Long-term impact on cardiopulmonary function and quality of life among patients recovered from SARS-CoV-2 infection in a 6-month follow-up period in Lima, Peru: FUNCTION cohort study protocol

Introduction
The sequelae of COVID-19 have been described as a multisystemic condition, with a great impact on the cardiovascular and pulmonary systems with abnormalities in pulmonary function tests, such as lower diffusing capacity of the lung for carbon monoxide (DLco) levels and pathological patterns in spirometry; persistence of radiological lesions; cardiac involvement such as myocarditis and pericarditis; and an increase in mental disorders such as anxiety and depression. Several factors, such as infection severity during the acute phase as well as vaccination status, have shown some variable effects on these post-COVID-19 conditions, mainly at a clinical level such as symptoms persistence. Longitudinal assessments and reversibility of changes across the spectrum of disease severity are required to understand the long-term impact of COVID-19.

Methods and analysis
A prospective cohort study aims to assess the impact of SARS-CoV-2 infection on cardiopulmonary function and quality of life after the acute phase of the disease over a 6-month follow-up period. Sample size was calculated to recruit 200 participants with confirmatory COVID-19 tests who will be subsequently classified according to infection severity. Four follow-up visits at baseline, month 1, month 3 and month 6 after discharge from the acute phase of the infection will be scheduled as well as procedures such as spirometry, DLco test, 6-minute walk test, chest CT scan, echocardiogram, ECG, N-terminal pro-B-type natriuretic peptide measurement and RAND-36 scale. Primary outcomes are defined as abnormal pulmonary function test considered as DLco

Leggi
Aprile 2023

COVID-19 vaccine effectiveness and variants in Nepal: study protocol for a test-negative case-control study with SARS-CoV-2 genetic sequencing

Introduction
Inactivated, viral vector and mRNA vaccines have been used in the Nepali COVID-19 vaccination programme but there is little evidence on the effectiveness of these vaccines in this setting. The aim of this study is to describe COVID-19 vaccine effectiveness in Nepal and provide information on infections with SARS-CoV-2 variants.

Methods and analysis
This is a hospital-based, prospective test-negative case–control study conducted at Patan Hospital, Kathmandu. All patients >18 years of age presenting to Patan Hospital with COVID-19-like symptoms who have received a COVID-19 antigen/PCR test are eligible for inclusion. The primary outcome is vaccine effectiveness of licensed COVID-19 vaccines against laboratory-confirmed COVID-19 disease.
After enrolment, information will be collected on vaccine status, date of vaccination, type of vaccine, demographics and other medical comorbidities. The primary outcome of interest is laboratory-confirmed SARS-CoV-2 infection. Cases (positive for SARS-CoV-2) and controls (negative for SARS-CoV-2) will be enrolled in a 1:4 ratio. Vaccine effectiveness against COVID-19 disease will be analysed by comparing vaccination status with SARS-CoV-2 test results.
Positive SARS-CoV-2 samples will be sequenced to identify circulating variants and estimate vaccine effectiveness against common variants.
Measuring vaccine effectiveness and identifying SARS-CoV-2 variants in Nepal will help to inform public health efforts. Describing disease severity in relation to specific SARS-CoV-2 variants and vaccine status will also inform future prevention and care efforts.

Ethics and dissemination
Ethical approval was obtained from the University of Oxford Tropical Ethics Committee (OxTREC) (ref: 561-21) and the Patan Academy of Health Sciences Institutional Review Board (ref: drs2111121578). The protocol and supporting study documents were approved for use by the Nepal Health Research Council (NHRC 550-2021). Results will be disseminated in peer-reviewed journals and to the public health authorities in Nepal.

Leggi
Aprile 2023

Cold Virus Provided Cross-reactivity Against SARS-CoV-2 in Children

Memory CD4 T cells generated after infection with OC43, a common cold coronavirus, also exhibited an immune response against SARS-CoV-2 in early childhood, according to results from 2- and 6-year-old children and adults who did not have antibodies against the novel coronavirus and from a group of adults who had recovered from COVID-19. By age 2 years, many children had antibodies against OC43; by age 6, the reactivity of the CD4 T cells had peaked and then declined in adulthood.

