Incidence of SARS-COV-2 infection among previously infected or vaccinated employees

  

View ORCID ProfileN Kojima, A Roshani, M Brobeck, A Baca, JD Klausner

doi: https://doi.org/10.1101/2021.07.03.21259976

This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.07.03.21259976v2.full.pdf

Abstract

Introduction The protective effect of previous infection versus vaccination is poorly studied. Among a clinical laboratory that has been conducting routine workforce screening since the beginning of the pandemic, we aimed to assess the relative risk of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection among individuals who were SARS-CoV-2 naïve, previously infected, or vaccinated.

Methods Using an electronic laboratory information system, employees were divided into three groups: (1) SARS-CoV-2 naïve and unvaccinated, (2) previous SARS-CoV-2 infection, and (3) vaccinated. Person-days were measured from the date of the employee first test and truncated at the end of the observation period. SARS-CoV-2 infection was defined as two positive SARS-CoV-2 PCR tests in a 30-day period. Individuals with fewer than 14 days of follow up were excluded. Incidence estimates and the 95% confidence intervals were calculated using the Poisson Exact equation. The incidence rate ratio (IRR) was used as a measure of association between groups. Analyses were performed on StataSE (StataCorp, College Station, TX).

Results We identified 4313, 254 and 739 employee records for groups 1, 2, and 3, respectively. The median age of employees was 29.0 years (interquartile range: 23.6, 39.9). During the observation period, 254, 0, and 4 infections were identified among groups 1, 2, and 3, respectively. Group 1 had an incidence of 25.9 per 100 person-years (95% CI: 22.8-29.3). Group 2 had an incidence of 0 per 100 person-years (95% CI: 0-5.0). Group 3 had an incidence of 1.6 per 100 person-years (95% CI: 0.04-4.2). The IRR of reinfection among those with previous infection compared to SARS-CoV-2 naïve was 0 (95% CI: 0-0.19). The IRR of those vaccinated compared to SARS-CoV-2 naïve was 0.06 (95% CI: 0.02-0.16). The IRR of those vaccinated compared to prior SARS-CoV-2 was 0 (95% CI: 0-4.98).

Conclusion Previous SARS-CoV-2 infection and vaccination for SARS-CoV-2 were associated with decreased risk for infection or re-infection with SARS-CoV-2 in a routinely screened workforce. The was no difference in the infection incidence between vaccinated individuals and individuals with previous infection. Further research is needed to determine whether our results are consistent with the emergence of new SARS-CoV-2 variants.

Competing Interest Statement

Declaration of competing interests NK is a consultant for Curative. AR, MB, and AB are employed by Curative. JDK is an independent consultant and serves as the Medical Director of Curative.

Funding Statement

There was no funding for this manuscript.

https://www.medrxiv.org/content/10.1101/2021.07.03.21259976v2

Clinical characteristics of 152 fully-vaccinated hospitalized COVID-19 patients in Israel

 

• Tal Brosh-Nissimov
• Efrat Orenbuch-Harroch
• Michal Chowers
• Hiba Zayyad
• Galia Rahav
• Yonit Wiener-Well
• Show all authors

DOI:https://doi.org/10.1016/j.cmi.2021.06.036

PDF: https://www.clinicalmicrobiologyandinfection.com/action/showPdf?pii=S1198-743X%2821%2900367-0

Abstract

Objectives

mRNA COVID-19 vaccines have shown high effectiveness in the prevention of symptomatic COVID-19, hospitalization, severe disease, and death. Nevertheless, a minority of vaccinated individuals might get infected and suffer significant morbidity. Characteristics of vaccine breakthrough infections have not been studied. We sought to portray the population of Israeli patients, who were hospitalized with COVID-19 despite full vaccination.

Methods

A retrospective multicenter cohort study of 17 hospitals included Pfizer/BioNTech's BNT162b2 fully-vaccinated patients who developed COVID-19 more than 7 days after the second vaccine dose and required hospitalization. The risk for poor outcome, defined as a composite of mechanical ventilation or death, was assessed.

