September 22, 2022

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Clinical Reports

Monkeypox in a Young Infant — Florida, 2022
This is the report of a case of monkeypox in an infant aged <2 months who was admitted to a Florida hospital with a rash and cellulitis. The infant was initially evaluated in an emergency department (ED) for a raised erythematous rash on the arms, legs, and trunk which had been present for 5 days. A rash swab was collected for bacterial culture and yielded a negative test result. Varicella, herpes simplex virus, and HIV testing were also negative. The patient returned to the ED 2 days later, at which time the rash had progressed to include numerous, diffusely scattered papulovesicular lesions over the body, many with central umbilication. The infant was admitted to the hospital with a diagnosis of molluscum contagiosum. The lesions subsequently spread to the back, soles of feet, face, and eyelid and became pustular over the first few days of admission. Swabs from forehead and back lesions by PCR 10 days after rash onset. The infant was treated with oral tecovirimat and Vaccinia Immune Globulin Intravenous. Prophylactic trifluridinedrops were administered to prevent ophthalmic complications from the eyelid lesion. The infant remained afebrile and stable throughout the course of illness, tolerated the treatments well, and fully recovered. To date, 27 confirmed cases of monkeypox in pediatric patients aged 0–15 years have been reported in the United States during the 2022 outbreak.
Health Care Personnel Exposures to Subsequently Laboratory-Confirmed Monkeypox Patients — Colorado, 2022
Although risk for monkeypox transmission to health care personnel (HCP) is thought to be low, CDC recommends that HCP wear personal protective equipment (PPE) consisting of gown, gloves, eye protection, and an N95 (or higher-level) respirator while caring for patients with suspected or confirmed monkeypox. Among 313 Colorado HCP exposed to patients with monkeypox, recommended PPE use and receipt of postexposure prophylaxis vaccination was low. HCP were assessed for risk and actively monitored for 21 days when indicated; none acquired monkeypox. The risk for acquiring monkeypox among U.S. HCP after exposure to patients with monkeypox is very low. HCP in all health care settings can benefit from public health outreach regarding infection prevention education and training.
Public Health Response to a Case of Paralytic Poliomyelitis in an Unvaccinated Person and Detection of Poliovirus in Wastewater — New York, June–August 2022
Sustained poliovirus transmission has been eliminated from the United States for approximately 40 years; vaccines are highly effective in preventing paralysis after exposure. In June 2022, poliovirus was confirmed in an unvaccinated immunocompetent adult resident of New York hospitalized with flaccid lower limb weakness. Vaccine-derived poliovirus type 2 was isolated from the patient and identified from wastewater samples in two neighboring New York counties. Unvaccinated persons in the United States remain at risk for paralytic poliomyelitis if they are exposed to either wild or vaccine-derived poliovirus; all persons in the United States should stay up to date on recommended poliovirus vaccination.
Association of COVID-19 with New-Onset Alzheimer’s Disease
An infectious etiology of Alzheimer’s disease has been postulated for decades. It remains unknown whether SARS-CoV-2 viral infection is associated with increased risk for Alzheimer’s disease. In this retrospective cohort study of 6,245,282 older adults (age ≥65 years) who had medical encounters between 2/2020–5/2021, researchers show that people with COVID-19 were at significantly increased risk for new diagnosis of Alzheimer’s disease within 360 days after the initial COVID-19 diagnosis (hazard ratio or HR:1.69, 95% CI: 1.53–1.72), especially in people age ≥85 years and in women. These findings call for research to understand the underlying mechanisms and for continuous surveillance of long-term impacts of COVID-19 on Alzheimer’s disease.

