, Australia, was negligible until a wave of Omicron variant infections emerged in February 2022, when >90% of adults had been vaccinated. This unique pandemic enabled assessment of SARS-CoV-2 vaccine effectiveness (VE) without potential interference from background immunity from prior infection. We matched 188,950 persons who had a positive PCR test result during February-May 2022 to negative controls by age, week of test, and other possible confounders. Overall, 3-dose VE was 42.0% against infection and 81.7% against hospitalization or death. A primary series of 2 viral-vectored vaccines followed by an mRNA booster provided significantly longer protection against infection >60 days after vaccination than a 3-dose series of mRNA vaccine. In a population free from non-vaccine-derived background immunity, vaccines against the ancestral spike protein were ≈80% effective for preventing serious outcomes from infection with the SARS-CoV-2 Omicron variant.

US National Institutes of Health Prioritization of SARS-CoV-2 Variants.

Since late 2020, SARS-CoV-2 variants have regularly emerged with competitive and phenotypic differences from previously circulating strains, sometimes with the potential to escape from immunity produced by prior exposure and infection. The Early Detection group is one of the constituent groups of the US National Institutes of Health National Institute of Allergy and Infectious Diseases SARS-CoV-2 Assessment of Viral Evolution program. The group uses bioinformatic methods to monitor the emergence, spread, and potential phenotypic properties of emerging and circulating strains to identify the most relevant variants for experimental groups within the program to phenotypically characterize. Since April 2021, the group has prioritized variants monthly. Prioritization successes include rapidly identifying most major variants of SARS-CoV-2 and providing experimental groups within the National Institutes of Health program easy access to regularly updated information on the recent evolution and epidemiology of SARS-CoV-2 that can be used to guide phenotypic investigations.

A Case of COVID-19-Induced Immune Thrombocytopenia (ITP) in an Adult Female: An Under-Recognized Emerging Phenomenon.

Coronavirus disease 2019 (COVID-19) follows a mild course in majority of cases, but some patients may develop non-pulmonary yet life-threatening complications. A Pandora's box had been opened when multisystem hyper-inflammatory syndromes and autoimmune diseases that had been described previously in children and young adults, that are associated with COVID-19, have now emerged in adults. They need to be recognized as important sequelae of severe COVID-19 disease. Immune thrombocytopenia (ITP) or thrombocytopenic purpura is an autoantibody and T-cell-mediated autoimmune disorder characterized by isolated thrombocytopenia, which can be triggered by different infections. First-line treatment of severe ITP includes platelet transfusions in life-threatening cases, followed by corticosteroids and intravenous immunoglobulins (IVIG). Since the beginning of the pandemic, more and more cases of COVID-19-associated ITP have been reported. We report a case of acquired ITP in a young woman that could only be attributed to her COVID-19 infection and was refractory to platelet transfusion, requiring further treatments. The aim of this report is to review some of the etiologies and purposed molecular mechanisms of the autoimmune nature of the disease and to focus on diagnosis and treatment. We will review the current literature surrounding this non-pulmonary manifestation of COVID-19 and current treatment options for this uncommon presentation of ITP.

Human-to-Animal Transmission of SARS-CoV-2, South Korea, 2021.

To investigate SARS-CoV-2 transmission from humans to animals in Seoul, South Korea, we submitted samples from companion animals owned by persons with confirmed COVID-19. Real-time PCR indicated higher SARS-CoV-2 viral infection rates for dogs and cats than previously reported from the United States and Europe. Host-specific adaptations could introduce mutant SARS-CoV-2 to humans.

Can Some Viral Respiratory Infections Observed Before the Pandemic Announcement Be Related to SARS-CoV-2?

