December 8, 2022

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Clinical Reports

SARS-CoV-2 Serology and Self-Reported Infection Among Adults — National Health and Nutrition Examination Survey, United States, August 2021–May 2022
- A high percentage of U.S. adults have antibodies to SARS-CoV-2, attained through vaccination, infection, or both. During August 2021–May 2022, 41.6% of a convenience sample of adults had both anti-spike antibodies (indicating previous infection or vaccination) and anti-nucleocapsid antibodies (indicating previous infection only); 43.7% of these persons were possibly asymptomatically infected. Prevalence of serologic patterns consistent with vaccination without infection was lower among adults who were younger, Hispanic and non-Hispanic Black or African American adults, and persons with less education. CDC recommends that everyone stay up to date with COVID-19 vaccination. These results can guide ongoing efforts that are needed to achieve equity in primary series vaccination and booster dose coverage.
Data-driven identification of post-acute SARS-CoV-2 infection subphenotypes
- The post-acute sequelae of SARS-CoV-2 infection (PASC) refers to a broad spectrum of symptoms and signs that are persistent, exacerbated or newly incident in the period after acute SARS-CoV-2 infection. Most studies have examined these conditions individually without providing evidence on co-occurring conditions. In this study, we leveraged the electronic health record data of two large cohorts, INSIGHT and OneFlorida+, from the national Patient-Centered Clinical Research Network. We created a development cohort from INSIGHT and a validation cohort from OneFlorida+ including 20,881 and 13,724 patients, respectively, who were SARS-CoV-2 infected, and we investigated their newly incident diagnoses 30–180 days after a documented SARS-CoV-2 infection. Through machine learning analysis of over 137 symptoms and conditions, we identified four reproducible PASC subphenotypes, dominated by cardiac and renal (including 33.75% and 25.43% of the patients in the development and validation cohorts); respiratory, sleep and anxiety (32.75% and 38.48%); musculoskeletal and nervous system (23.37% and 23.35%); and digestive and respiratory system (10.14% and 12.74%) sequelae. These subphenotypes were associated with distinct patient demographics, underlying conditions before SARS-CoV-2 infection and acute infection phase severity. Our study provides insights into the heterogeneity of PASC and may inform stratified decision-making in the management of PASC conditions.

Antiviral Therapeutics and Vaccines

Serological markers of SARS-CoV-2 infection; anti-nucleocapsid antibody positivity may not be the ideal marker of natural infection in vaccinated individuals
- As part of a large seroprevalence study in hospital healthcare workers, we measured antibody response following vaccination in over 4000 hospital healthcare workers (HCW), coupled with a questionnaire about previous symptoms and confirmed infection. We measured anti-S and anti-N antibodies using Roche Elecsys total antibody assays to determine both serological response to vaccination and to natural infection. Twenty-three participants reported a breakthrough infection post-vaccination, defined as PCR-confirmed SARS-CoV-2 infection ≥14 days after completion of vaccination. This represented 0.6% (23/4111) of all fully vaccinated participants in the study. All had received Pfizer vaccine (which was the vaccine received by most study participants). For these 23 participants, the median number of days between second vaccine dose and positive PCR was 30 days (IQR 25–50 days). Five (22%) had symptoms at the time of the positive PCR test and 18 (78%) did not have symptoms (they were tested as close contacts or as part of hospital outbreaks). All 23 participants had detectable anti-S antibodies, as expected post vaccination. Notably, only 6/23 (26%, 95%CI: 11–49) had detectable anti-N antibodies in response to their infection, compared to 663/812 (82%, 95%CI: 79–84, p-value= <0.001 (Chi-squared) of all participants in the study with previous PCR-confirmed infection having detectable anti-N antibodies. Of the 17 that were anti-N negative, median number of days between PCR positivity and sampling mid-point was 52 (range 9–67) so it is surprising that the majority of these had not mounted an anti-N antibody response. This low number of seroconversions might suggest that anti-N antibodies may be insensitive as a marker of natural infection post vaccination. It is possible that early viral neutralization, perhaps even at mucosal surfaces, might modify the natural humoral response and limit the development of anti-N antibodies.
Sensitivity of anti-SARS-CoV-2 nucleocapsid protein antibody for breakthrough infections during the epidemic of the Omicron variants
- In this well-defined cohort with repeat serological assessments and rigorous registration of COVID-19, the performance of the Roche Ig-N assay was decreased by approximately 20-percentage points for the breakthrough infections occurred within 2 months after the booster dose, whereas it performed well for those occurred 3 months or more after the second or third dose. The decreased performance observed shortly after the booster needs to be considered in the planning of seroepidemiological study and interpretation of the results.

