Prevalence and functional profile of SARS-CoV-2 T cells in asymptomatic Kenyan adults.

BackgroundSARS-CoV-2 infection in Africa has been characterized by a less severe disease profile than what has been observed elsewhere, but the profile of SARS-CoV-2-specific adaptive immunity in these mainly asymptomatic patients has not, to our knowledge, been analyzed.MethodsWe collected blood samples from residents of rural Kenya (n = 80), who had not experienced any respiratory symptoms or had contact with individuals with COVID-19 and had not received COVID-19 vaccines. We analyzed spike-specific antibodies and T cells specific for SARS-CoV-2 structural (membrane, nucleocapsid, and spike) and accessory (ORF3a, ORF7, ORF8) proteins. Pre-pandemic blood samples collected in Nairobi (n = 13) and blood samples from mild-to-moderately symptomatic COVID-19 convalescent patients (n = 36) living in the urban environment of Singapore were also studied.ResultsAmong asymptomatic Africans, we detected anti-spike antibodies in 41.0% of the samples and T cell responses against 2 or more SARS-CoV-2 proteins in 82.5% of samples examined. Such a pattern was absent in the pre-pandemic samples. Furthermore, distinct from cellular immunity in European and Asian COVID-19 convalescents, we observed strong T cell immunogenicity against viral accessory proteins (ORF3a, ORF8) but not structural proteins, as well as a higher IL-10/IFN-γ cytokine ratio profile.ConclusionsThe high incidence of T cell responses against different SARS-CoV-2 proteins in seronegative participants suggests that serosurveys underestimate SARS-CoV-2 prevalence in settings where asymptomatic infections prevail. The functional and antigen-specific profile of SARS-CoV-2-specific T cells in African individuals suggests that environmental factors can play a role in the development of protective antiviral immunity.FundingUS Centers for Disease Control and Prevention, Division of Global Health Protection; the Singapore Ministry of Health's National Medical Research Council (COVID19RF3-0060, COVID19RF-001, COVID19RF-008, MOH-StaR17Nov-0001).

First cases of SARS-CoV-2 infection and secondary transmission in Kisumu, Kenya

We investigated the first 152 laboratory-confirmed SARS-CoV-2 cases (125 primary and 27 secondary) and their 248 close contacts in Kisumu County, Kenya. Conducted June 10–October 8, 2020, this study included interviews and sample collection at enrolment and 14–21 days later. Median age was 35 years (IQR 28–44);69.0% reported COVID-19 related symptoms, most commonly cough (60.0%), headache (55.2%), fever (53.3%) and loss of taste or smell (43.8%). One in five were hospitalized, 34.4% >25 years of age had at least one comorbidity, and all deaths had comorbidities. Adults ≥25 years with a comorbidity were 3.15 (95% CI 1.37–7.26) times more likely to have been hospitalized or died than participants without a comorbidity. Infectious comorbidities included HIV, tuberculosis, and malaria, but no current cases of influenza, respiratory syncytial virus, dengue fever, leptospirosis or chikungunya were identified. Thirteen (10.4%) of the 125 primary infections transmitted COVID-19 to 27 close contacts, 158 (63.7%) of whom resided or worked within the same household. Thirty-one percent (4 of 13) of those who transmitted COVID-19 to secondary cases were health care workers;no known secondary transmissions occurred between health care workers. This rapid assessment early in the course of the COVID-19 pandemic identified some context-specific characteristics which conflicted with the national line-listing of cases, and which have been substantiated in the year since. These included over two-thirds of cases reporting the development of symptoms during the two weeks after diagnosis, compared to the 7% of cases reported nationally;over half of cases reporting headaches, and nearly half of all cases reporting loss of taste and smell, none of which were reported at the time by the World Health Organization to be common symptoms. This study highlights the importance of rapid in-depth assessments of outbreaks in understanding the local epidemiology and response measures required.