Antiviral Therapeutics and Vaccines

Impact of mandatory vaccination of healthcare personnel on rates of influenza and other viral respiratory pathogens
Researchers examined the effect of mandatory influenza vaccination policies among HCP working in outpatient settings. Influenza vaccination was associated with a decreased risk of influenza (odds ratio, 0.17; 95% confidence interval [CI], 0.13–0.22) but an increased risk of other respiratory viral infections (incidence rate ratio, 1.26; 95% CI, 1.02–1.57). Researchers fitted regression models suggest that if influenza vaccination rates in clinics where vaccination was not mandated had equaled those where vaccine was mandated, HCP influenza infections would have been reduced by 52.1% (95% CI, 51.3%–53.0%). These observations, their possible causes, and additional strategies to reduce influenza and other viral respiratory illnesses among HCP working in ambulatory clinics warrant further investigation.
Monkeypox in Patient Immunized with ACAM2000 Smallpox Vaccine During 2022 Outbreak
Study authors report a patient in Washington, USA, who contracted monkeypox despite being successfully immunized against smallpox with the ACAM2000 smallpox vaccine 8 years earlier. This poses major questions regarding the efficacy of ACAM2000 vaccine amidst ongoing shortages of the JYNNEOS 2-dose monkeypox vaccine. The patient was a previously healthy 34-year-old man who had sex with men came to a walk-in sexually transmitted infections clinic because of a 4-day history of malaise, fatigue, and headache and a 2-day history of 4 painless penile lesions. The patient had sought evaluation at a local emergency department 2 days before he visited the clinic. Results for testing performed in the emergency department were negative for Neisseria gonorrhea, Chlamydia trachomatis, and herpes simplex virus. His constitutional symptoms improved over the next 2 days. However, his penile ulcers progressed into white papular lesions, prompting him to seek reevaluation. Given the condition of the patient and his sexual history in the setting of an emerging monkeypox outbreak throughout the United States, a nonvariola orthopoxvirusPCR was conducted, and the result was positive. Subsequent confirmatory testing by the Centers for Disease Control and Prevention later identified the infection as the clade II strain (formerly West African clade). Clinically the patient did well, only requiring supportive care with oral acetaminophen for constitutional symptoms, which resolved 10 days after symptom onset. Although vaccination is foundational for prevention of infectious disease, this case highlights that vaccination alone does not guarantee immunity from monkeypox. Public health leaders should taper expectations that vaccination alone will end the outbreak. Vaccine should complement, not replace, public health campaigns that aim to minimize high-risk health behaviors.
Qualitative Subgenomic RNA to Monitor the Response to Remdesivir in Hospitalized Patients with COVID-19: impact on the length of hospital stay and mortality
There is no reliable microbiological marker to guide the indication and the response to antiviral treatment in patients with COVID-19. We aim to evaluate the dynamics of subgenomic RNA (sgRNA) in patients with COVID-19 before and after receiving treatment with remdesivir. Researchers included consecutive patients admitted for COVID-19 who received remdesivir according to our institutional protocol and accepted to participate in the study. A nasopharyngeal swab for qRT-PCR was collected at baseline, and after 3 and 5 days of treatment with remdesivir. Genomic and sgRNA were analyzed in those samples and main co-morbidities and evolution were collected for the analyses. The main outcomes were early discharge (≤10 days) and 30-day mortality. A total of 117 patients were included in the study, from which 24 had a negative sgRNA at baseline with a 62.5% (15/24) of early discharge (≤10 days) and no deaths in this group. From the 93 remaining patients, 62 of them had a negative sgRNA at day 5 with 37/62 (59.6%) of early discharge and a mortality of 4.8% (3/62). In the 31 patients subgroup with positive sgRNA after 5 days of RDV, the early discharge rate was 29% (9/31) and the mortality rate was 16.1% (5/31). In the multivariable analyses, the variables associated with early discharge were negative sgRNA at day 3, and not needing treatment with corticosteroids or ICU admission. Qualitative sgRNA could help monitoring the virological response in patients who receive remdesivir. Further studies are needed to confirm these findings.
Anti-Spike Mucosal IgA Protection against SARS-CoV-2 Omicron Infection
These study findings suggest that wild-type SARS-CoV-2 spike-specific mucosal IgA is protective against omicron infection. Further studies are warranted to determine whether vaccines that induce a combination of mucosal and systemic immune responses would confer stronger protection than intramuscular vaccines.
Usage and awareness of antiviral medications for COVID-19 among individuals at risk for severe COVID-19, March 2021 to 1 August 2022
These results are from 44,948 respondents and researchers learn that of individuals aged 65 years and older, 66% were aware of treatment for COVID-19, 36.3% sought treatment and only 1.7% ended up getting antiviral therapy. These findings demonstrate that increased awareness and use of antivirals for SARS2 CoV-2 infection among older adults at risk for severe disease due to COVID-19 is urgently needed.
Comparable outcomes for bebtelovimab and ritonavir-boosted nirmatrelvir treatment in high-risk patients with coronavirus disease-2019 during severe acute respiratory syndrome coronavirus 2 BA.2 Omicron epoch
The effectiveness of bebtelovimab in real-world settings has not been assessed. In this retrospective cohort study of 3607 high-risk patients, bebtelovimab was used more commonly than nirmatrelvir-ritonavir for treatment of coronavirus disease 2019 (COVID-19) among older patients, immunosuppressed patients, and those with multiple comorbid conditions. Despite its use in patients with multiple comorbid conditions, the rate of progression to severe disease after bebtelovimab (1.4% [95% confidence interval, 1.2%–1.7%]) was not significantly different from that for nirmatrelvir-ritonavir treatment (1.2% [.8%–1.5%]). Our findings support the emergency use authorization of bebtelovimab for treatment of COVID-19 during the Omicron epoch dominated by BA.2 and subvariants.
Bebtelovimab in the Real World: Promise and Fulfillment
The study by Razonable et al is important and timely, given the worrisome prospect of a loss of funding for bebtelovimab in the near future. This study confirms what front-line clinicians have already observed about excellent outcomes with bebtelovimab. It is to be hoped that these data will inform policy and funding decisions, potentially to the great benefit of high-risk patients who might otherwise not have the opportunity to receive this treatment.

