A living WHO guideline on drugs for covid-19

UPDATES: This is the twelfth version (eleventh update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline. CLINICAL QUESTION: What is the role of drugs in the treatment of patients with covid-19? CONTEXT: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and under way. The emerging SARS-CoV-2 variants (such as omicron) and subvariants are also changing the role of therapeutics. This update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers, and janus kinase (JAK) inhibitors in patients with severe or critical covid-19, and modifies previous recommendations for the neutralising monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe covid-19. NEW OR UPDATED RECOMMENDATIONS: • Remdesivir: a conditional recommendation for its use in patients with severe covid-19; and a conditional recommendation against its use in patients with critical covid-19. • Concomitant use of IL-6 receptor blockers (tocilizumab or sarilumab) and the JAK inhibitor baricitinib: these drugs may now be combined, in addition to corticosteroids, in patients with severe or critical covid-19. • Sotrovimab and casirivimab-imdevimab: strong recommendations against their use in patients with covid-19, replacing the previous conditional recommendations for their use. UNDERSTANDING THE NEW RECOMMENDATIONS: When moving from new evidence to updated recommendations, the Guideline Development Group (GDG) considered a combination of evidence assessing relative benefits and harms, values and preferences, and feasibility issues. For remdesivir, new trial data were added to a previous subgroup analysis and provided sufficiently trustworthy evidence to demonstrate benefits in patients with severe covid-19, but not critical covid-19. The GDG considered benefits of remdesivir to be modest and of moderate certainty for key outcomes such as mortality and mechanical ventilation, resulting in a conditional recommendation. For baricitinib, the GDG considered clinical trial evidence (RECOVERY) demonstrating reduced risk of death in patients already receiving corticosteroids and IL-6 receptor blockers. The GDG acknowledged that the clinical trials were not representative of the world population and that the risk-benefit balance may be less advantageous, particularly in patients who are immunosuppressed at higher risk of opportunistic infections (such as serious fungal, viral, or bacteria), those already deteriorating where less aggressive or stepwise addition of immunosuppressive medications may be preferred, and in areas where certain pathogens such as HIV or tuberculosis, are of concern. The panel anticipated that there would be situations where clinicians may opt for less aggressive immunosuppressive therapy or to combine medications in a stepwise fashion in patients who are deteriorating. The decision to combine the medications will depend on their availability, and the treating clinician's perception of the risk-benefit balance associated with combination immunosuppressive therapy, particularly in patient populations at risk of opportunistic infections who may have been under-represented in clinical trials. When making a strong recommendation against the use of monoclonal antibodies for patients with covid-19, the GDG considered in vitro neutralisation data demonstrating that sotrovimab and casirivimab-imdevimab evaluated in clinical trials have meaningfully reduced neutralisation activity of the currently circulating variants of SARS-CoV-2 and their subvariants. There was consensus among the panel that the absence of in vitro neutralisation activity strongly suggests absence of clinical effectiveness of these monoclonal antibodies. However, there was also consensus regarding the need for clinical trial evidence in order to confirm clinical efficacy of new monoclonal antibodies that reliably neutralise the circulating strains in vitro. Whether emerging new variants and subvariants might be susceptible to sotrovimab, casirivimab-imdevimab, or other anti-SARS-CoV-2 monoclonal antibodies cannot be predicted. PRIOR RECOMMENDATIONS: • Recommended for patients with severe or critical covid-19­strong recommendations for systemic corticosteroids; IL-6 receptor blockers (tocilizumab or sarilumab) in combination with corticosteroids; and baricitinib as an alternative to IL-6 receptor blockers, in combination with corticosteroids. • Recommended for patients with non-severe covid-19 at highest risk of hospitalisation­a strong recommendation for nirmatrelvir/ritonavir; conditional recommendations for molnupiravir and remdesivir. • Not recommended for patients with non-severe covid-19­a conditional recommendation against systemic corticosteroids; a strong recommendation against convalescent plasma; a recommendation against fluvoxamine, except in the context of a clinical trial; and a strong recommendation against colchicine. • Not recommended for patients with non-severe covid-19 at low risk of hospitalisation­a conditional recommendation against nirmatrelvir/ritonavir. • Not recommended for patients with severe or critical covid-19­a recommendation against convalescent plasma except in the context of a clinical trial; and a conditional recommendation against the JAK inhibitors ruxolitinib and tofacitinib. • Not recommended, regardless of covid-19 disease severity­a strong recommendations against hydroxychloroquine and against lopinavir/ritonavir; and a recommendation against ivermectin except in the context of a clinical trial. ABOUT THIS GUIDELINE: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact. Future recommendations: Recommendations on anticoagulation are planned for the next update to this guideline.

