Aminoglycoside-Induced Ototoxicity: Test Before You Treat?

COMMENTARY Aminoglycoside-induced deafness is discussed in the Online Mendelian Inheritance in Man (OMIM) website as condition 580000.1 The ototoxicity is not dose-related and was reported with the use of streptomycin for tuberculosis in Africa during the second half of the 20th century.1 Maternal transmission of risk was identified, and affected kindreds were characterized in China and the Middle East.1 A thorough literature review revealed that the A1555G mutation is most common and that a related mutation C1494T results in similarly affected patients;14 patients with other mutations also have been identified.2 The two most common mutations usually are seen in individuals of Chinese ancestry.2 Ding and colleagues reported successful testing for the mitochondrial mutations conferring risk of ototoxicity with aminoglycoside use, but the rapidity of result availability was not explicitly described.3 The various steps of their assay require approximately 15 minutes, but they did not describe the duration of intervening cooling phases,3 and it is not known if their assay would yield results rapidly enough to alter treatment in individuals who need life-saving antimicrobial therapy. A Chinese study of one family over three generations suggested that children carrying the mitochondrial mutation who received an aminoglycoside at younger ages were more susceptible to more profound hearing loss than were children treated with an aminoglycoside later in childhood.4 Thus, initial implementation of testing could, indeed, be targeted in neonatal and pediatric settings. Knowing that one of each 500 individuals treated with an aminoglycoside is at risk of profound hearing loss (separate from the renal and ocular toxicity that can be largely prevented by checking levels and adjusting doses to keep trough levels below a range of potential toxicity), one wonders if testing for the relevant mitochondrial mutations will be required one day before allowing aminoglycoside treatment. 1.

Children Hospitalized with SARS-CoV-2

Some other patients (17 of 163 overall infected patients in the study) were categorized by physician diagnosis (following Centers for Disease Control and Prevention [CDC] diagnostic criteria] as having multisystem inflammatory syndrome in children (MIS-C). [...]Kushner and colleagues did a similar retrospective study, but from May 2020 to February 2021 (thus, including the winter respiratory season) and including only patients younger than 18 years of age (not 22 years, as in the other study) at a university-based quaternary children’s hospital in northern California. [...]related to the Delta variant or not, widespread screening reveals that many children are infected (often without symptoms), but it still is inappropriate to assign COVID-19 as the cause of hospitalization in all hospitalized children who happen to be infected.

MIS-C: Steroids and/or IVIG?

A total of 614 individuals were included, and the majority (81%) met Centers for Disease Control and Prevention (CDC) criteria for a diagnosis of MIS-C. Inclusion was based on meeting six criteria, as detailed by the CDC: serious illness prompting hospitalization, age younger than 21 years, fever for at least 24 hours, laboratory evidence of inflammation, involvement of at least two organ systems, and confirmed SARS-CoV-2 infection or association with an infected person. [...]there were many factors making these two studies dissimilar: variations in treating physician management decisions, patients included, location, time (with resulting variations in viral variants in circulation), and statistical analyses.

Vitamin D and COVID-19?

[...]vitamin D deficiency has been associated with both an elevated risk of acute respiratory infection and worse clinical outcomes following critical illnesses. Vitamin D deficiency also is associated with problems, such as obesity, older age, and cardiac disease, that are risk factors for bad outcomes with COVID-19. [...]investigators have wondered if vitamin D deficiency (and potential treatment) might influence the clinical course of COVID-19. Griffin and colleagues recently summarized the various stages of COVID-19 and eloquently reviewed potential effects of various interventions at various times before, during, and after the actual infection.2 A recent placebo-controlled study of high-dose vitamin D as treatment of established COVID-19 infection included 236 hospitalized adults in multiple centers in Brazil (mean age 56 years, mean 25-hydroxyvitamin D level 21 ng/mL at entry into the study, with 20 ng/mL being the upper limit of “deficiency”).3 Vitamin D levels increased significantly with treatment, and no significant adverse events were noted.3 However, hospital length-of-stay, need for intensive care, need for mechanical ventilation, and mortality were not altered by vitamin D treatment.3 Thus, these new data remind us that hypovitaminosis D is at least associated with respiratory infections, but that preventive supplementation only modestly reduces the risk of acquiring infection (in children for non-COVID-19 infection), and therapeutic administration of vitamin D does not alter the course of adults being hospitalized with COVID-19.

COVID, Lockdowns, and Dengue Fever

Singapore adopted strict stay-at-home programs to supplement personal social distancing to reduce the spread of SARS-CoV-2. [...]migrant workers had a 69% reduction in the incidence of dengue during the weeks they stayed at home. [...]while staying with groups in dormitories facilitated transmission of SARS-CoV-2, it kept migrant workers indoors in environments less conducive to Aedes mosquitoes and reduced transmission of dengue virus. Staying away from groups of people was associated with reductions in acute illness visits, emergency department visits, and overall hospitalizations for medical problems.