Diagnostics

Monkeypox testing delays: The need for drastic expansion of education and testing for monkeypox virus
Observed delays in testing for MPX could be due to several factors including lack of patient awareness of MPX, underrecognition by healthcare providers, and/or lack of availability of testing. Early in the testing period, not all emergency departments in our healthcare system had access to testing supplies, which might have particularly affected our findings. Delays in recognition of symptoms of MPX have multiple implications. For the patient, delayed recognition and testing leads to delays in treatment with antiviral agents as well as increased cost of care due to multiple visits to healthcare. For the HCWs, lack of early recognition of MPX symptoms may lead to increased exposures due to lack of use of appropriate personal protective equipment. Aggressive education on the clinical presentation of MPX cases including visuals of the myriad skin presentations is urgently needed, particularly in emergency department and urgent care settings. In addition to further clinical education on the current atypical presentation of MPX in the 2022 outbreak, reinforcement of the use of standard precautions with all patients and adherence to universal mask protocols in healthcare are needed to prevent HCW exposure to patients with MPX while infectious.
Detection and Kinetics of Subgenomic Severe Acute Respiratory Syndrome Coronavirus 2 RNA Viral Load in Longitudinal Diagnostic RNA–Positive Samples
While detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by diagnostic reverse-transcription polymerase chain reaction (RT-PCR) is highly sensitive for viral RNA, the nucleic acid amplification of subgenomic RNAs (sgRNAs) that are the product of viral replication may more accurately identify replication. Researchers characterized the diagnostic RNA and sgRNA detection by RT-PCR from nasal swab samples collected daily by participants in postexposure prophylaxis or treatment studies for SARS-CoV-2. Among 1932 RT-PCR–positive swab samples with sgRNA tests, 40% (767) had detectable sgRNA. Above a diagnostic RNA viral load (VL) threshold of 5.1 log₁₀copies/mL, 96% of samples had detectable sgRNA with VLs that followed a linear trend. The trajectories of diagnostic RNA and sgRNA VLs differed, with 80% peaking on the same day but duration of sgRNA detection being shorter (8 vs 14 days). With a large sample of daily swab samples we provide comparative sgRNA kinetics and a diagnostic RNA threshold that correlates with replicating virus independent of symptoms or duration of illness.