Impact of the COVID-19 Pandemic on Tuberculosis Testing and Treatment at a Tertiary Hospital in Zambia.

Globally, tuberculosis (TB) testing and treatment have declined dramatically during the COVID-19 pandemic. We quantified the change in TB visits, testing, and treatment compared with a 12-month pre-pandemic baseline at the national referral hospital's TB Clinic in Lusaka, Zambia, in the first year of the pandemic. We stratified the results into early and later pandemic periods. In the first 2 months of the pandemic, the mean number of monthly TB clinic visits, prescriptions, and positive TB polymerase chain reaction (PCR) tests decreased as follow: -94.1% (95% CI: -119.4 to -68.8%), -71.4% (95% CI: -80.4 to -62.4%), and -73% (95% CI: -95.5 to -51.3%), respectively. TB testing and treatment counts rebounded in the subsequent 10 months, although the number of prescriptions and TB-PCR tests performed remained significantly lower than pre-pandemic. The COVID-19 pandemic significantly disrupted TB care in Zambia, which could have long-lasting impacts on TB transmission and mortality. Future pandemic preparedness planning should incorporate strategies developed over the course of this pandemic to safeguard consistent, comprehensive TB care.

Treatment-Experienced Patients on Third-Line Therapy: A Retrospective Cohort of Treatment Outcomes at the HIV Advanced Treatment Centre, University Teaching Hospital, Zambia.

Antiretroviral therapy (ART) uptake continues to increase across sub-Saharan Africa and emergence of drug-resistant HIV mutations poses significant challenges to management of treatment-experienced patients with virologic failure. In Zambia, new third-line ART (TLART) guidelines including use of dolutegravir (DTG) were introduced in 2018. We assessed virologic suppression, immunologic response, and HIV drug-resistant mutations (DRMs) among patients on TLART at the University Teaching Hospital (UTH) in Lusaka, Zambia. We conducted a retrospective review of patients enrolled at UTH on TLART for >6 months between January 2010 and June 30, 2021. CD4 and HIV viral load (VL) at TLART initiation and post-initiation were assessed to determine virologic and immunologic outcomes. Regression analysis using bivariate and multivariate methods to describe baseline characteristics, virologic, and immunologic response to TLART was performed. A total of 345 patients met inclusion criteria; women comprised 57.6% (199/345) of the cohort. Median age at HIV diagnosis was 30 (interquartile range: 17.3-36.8). In 255 (73.8%) patients with at least two VLs, VL decreased from mean of 3.45 log10 copies/mL (standard deviation [SD]: 2.02) to 1.68 log10 copies/mL (SD: 1.79). Common ARVs prescribed included DTG (89.9%), tenofovir disoproxil fumarate (68.7%), and darunavir boosted with ritonavir (66.4%); 170 (49.3%) patients had genotypes; mutations consisted of 88.8% nucleoside reverse transcriptase inhibitor, 86.5% non-nucleoside reverse transcriptase inhibitor, and 55.9% protease inhibitor. VL suppression to <1,000 copies/mL was achieved in 225 (78.9%) patients. DRM frequency ranged from 56% to 89% depending on drug class. Treatment-experienced patients receiving TLART in Zambia achieved high rates of suppression despite high proportions of HIV mutations illustrating TLART effectiveness in the DTG era.

Clinical Characteristics and Outcomes of Patients Hospitalized With COVID-19 During the First 4 Waves in Zambia.