OBJECTIVE: There have been doubts that SARS-CoV-2 has been circulating before the first case was announced. The aim of this study was to evaluate the possibility of COVID-19 in some cases diagnosed to be viral respiratory tract infection in the pre-pandemic period in our center. MATERIAL AND METHODS: Patients who were admitted to our hospital's pulmonary diseases, infectious diseases, and intensive care clinics with the diagnosis of viral respiratory system infection within a 6-month period between October 2019 and March 12, 2020, were screened. Around 248 archived respiratory samples from these patients were analyzed for SARS-CoV-2 ribonucleic acid by real-time-quantitative polymerase chain reaction. The clinical, laboratory, and radiological data of the patients were evaluated. RESULT(S): The mean age of the study group was 47.5 (18-89 years);103 (41.5%) were female and 145 (58.4%) were male. The most common presenting symptoms were cough in 51.6% (n = 128), fever in 42.7% (n = 106), and sputum in 27.0% (n = 67). Sixty-nine percent (n = 172) of the patients were pre-diagnosed to have upper respiratory tract infection and 22.0% (n = 55) had pneumonia, one-third of the patients (n = 84, 33.8%) were followed in the service. Respiratory viruses other than SARS-CoV-2 were detected in 123 (49.6%) patients. Influenza virus (31.9%), rhinovirus (10.5%), and human metapneumovirus (6.5%) were the most common pathogens, while none of the samples were positive for SARS-CoV-2 RNA. Findings that could be significant for COVID-19 pneumonia were detected in the thorax computed tomography of 7 cases. CONCLUSION(S): The negative SARS-CoV-2 real-time-quantitative polymerase chain reaction results in the respiratory samples of the cases followed up in our hospital for viral pneumonia during the pre-pandemic period support that there was no COVID-19 among our cases during the period in question. However, if clinical suspicion arises, both SARS and non-SARS respiratory viral pathogens should be considered for differential diagnosis.Copyright © Author(s).

Perceived Stress and Psychological Impact Among Healthcare Workers at a Tertiaty Hospital in China During the COVID-19 Outbreak: The Moderating Role of Resilience and Social Support.

Aims: To investigate the psychological distress experienced by healthcare workers (HCWs) at a tertiary hospital in Changzhou, China, outside Wuhan, during the early stage of COVID-19 and evaluate the moderating effects of resilience and social support on the relationship between stress and psychological distress. Methods: The study was conducted between February 10 and 15, 2020, in a non-probabilistic way. The survey included questions regarding the risk of exposure, sociodemographics, perceived stress [10-item Perceived Stress Scale (PSS-10)], resilience [10-item Connor-Davidson Psychological Resilience (CD-RISC-10)], social support [Multidimensional Scale of Perceived Social Support (MSPSS)], and psychological distress [12-item General Health Questionnaire (GHQ-12)]. We applied the PROCESS macro for SPSS to test the hypotheses that resilience and social support moderated the stress response. In addition, a simple slope analysis was conducted when the interaction effect was statistically significant. Results: Some 33.6% of participants suffered from psychological distress (GHQ-12 ≥ 12). Perceived stress was positively related to psychological distress (r = 0.42, p < 0.001). In addition, resilience (ΔR2 = 0.03, p for interaction < 0.001) and social support (ΔR2 = 0.01, p for interaction <0.01) moderated the stress response. The impact of perceived stress on psychological distress was attenuated when subjects who were resilient (high ß = 0.15, p < 0.001; low ß = 0.36, p < 0.001), and perceived stress had less impact on psychological distress when social support was high (ß = 0.24, p < 0.001) rather than low (ß = 0.34, p < 0.001). Limitations: The cross-sectional design led to a lack of causal relationships between variables. Conclusions: Our data showed that resilience and social support moderated the stress response among HCWs in the pandemic, suggesting that improving resilience and social support could be appropriate targets to improve HCWs' mental health in the pandemic.

Effectiveness of BNT162b2 Vaccine against Omicron Variant Infection among Children 5-11 Years of Age, Israel.

