Ongoing symptoms might follow acute COVID-19. Using electronic health information, we compared pre‒ and post‒COVID-19 diagnostic codes to identify symptoms that had higher encounter incidence in the post‒COVID-19 period as sequelae. This method can be used for hypothesis generation and ongoing monitoring of sequelae of COVID-19 and future emerging diseases.

BACKGROUND: Clinical severity of coronavirus disease 2019 (COVID-19) may vary over time; trends in clinical severity at admission during the pandemic among hospitalized patients in the United States have been incompletely described, so a historical record of severity over time is lacking. METHODS: We classified 466677 hospital admissions for COVID-19 from April 2020 to April 2021 into 4 mutually exclusive severity grades based on indicators present on admission (from most to least severe): Grade 4 included intensive care unit (ICU) admission and invasive mechanical ventilation (IMV); grade 3 included non-IMV ICU and/or noninvasive positive pressure ventilation; grade 2 included diagnosis of acute respiratory failure; and grade 1 included none of the above indicators. Trends were stratified by sex, age, race/ethnicity, and comorbid conditions. We also examined severity in states with high vs low Alpha (B.1.1.7) variant burden. RESULTS: Severity tended to be lower among women, younger adults, and those with fewer comorbidities compared to their counterparts. The proportion of admissions classified as grade 1 or 2 fluctuated over time, but these less-severe grades comprised a majority (75%-85%) of admissions every month. Grades 3 and 4 consistently made up a minority of admissions (15%-25%), and grade 4 showed consistent decreases in all subgroups, including states with high Alpha variant burden. CONCLUSIONS: Clinical severity among hospitalized patients with COVID-19 has varied over time but has not consistently or markedly worsened over time. The proportion of admissions classified as grade 4 decreased in all subgroups. There was no consistent evidence of worsening severity in states with higher vs lower Alpha prevalence.

BACKGROUND: Late sequelae of COVID-19 have been reported; however, few studies have investigated the time-course or incidence of late new COVID-19-related health conditions (post-COVID conditions) after COVID-19 diagnosis. Studies distinguishing post-COVID conditions from late conditions caused by other etiologies are lacking. Using data from a large administrative all-payer database, we assessed the type, association, and timing of post-COVID conditions following COVID-19 diagnosis. METHODS: Using the Premier Healthcare Database Special COVID-19 Release (PHD-SR) (release date, October 20, 2020) data, during March-June 2020, 27,589 inpatients and 46,857 outpatients diagnosed with COVID-19 (case-patients) were 1:1 matched with patients without COVID-19 through the 4-month follow-up period (control-patients) by using propensity score matching. In this matched-cohort study, adjusted odds ratios were calculated to assess for late conditions that were more common in case-patients compared with control-patients. Incidence proportion was calculated for conditions that were more common in case-patients than control-patients during 31-120 days following a COVID-19 encounter. RESULTS: During 31-120 days after an initial COVID-19 inpatient hospitalization, 7.0% of adults experienced at least one of five post-COVID conditions. Among adult outpatients with COVID-19, 7.7% experienced at least one of ten post-COVID conditions. During 31-60 days after an initial outpatient encounter, adults with COVID-19 were 2.8 times as likely to experience acute pulmonary embolism as outpatient control-patients and were also more likely to experience a range of conditions affecting multiple body systems (e.g. nonspecific chest pain, fatigue, headache, and respiratory, nervous, circulatory, and gastrointestinal system symptoms) than outpatient control-patients. Children with COVID-19 were not more likely to experience late conditions than children without COVID-19. CONCLUSIONS: These findings add to the evidence of late health conditions possibly related to COVID-19 in adults following COVID-19 diagnosis and can inform health care practice and resource planning for follow-up COVID-19 care.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified in infants <12 months old. Clinical characteristics and follow-up data of MIS-C in infants have not been well described. We sought to describe the clinical course, laboratory findings, therapeutics and outcomes among infants diagnosed with MIS-C. METHODS: Infants of age <12 months with MIS-C were identified by reports to the CDC's MIS-C national surveillance system. Data were obtained on clinical signs and symptoms, complications, treatment, laboratory and imaging findings, and diagnostic SARS-CoV-2 testing. Jurisdictions that reported 2 or more infants were approached to participate in evaluation of outcomes of MIS-C. RESULTS: Eighty-five infants with MIS-C were identified and 83 (97.6%) tested positive for SARS-CoV-2 infection; median age was 7.7 months. Rash (62.4%), diarrhea (55.3%) and vomiting (55.3%) were the most common signs and symptoms reported. Other clinical findings included hypotension (21.2%), pneumonia (21.2%) and coronary artery dilatation or aneurysm (13.9%). Laboratory abnormalities included elevated C-reactive protein, ferritin, d-dimer and fibrinogen. Twenty-three infants had follow-up data; 3 of the 14 patients who received a follow-up echocardiogram had cardiac abnormalities during or after hospitalization. Nine infants had elevated inflammatory markers up to 98 days postdischarge. One infant (1.2%) died after experiencing multisystem organ failure secondary to MIS-C. CONCLUSIONS: Infants appear to have a milder course of MIS-C than older children with resolution of their illness after hospital discharge. The full clinical picture of MIS-C across the pediatric age spectrum is evolving.