COVID-19 and Children

Children were characterized as having suspected COVID-19 if they were high risk (i.e., exposed to a known COVID-19 case) and had at least two of the following features: symptoms (i.e., upper respiratory symptoms, digestive symptoms, fever, or fatigue);laboratory abnormalities (i.e., normal or decreased white blood cell count, increased lymphocyte count, or increased C-reactive protein);or abnormal chest X-ray. Pediatric patients were classified as having confirmed COVID-19 if a nasal, pharyngeal, or blood sample either tested positive for SARS-CoV-2 nucleic acid using real time polymerase chain reaction (RT-PCR) or exhibited highly homologous genetic sequencing with SARS-CoV-2. [...]each pediatric case was classified by severity: asymptomatic (i.e., positive SARS-CoV-2 nucleic test without clinical symptoms or chest imaging abnormalities);mild (i.e., symptoms of upper respiratory tract infection or digestive symptoms without auscultory or chest imaging abnormalities);moderate (i.e., lung lesions on chest imaging or more severe respiratory symptoms, such as pneumonia without hypoxemia);severe (i.e., respiratory symptoms that progress to central cyanosis with oxygen saturation less than 92%);and critical (i.e., acute respiratory distress, shock, encephalopathy, myocardial injury, acute kidney injury, or coagulation dysfunction). Specifically, the infant in the case study conducted by Dong and colleagues was positive for both SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) despite negative SARS-CoV-2 PCR tests.5 Similarly, two of the six neonates studied by H. Zeng and colleagues were positive for both SARS-CoV-2 IgG and IgM, and three were positive for IgG.6 Whether a positive SARS-CoV-2 IgM represents a response to infection or is simply a false positive has not been determined yet.

Respiratory Syncytial Virus: Effective Prevention Still Needed

[...]an extended half-life RSV-specific monoclonal antibody was given to preterm babies. COMMENTARY RSV is an RNA virus with two surface proteins responsible for much of its pathogenesis and infectivity.1 The fusion protein accounts for viral entry into the host cell and is the target of natural neutralizing antibodies.1 This protein was the basis of the vaccine tested in pregnant women in the Madhi et al study and of the monoclonal antibody used in the Griffin et al study. While supportive care (e.g., fluids, nutrition, comfort measures, oxygen as needed) has proven efficacy, various disproven treatments, such as bronchodilators, hypertonic saline, steroids, antibiotics, and high-technology oxygen delivery systems, have been used widely (albeit ineffectively).2-5 Quality improvement efforts can be effective in reducing unnecessary treatments.6-8 All around the planet, there is eager expectation of a vaccine for SARS-CoV-2.

Ethical Issues Affecting COVID-19 Vaccination

[...]supplies are likely to be limited, at least initially. [...]various groups have suggested prioritization schemes to allocate limited vaccine supplies. [...]they believe that it is fundamental to prioritize disadvantaged populations, including the medically vulnerable who risk earlier death if infected, as well as those who have been subject to socioeconomic deprivation and oppression. [...]they suggest that differences of race, gender, and religion should not enter into consideration in simplistic ways that could actually harm or de-prioritize disadvantaged population groups — while, of course, not ignoring relevant differences. [...]the authors urge that COVID-19 vaccines be allocated to prevent harm, prioritize those who are disadvantaged, and achieve equal treatment.

Biologic Warfare: A Game-Changer in the Battle Against Malaria?

[...]Herren and colleagues found that Microsporidia MB-infected mosquitoes could ingest Plasmodium parasites with blood meals, but that the parasites then would not progress through necessary stages of development and migration to reach the salivary glands of the mosquitoes. [...]the researchers noted that Microsporidia MB did not alter the survival or reproductive potential of the infected mosquitoes. [...]infection by the symbiotic microsporidian would not be a “dead end,” but is associated with the production of subsequent generations of infected mosquitoes that also would be able to block the development and transmission of malaria parasites. The symbiont promoted increased transcription of genes related to digestion, immunity, and salivary gland activity. [...]the mechanism by which Microsporidia MB acts on the mosquito not only blocks malaria transmission but also might enhance the health of the mosquito.

Unexpected Pediatric Benefits of the COVID-19 Pandemic

The loss of life and health is staggering. Since the beginning of the pandemic, though, it seemed clear that children were less severely affected by SARS-CoV-2 than were and are adults. Pines and colleagues characterized pediatric care in U.S. emergency departments using data from more than 2 million episodes of care.1 Adult non-COVID emergency care visits dropped by 60% in early 2020 as compared to 2019, and pediatric visits dropped even more (74% drop for children younger than 10 years of age, 67% drop for children aged 14 to 17 years).1 The declines in care utilization were seen across all types of visits, but especially with non-COVID infections;serious pediatric conditions, including appendicitis, dropped by 22%.1 Why was medical care used less frequently? In Italy, 102 children known to be susceptible to otitis media were followed remotely when in-person visits seemed unwise.2 There was notable clinical improvement in 82% of children with fewer bouts of otitis and less antibiotic use as compared to the previous year.2 In the 27% of children who were evaluated face-to-face (actually, eye-to-ear), 89% had normal middle ear evaluations.2 Although some of the improvement could have been due to the increasing age of the children, it does seem like upper airway infections and illnesses, like emergency care utilization, have decreased significantly during the era of pandemic-induced restrictions.

SARS-CoV-2 Antibodies and Multisystem Inflammatory Syndrome in Children

The clinical features of this condition, now commonly termed multisystem inflammatory syndrome in children (MIS-C), have been described, but serologic correlates had not been described. [...]Rostad and colleagues measured various SARS-CoV-2-related antibodies in the serum of 10 children hospitalized with MIS-C, 10 children with symptomatic COVID-19 who did not meet Centers for Disease Control and Prevention criteria for having MIS-C, five children with Kawasaki disease (three with complete and two with incomplete Kawasaki disease), and four hospitalized control children in Atlanta from March to May 2020. RBD IgG antibody titers in children with MIS-C were positively correlated with erythrocyte sedimentation rates (but not peak C-reactive protein levels), total length of hospitalizations, and the duration of intensive care unit stays. Interestingly, none of the MIS-C patients had a recent history of a respiratory and/or febrile illness (despite having SARS-CoV-2 antibodies), but two had positive polymerase chain reaction (PCR) tests for SARS-CoV-2 when they presented with MIS-C.