key: cord-0689799-b4p5pru5
authors: Nunes, Marta C; Baillie, Vicky L; Kwatra, Gaurav; Bhikha, Sutika; Verwey, Charl; Menezes, Colin; Cutland, Clare L; Moore, David P; Dangor, Ziyaad; Adam, Yasmin; Mathivha, Rudo; Velaphi, Sithembiso C; Tsitsi, Merika; Aguas, Ricardo; Madhi, Shabir A
title: SARS-CoV-2 infection among healthcare workers in South Africa: a longitudinal cohort study
date: 2021-05-05
journal: Clin Infect Dis
DOI: 10.1093/cid/ciab398
sha: 327462d2e53ace09837abba28a372e625ca76ba0
doc_id: 689799
cord_uid: b4p5pru5

From April to September 2020, we investigated SARS-CoV-2 infections in a cohort of 396 healthcare workers (HCWs) from five departments at Chris Hani Baragwanath Hospital, South Africa. Overall, 34.6% of HCWs had PCR-confirmed SARS-CoV-2 infection (132.1 [95%CI: 111.8, 156.2] per 1,000 person-months), an additional 27 infections were identified by serology. HCWs in the Internal Medicine department had the highest rate of infection (61.7%). Among PCR-confirmed cases, 10.4% remained asymptomatic, 30.4% were pre-symptomatic and 59.3% symptomatic.

M a n u s c r i p t infection irrespective of symptomatology, could reduce transmission by 16%-23%, if results were available within 24-hours [2] . Studies from Europe reported rates of SARS-CoV-2 polymerase chain reaction (PCR) positivity in up to 24% of symptomatic and 7.1% asymptomatic HCWs [3] [4] [5] . A crosssectional study from Egypt among asymptomatic HCWs identified a 14.3 % PCR positivity rate at the height of the pandemic in the country [6] . Paired serologic testing for SARS-CoV-2 antibodies, can supplement PCR testing. Cross-sectional seroprevalence surveys among HCWs in Europe and the USA during the first wave of the COVID-19 outbreak, reported sero-positivity prevalence between 4% to 24% [7] [8] [9] [10] . Similarly, a study in Cape Town, South Africa, reported 10.4% seroprevalence among HCWs from paediatric facilities enrolled between May and July 2020 [11] .

This longitudinal cohort surveillance of HCWs aimed to determine the incidence of SARS-CoV-2 infection and describe the clinical presentation thereof among HCWs at a large tertiary care hospital in South Africa, during the first COVID-19 wave.

We enrolled HCWs across five departments, including Internal Medicine (IM), Intensive Care, Paediatrics, Obstetrics & Gynaecology, and the Vaccines and Infectious Diseases Analytics (VIDA) research unit, at Chris Hani Baragwanath Academic Hospital (CHBAH) in South Africa which is Africa's A c c e p t e d M a n u s c r i p t 5 largest hospital. Details of the epidemic progression and management of COVID-19 cases at CHBAH are outlined in the supplement. Enrolment occurred between 22 nd April to 19 th June 2020, whilst VIDA staff were enrolled until 24 th July. The current analysis was censored to events occurring until 15 th September 2020. Nasal mid-turbinate swabs were collected weekly for PCR testing, irrespective of symptoms suggestive of COVD-19. Venous blood samples were collected at the time of enrolment and every two weeks thereafter. For the current analysis, serology testing was done on the blood samples obtained at enrolment and last study visit. HCWs who tested PCR-positive completed a daily symptoms log for the following 10-days. SARS-CoV-2-infected participants had repeat swabs approximately 2-4 days until at least two consecutive negative tests. Classification of participants accordingly to symptoms in the supplement.

Details in supplement. Reverse-transcriptase PCR results were classified as positive for SARS-CoV-2 when both the nucleocapsid genes (N1 and N2) were detected at cycle threshold (Ct) value <40. 

The study was approved by the Human Research Ethics Committee of the University of the Witwatersrand (200405). All study participants provided written informed consent.

Overall, 396 HCWs were enrolled, including 167 (42.2%) from the IM department. The mean age was 38.0 (±9.4) years, 82.6% were female and the majority were black-Africans. Fifty-seven percent reported having at least one comorbidity, including 38.8% being obese (body mass index >30) and

13.2% with hypertension; Table- Accordingly, in a lower percentage of symptomatic participants (7.6%), SARS-CoV-2 was persistently detected at Ct values ≥30 than asymptomatic (42.9%, p<0.001); Table-S4. Overall, SARS-CoV-2 was detected for a mean of 17.9 (±8.8) days in nasal swabs. Detection was longer in symptomatic participants at the time of diagnosis (18.9±8.5 days), than those remaining asymptomatic (13.0±6.0 days, p=0.040); Table- being a nurse, black-African, female, older than 38 years, being hypertensive or obese and using public transport to work were associated with increased risk of SARS-CoV-2 infection. Conversely, receipt of influenza vaccine and smoking were associated with decreased risk. In multivariate analysis, however, only working in the IM department was associated with increased risk, with participants from other departments having an adjusted odds ratio of 0.29 (95%CI: 0.17, 0.49); Table. A c c e p t e d M a n u s c r i p t 8

In this longitudinal study, we evaluated the risk of SARS-CoV-2 infection at a large academic hospital in South Africa from end-April through mid-September 2020. The rate of PCR-confirmed SARS-CoV-2 infection across the study population was 34.6%, which increased to 41.9% when including HCW sero-positive at enrolment or sero-response during the study.