IMPORTANCE: Multiple inflammatory syndrome in children (MIS-C) occurs in association with the COVID-19 pandemic. OBJECTIVE: To describe the clinical characteristics and geographic and temporal distribution of the largest cohort of patients with MIS-C in the United States to date. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis was conducted on clinical and laboratory data collected from patients with MIS-C. The analysis included patients with illness onset from March 2020 to January 2021 and met MIS-C case definition. MAIN OUTCOMES AND MEASURES: Geographic and temporal distribution of MIS-C was compared with that of COVID-19 nationally, by region, and level of urbanicity by county. Clinical and laboratory findings and changes over time were described by age group and by presence or absence of preceding COVID-19. RESULTS: A total of 1733 patients with MIS-C were identified; 994 (57.6%) were male and 1117 (71.3%) were Hispanic or non-Hispanic Black. Gastrointestinal symptoms, rash, and conjunctival hyperemia were reported by 53% (n = 931) to 67% (n = 1153) of patients. A total of 937 patients (54%) had hypotension or shock, and 1009 (58.2%) were admitted for intensive care. Cardiac dysfunction was reported in 484 patients (31.0%), pericardial effusion in 365 (23.4%), myocarditis in 300 (17.3%), and coronary artery dilatation or aneurysms in 258 (16.5%). Patients aged 0 to 4 years had the lowest proportion of severe manifestations, although 171 patients (38.4%) had hypotension or shock and 197 (44.3%) were admitted for intensive care. Patients aged 18 to 20 years had the highest proportions with myocarditis (17 [30.9%]), pneumonia (20 [36.4%]), acute respiratory distress syndrome (10 [18.2%]), and polymerase chain reaction positivity (39 [70.9%]). These older adolescents also had the highest proportion reporting preceding COVID-19-like illness (63%). Nationally, the first 2 MIS-C peaks followed the COVID-19 peaks by 2 to 5 weeks. The cumulative MIS-C incidence per 100 000 persons younger than 21 years was 2.1 and varied from 0.2 to 6.3 by state. Twenty-four patients (1.4%) died. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of a large cohort of patients with MIS-C, 2 peaks that followed COVID-19 peaks by 2 to 5 weeks were identified. The geographic and temporal association of MIS-C with the COVID-19 pandemic suggested that MIS-C resulted from delayed immunologic responses to SARS-CoV-2 infection. The clinical manifestations varied by age and by presence or absence of preceding COVID-19.

Idiopathic intussusception is a common cause of bowel obstruction in infants, presenting as refractory abdominal pain or mass, vomiting, lethargy, and currant jelly stool. Coronavirus disease 2019 is not well characterized in children, especially infants, but symptoms in children have included nausea, vomiting, diarrhea, and abdominal pain. From January to July 2020, intussusception was reported in 5 infants 4-10 months of age who had laboratory-confirmed SARS-CoV-2 infection. All 5 infants presented with currant jelly stool and at least 1 other abdominal symptom, and none presented with respiratory symptoms. Four infants recovered but the fifth infant progressed to a critical illness and death. While an association between SARS-CoV-2 infection and intussusception has not been established, infants with symptoms consistent with intussusception may warrant testing for viral pathogens, including SARS-CoV-2, especially if presenting to healthcare with a history of SARS-CoV-2 exposure or with signs and symptoms of COVID-19. More investigation is needed to determine whether intussusception is part of the clinical spectrum of COVID-19 in infants or a coincidental finding among infants with SARS-CoV-2 infection.