We assessed effectiveness of the BNT162b2 vaccine against infection with the B.1.1.529 (Omicron) variant (mostly BA.1 subvariant), among children 5-11 years of age in Israel. Using a matched case-control design, we matched SARS-CoV-2-positive children (cases) and SARS-CoV-2-negative children (controls) by age, sex, population group, socioeconomic status, and epidemiologic week. Vaccine effectiveness estimates after the second vaccine dose were 58.1% for days 8-14, 53.9% for days 15-21, 46.7% for days 22-28, 44.8% for days 29-35, and 39.5% for days 36-42. Sensitivity analyses by age group and period demonstrated similar results. Vaccine effectiveness against Omicron infection among children 5-11 years of age was lower than vaccine efficacy and vaccine effectiveness against non-Omicron variants, and effectiveness declined early and rapidly.

Insights into COVID-19-associated critical illness: a narrative review.

Background and Objective: Since the outbreak of the 2019 novel coronavirus disease (COVID-19), acute respiratory distress syndrome (ARDS) and sepsis resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have surged in intensive care units around the world. The heterogeneity of ARDS and sepsis has long been observed, and multiple subphenotypes and endotypes correlated with different outcomes and treatment response have been identified in the search for treatable traits. Despite their similarity to typical ARDS and sepsis, COVID-19-associated ARDS and sepsis harbor distinct features, raising the question as to whether they could be considered as subphenotypes or endotypes of the historical syndromes and, accordingly, benefit from specific therapeutic strategies. This review aimed to summarize and discuss the current knowledge of COVID-19-associated critical illness and the intrinsic subphenotypes or endotypes. Methods: Literature on the pathogenesis of COVID-19 and the subphenotyping of COVID-19-associated critical illness was derived from the PubMed database and reviewed. Key Content and Findings: Accumulating evidence, varying from clinical observation to basic research, has contributed to revealing the fundamental pathophysiological features of severe COVID-19 and has advanced our knowledge of the disease. COVID-19-associated ARDS and sepsis exhibit some distinctive features compared to the classic syndromes, including remarkable vascular abnormality and coagulopathy, and distinct respiratory mechanics and immune response. Some conventional subphenotypes derived from classic ARDS and sepsis have been validated in COVID-19, while novel subphenotypes and endotypes have also been identified in patients with this disease, who experience variable clinical outcomes and treatment responses. Conclusions: Subphenotyping of COVID-19-associated ARDS and sepsis can provide new insights into the development and management of these illnesses.

SARS-CoV-2 Seroprevalence Compared with Confirmed COVID-19 Cases among Children, Colorado, USA, May-July 2021.

To compare SARS-CoV-2 antibody seroprevalence among children with seropositive confirmed COVID-19 case counts (case ascertainment by molecular amplification) in Colorado, USA, we conducted a cross-sectional serosurvey during May-July 2021. For a convenience sample of 829 Colorado children, SARS-CoV-2 seroprevalence was 36.7%, compared with prevalence of 6.5% according to individually matched COVID-19 test results reported to public health. Compared with non-Hispanic White children, seroprevalence was higher among Hispanic, non-Hispanic Black, and non-Hispanic other race children, and case ascertainment was significantly lower among Hispanic and non-Hispanic Black children. This serosurvey accurately estimated SARS-CoV-2 prevalence among children compared with confirmed COVID-19 case counts and revealed substantial racial/ethnic disparities in infections and case ascertainment. Continued efforts to address racial and ethnic differences in disease burden and to overcome potential barriers to case ascertainment, including access to testing, may help mitigate these ongoing disparities.

SARS-CoV-2 Molecular Evolutionary Dynamics in the Greater Accra Region, Ghana.

To assess dynamics of SARS-CoV-2 in Greater Accra Region, Ghana, we analyzed SARS-CoV-2 genomic sequences from persons in the community and returning from international travel. The Accra Metropolitan District was a major origin of virus spread to other districts and should be a primary focus for interventions against future infectious disease outbreaks.

Seroprevalence of Specific SARS-CoV-2 Antibodies during Omicron BA.5 Wave, Portugal, April-June 2022.

After the rapid spread of SARS-CoV-2 BA.5 Omicron lineage in Portugal, we developed a seroepidemiologic survey based on a sample of 3,825 residents. Results indicated that from April 27 through June 8, 2022, the estimated seroprevalence of SARS-CoV-2 nucleocapsid or spike IgG was 95.8%, which indicates a high level of protection.