Although multiple studies have investigated SARS-CoV-2 infection among HCWs and suggested that exposure to COVID-19 patients poses increased risk, the rates identified in our study are higher than those previously described in Europe and the USA using either PCR testing or serology surveys (4% to 24%) [3, 4, [7] [8] [9] [10] . At CHBAH, new strategies were developed to accommodate the unexpected increase in number of patients, including establishing specific wards for suspected and confirmed COVID-19 cases. The majority, of these wards, however, had poor ventilation and lacked isolation cubicles for individual patient management. These characteristics, together with crowded wards, likely contributed to these HCWs being at greater risk of SARS-CoV-2 infection compared to that reported from high-income countries where hospitals are better resourced with facilities to reduce the risk of infections. Moreover, owing to the global shortage of high-quality filtering facepiece respirators, alternate products were sourced. A preliminary study contemporaneous with ours evaluating 12 brands of KN95 masks available in South Africa found that none of the brands met stipulated safety requirements, including mask material filtration efficacy and passing a seal and a qualitative fitting test [12] .

A c c e p t e d M a n u s c r i p t 9 We identified a differential risk of SARS-CoV-2 infection, with HCWs from the IM wards having the highest rate of infection. This group was the one mostly exposed to COVID-19 patients; other reasons for the differential rate of infection might be accessibility to training, space and type of personal protective equipment usage. Although in univariate analysis we observed varying risk associated with job category and demographic factors, only working in the IM department remained a significant risk-factor in multivariate analysis.

We identified a 97.8% sero-response rate using the RBD IgG assay among HCWs with PCR-confirmed SARS-CoV-2 infection, which is consistent with previous reports [10] . When the respiratory samples of the three participants who failed to mount an immune response were re-tested, all of them were positive for N1 and N2, and two participants had PCR-positive samples collected at different timepoints, confirming true PCR-positivity. The lack of antibodies against RBD does not imply lack of protection from future infections, since they might have produced antibodies against other targets and be protected by other components of the immune system. We identified two PCR-confirmed SARS-CoV-2 infections in participants with detectable antibodies against RBD prior to diagnosis.

These re-infections were detected in early June and July before a new SARS-CoV-2 variant was identified in South Africa [13] . The antibody threshold defined during our Luminex assay validation was based on the identification of specific RBD IgG in clinical specimens and it does not necessarily corresponds to a correlate of protection required for functional immunity, and higher levels of antibodies may be required to prevent upper respiratory tract re-infections.

In our study, 40.1% of participants were asymptomatic at the time of diagnosis, and 10.4% did not develop any symptoms within 10-days of diagnosis. Asymptomatic SARS-CoV-2 infections had lower viral load and shorter shedding duration, compared to symptomatic infections. A limitation of our A c c e p t e d M a n u s c r i p t 10 study, however, is that detection of viral RNA does not necessarily imply presence of infectious viruses in the respiratory tract. Nevertheless, current data suggest that viable virus is not shed beyond 20 days after symptom onset, with the probability of detecting live virus significantly decreasing after 5 days [14, 15] . Other study limitations are discussed in the supplement.

Providing HCWs with data about their SARS-CoV-2 virus exposure is important, so that they For individual comorbidities the reference is absence of that particular comorbidity.

Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study

Role of testing in COIVD-19 control

First experience of COVID-19 screening of health-care workers in England

COVID-19: PCR screening of asymptomatic health-care workers at London hospital

Characteristics of 1573 healthcare workers who underwent nasopharyngeal swab testing for SARS-CoV-2 in Milan

SARS-CoV-2 infection among asymptomatic healthcare workers of the emergency department in a tertiary care facility

COVID-19 seropositivity and asymptomatic rates in healthcare workers are associated with job function and masking

Seroprevalence of SARS-CoV-2 Among Frontline Health Care Personnel in a Multistate Hospital Network -13 Academic Medical Centers

Prevalence of SARS-CoV-2 Antibodies in Health Care Personnel in the New York City Area

Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a large Spanish reference hospital

Cross Sectional Prevalence of SARS-CoV-2 antibodies in Health Care Workers in Paediatric Facilities in Eight Countries

KN95 filtering facepiece respirators distributed in South Africa fail safety testing protocols

Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa

Virological assessment of hospitalized patients with COVID-2019

Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key determinants

Acknowledgements: The authors would like to express special appreciation to the study participants.We also thank Florian Krammer at Icahn School of Medicine at Mount Sinai, New York, USA, for providing the RBD plasmid and Penny Moore's laboratory at the National Institute for 

A c c e p t e d M a n u s c r i p t 12