The United States is in an acceleration phase of the COVID-19 pandemic. Currently there is no known effective therapy or vaccine for treatment of SARS-CoV-2, highlighting urgency around identifying effective therapies. The purpose of this study was to evaluate the role of hydroxychloroquine therapy alone and in combination with azithromycin in hospitalized patients positive for COVID-19. Multi-center retrospective observational study. The Henry Ford Health System (HFHS) in Southeast Michigan: large six hospital integrated health system; the largest of hospitals is an 802-bed quaternary academic teaching hospital in urban Detroit, Michigan. Consecutive patients hospitalized with a COVID-related admission in the health system from March 10, 2020 to May 2, 2020 were included. Only the first admission was included for patients with multiple admissions. All patients evaluated were 18 years of age and older and were treated as inpatients for at least 48 h unless expired within 24 h. Receipt of hydroxychloroquine alone, hydroxychloroquine in combination with azithromycin, azithromycin alone, or neither. The primary outcome was in-hospital mortality. Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4–10 days), median age was 64 years (IQR:53–76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3–53). Overall in-hospital mortality was 18.1% (95% CI:16.6%–19.7%); by treatment: hydroxychloroquine + azithromycin, 157/783 (20.1% [95% CI: 17.3%–23.0%]), hydroxychloroquine alone, 162/1202 (13.5% [95% CI: 11.6%–15.5%]), azithromycin alone, 33/147 (22.4% [95% CI: 16.0%–30.1%]), and neither drug, 108/409 (26.4% [95% CI: 22.2%–31.0%]). Primary cause of mortality was respiratory failure (88%); no patient had documented torsades de pointes. From Cox regression modeling, predictors of mortality were age>65 years (HR:2.6 [95% CI:1.9–3.3]), white race (HR:1.7 [95% CI:1.4–2.1]), CKD (HR:1.7 [95%CI:1.4–2.1]), reduced O2 saturation level on admission (HR:1.5 [95%CI:1.1–2.1]), and ventilator use during admission (HR: 2.2 [95%CI:1.4–3.3]). Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine + azithromycin 71% compared to neither treatment (p < 0.001). In this multi-hospital assessment, when controlling for COVID-19 risk factors, treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality. Prospective trials are needed to examine this impact.

SUMMARY Pertussis is a severe respiratory infection caused by Bordetella pertussis, and in 2008, pertussis was associated with an estimated 16 million cases and 195,000 deaths globally. Sizeable outbreaks of pertussis have been reported over the past 5 years, and disease reemergence has been the focus of international attention to develop a deeper understanding of pathogen virulence and genetic evolution of B. pertussis strains. During the past 20 years, the scientific community has recognized pertussis among adults as well as infants and children. Increased recognition that older children and adolescents are at risk for disease and may transmit B. pertussis to younger siblings has underscored the need to better understand the role of innate, humoral, and cell-mediated immunity, including the role of waning immunity. Although recognition of adult pertussis has increased in tandem with a better understanding of B. pertussis pathogenesis, pertussis in neonates and adults can manifest with atypical clinical presentations. Such disease patterns make pertussis recognition difficult and lead to delays in treatment. Ongoing research using newer tools for molecular analysis holds promise for improved understanding of pertussis epidemiology, bacterial pathogenesis, bioinformatics, and immunology. Together, these advances provide a foundation for the development of new-generation diagnostics, therapeutics, and vaccines.

The decision to develop rotavirus vaccines was predicated on the extensive burden of rotavirus disease among children worldwide. US reports on nationwide hospitalizations (1979–1992) and deaths (1968–1991) due to diarrhea and weekly reports of rotavirus infection by 74 laboratories were reviewed to estimate the burden of rotavirus disease, identify epidemiologic trends, and consider methods for evaluating an immunization program when a vaccine becomes available. From 1968 to 1985, diarrhea-related deaths among US children <5 years old declined from 1100 to 300/year. This decline was associated with the disappearance of winter peaks for diarrhea-related deaths previously associated with rotavirus infection among children 4–23 months old. From 1979 to 1992, however, hospitalizations for diarrhea averaged 186,000/year and retained their winter peaks, which have been linked to rotavirus infections. Each year an estimated 54,000–55,000 US children are hospitalized for diarrhea, but < 40 die with rotavirus. A rotavirus vaccine program will require improved surveillance, including the timely collection of data from sentinel hospitals, in which a diagnosis of rotavirus can be established or ruled out for all children hospitalized for diarrhea.

The interplay between nasopharyngeal bacterial carriage, viral coinfection, and lower respiratory tract infections (LRTIs) is poorly understood. We explored this association in Vietnamese children aged less than 5 years. A hospital-based case-control study of pediatric LRTIs was conducted in Nha Trang, Vietnam. A total of 550 hospitalized children (274 radiologically confirmed pneumonia [RCP] and 276 other LRTIs) were enrolled and 350 healthy controls were randomly selected from the community. Polymerase chain reaction-based methods were used to measure bacterial loads of Streptococcus pneumoniae (SP), Haemophilus influenzae, and Moraxella catarrhalis and to detect 13 respiratory viruses and bacterial serotypes in nasopharyngeal samples of study participants. The median nasopharyngeal bacterial load of SP was substantially higher in children with RCP compared with healthy controls or children with other LRTIs (P < 0.001). SP load was 15-fold higher in pneumonia children with viral coinfection compared with those children without viral coinfection (1.4 × 107/mL vs. 9.1 × 105/mL; P = 0.0001). SP load was over 200-fold higher in serotypeable SP compared with nontypeable SP (2.5 × 106/mL vs. 1 × 104/mL; P < 0.0001). These associations were independent of potential confounders in multiple regression models. No clear association was found between nasopharyngeal load of Haemophilus influenzae or Moraxella catarrhalis and viral coinfection in either RCP or other LRTIs groups. An increased load of SP in the nasopharynx was associated with RCP, viral coinfection, and presence of pneumococcal capsule.

Bolivian hemorrhagic fever (BHF) is a potentially severe febrile illness caused by Machupo virus (family Arenaviridae). Initial symptoms include headache, fever, arthralgia, and myalgia. In the later stages of this illness, patients may develop hemorrhagic manifestations including subconjunctival hemorrhage, epistaxis, hematemesis, melena, and hematuria, as well as neurological signs including tremor, seizures, and coma. During the BHF epidemics of the 1960s, convalescent-phase immune plasma from survivors of BHF was administered to selected patients infected with Machupo virus. However, there is currently a paucity of survivors of BHF who can donate immune plasma, and there is no active program for collection and storage of BHF immune plasma; therefore, we had the opportunity to offer intravenous ribavirin to two of three patients with this potentially lifethreatening infection. One patient with laboratory-confirmed Machupo virus infection who received ribavirin recovered without sequelae, as did a second patient with suspected BHF whose epidemiological and clinical features were similar to those of the first patient. This report describes the first use of intravenous ribavirin therapy for BHF in humans, and the results suggest the need for more extensive clinical studies to assess the usefulness of ribavirin for treating BHF.