Leggi
Aprile 2023

RECAST: Study protocol for an observational study for the understanding of the increased REsilience of Children compared to Adults in SARS-CoV-2 infecTion

Introduction
The SARS-CoV-2 pandemic remains a threat to public health. Soon after its outbreak, it became apparent that children are less severely affected. Indeed, opposing clinical manifestations between children and adults are observed for other infections. The SARS-CoV-2 outbreak provides the unique opportunity to study the underlying mechanisms. This protocol describes the methods of an observational study that aims to characterise age dependent differences in immune responses to primary respiratory infections using SARS-CoV-2 as a model virus and to assess age differences in clinical outcomes including lung function.

Methods and analysis
The study aims to recruit at least 120 children and 60 adults that are infected with SARS-CoV-2 and collect specimen for a multiomics analysis, including single cell RNA sequencing of nasal epithelial cells and peripheral blood mononuclear cells, mass cytometry of whole blood samples and nasal cells, mass spectrometry-based serum and plasma proteomics, nasal epithelial cultures with functional in vitro analyses, SARS-CoV-2 antibody testing, sequencing of the viral genome and lung function testing. Data obtained from this multiomics approach are correlated with medical history and clinical data. Recruitment started in October 2020 and is ongoing.

Ethics and dissemination
The study was reviewed and approved by the Ethics Committee of Charité – Universitätsmedizin Berlin (EA2/066/20). All collected specimens are stored in the central biobank of Charité – Universitätsmedizin Berlin and are made available to all participating researchers and on request.

Trial registration number
DRKS00025715, pre-results publication.

Leggi
Aprile 2023

Monitoring SARS-CoV-2 incidence and seroconversion among university students and employees: a longitudinal cohort study in California, June-August 2020

Objectives
To identify incident SARS-CoV-2 infections and inform effective mitigation strategies in university settings, we piloted an integrated symptom and exposure monitoring and testing system among a cohort of university students and employees.

Design
Prospective cohort study.

Setting
A public university in California from June to August 2020.

Participants
2180 university students and 738 university employees.

Primary outcome measures
At baseline and endline, we tested participants for active SARS-CoV-2 infection via quantitative PCR (qPCR) test and collected blood samples for antibody testing. Participants received notifications to complete additional qPCR tests throughout the study if they reported symptoms or exposures in daily surveys or were selected for surveillance testing. Viral whole genome sequencing was performed on positive qPCR samples, and phylogenetic trees were constructed with these genomes and external genomes.

Results
Over the study period, 57 students (2.6%) and 3 employees (0.4%) were diagnosed with SARS-CoV-2 infection via qPCR test. Phylogenetic analyses revealed that a super-spreader event among undergraduates in congregate housing accounted for at least 48% of cases among study participants but did not spread beyond campus. Test positivity was higher among participants who self-reported symptoms (incidence rate ratio (IRR) 12.7; 95% CI 7.4 to 21.8) or had household exposures (IRR 10.3; 95% CI 4.8 to 22.0) that triggered notifications to test. Most (91%) participants with newly identified antibodies at endline had been diagnosed with incident infection via qPCR test during the study.

Conclusions
Our findings suggest that integrated monitoring systems can successfully identify and link at-risk students to SARS-CoV-2 testing. As the study took place before the evolution of highly transmissible variants and widespread availability of vaccines and rapid antigen tests, further research is necessary to adapt and evaluate similar systems in the present context.

Leggi
Aprile 2023

Real-world effectiveness of COVID-19 vaccines and anti-SARS-CoV-2 monoclonal antibodies against postacute sequelae of SARS-CoV-2: analysis of a COVID-19 observational registry for a diverse US metropolitan population

Objectives
We evaluated the effectiveness of COVID-19 vaccines and monoclonal antibodies (mAbs) against postacute sequelae of SARS-CoV-2 infection (PASC).