Improving water, sanitation, and hygiene (WASH), with a focus on hand hygiene, globally for community mitigation of COVID-19

Continuity of key water, sanitation, and hygiene (WASH) infrastructure and WASH practices—for example, hand hygiene—are among several critical community preventive and mitigation measures to reduce transmission of infectious diseases, including COVID-19 and other respiratory diseases. WASH guidance for COVID-19 prevention may combine existing WASH standards and new COVID-19 guidance. Many existing WASH tools can also be modified for targeted WASH assessments during the COVID-19 pandemic. We partnered with local organizations to develop and deploy tools to assess WASH conditions and practices and subsequently implement, monitor, and evaluate WASH interventions to mitigate COVID-19 in low- and middle-income countries in Latin America and the Caribbean and Africa, focusing on healthcare, community institution, and household settings and hand hygiene specifically. Employing mixed-methods assessments, we observed gaps in access to hand hygiene materials specifically despite most of those settings having access to improved, often onsite, water supplies. Across countries, adherence to hand hygiene among healthcare providers was about twice as high after patient contact compared to before patient contact. Poor or non-existent management of handwashing stations and alcohol-based hand rub (ABHR) was common, especially in community institutions. Markets and points of entry (internal or external border crossings) represent congregation spaces, critical for COVID-19 mitigation, where globally-recognized WASH standards are needed. Development, evaluation, deployment, and refinement of new and existing standards can help ensure WASH aspects of community mitigation efforts that remain accessible and functional to enable inclusive preventive behaviors.

Diagnostic accuracy of the Panbio COVID-19 antigen rapid test device for SARS-CoV-2 detection in Kenya, 2021: A field evaluation.

BACKGROUND: Accurate and timely diagnosis is essential in limiting the spread of SARS-CoV-2 infection. The reference standard, rRT-PCR, requires specialized laboratories, costly reagents, and a long turnaround time. Antigen RDTs provide a feasible alternative to rRT-PCR since they are quick, relatively inexpensive, and do not require a laboratory. The WHO requires that Ag RDTs have a sensitivity ≥80% and specificity ≥97%. METHODS: This evaluation was conducted at 11 health facilities in Kenya between March and July 2021. We enrolled persons of any age with respiratory symptoms and asymptomatic contacts of confirmed COVID-19 cases. We collected demographic and clinical information and two nasopharyngeal specimens from each participant for Ag RDT testing and rRT-PCR. We calculated the diagnostic performance of the Panbio™ Ag RDT against the US Centers for Disease Control and Prevention's (CDC) rRT-PCR test. RESULTS: We evaluated the Ag RDT in 2,245 individuals where 551 (24.5%, 95% CI: 22.8-26.3%) tested positive by rRT-PCR. Overall sensitivity of the Ag RDT was 46.6% (95% CI: 42.4-50.9%), specificity 98.5% (95% CI: 97.8-99.0%), PPV 90.8% (95% CI: 86.8-93.9%) and NPV 85.0% (95% CI: 83.4-86.6%). Among symptomatic individuals, sensitivity was 60.6% (95% CI: 54.3-66.7%) and specificity was 98.1% (95% CI: 96.7-99.0%). Among asymptomatic individuals, sensitivity was 34.7% (95% CI 29.3-40.4%) and specificity was 98.7% (95% CI: 97.8-99.3%). In persons with onset of symptoms <5 days (594/876, 67.8%), sensitivity was 67.1% (95% CI: 59.2-74.3%), and 53.3% (95% CI: 40.0-66.3%) among those with onset of symptoms >7 days (157/876, 17.9%). The highest sensitivity was 87.0% (95% CI: 80.9-91.8%) in symptomatic individuals with cycle threshold (Ct) values ≤30. CONCLUSION: The overall sensitivity and NPV of the Panbio™ Ag RDT were much lower than expected. The specificity of the Ag RDT was high and satisfactory; therefore, a positive result may not require confirmation by rRT-PCR. The kit may be useful as a rapid screening tool only for symptomatic patients in high-risk settings with limited access to rRT-PCR. A negative result should be interpreted based on clinical and epidemiological information and may require retesting by rRT-PCR.

Incorporating COVID-19 into Acute Febrile Illness Surveillance Systems, Belize, Kenya, Ethiopia, Peru, and Liberia, 2020-2021.

Existing acute febrile illness (AFI) surveillance systems can be leveraged to identify and characterize emerging pathogens, such as SARS-CoV-2, which causes COVID-19. The US Centers for Disease Control and Prevention collaborated with ministries of health and implementing partners in Belize, Ethiopia, Kenya, Liberia, and Peru to adapt AFI surveillance systems to generate COVID-19 response information. Staff at sentinel sites collected epidemiologic data from persons meeting AFI criteria and specimens for SARS-CoV-2 testing. A total of 5,501 patients with AFI were enrolled during March 2020-October 2021; >69% underwent SARS-CoV-2 testing. Percentage positivity for SARS-CoV-2 ranged from 4% (87/2,151, Kenya) to 19% (22/115, Ethiopia). We show SARS-CoV-2 testing was successfully integrated into AFI surveillance in 5 low- to middle-income countries to detect COVID-19 within AFI care-seeking populations. AFI surveillance systems can be used to build capacity to detect and respond to both emerging and endemic infectious disease threats.

