Clinical Presentation and Outcomes of Care in Adults with Diabetic Ketoacidosis Pre-COVID-19 and during-COVID-19 at a Tertiary, Referral Hospital in Nairobi, Kenya (preprint)

Background Diabetic Ketoacidosis (DKA) is a potentially life-threatening diabetic emergency requiring prompt recognition and care. The prognosis of DKA has improved over time with the availability of evidence-based protocols and resources. However, in Kenya, there are limited resources for the appropriate diagnosis and management of DKA, and these are limited to tertiary-level referral facilities. This study aimed to review the clinical presentation, management, and outcomes of adult patients admitted with DKA at the Aga Khan University Hospital, Nairobi, over five years and assess differences in these parameters before and during the COVID-19 pandemic.Methods This was a retrospective study of DKA admissions from January 2017 to December 2021. Patient data were retrieved from the medical records department using ICD-10 codes, and individual details were abstracted on clinical presentation, management, and outcomes of DKA. Comparisons were made between pre-COVID-19 and during COVID-19 durations.Results 150 patients admitted with DKA were included (n = 48 pre- COVID-19, n = 102 during COVID-19 (n = 23 COVID-19 positive, n = 79 COVID-19 negative)). Median age was 47 years (IQR 33.0, 59.0), median HbA1C was 12.4% [IQR 10.8, 14.6]), and most patients had severe DKA (46%). Most common DKA precipitants were infections (40.7%), newly diagnosed diabetes (33.3%) and missed medication (25.3%). There was a significant difference in pulmonary infections as a DKA precipitant, between the pre- COVID and during COVID-19 pandemic (21.6% during COVID-19 versus 6.3% pre- COVID-19; p = 0.012). Median total insulin dose used was 110.0 units [IQR 76.0, 173.0], and a 100% of patients received basal insulin. The median length of hospital stay was 4.0 days [IQR 3.0, 6.0] and time to DKA resolution was 30.0 hours [IQR 24.0, 48.0]. There were 2 deaths (1.3%), none directly attributable to DKA. Severity of DKA significantly differed between pre- COVID-19, COVID-19 positive and COVID-19 negative DKA (52.2% of COVID-19 positive had moderate DKA compared to 26.6% of COVID-19 negative and 22.9% of Pre-COVID-19 (p = 0.006)).Conclusion These findings indicate that even in developing regions, good outcomes can be achieved with the appropriate facilities for DKA management. Clinician and patient education is necessary to ensure early detection and prompt referral to avoid patients presenting with severe DKA. Exploratory studies are needed to assess reasons for prolonged time to DKA resolution found in this study.

Kinetics of naturally induced binding and neutralizing anti-SARS-CoV-2 antibody levels and potencies among Kenyan patients with diverse grades of COVID-19 severity (preprint)

Background: Given the low levels of COVID-19 vaccine coverage in Sub-Saharan Africa, despite high levels of natural SARS-CoV-2 exposures, strategies for extending the breadth and longevity of naturally acquired immunity are warranted. Designing such strategies will require a good understanding of natural immunity. Methods: We used ELISA to measure whole-spike IgG and spike-receptor binding domain (RBD) total immunoglobulins (Igs) on 585 plasma samples collected longitudinally over five successive time points within six months of COVID-19 diagnosis in 309 COVID-19 patients. We measured antibody neutralizing potency against the wild-type (Wuhan) SARS-CoV-2 pseudo-virus in a subset of 51 patients over three successive time points. Binding and neutralizing antibody levels and potencies were then tested for correlations with COVID-19 severities, graded according to the National Institute of Health (NIH), USA criteria. Results: Rates of sero-conversion increased from Day 0 (day of PCR testing) to Day 180 (six months) (63.6% to 100 %) and (69.3 % to 97%) for anti-spike IgG and anti-spike-RBD binding Igs, respectively. Levels of these binding antibodies peaked at Day 28 (P<0.0001) and were subsequently maintained for six months without significant decay (p>0.99). Similarly, antibody neutralizing potencies peaked at Day 28 (p<0.0001) but had decreased by three-folds, six months after COVID-19 diagnosis (p<0.0001). Binding antibodies levels were highly correlated with neutralizing antibody potencies at all the time points analyzed (r>0.6, P<0.0001). Levels and potencies of binding and neutralizing antibodies increased with disease severity. Conclusion: Most COVID-19 patients from Sub-Saharan Africa generate SARS-CoV-2 specific binding antibodies that remain stable during the first six months of infection. Although antibody binding levels and neutralizing potencies were directly correlated, the respective neutralizing antibodies decayed three-fold by the sixth month of COVID-19 diagnosis suggesting that they are short-lived, consistent with what has been observed elsewhere. Thus, just like for other populations, regular vaccination boosters will be required to broaden and sustain the high levels of predominantly naturally acquired anti-SARS-CoV-2 neutralizing antibodies.