Importance: Few epidemiologic studies related to COVID-19 have emerged from countries in Africa, where demographic characteristics, epidemiology, and health system capacity differ from other parts of the world. Objectives: To describe the characteristics and outcomes of patients admitted to COVID-19 treatment centers, assess risk factors for in-hospital death, and explore how treatment center admissions were affected by COVID-19 waves in Zambia. Design, Setting, and Participants: This retrospective cohort study assessed patients admitted to COVID-19 treatment centers in 5 Zambian cities between March 1, 2020, and February 28, 2022. Exposures: Risk factors for in-hospital mortality, including patient age and severity of COVID-19, at treatment center admission. Main Outcomes and Measures: Patient information was collected, including inpatient disposition (discharged or died). Differences across and within COVID-19 waves were assessed. Mixed-effects logistic regression models were used to assess associations between risk factors and in-hospital mortality as well as between characteristics of admitted patients and timing of admission. Results: A total of 3876 patients were admitted during 4 COVID-19 waves (mean [SD] age, 50.6 [19.5] years; 2103 male [54.3%]). Compared with the first 3 waves (pooled), the proportion of patients who were 60 years or older admitted during wave 4, when the Omicron variant was circulating, was significantly lower (250 of 1009 [24.8%] vs 1116 of 2837 [39.3%]; P < .001). Factors associated with in-hospital mortality included older age (≥60 vs <30 years; adjusted odds ratio [aOR], 3.55; 95% CI, 2.34-5.52) and HIV infection (aOR, 1.39; 95% CI, 1.07-1.79). Within waves, patients who were admitted during weeks 5 to 9 had significantly higher odds of being 60 years or older (aOR, 2.09; 95% CI, 1.79-2.45) or having severe COVID-19 at admission (aOR, 2.49; 95% CI, 2.14-2.90) than those admitted during the first 4 weeks. Conclusions and Relevance: The characteristics of admitted patients during the Omicron wave and risk factors for in-hospital mortality in Zambia reflect data reported elsewhere. Within-wave analyses revealed a pattern in which it appeared that admission of higher-risk patients was prioritized during periods when there were surges in demand for health services during COVID-19 waves. These findings support the need to expand health system capacity and improve health system resiliency in Zambia and other countries with resource-limited health systems.

COVID-19 Vaccine Effectiveness Against Progression to In-Hospital Mortality in Zambia, 2021-2022.

Background: Coronavirus disease 2019 (COVID-19) vaccines are highly effective for reducing severe disease and mortality. However, vaccine effectiveness data are limited from Sub-Saharan Africa. We report COVID-19 vaccine effectiveness against progression to in-hospital mortality in Zambia. Methods: We conducted a retrospective cohort study among admitted patients at 8 COVID-19 treatment centers across Zambia during April 2021 through March 2022, when the Delta and Omicron variants were circulating. Patient demographic and clinical information including vaccination status and hospitalization outcome (discharged or died) were collected. Multivariable logistic regression was used to assess the odds of in-hospital mortality by vaccination status, adjusted for age, sex, number of comorbid conditions, disease severity, hospitalization month, and COVID-19 treatment center. Vaccine effectiveness of ≥1 vaccine dose was calculated from the adjusted odds ratio. Results: Among 1653 patients with data on their vaccination status and hospitalization outcome, 365 (22.1%) died. Overall, 236 (14.3%) patients had received ≥1 vaccine dose before hospital admission. Of the patients who had received ≥1 vaccine dose, 22 (9.3%) died compared with 343 (24.2%) among unvaccinated patients (P < .01). The median time since receipt of a first vaccine dose (interquartile range) was 52.5 (28-107) days. Vaccine effectiveness for progression to in-hospital mortality among hospitalized patients was 64.8% (95% CI, 42.3%-79.4%). Conclusions: Among patients admitted to COVID-19 treatment centers in Zambia, COVID-19 vaccination was associated with lower progression to in-hospital mortality. These data are consistent with evidence from other countries demonstrating the benefit of COVID-19 vaccination against severe complications. Vaccination is a critical tool for reducing the consequences of COVID-19 in Zambia.

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Among Healthcare Workers-Zambia, July 2020.

BACKGROUND: Healthcare workers (HCWs) in Zambia have become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). However, SARS-CoV-2 prevalence among HCWs is not known in Zambia. METHODS: We conducted a cross-sectional SARS-CoV-2 prevalence survey among Zambian HCWs in 20 health facilities in 6 districts in July 2020. Participants were tested for SARS-CoV-2 infection using polymerase chain reaction (PCR) and for SARS-CoV-2 antibodies using enzyme-linked immunosorbent assay (ELISA). Prevalence estimates and 95% confidence intervals (CIs), adjusted for health facility clustering, were calculated for each test separately, and a combined measure for those who had PCR and ELISA was performed. RESULTS: In total, 660 HCWs participated in the study, with 450 (68.2%) providing a nasopharyngeal swab for PCR and 575 (87.1%) providing a blood specimen for ELISA. Sixty-six percent of participants were females, and median age was 31.5 years (interquartile range, 26.2-39.8). The overall prevalence of the combined measure was 9.3% (95% CI, 3.8%-14.7%). PCR-positive prevalence of SARS-CoV-2 was 6.6% (95% CI, 2.0%-11.1%), and ELISA-positive prevalence was 2.2% (95% CI, .5%-3.9%). CONCLUSIONS: SARS-CoV-2 prevalence among HCWs was similar to a population-based estimate (10.6%) during a period of community transmission in Zambia. Public health measures such as establishing COVID-19 treatment centers before the first cases, screening for COVID-19 symptoms among patients who access health facilities, infection prevention and control trainings, and targeted distribution of personal protective equipment based on exposure risk might have prevented increased SARS-CoV-2 transmission among Zambian HCWs.