Correlates of Protection, Thresholds of Protection, and Immunobridging among Persons with SARS-CoV-2 Infection.

Several studies have shown that neutralizing antibody levels correlate with immune protection from COVID-19 and have estimated the relationship between neutralizing antibodies and protection. However, results of these studies vary in terms of estimates of the level of neutralizing antibodies required for protection. By normalizing antibody titers, we found that study results converge on a consistent relationship between antibody levels and protection from COVID-19. This finding can be useful for planning future vaccine use, determining population immunity, and reducing the global effects of the COVID-19 pandemic.

Exploratory Literature Review of the Role of National Public Health Institutes in COVID-19 Response.

To help explain the diversity of COVID-19 outcomes by country, research teams worldwide are studying national government response efforts. However, these attempts have not focused on a critical national authority that exists in half of the countries in the world: national public health institutes (NPHIs). NPHIs serve as an institutional home for public health systems and expertise and play a leading role in epidemic responses. To characterize the role of NPHIs in the COVID-19 response, we conducted a descriptive literature review that explored the research documented during March 2020-May 2021. We conducted a name-based search of 61 NPHIs in the literature, representing over half of the world's NPHIs. We identified 33 peer-reviewed and 300 gray articles for inclusion. We describe the most common NPHI-led COVID-19 activities that are documented and identify gaps in the literature. Our findings underscore the value of NPHIs for epidemic control and establish a foundation for primary research.

Leveraging HIV Program and Civil Society to Accelerate COVID-19 Vaccine Uptake, Zambia.

To accelerate COVID-19 vaccination delivery, Zambia integrated COVID-19 vaccination into HIV treatment centers and used World AIDS Day 2021 to launch a national vaccination campaign. This campaign was associated with significantly increased vaccinations, demonstrating that HIV programs can be leveraged to increase COVID-19 vaccine uptake.

Outcomes after Acute Malnutrition Program Adaptations to COVID-19, Uganda, Ethiopia, and Somalia.

At the onset of the COVID-19 pandemic, protocols for community-based management of acute malnutrition (CMAM) were implemented to support continuity of essential feeding services while mitigating COVID-19 transmission. To assess correlations between adaptation timing and CMAM program indicators, we evaluated routine program data in Uganda, Ethiopia, and Somalia for children 6-59 months of age. We specifically analyzed facility-level changes in total admissions, average length of stay (ALOS), total children screened for admission, and recovery rates before and after adaptations. We found no statistically significant changes in program indicators after adaptations. For Somalia, we also analyzed child-level changes in ALOS and in weight and mid-upper arm circumference at admission and discharge. ALOS significantly increased immediately after adaptations and then decreased to preadaptation levels. We found no meaningful changes in either weight or mid-upper arm circumference at admission or discharge. These findings indicate that adapted CMAM programs can remain effective.

Effects of COVID-19 Pandemic on Voluntary Medical Male Circumcision Services for HIV Prevention, Sub-Saharan Africa, 2020.

Beginning in March 2020, to reduce COVID-19 transmission, the US President's Emergency Plan for AIDS Relief supporting voluntary medical male circumcision (VMMC) services was delayed in 15 sub-Saharan African countries. We reviewed performance indicators to compare the number of VMMCs performed in 2020 with those performed in previous years. In all countries, the annual number of VMMCs performed decreased 32.5% (from 3,898,960 in 2019 to 2,631,951 in 2020). That reduction is largely attributed to national and local COVID-19 mitigation measures instituted by ministries of health. Overall, 66.7% of the VMMC global annual target was met in 2020, compared with 102.0% in 2019. Countries were not uniformly affected; South Africa achieved only 30.7% of its annual target in 2020, but Rwanda achieved 123.0%. Continued disruption to the VMMC program may lead to reduced circumcision coverage and potentially increased HIV-susceptible populations. Strategies for modifying VMMC services provide lessons for adapting healthcare systems during a global pandemic.

Seasonality of Common Human Coronaviruses, United States, 2014-20211.

