November 2, 2022

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Clinical Reports

Severe Monkeypox in Hospitalized Patients — United States, August 10–October 10, 2022
Severe manifestations of monkeypox in immunocompromised persons have been observed in previous outbreaks. During August–October 2022, CDC provided clinical consultation for 57 hospitalized patients with severe manifestations of monkeypox, most of whom were Black men with AIDS. Delays were observed in initiation of monkeypox-directed therapies. Twelve patients died, and monkeypox was a cause of death or contributing factor in five patients to date, with several other deaths still under investigation. Clinicians should consider early treatment with available therapeutics for those at risk for severe monkeypox disease, particularly patients with AIDS. Engaging all persons with HIV in care remains a critical public health priority.
Reinfections with Different SARS-CoV-2 Omicron Subvariants, France (CDC)
Researchers describe 188 patients in France who were successively infected with different SARS-CoV-2 Omicron subvariants, including BA.1, BA.2, and BA.5. Time between 2 infections was <90 days for 50 (26.6%) patients and <60 days for 28 (14.9%) patients. This finding suggests that definitions for SARS-CoV-2 reinfection require revision.
In adults with COVID-19, melatonin was assessed for effects on inflammatory markers, clinical signs and symptoms, and mortality
Ten articles were included in this study. It seems melatonin can decrease inflammatory markers, inflammatory cytokines, and the expression of some genes, including the signal transducer and activator of transcription (STAT)4, STAT6, T-box expressed in T cell (T-bet), GATA binding protein 3 (GATA3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 (CASP1). In addition, melatonin appears to alleviate some clinical signs and symptoms and accelerate recovery. The use of melatonin in severe cases reduces thrombosis, sepsis, and mortality rate. This systematic review highlights the probable role of melatonin as a potential adjuvant in the treatment of COVID-19 after about two weeks of consumption. However, further high-quality randomized clinical trials are required.

Antiviral Therapeutics and Vaccines

Influenza Incidence and Vaccine Effectiveness During the Southern Hemisphere Influenza Season — Chile, 2022
Influenza transmission has changed during the COVID-19 pandemic. In 2022, influenza A(H3N2) virus, clade 3C.2a1b.2a.2, circulated in Chile months earlier than during prepandemic influenza seasons and was associated with 1,002 hospitalizations. Influenza vaccination reduced risk for A(H3N2) virus hospitalization by 49%. Like certain Southern Hemisphere countries during the 2022 influenza season, Northern Hemisphere countries might face influenza activity with atypical timing and intensity during the 2022–23 season. Health authorities should encourage all eligible persons to seek influenza vaccination and take precautions to reduce transmission of influenza (e.g., avoiding close contact with persons who are ill).
Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants
A total of 1490 infants underwent randomization: 994 were assigned to the nirsevimab group and 496 to the placebo group. Medically attended RSV-associated lower respiratory tract infection occurred in 12 infants (1.2%) in the nirsevimab group and in 25 infants (5.0%) in the placebo group; these findings correspond to an efficacy of 74.5% (95% confidence interval [CI], 49.6 to 87.1; P<0.001) for nirsevimab. Hospitalization for RSV-associated lower respiratory tract infection occurred in 6 infants (0.6%) in the nirsevimab group and in 8 infants (1.6%) in the placebo group (efficacy, 62.1%; 95% CI, −8.6 to 86.8; P=0.07). Among infants with data available to day 361, antidrug antibodies after baseline were detected in 58 of 951 (6.1%) in the nirsevimab group and in 5 of 473 (1.1%) in the placebo group. Serious adverse events were reported in 67 of 987 infants (6.8%) who received nirsevimab and in 36 of 491 infants (7.3%) who received placebo. A single injection of nirsevimab administered before the RSV season protected healthy late-preterm and term infants from medically attended RSV-associated lower respiratory tract infection.
Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses
The SARS-CoV-2 pandemic has highlighted the need for vaccines that not only prevent disease, but also prevent transmission. Parenteral vaccines induce robust systemic immunity, but poor immunity at the respiratory mucosa. Here researchers describe the development of a vaccine strategy we term “prime and spike” that leverages existing immunity generated by primary vaccination (prime) to elicit mucosal immune memory within the respiratory tract using unadjuvanted intranasal spike boosters (spike). They show that prime and spike induces robust resident memory B and T cell responses, IgA at the respiratory mucosa, boosts systemic immunity, and completely protects mice with partial immunity from lethal SARS-CoV-2 infection. Using divergent spike proteins, prime and spike enables induction of cross-reactive immunity against sarbecoviruses.
Antibody responses to Omicron BA.4/BA.5 bivalent mRNA vaccine booster shot
The SARS-CoV-2 Omicron variant and its numerous sub-lineages have exhibited a striking ability to evade humoral immune responses induced by prior vaccination or infection. The Food and Drug Administration (FDA) has recently granted Emergency Use Authorizations (EUAs) to new bivalent formulations of the original Moderna and Pfizer mRNA SARS-CoV-2 vaccines that target both the ancestral strain as well as the Omicron BA.4/BA.5 variant. Despite their widespread use as a vaccine boost, little is known about the antibody responses induced in humans. Here, researchers collected sera from several clinical cohorts: individuals after three or four doses of the original monovalent mRNA vaccines, individuals receiving the new bivalent vaccines as a fourth dose, and individuals with BA.4/BA.5 breakthrough infection following mRNA vaccination. Using pseudovirus neutralization assays, these sera were tested for neutralization against an ancestral SARS-CoV-2 strain, several Omicron sub-lineages, and several related sarbecoviruses. At ~3-5 weeks post booster shot, individuals who received a fourth vaccine dose with a bivalent mRNA vaccine targeting BA.4/BA.5 had similar neutralizing antibody titers as those receiving a fourth monovalent mRNA vaccine against all SARS-CoV-2 variants tested, including BA.4/BA.5. Those who received a fourth monovalent vaccine dose had a slightly higher neutralizing antibody titers than those who received the bivalent vaccine against three related sarbecoviruses: SARS-CoV, GD-Pangolin, and WIV1. When given as a fourth dose, a bivalent mRNA vaccine targeting Omicron BA.4/BA.5 and an ancestral SARS-CoV-2 strain did not induce superior neutralizing antibody responses in humans, at the time period tested, compared to the original monovalent vaccine formulation.
Immunogenicity of the BA.5 Bivalent mRNA Vaccine Boosters
Waning immunity following mRNA vaccination and the emergence of SARS-CoV-2 variants has led to reduced mRNA vaccine efficacy against both symptomatic infection and severe disease. Bivalent mRNA boosters expressing the Omicron BA.5 and ancestral WA1/2020 Spike proteins have been developed and approved, because BA.5 is currently the dominant SARS-CoV-2 variant and substantially evades neutralizing antibodies (NAbs). Our data show that BA.5 NAb titers were comparable following monovalent and bivalent mRNA boosters.