Epidemiology

Mpox (formerly monkeypox) in women: epidemiological features and clinical characteristics of mpox cases in Spain, April to November 2022
- Over 79,000 confirmed cases of mpox were notified worldwide between May and November 2022, most of them in men who have sex with men. Cases in women, for whom mpox might pose different risks, are rare, and Spain has reported more than one third of those in Europe. Using surveillance data, our study found similar time trends, but differences in delay of diagnosis, sexual transmission and signs and symptoms between men and women.
Triage of patients with Ebola virus disease
- Study results suggest that in an early symptomatic phase (ie, days 0–2), epidemiological links such as history of contact with an individual known to have Ebola virus disease, funeral attendance, or health facility consultations in the previous days were better predictors for disease positivity than clinical parameters. Later during the disease process (ie, ≥day 3) some clinical signs were identified as additional predictors of disease (eg, signs of bleeding, conjunctivitis, asthenia, dysphagia, and diarrhea). The relevance of these results is best described in the context of a comprehensive Ebola virus disease surveillance and control strategy, which includes infection prevention and control measures in communities and health facilities.2 The widespread use of the rVSV-EBOV-GP (Ervebo)2 vaccine for ring vaccination (of close contacts and their contacts) and vaccination of health-care workers reduced the risk of Ebola virus infections in the Democratic Republic of the Congo and played a major role in the outbreak response.2 Nsio and colleagues1 document that of 1950 patients with confirmed Ebola virus disease, 309 (15·8%) self-reported previous vaccination. Among these patients’ symptom severity at presentation to an Ebola virus treatment centre appeared less severe compared with unvaccinated patients with Ebola virus disease
Effect of Wearing Glasses on Risk of Infection With SARS-CoV-2 in the Community: A Randomized Clinical Trial
- Observational studies have reported an association between the use of eye protection and reduced risk of infection with SARS-CoV-2 and other respiratory viruses, but, as with most infection control measures, no randomized clinical trials have been conducted. A randomized clinical trial was conducted in Norway from February 2 to April 24, 2022; all adult members of the public who did not regularly wear glasses, had no symptoms of COVID-19, and did not have COVID-19 in the last 6 weeks were eligible. The primary outcome was a positive COVID-19 test result reported to the Norwegian Surveillance System for Communicable Diseases. Secondary outcomes included a positive COVID-19 test result and respiratory infection based on self-report. All analyses adhered to the intention-to-treat. A total of 3717 adults (2439 women [65.6%]; mean [SD] age, 46.9 [15.1] years) were randomized. All were identified and followed up in the registries, and 3231 (86.9%) responded to the end of study questionnaire. The proportions with a reported positive COVID-19 test result in the national registry were 3.7% (68 of 1852) in the intervention group and 3.5% (65 of 1865) in the control group (absolute risk difference, 0.2%; 95% CI, −1.0% to 1.4%; relative risk, 1.10; 95% CI, 0.75-1.50). The proportions with a positive COVID-19 test result based on self-report were 9.6% (177 of 1852) in the intervention group and 11.5% (214 of 1865) in the control group (absolute risk difference, –1.9%; 95% CI, −3.9% to 0.1%; relative risk, 0.83; 95% CI, 0.69-1.00). The risk of respiratory infections based on self-reported symptoms was lower in the intervention group (30.8% [571 of 1852]) than in the control group (34.1% [636 of 1865]; absolute risk difference, –3.3%; 95% CI, −6.3% to −0.3%; relative risk, 0.90; 95% CI, 0.82-0.99). In this randomized clinical trial, wearing glasses in the community was not protective regarding the primary outcome of a reported positive COVID-19 test. However, results were limited by a small sample size and other issues. Glasses may be worth considering as one component in infection control, pending further studies.