Post-mortem examination of Hospital Inpatient COVID-19 Deaths in Lusaka, Zambia - A Descriptive Whole-body Autopsy Series.

BACKGROUND: Since information on the pathology of COVID-19 from sub-Saharan Africa (SSA) remains scarce, the objective of our study was to define the gross pathology and histological features of COVID-19. We report data from 29 whole-body autopsies of COVID-19 deaths occurring in hospitals in Lusaka, Zambia - the first large autopsy case series from Africa. METHODS: We performed a descriptive post-mortem examination study of inpatient COVID-19 related deaths at two hospitals in Lusaka, Zambia. Whole-body autopsies were conducted according to Standard Operating Procedures. Gross and histopathological examinations of all organs were performed. Patient demographics, history, co-morbidities, autopsy gross and microscopic findings, and cause(s) of death were recorded and analyzed using STATA version 14. Variables were grouped and presented as frequencies and percentages. FINDINGS: Autopsies were performed on 29 decedents (mean age = 44 ± 15.8years; age range = 19-82; 17/29 [58.8%] males). 22/29 [75.9%] cases were <55 years of age. A spectrum of pathological manifestations of COVID-19 were seen in all organs. The commonest causes of death were pulmonary thromboembolism (13/29, 45%), Diffuse Alveolar Damage (9/29, 31%), and COVID-19 pneumonia (7/29, 25%). 22/29 (76%) had co-morbidities. Common co-morbidities included HIV (8/29, 28%), Hypertension (6/29, 20%) Tuberculosis (3/29, 10%), Diabetes (3/29, 10%). CONCLUSIONS: A spectrum of gross anatomical and histopathological findings are seen in COVID-19 deaths in hospitalized decedents. These appear broadly similar to those reported from China, Europe and USA. Differences include a younger age group, and co-morbidities of HIV and TB co-infection which require further investigation.

Prevalence of SARS-CoV-2 in six districts in Zambia in July, 2020: a cross-sectional cluster sample survey.

BACKGROUND: Between March and December, 2020, more than 20 000 laboratory-confirmed cases of SARS-CoV-2 infection were reported in Zambia. However, the number of SARS-CoV-2 infections is likely to be higher than the confirmed case counts because many infected people have mild or no symptoms, and limitations exist with regard to testing capacity and surveillance systems in Zambia. We aimed to estimate SARS-CoV-2 prevalence in six districts of Zambia in July, 2020, using a population-based household survey. METHODS: Between July 4 and July 27, 2020, we did a cross-sectional cluster-sample survey of households in six districts of Zambia. Within each district, 16 standardised enumeration areas were randomly selected as primary sampling units using probability proportional to size. 20 households from each standardised enumeration area were selected using simple random sampling. All members of selected households were eligible to participate. Consenting participants completed a questionnaire and were tested for SARS-CoV-2 infection using real-time PCR (rtPCR) and anti-SARS-CoV-2 antibodies using ELISA. Prevalence estimates, adjusted for the survey design, were calculated for each diagnostic test separately, and combined. We applied the prevalence estimates to census population projections for each district to derive the estimated number of SARS-CoV-2 infections. FINDINGS: Overall, 4258 people from 1866 households participated in the study. The median age of participants was 18·2 years (IQR 7·7-31·4) and 50·6% of participants were female. SARS-CoV-2 prevalence for the combined measure was 10·6% (95% CI 7·3-13·9). The rtPCR-positive prevalence was 7·6% (4·7-10·6) and ELISA-positive prevalence was 2·1% (1·1-3·1). An estimated 454 708 SARS-CoV-2 infections (95% CI 312 705-596 713) occurred in the six districts between March and July, 2020, compared with 4917 laboratory-confirmed cases reported in official statistics from the Zambia National Public Health Institute. INTERPRETATION: The estimated number of SARS-CoV-2 infections was much higher than the number of reported cases in six districts in Zambia. The high rtPCR-positive SARS-CoV-2 prevalence was consistent with observed community transmission during the study period. The low ELISA-positive SARS-CoV-2 prevalence might be associated with mitigation measures instituted after initial cases were reported in March, 2020. Zambia should monitor patterns of SARS-CoV-2 prevalence and promote measures that can reduce transmission. FUNDING: US Centers for Disease Control and Prevention.