The 4 common types of human coronaviruses (HCoVs)-2 alpha (HCoV-NL63 and HCoV-229E) and 2 beta (HCoV-HKU1 and HCoV-OC43)-generally cause mild upper respiratory illness. Seasonal patterns and annual variation in predominant types of HCoVs are known, but parameters of expected seasonality have not been defined. We defined seasonality of HCoVs during July 2014-November 2021 in the United States by using a retrospective method applied to National Respiratory and Enteric Virus Surveillance System data. In the 6 HCoV seasons before 2020-21, season onsets occurred October 21-November 12, peaks January 6-February 13, and offsets April 18-June 27; most (>93%) HCoV detection was within the defined seasonal onsets and offsets. The 2020-21 HCoV season onset was 11 weeks later than in prior seasons, probably associated with COVID-19 mitigation efforts. Better definitions of HCoV seasonality can be used for clinical preparedness and for determining expected patterns of emerging coronaviruses.

Kawasaki disease in the time of COVID-19-the international kawasaki disease registry

Background and Aim: The considerable overlap in case definition and clinical features between patients with COVID-19 associated Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki disease (KD) suggests shared pathogenesis. We sought to compare demographic, clinical presentation, management and outcomes of patients by COVID-19 status. Method(s): The International KD Registry (IKDR) began enrolling patients with clinical features of either acute MIS-C or KD or fever with hyperinflammation beginning in January 2020. The IKDR is unique regarding broad patient selection and includes sites from North, Central and South America, Europe, Asia and the Middle East. Patient groups stratified by COVID-19 status were compared. Result(s): As of October 6, 2021, 1330 patients were registered from 31 sites. COVID status was POSITIVE for 59% (confirmed household COVID-19 contact and/or positive SARS-CoV-2 PCR or serology), POSSIBLE for 4% (suggestive clinical features but some negative tests or absent exposure), NEGATIVE for 23%, and UNKNOWN (no known exposure and testing not com-pleted) for 14% (TABLE). Most of the UNKNOWN patients were from early in the COVID-19 pandemic before MIS-C was defined and before COVID-19 serologic testing was widely used. POSITIVE and POSSIBLE patients were older, had fewer KD clinical criteria, greater gastrointestinal symptoms, were more likely to present with shock and require ICU admission and inotropic support. POSSIBLE patients had greater days from symptom onset to first immune modulation treatment, with no differences between groups regarding days from admission to first treatment. Most patients in each group received intravenous immune globu-lin, with POSITIVE and POSSIBLE patients more likely to have received steroids and anakinra. NEGATIVE and UNKNOWN patients had higher maximal coronary artery Z scores, with a trend to having higher categories of aneurysm involvement. Conclusion(s): While there was considerable overlap in presentation, management and outcomes between COVID-19 POSITIVE/POSSIBLE (presumed MIS-C) and COVID NEGATIVE/UNKNOWN patients (presumed KD), COVID-19 POSITIVE/POSSIBLE patients had more severe presentations and required more intensive management, although coronary artery outcomes trended to be less severe. Patient recruitment con-tinues, and in-depth comparison of laboratory features and appli-cation of machine learning approaches to patient differentiation and prediction of optimal management pathways are forthcoming.

SARS-CoV-2 Vaccine Breakthrough by Omicron and Delta Variants, New York, USA.

Recently emerged SARS-CoV-2 variants have greater potential than earlier variants to cause vaccine breakthrough infections. During emergence of the Delta and Omicron variants, a matched case-control analysis used a viral genomic sequence dataset linked with demographic and vaccination information from New York, USA, to examine associations between virus lineage and patient vaccination status, patient age, vaccine type, and time since vaccination. Case-patients were persons infected with the emerging virus lineage, and controls were persons infected with any other virus lineage. Infections in fully vaccinated and boosted persons were significantly associated with the Omicron lineage. Odds of infection with Omicron relative to Delta generally decreased with increasing patient age. A similar pattern was observed with vaccination status during Delta emergence but was not significant. Vaccines offered less protection against Omicron, thereby increasing the number of potential hosts for emerging variants.