Design and setting
A retrospective cohort study using a COVID-19 specific, electronic medical record-based surveillance and outcomes registry from an eight-hospital tertiary hospital system in the Houston metropolitan area. Analyses were replicated across a global research network database.

Participants
We identified adult (≥18) patients with PASC. PASC was defined as experiencing constitutional (palpitations, malaise/fatigue, headache) or systemic (sleep disorder, shortness of breath, mood/anxiety disorders, cough and cognitive impairment) symptoms beyond the 28-day postinfection period.

Statistical analysis
We fit multivariable logistic regression models and report estimated likelihood of PASC associated with vaccination or mAb treatment as adjusted ORs with 95% CIs.

Results
Primary analyses included 53 239 subjects (54.9% female), of whom 5929, 11.1% (95% CI 10.9% to 11.4%), experienced PASC. Both vaccinated breakthrough cases (vs unvaccinated) and mAb-treated patients (vs untreated) had lower likelihoods for developing PASC, aOR (95% CI): 0.58 (0.52–0.66), and 0.77 (0.69–0.86), respectively. Vaccination was associated with decreased odds of developing all constitutional and systemic symptoms except for taste and smell changes. For all symptoms, vaccination was associated with lower likelihood of experiencing PASC compared with mAb treatment. Replication analysis found identical frequency of PASC (11.2%, 95% CI 11.1 to 11.3) and similar protective effects against PASC for the COVID-19 vaccine: 0.25 (0.21–0.30) and mAb treatment: 0.62 (0.59–0.66).

Conclusion
Although both COVID-19 vaccines and mAbs decreased the likelihood of PASC, vaccination remains the most effective tool for the prevention of long-term consequences of COVID-19.

Leggi
Aprile 2023

Stroke After SARS-CoV-2 mRNA Vaccine: A Nationwide Registry Study

Stroke, Ahead of Print. BACKGROUND:Whether the SARS-CoV-2 mRNA vaccines may cause a transient increased stroke risk is uncertain.METHODS:In a registry-based cohort of all adult residents at December 27, 2020, in Norway, we linked individual-level data on COVID-19 vaccination, positive SARS-CoV-2 test, hospital admissions, cause of death, health care worker status, and nursing home resident status extracted from the Emergency Preparedness Register for COVID-19 in Norway. The cohort was followed for incident intracerebral bleeding, ischemic stroke, and subarachnoid hemorrhage within the first 28 days after the first/second or third dose of mRNA vaccination until January 24, 2022. Stroke risk after vaccination relative to time not exposed to vaccination was assessed by Cox proportional hazard ratio, adjusted for age, sex, risk groups, health care personnel, and nursing home resident.RESULTS:The cohort included 4 139 888 people, 49.8% women, and 6.7% were ≥80 years of age. During the first 28 days after an mRNA vaccine, 2104 people experienced a stroke (82% ischemic stroke, 13% intracerebral hemorrhage, and 5% subarachnoid hemorrhage). Adjusted hazard ratios (95% CI) after the first/second and after the third mRNA vaccine doses were 0.92 (0.85–1.00) and 0.89 (0.73–1.08) for ischemic stroke, 0.81 (0.67–0.98) and 1.05 (0.64–1.71) for intracerebral hemorrhage, and 0.64 (0.46–0.87) and 1.12 (0.57–2.19) for subarachnoid hemorrhage, respectively.CONCLUSIONS:We did not find increased risk of stroke during the first 28 days after an mRNA SARS-CoV-2 vaccine.

Leggi
Marzo 2023

Neonatal outcomes and indirect consequences following maternal SARS-CoV-2 infection in pregnancy: a systematic review

Objectives
To identify the association between maternal SARS-CoV-2 infection in pregnancy and individual neonatal morbidities and outcomes, particularly longer-term outcomes such as neurodevelopment.

Design
Systematic review of outcomes of neonates born to pregnant women diagnosed with a SARS-CoV-2 infection at any stage during pregnancy, including asymptomatic women.