Results

152 patients were included, accounting for half of hospitalized fully-vaccinated patients in Israel. Poor outcome was noted in 38 patients and mortality rate reached 22% (34/152). Notable, the cohort was characterized by a high rate of comorbidities predisposing to severe COVID-19, including hypertension (108, 71%), diabetes (73, 48%), CHF (41, 27%), chronic kidney and lung diseases (37, 24% each), dementia (29, 19%), and cancer (36, 24%), and only 6 (%) had no comorbidities. Sixty (40%) of the patients were immunocompromised. Higher SARS-CoV-2 viral-load was associated with a significant risk for poor outcome. Risk also appeared higher in patients receiving anti-CD20 treatment and in patients with low titers of anti-spike IgG, but these differences did not reach statistical significance.

Conclusions

We found that severe COVID-19 infection, associated with a high mortality rate, might develop in a minority of fully-vaccinated individuals with multiple comorbidities. Our patients had a higher rate of comorbidities and immunosuppression compared to previously reported non-vaccinated hospitalized COVID-19 patients. Further characterization of this vulnerable population may help to develop guidance to augment their protection, either by continued social-distancing, or by additional active or passive vaccinations.

https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(21)00367-0/fulltext

Modular protein subunit vaccine candidate produced in yeast protects against SARS-CoV-2 in non-human primates

  

View ORCID ProfileNeil C. Dalvie, Lisa H. Tostanoski, Sergio A Rodriguez-Aponte, Kawaljit Kaur, Sakshi Bajoria, Ozan S. Kumru, Amanda J. Martinot, Abishek Chandrashekar, Katherine McMahan, Noe B. Mercado, Jingyou Yu, Aiquan Chang, Victoria M. Giffin, Felix Nampanya, Shivani Patel, Lesley Bowman, Christopher A. Naranjo, Dongsoo Yun, Zach Flinchbaugh, Laurent Pessaint, Renita Brown, Jason Velasco, Elyse Teow, Anthony Cook, Hanne Andersen, Mark G. Lewis, Danielle L. Camp, Judith Maxwell Silverman, Harry Kleanthous, Sangeeta B. Joshi, David B. Volkin, Sumi Biswas,  View ORCID ProfileJ. Christopher Love, Dan H. Barouch

doi: https://doi.org/10.1101/2021.07.13.452251

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2021.07.13.452251v1.full.pdf

Abstract

Vaccines against SARS-CoV-2 have been distributed at massive scale in developed countries, and have been effective at preventing COVID-19. Access to vaccines is limited, however, in low- and middle-income countries (LMICs) due to insufficient supply, high costs, and cold storage requirements. New vaccines that can be produced in existing manufacturing facilities in LMICs, can be manufactured at low cost, and use widely available, proven, safe adjuvants like alum, would improve global immunity against SARS-CoV-2. One such protein subunit vaccine is produced by the Serum Institute of India Pvt. Ltd. and is currently in clinical testing. Two protein components, the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen virus-like particles (VLPs), are each produced in yeast, which would enable a low-cost, high-volume manufacturing process. Here, we describe the design and preclinical testing of the RBD-VLP vaccine in cynomolgus macaques. We observed titers of neutralizing antibodies (>104) above the range of protection for other licensed vaccines in non-human primates. Interestingly, addition of a second adjuvant (CpG1018) appeared to improve the cellular response while reducing the humoral response. We challenged animals with SARS-CoV-2, and observed a ~3.4 and ~2.9 log10 reduction in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, compared to sham controls. These results inform the design and formulation of current clinical COVID-19 vaccine candidates like the one described here, and future designs of RBD-based vaccines against variants of SARS-CoV-2 or other betacoronaviruses.