Epidemiology

Impact of community masking on COVID-19: A cluster-randomized trial in Bangladesh
Researchers conducted a cluster-randomized trial to measure the effect of community-level mask distribution and promotion on symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in rural Bangladesh from November 2020 to April 2021 (N= 600 villages, N = 342,183 adults). They cross-randomized mask type (cloth versus surgical) and promotion strategies at the village and household level. Proper mask-wearing increased from 13.3% in the control group to 42.3% in the intervention arm (adjusted percentage point difference = 0.29; 95% confidence interval = [0.26, 0.31]). The intervention reduced symptomatic seroprevalence (adjusted prevalence ratio = 0.91 [0.82, 1.00]), especially among adults ≥60 years old in villages where surgical masks were distributed (adjusted prevalence ratio = 0.65 [0.45, 0.85]). Mask distribution with promotion was a scalable and effective method to reduce symptomatic SARS-CoV-2 infections.
Long-term gastrointestinal sequelae following COVID-19: A prospective follow-up cohort study
Of 320 cases,at 1 month, 36 (11.3%) developed FGID symptoms. Persistent symptoms were noted in 27 (8.4%) at 3 months, and in 21 (6.6%) at 6 months. At 3 months, 8 (2.5%) had irritable bowel syndrome, 7 (2.2%) had functional diarrhea, 6 (1.9%) had functional dyspepsia, 3 (0.9%) had functional constipation, 2 (0.6%) had FD-IBS overlap, and 1 (0.3%) had functional abdominal bloating/distension. Among symptomatic individuals at 3 months, 8 (29.6%) were positive for isolated carbohydrate malabsorption, 1 (3.7%) was positive for post infection malabsorption syndrome (PI-MAS) and 1 (3.7%) was positive for Intestinal methanogen overgrowth (IMO). None of the healthy controls developed FGID up to 6 months of follow up (p<0.01). Predictive factors at 3 and 6 months were severity of infection (p<0.01) and presence of GI symptoms at the time of infection (p<0.01). COVID-19 led to significantly higher number of new onset PI-FGID/DGBI compared to healthy controls at 3 and 6 months of follow-up. If further investigated some patients can be diagnosed with underlying malabsorption.
Evaluation of an Automated Text Message–Based Program to Reduce Use of Acute Health Care Resources After Hospital Discharge
Patients received automated check-in text messages from their primary care practice on a tapering schedule during the 30 days after discharge. Any needs identified by the automated messaging platform were escalated to practice staff for follow-up via an electronic medical record inbox. The primary study outcome was any emergency department (ED) visit or readmission within 30 days of discharge. Secondary outcomes included any ED visit or any readmission within 30 days, analyzed separately, and 30- and 60-day mortality. Analyses were based on intention to treat. A total of 1885 patients (mean [SD] age, 63.2 [17.3] years; 1101 women [58.4%]) representing 2617 discharges (447 before and 604 after the intervention at the intervention practice; 613 before and 953 after the intervention at the control practice) were included in the analysis. The adjusted odds ratio (aOR) for any use of acute care resources after implementation of the intervention was 0.59 (95% CI, 0.38-0.92). The aOR for an ED visit was 0.77 (95% CI, 0.45-1.30) and for a readmission was 0.45 (95% CI, 0.23-0.86). The aORs for death within 30 and 60 days of discharge at the intervention practice were 0.92 (95% CI, 0.23-3.61) and 0.63 (95% CI, 0.21-1.85), respectively. The findings of this cohort study suggest that an automated texting program to support primary care patients after hospital discharge was associated with significant reductions in use of acute care resources. This patient-centered approach may serve as a model for improving post discharge care.