In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

As malaria control programmes concentrate their efforts towards malaria elimination a better understanding of malaria transmission patterns at fine spatial resolution units becomes necessary. Defining spatial units that consider transmission heterogeneity, human movement and migration will help to set up achievable malaria elimination milestones and guide the creation of efficient operational administrative control units. Using a combination of genetic and epidemiological data we defined a malaria transmission unit as the area contributing 95% of malaria cases diagnosed at the catchment facility located in the town of Guapi in the South Pacific Coast of Colombia. We provide data showing that P. falciparum malaria transmission is heterogeneous in time and space and analysed, using topological data analysis, the spatial connectivity, at the micro epidemiological level, between parasite populations circulating within the unit. To illustrate the necessity to evaluate the efficacy of malaria control measures within the transmission unit in order to increase the efficiency of the malaria control effort, we provide information on the size of the asymptomatic reservoir, the nature of parasite genotypes associated with drug resistance as well as the frequency of the Pfhrp2/3 deletion associated with false negatives when using Rapid Diagnostic Tests.

This paper investigates different approaches for causal estimation under multiple concurrent medications. Our parameter of interest is the marginal mean counterfactual outcome under different combinations of medications. We explore parametric and non-parametric methods to estimate the generalized propensity score. We then apply three causal estimation approaches (inverse probability of treatment weighting, propensity score adjustment, and targeted maximum likelihood estimation) to estimate the causal parameter of interest. Focusing on the estimation of the expected outcome under the most prevalent regimens, we compare the results obtained using these methods in a simulation study with four potentially concurrent medications. We perform a second simulation study in which some combinations of medications may occur rarely or not occur at all in the dataset. Finally, we apply the methods explored to contrast the probability of patient treatment success for the most prevalent regimens of antimicrobial agents for patients with multidrug-resistant pulmonary tuberculosis.

In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV).

In 2018, the family Arenaviridae was expanded by inclusion of 1 new genus and 5 novel species. At the same time, the recently established order Bunyavirales was expanded by 3 species. This article presents the updated taxonomy of the family Arenaviridae and the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.

Human cryptosporidiosis is caused primarily by Cryptosporidium hominis, Cryptosporidium parvum and Cryptosporidium meleagridis. To accelerate research on parasites in the genus Cryptosporidium, we generated annotated, draft genome sequences of human C. hominis isolates TU502_2012 and UKH1, C. meleagridis UKMEL1, also isolated from a human patient, and the avian parasite Cryptosporidium baileyi TAMU-09Q1. The annotation of the genome sequences relied in part on RNAseq data generated from the oocyst stage of both C. hominis and C. baileyi The genome assembly of C. hominis is significantly more complete and less fragmented than that available previously, which enabled the generation of a much-improved gene set for this species, with an increase in average gene length of 500 bp relative to the protein-encoding genes in the 2004 C. hominis annotation. Our results reveal that the genomes of C. hominis and C. parvum are very similar in both gene density and average gene length. These data should prove a valuable resource for the Cryptosporidium research community.

There have been substantial improvements in preventing waterborne disease and outbreaks in developed countries over the past two decades. Consequently, it can be easy to get complacent about pathogens in drinking water in the absence of large, well-publicized waterborne disease outbreaks such as Milwaukee, Wis., in 1993 and Clark County, Nev., in 1994 (Goldstein et al. 1996, MacKenzie et al. 1994). However, waterborne microbial diseases are still a cause of substantial morbidity (and some mortality), even in developed countries; for example, an estimated 4 million to 16 million cases of waterborne gastroenteritis occur annually in the United States (Colford et al. 2006, Messner et al. 2006). Therefore, persistent vigilance is required to continue controlling the risks posed by waterborne pathogens. | Pathogens in drinking water have received considerable media attention recently in the United States. Over the past 10 years, Legionella has become the most frequent cause of waterborne disease outbreaks in the United States, as shown in Figure 1 (Beer et al. 2015). Also, a cryptosporidiosis outbreak in Oregon in 2013 (Oregon Health Authority 2014) was the first time since Clark County, Nev., over 20 years ago in which a US disease outbreak was linked to municipal drinking water. And setting an unwelcome precedent, the first cases of fatal primary amoebic meningoencephalitis (caused by N. fowleri) linked to treated municipal drinking water were reported in 2012 in Louisiana (Yoder et al. 2012). Therefore, it is not surprising that all three of these pathogens were discussed in detail at the 6th ISWP. This symposium, which is organized every three to five years by AWWA’s Organisms in Water Committee, provides a forum to discuss all aspects of pathogen occurrence, detection, and treatment in water. | The 2015 meeting hosted 141 attendees from six countries—the United States, Japan, the United Kingdom, Canada, the Netherlands, and New Zealand; attendees represented water utilities, academia, public health and other government agencies, equipment manufacturers, and environmental consulting firms. Speaker affiliations and locations are shown in Table 1. In addition to sessions and discussions about the three pathogens noted here, two days of intense, single-track sessions covered P. aeruginosa, Norovirus, toxigenic E. coli, fecal indicator bacteria, pathogen risk modeling, water reuse, pathogens in wastewater, and antibiotic-resistant bacteria.