Adopting World Health Organization Multimodal Infection Prevention and Control Strategies to Respond to COVID-19, Kenya.

The World Health Organization advocates a multimodal approach to improving infection prevention and control (IPC) measures, which Kenya adopted in response to the COVID-19 pandemic. The Kenya Ministry of Health formed a national IPC committee for policy and technical leadership, coordination, communication, and training. During March-November 2020, a total of 69,892 of 121,500 (57.5%) healthcare workers were trained on IPC. Facility readiness assessments were conducted in 777 health facilities using a standard tool assessing 16 domains. A mean score was calculated for each domain across all facilities. Only 3 domains met the minimum threshold of 80%. The Ministry of Health maintained a national list of all laboratory-confirmed SARS-CoV-2 infections. By December 2020, a total of 3,039 healthcare workers were confirmed to be SARS-CoV-2-positive, an infection rate (56/100,000 workers) 12 times higher than in the general population. Facility assessments and healthcare workers' infection data provided information to guide IPC improvements.

Adapting Longstanding Public Health Collaborations between Government of Kenya and CDC Kenya in Response to the COVID-19 Pandemic, 2020-2021.

Kenya's Ministry of Health (MOH) and the US Centers for Disease Control and Prevention in Kenya (CDC Kenya) have maintained a 40-year partnership during which measures were implemented to prevent, detect, and respond to disease threats. During the COVID-19 pandemic, the MOH and CDC Kenya rapidly responded to mitigate disease impact on Kenya's 52 million residents. We describe activities undertaken jointly by the MOH and CDC Kenya that lessened the effects of COVID-19 during 5 epidemic waves from March through December 2021. Activities included establishing national and county-level emergency operations centers and implementing workforce development and deployment, infection prevention and control training, laboratory diagnostic advancement, enhanced surveillance, and information management. The COVID-19 pandemic provided fresh impetus for the government of Kenya to establish a national public health institute, launched in January 2022, to consolidate its public health activities and counter COVID-19 and future infectious, vaccine-preventable, and emerging zoonotic diseases.

First cases of SARS-CoV-2 infection and secondary transmission in Kisumu, Kenya.

We investigated the first 152 laboratory-confirmed SARS-CoV-2 cases (125 primary and 27 secondary) and their 248 close contacts in Kisumu County, Kenya. Conducted June 10-October 8, 2020, this study included interviews and sample collection at enrolment and 14-21 days later. Median age was 35 years (IQR 28-44); 69.0% reported COVID-19 related symptoms, most commonly cough (60.0%), headache (55.2%), fever (53.3%) and loss of taste or smell (43.8%). One in five were hospitalized, 34.4% >25 years of age had at least one comorbidity, and all deaths had comorbidities. Adults ≥25 years with a comorbidity were 3.15 (95% CI 1.37-7.26) times more likely to have been hospitalized or died than participants without a comorbidity. Infectious comorbidities included HIV, tuberculosis, and malaria, but no current cases of influenza, respiratory syncytial virus, dengue fever, leptospirosis or chikungunya were identified. Thirteen (10.4%) of the 125 primary infections transmitted COVID-19 to 27 close contacts, 158 (63.7%) of whom resided or worked within the same household. Thirty-one percent (4 of 13) of those who transmitted COVID-19 to secondary cases were health care workers; no known secondary transmissions occurred between health care workers. This rapid assessment early in the course of the COVID-19 pandemic identified some context-specific characteristics which conflicted with the national line-listing of cases, and which have been substantiated in the year since. These included over two-thirds of cases reporting the development of symptoms during the two weeks after diagnosis, compared to the 7% of cases reported nationally; over half of cases reporting headaches, and nearly half of all cases reporting loss of taste and smell, none of which were reported at the time by the World Health Organization to be common symptoms. This study highlights the importance of rapid in-depth assessments of outbreaks in understanding the local epidemiology and response measures required.