Competing Interest Statement

J.C.L. has interests in Sunflower Therapeutics PBC, Pfizer, Honeycomb Biotechnologies, OneCyte Biotechnologies, QuantumCyte, Amgen, and Repligen. J.C.L's interests are reviewed and managed under MIT's policies for potential conflicts of interest. J.M.S. is an employee of the Bill & Melinda Gates Medical Research Institute. H.K. is an employee of the Bill & Melinda Gates Foundation. Sumi Biswas is the CEO and co-founder of SpyBiotech Ltd. which holds the exclusive rights for the use of Spytag/Spyctacher in the field of vaccines. Lesley Bowman is an employee of SpyBiotech Ltd.

https://www.biorxiv.org/content/10.1101/2021.07.13.452251v1

Comparative immunogenicity of mRNA and inactivated vaccines against COVID-19

 

• Wey Wen Lim
• Loretta Mak
• Gabriel M Leung
• Benjamin J Cowling
• Malik Peiris

DOI:https://doi.org/10.1016/S2666-5247(21)00177-4

PDF: https://www.thelancet.com/cms/10.1016/S2666-5247(21)00177-4/attachment/6a8fe800-5606-471c-9b10-d77aa89dd0db/mmc1.pdf

We report here comparative data on SARS-CoV-2 vaccine immunogenicity in health-care workers in Hong Kong who received either the BNT162b2 vaccine (Comirnaty; Fosun–BioNTech) or the inactivated virus (vero cell) vaccine (Coronavac; Sinovac). We collected blood samples before vaccination, before the second dose, and 21–35 days after the second dose. We tested the samples for antibodies to SARS-CoV-2 using an ELISA to detect antibodies that bind to the receptor binding domain of the spike protein, testing ELISA-positive samples for neutralising antibodies with a surrogate virus neutralisation (sVNT) assay, and then a plaque reduction neutralisation test (PRNT) with live SARS-CoV-2 virus.

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We enrolled a cohort of 1442 health-care workers from public and private hospitals and medical clinics in Hong Kong and arranged for longitudinal collection of blood samples after obtaining informed consent. Here we present our preliminary laboratory testing results on 93 participants for whom we have complete data on antibody concentrations before vaccination, after the first dose, and after the second dose. These included 63 participants (55·6% male, median age 37 years, range 26–60 years) who were fully vaccinated with the BNT162b2 vaccine and 30 participants (23·3% male, median age 47 years, range 31–65 years) who received both doses of the inactivated vaccine.

In health-care workers who received the BNT162b2 vaccine, antibody concentrations measured by ELISA and sVNT rose substantially after the first dose and then rose again after the second dose of vaccination (appendix). In a subset of 12 participants for whom we also had PRNT results, after the second dose the geometric mean PRNT50 titre was 269 and the geometric mean PRNT90 titre was 113. In contrast, the health-care workers who received the inactivated vaccine had low antibody concentrations by ELISA and sVNT after the first dose, rising to moderate concentrations after the second dose. In a subset of 12 participants, after the second dose, the geometric mean PRNT50 titre was 27 and the geometric mean PRNT90 titre was 8·4.

Neutralising antibody titres have been proposed as a correlate of protection for SARS-CoV-2 vaccines.

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 The difference in concentrations of neutralising antibodies identified in our study could translate into substantial differences in vaccine effectiveness. Our study did not include data on other potential correlates of protection such as T cells or antibody-dependent cellular cytotoxicity antibody. Future studies could investigate alternative strategies to increase antibody concentrations and clinical protection in recipients of inactivated vaccines, including administration of booster doses.

This work was supported by the Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong. BJC is supported by the AIR@innoHK programme of the Innovation and Technology Commission of the Government of Hong Kong. BJC reports honoraria from Sanofi Pasteur, GlaxoSmithKlein, Moderna, and Roche. All other authors report no other potential competing interests.

https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00177-4/fulltext

Long-term Symptoms After SARS-CoV-2 Infection in Children, Adolescents

 Thomas Radtke, PhD¹; Agne Ulyte, MD, PhD¹; Milo A. Puhan, MD, PhD¹; et al

 doi:10.1001/jama.2021.11880

Children can experience SARS-CoV-2 postviral syndromes, but it is unclear to what extent these individuals are affected by long COVID. Evidence is predominantly limited to select populations without control groups,^1-4 which does not allow estimating the overall prevalence and burden in a general pediatric population. We compared symptoms compatible with long COVID in children and adolescents (hereafter “children”) reported within 6 months after SARS-CoV-2 serologic testing.