Despite long-recognized challenges and constraints associated with their updating and manufacture, influenza vaccines remain at the heart of public health preparedness and response efforts against both seasonal and potentially pandemic influenza viruses. Globally coordinated virological and epidemiological surveillance is the foundation of the influenza vaccine virus selection and development process. Although national influenza surveillance and reporting capabilities are being strengthened and expanded, sustaining and building upon recent gains has become a major challenge. Strengthening the vaccine virus selection process additionally requires the continuation of initiatives to improve the timeliness and representativeness of influenza viruses shared by countries for detailed analysis by the WHO Global Influenza Surveillance and Response System (GISRS). Efforts are also continuing at the national, regional, and global levels to better understand the dynamics of influenza transmission in both temperate and tropical regions. Improved understanding of the degree of influenza seasonality in tropical countries of the world should allow for the strengthening of national vaccination policies and use of the most appropriate available vaccines. There remain a number of limitations and difficulties associated with the use of HAI assays for the antigenic characterization and selection of influenza vaccine viruses by WHOCCs. Current approaches to improving the situation include the more-optimal use of HAI and other assays; improved understanding of the data produced by neutralization assays; and increased standardization of serological testing methods. A number of new technologies and associated tools have the potential to revolutionize influenza surveillance and response activities. These include the increasingly routine use of whole genome next-generation sequencing and other high-throughput approaches. Such approaches could not only become key elements in outbreak investigations but could drive a new surveillance paradigm. However, despite the advances made, significant challenges will need to be addressed before next-generation technologies become routine, particularly in low-resource settings. Emerging approaches and techniques such as synthetic genomics, systems genetics, systems biology and mathematical modelling are capable of generating potentially huge volumes of highly complex and diverse datasets. Harnessing the currently theoretical benefits of such bioinformatics ("big data") concepts for the influenza vaccine virus selection and development process will depend upon further advances in data generation, integration, analysis and dissemination. Over the last decade, growing awareness of influenza as an important global public health issue has been coupled to ever-increasing demands from the global community for more-equitable access to effective and affordable influenza vaccines. The current influenza vaccine landscape continues to be dominated by egg-based inactivated and live attenuated vaccines, with a small number of cell-based and recombinant vaccines. Successfully completing each step in the annual influenza vaccine manufacturing cycle will continue to rely upon timely and regular communication between the WHO GISRS, manufacturers and regulatory authorities. While the pipeline of influenza vaccines appears to be moving towards a variety of niche products in the near term, it is apparent that the ultimate aim remains the development of effective "universal" influenza vaccines that offer longer-lasting immunity against a broad range of influenza A subtypes.

The microbial diversity of wastewater used for irrigation and fertilization was assessed using specific polymerase chain reaction (PCR) assays to detect and genotype several pathogenic protists including Cryptosporidium spp., Giardia duodenalis, Cyclospora spp., Eimeria spp. and Enterocytozoon bieneusi. A total of 220 wastewater samples (110 raw, 110 treated) and 12 sludge samples were collected from 2005 to 2008 from 18 treatment plants located throughout Tunisia. Except for Cyclospora, which was detected only once, E. bieneusi (61%), G. duodenalis (28%), Cryptosporidium spp. (27%) and Eimeria spp. (45%) were frequently observed in wastewater and sludge. Sequencing of PCR products showed that C. hominis, C. andersoni, G. duodenalis sub-assemblage A-II and E. bieneusi genotypes D and IV were the most prevalent. An analysis of the distribution of 209 internal transcribed spacer sequences of E. bieneusi originating from wastewater at the 18 treatment plants showed a similar genetic diversity, regardless of the geographical location. The identification of these parasite species and genotypes and of host-specific Eimeria species indicates that the microbial quality of wastewater was impacted by humans, livestock and rodents. Given the public health risks that some of these parasites represent, guidelines on wastewater usage are needed to minimize human exposure to these pathogens.