A living WHO guideline on drugs to prevent covid-19.

CLINICAL QUESTION: What is the role of drugs in preventing covid-19? WHY DOES THIS MATTER?: There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19. RECOMMENDATION: The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty). HOW THIS GUIDELINE WAS CREATED: This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. UNDERSTANDING THE NEW RECOMMENDATION: The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19. UPDATES: This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline. READERS NOTE: This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity.

First 100 Persons with COVID-19 - Zambia, March 18-April 28, 2020.

Zambia is a landlocked, lower-middle income country in southern Africa, with a population of 17 million (1). The first known cases of coronavirus disease 2019 (COVID-19) in Zambia occurred in a married couple who had traveled to France and were subject to port-of-entry surveillance and subsequent remote monitoring of travelers with a history of international travel for 14 days after arrival. They were identified as having suspected cases on March 18, 2020, and tested for COVID-19 after developing respiratory symptoms during the 14-day monitoring period. In March 2020, the Zambia National Public Health Institute (ZNPHI) defined a suspected case of COVID-19 as 1) an acute respiratory illness in a person with a history of international travel during the 14 days preceding symptom onset; or 2) acute respiratory illness in a person with a history of contact with a person with laboratory-confirmed COVID-19 in the 14 days preceding symptom onset; or 3) severe acute respiratory illness requiring hospitalization; or 4) being a household or close contact of a patient with laboratory-confirmed COVID-19. This definition was adapted from World Health Organization (WHO) interim guidance issued March 20, 2020, on global surveillance for COVID-19 (2) to also include asymptomatic contacts of persons with confirmed COVID-19. Persons with suspected COVID-19 were identified through various mechanisms, including port-of-entry surveillance, contact tracing, health care worker (HCW) testing, facility-based inpatient screening, community-based screening, and calls from the public into a national hotline administered by the Disaster Management and Mitigation Unit and ZNPHI. Port-of-entry surveillance included an arrival screen consisting of a temperature scan, report of symptoms during the preceding 14 days, and collection of a history of travel and contact with persons with confirmed COVID-19 in the 14 days before arrival in Zambia, followed by daily remote telephone monitoring for 14 days. Travelers were tested for SARS-CoV-2, the virus that causes COVID-19, if they were symptomatic upon arrival or developed symptoms during the 14-day monitoring period. Persons with suspected COVID-19 were tested as soon as possible after evaluation for respiratory symptoms or within 7 days of last known exposure (i.e., travel or contact with a confirmed case). All COVID-19 diagnoses were confirmed using real-time reverse transcription-polymerase chain reaction (RT-PCR) testing (SARS-CoV-2 Nucleic Acid Detection Kit, Maccura) of nasopharyngeal specimens; all patients with confirmed COVID-19 were admitted into institutional isolation at the time of laboratory confirmation, which was generally within 36 hours. COVID-19 patients were deemed recovered and released from isolation after two consecutive PCR-negative test results ≥24 hours apart. A Ministry of Health memorandum was released on April 13, 2020, mandating testing in public facilities of 1) all persons admitted to medical and pediatric wards regardless of symptoms; 2) all patients being admitted to surgical and obstetric wards, regardless of symptoms; 3) any outpatient with fever, cough, or shortness of breath; and 4) any facility or community death in a person with respiratory symptoms, and 5) biweekly screening of all HCWs in isolation centers and health facilities where persons with COVID-19 had been evaluated. This report describes the first 100 COVID-19 cases reported in Zambia, during March 18-April 28, 2020.

First COVID-19 case in Zambia - Comparative phylogenomic analyses of SARS-CoV-2 detected in African countries.

Since its first discovery in December 2019 in Wuhan, China, COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread rapidly worldwide. While African countries were relatively spared initially, the initial low incidence of COVID-19 cases was not sustained for long due to continuing travel links between China, Europe and Africa. In preparation, Zambia had applied a multisectoral national epidemic disease surveillance and response system resulting in the identification of the first case within 48 h of the individual entering the country by air travel from a trip to France. Contact tracing showed that SARS-CoV-2 infection was contained within the patient's household, with no further spread to attending health care workers or community members. Phylogenomic analysis of the patient's SARS-CoV-2 strain showed that it belonged to lineage B.1.1., sharing the last common ancestor with SARS-CoV-2 strains recovered from South Africa. At the African continental level, our analysis showed that B.1 and B.1.1 lineages appear to be predominant in Africa. Whole genome sequence analysis should be part of all surveillance and case detection activities in order to monitor the origin and evolution of SARS-CoV-2 lineages across Africa.