COVID-19 Knowledge, Attitudes and Practices and Vaccine Acceptability in Rural Western Kenya and an Urban Informal Settlement in Nairobi, Kenya: A Cross-Sectional Survey

An important step towards COVID-19 pandemic control is adequate knowledge and adherence to mitigation measures, including vaccination. We assessed the level of COVID-19 knowledge, attitudes, and practices (KAP) among residents from an urban informal settlement in the City of Nairobi (Kibera), and a rural community in western Kenya (Asembo). A cross-sectional survey was implemented from April to May 2021 among randomly selected adult residents from a population-based infectious diseases surveillance (PBIDS) cohort in Nairobi and Siaya Counties. KAP questions were adopted from previous studies. Factors associated with the level of COVID-19 KAP, were assessed using multivariable regression methods. COVID-19 vaccine acceptance was 83.6% for the participants from Asembo and 59.8% in Kibera. The reasons cited for vaccine hesitancy in Kibera were safety concerns (34%), insufficient information available to decide (18%), and a lack of belief in the vaccine (21%), while the reasons in Asembo were safety concerns (55%), insufficient information to decide (26%) and lack of belief in the vaccine (11%). Our study findings suggest the need for continued public education to enhance COVID-19 knowledge, attitudes, and practices to ensure adherence to mitigation measures. Urban informal settlements require targeted messaging to improve vaccine awareness, acceptability, and uptake.

Outbreak of Middle East Respiratory Syndrome Coronavirus in Camels and Probable Spillover Infection to Humans in Kenya.

The majority of Kenya's > 3 million camels have antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV), although human infection in Africa is rare. We enrolled 243 camels aged 0-24 months from 33 homesteads in Northern Kenya and followed them between April 2018 to March 2020. We collected and tested camel nasal swabs for MERS-CoV RNA by RT-PCR followed by virus isolation and whole genome sequencing of positive samples. We also documented illnesses (respiratory or other) among the camels. Human camel handlers were also swabbed, screened for respiratory signs, and samples were tested for MERS-CoV by RT-PCR. We recorded 68 illnesses among 58 camels, of which 76.5% (52/68) were respiratory signs and the majority of illnesses (73.5% or 50/68) were recorded in 2019. Overall, 124/4692 (2.6%) camel swabs collected from 83 (34.2%) calves in 15 (45.5%) homesteads between April-September 2019 screened positive, while 22 calves (26.5%) recorded reinfections (second positive swab following ≥ 2 consecutive negative tests). Sequencing revealed a distinct Clade C2 virus that lacked the signature ORF4b deletions of other Clade C viruses. Three previously reported human PCR positive cases clustered with the camel infections in time and place, strongly suggesting sporadic transmission to humans during intense camel outbreaks in Northern Kenya.

Transmission of SARS-CoV-2 in standardised first few X cases and household transmission investigations: A systematic review and meta-analysis.

We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for "Unity-aligned" First Few X cases (FFX) and HHTIs published 1 December 2019 to 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by Unity Studies collaborators) were retained in the systematic review; 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2% to 90% (95% prediction interval: 3%-71%; I 2 = 99.7%); I 2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.

High seroprevalence of SARS-CoV-2 but low infection fatality ratio eight months after introduction in Nairobi, Kenya.

BACKGROUND: The lower than expected COVID-19 morbidity and mortality in Africa has been attributed to multiple factors, including weak surveillance. This study estimated the burden of SARS-CoV-2 infections eight months into the epidemic in Nairobi, Kenya. METHODS: A population-based, cross-sectional survey was conducted using multi-stage random sampling to select households within Nairobi in November 2020. Sera from consenting household members were tested for antibodies to SARS-CoV-2. Seroprevalence was estimated after adjusting for population structure and test performance. Infection fatality ratios (IFRs) were calculated by comparing study estimates with reported cases and deaths. RESULTS: Among 1,164 individuals, the adjusted seroprevalence was 34.7% (95% CI 31.8-37.6). Half of the enrolled households had at least one positive participant. Seropositivity increased in more densely populated areas (spearman's r=0.63; p=0.009). Individuals aged 20-59 years had at least two-fold higher seropositivity than those aged 0-9 years. The IFR was 40 per 100,000 infections, with individuals ≥60 years old having higher IFRs. CONCLUSION: Over one-third of Nairobi residents had been exposed to SARS-CoV-2 by November 2020, indicating extensive transmission. However, the IFR was >10-fold lower than that reported in Europe and the USA, supporting the perceived lower morbidity and mortality in sub-Saharan Africa.