Data sources
MEDLINE, Embase, Global Health, WHOLIS and LILACS databases, last searched on 28 July 2021.

Eligibility criteria
Case–control and cohort studies published after 1 January 2020, including preprint articles were included. Study outcomes included neonatal mortality and morbidity, preterm birth, caesarean delivery, small for gestational age, admission to neonatal intensive care unit, level of respiratory support required, diagnosis of culture-positive sepsis, evidence of brain injury, necrotising enterocolitis, visual or hearing impairment, neurodevelopmental outcomes and feeding method. These were selected according to a core outcome set.

Data extraction and synthesis
Data were extracted into Microsoft Excel by two researchers, with statistical analysis completed using IBM SPSS (Version 27). Risk of bias was assessed using a modified Newcastle-Ottawa Scale.

Results
The search returned 3234 papers, from which 204 were included with a total of 45 646 infants born to mothers with SARS-CoV-2 infection during pregnancy across 36 countries. We found limited evidence of an increased risk of some neonatal morbidities, including respiratory disease. There was minimal evidence from low-income settings (1 study) and for neonatal outcomes following first trimester infection (17 studies). Neonatal mortality was very rare. Preterm birth, neonatal unit admission and small for gestational age status were more common in infants born following maternal SARS-CoV-2 infection in pregnancy in most larger studies.

Conclusions
There are limited data on neonatal morbidity and mortality following maternal SARS-CoV-2 infection, particularly from low-income countries and following early pregnancy infections. Large, representative studies addressing these outcomes are needed to understand the consequences for babies born to women with SARS-CoV-2.

PROSPERO registration number
CRD42021249818.

Leggi
Marzo 2023

Study: No New SARS-CoV-2 Variants in Recent Outbreak in China

After relaxing its “zero-COVID policy” in early December 2022, China’s SARS-CoV-2 infections surged, stoking concerns that new variants might appear. But none emerged in a genomic analysis of 413 COVID-19 cases collected in Beijing between November 14 and December 20, 2022. Two Omicron subvariants—BA.5.2 and BF.7—represented more than 90% of local infections, researchers in China reported in The Lancet.

Leggi
Marzo 2023

Investigation of SARS-CoV-2 seroprevalence in relation to natural infection and vaccination between October 2020 and September 2021 in the Czech Republic: a prospective national cohort study

Objective
Examine changes in SARS-CoV-2 seropositivity before and during the national vaccination campaign in the Czech Republic.

Design
Prospective national population-based cohort study.

Setting
Masaryk University, RECETOX, Brno.

Participants
22 130 persons provided blood samples at two time points approximately 5–7 months apart, between October 2020 and March 2021 (phase I, before vaccination), and between April and September 2021 (during vaccination campaign).

Outcome measures
Antigen-specific humoral immune response was analysed by detection of IgG antibodies against the SARS-CoV-2 spike protein by commercial chemiluminescent immunoassays. Participants completed a questionnaire that included personal information, anthropometric data, self-reported results of previous RT-PCR tests (if performed), history of symptoms compatible with COVID-19 and records of COVID-19 vaccination. Seroprevalence was compared between calendar periods, previous RT-PCR results, vaccination and other individual characteristics.

Results
Before vaccination (phase I), seroprevalence increased from 15% in October 2020 to 56% in March 2021. By the end of phase II, in September 2021, prevalence increased to 91%; the highest seroprevalence was seen among vaccinated persons with and without previous SARS-CoV-2 infection (99.7% and 97.2%, respectively), while the lowest seroprevalence was found among unvaccinated persons with no signs of disease (26%). Vaccination rates were lower in persons who were seropositive in phase I but increased with age and body mass index. Only 9% of unvaccinated subjects who were seropositive in phase I became seronegative by phase II.

Conclusions
The rapid increase in seropositivity during the second wave of the COVID-19 epidemic (covered by phase I of this study) was followed by a similarly steep rise in seroprevalence during the national vaccination campaign, reaching seropositivity rates of over 97% among vaccinated persons.

Leggi
Marzo 2023