Methods

Ciao Corona is a longitudinal cohort study investigating SARS-CoV-2 seroprevalence in 55 randomly selected schools in the canton of Zurich in Switzerland,^5,6 which has a linguistically and ethnically diverse population of 1.5 million residents in urban and rural settings. Schools were selected randomly from the 12 cantonal districts, with number of schools proportional to population size. In Switzerland, children attended schools in person (with protective measures) in 2020-2021, except during a 6-week nationwide lockdown (March 16 to May 10, 2020).

Within participating schools, we invited all children of randomly selected classes to participate. Between June 2020 and April 2021, 3 testing phases included collection of venous blood for serologic analysis and online questionnaires for symptoms. For serologic analysis, we used the ABCORA 2.0 test (eMethods in the Supplement).⁵

We compared children who tested positive for SARS-CoV-2 antibodies in October or November 2020 with those who tested negative. We excluded children who were seronegative in October or November 2020 and seroconverted or were not retested by March or April 2021. In March to May 2021, parents reported symptoms of their children occurring since October 2020 and lasting for at least 4 weeks, as well as whether the symptoms persisted for more than 12 weeks. The questionnaire contained a list of predefined symptoms and a free-text field.

Descriptive analysis was performed with R version 4.0.3 (R Foundation). The Ethics Committee of the Canton of Zurich, Switzerland, approved the study and parents provided written informed consent.

Results

Overall, 1355 of 2503 children (54%) (median age, 11 years; interquartile range, 9-13; 54% girls) with a serology result in October or November 2020 were included. Two hundred thirty-eight children were not eligible because they seroconverted, 292 because they were not retested, and 618 because they did not provide information on symptoms. Compared with children not included, those included in the analysis were younger (median age, 11 vs 12 years) and more likely to be girls (54% vs 49%), and their parents had a higher proportion of university or college education (77% vs 64%). Age and sex distribution was comparable between seropositive children (n = 109) and seronegative ones (n = 1246) (Table).

Between October and November 2020 and March and April 2021, 4 of 109 seropositive children (4%) vs 28 of 1246 seronegative ones (2%) reported at least 1 symptom lasting beyond 12 weeks (see Table for all symptoms lasting beyond 4 and 12 weeks). The most frequently reported symptoms lasting more than 12 weeks among seropositive children were tiredness (3/109, 3%), difficulty concentrating (2/109, 2%), and increased need for sleep (2/109, 2%). None of the seropositive children reported hospitalization after October 2020. Similar proportions of seropositive and seronegative children reported excellent or good health.

Discussion

This study found a low prevalence of symptoms compatible with long COVID in a randomly selected cohort of children assessed 6 months after serologic testing.

Although long COVID exists in children,^1,3,4 estimates of the prevalence of persisting symptoms based on scarce literature range from 0%² to 27%.¹ Initial SARS-CoV-2 infection severity, different methodological approaches (clinical assessment vs self-report), definition of cases (diagnosed vs suspected), variable follow-up times, and prevalence of preexisting clinical conditions likely contribute to the variability in prevalence estimates.

This study reports the distribution of symptoms compatible with long COVID on a population level; it did not capture severe SARS-CoV-2 infections because they are rare in children. A strength of this study is the population-based seronegative control group. Limitations include the relatively small number of seropositive children, lack of information on the exact time of SARS-CoV-2 infection, possible misclassification of some children with false seropositive results, potential recall bias, parental report of child’s symptoms, lack of information on symptom severity, and noncompletion of the questionnaire. Also, systematic differences existed between children included vs not included in the analysis, possibly affecting the representativeness of the sample.

https://jamanetwork.com/journals/jama/fullarticle/2782164