Seroprevalence, correlates and kinetics of SARS-CoV-2 Nucleocapsid IgG antibody in healthcare workers at a tertiary hospital: a prevaccine census study (preprint)

Background: Healthcare workers are perceived to be a high-risk group for acquiring SAR-CoV-2 infection, and more so in countries where COVID-19 vaccination uptake is low. Serosurveillance may best determine the true extent of SARS-CoV-2 infection since most infected HCWs may be asymptomatic or present with only mild symptoms. Over time, determining the true extent of SARS-CoV-2 infection could inform hospital management and staff whether the preventive measures instituted are effective and valuable in developing targeted solutions. Methods: This was a census survey study conducted at the Aga Khan University Hospital, Nairobi, between November 2020 and February 2021 before the implementation of the COVID-19 vaccination. The SARS-CoV-2 nucleocapsid IgG test was performed using a chemiluminescent assay. Results: One thousand six hundred thirty-one (1631) staff enrolled, totalling 60% of the workforce. The overall crude seroprevalence was 18.4% and the adjusted (for assay sensitivity of 86%) was 21.4% (95% CI; 19.2-23.7). The HCW groups with higher prevalence included pharmacy (25.6%), outreach (24%), hospital- based nursing (22.2%) and catering staff (22.6%). Independent predictors of a positive IgG result included prior COVID-19 like symptoms, odds ratio (OR) 1.9 [95% confidence interval (CI) 1.3-2.9, p=0.002]; a prior positive SARS-CoV-2 PCR result OR 11.7 (CI: 7.5-18.1, p<0.001) and working in a designated clinical COVID-19 location (high risk), OR 1.8 (CI: 1.04-3.11, p=0.033). Age, sex or comorbidities were not associated with seropositivity. The odds of testing positive for IgG after a positive PCR test were lowest if the antibody test was performed more than 2 months later OR 0.7 (CI: 0.48-0.95, p= 0.025). Conclusions: The prevalence of anti- SARS-CoV-2 nucleocapsid IgG among HCWs was lower than in the general population. Staff working in clinical areas were not at increased risk when compared to staff working in non-clinical areas.

Secondary Infections in Patients with COVID-19 Pneumonia Treated with Tocilizumab Compared to Those Not Treated with Tocilizumab: A Retrospective Study at a Tertiary Hospital in Kenya

Introduction From the first case of SARS-Co-2 in Wuhan, China, to the virus being declared as a pandemic in March 2020, the world has witnessed morbidity and mortality on a global scale. Scientists have worked at a record pace to deliver a vaccine for the prevention of this deadly disease. Tocilizumab, an interleukin-6 (IL-6) blocker, received an emergency use authorization (EUA) by the Federal Drug Agency (FDA) in June 2021. Methods This retrospective observational cohort study was conducted at the Aga Khan University Hospital, Nairobi, from March 8, 2020, to December 31, 2020. All patients with PCR confirmed COVID-19 pneumonia were included. Data were obtained from the medical records, and the admission registry was used to identify the patients, and both their electronic and paper-based files were retrieved from the medical records. Patient demographic data, medical history, baseline comorbidities, clinical characteristics, and outcome data were collected to study the infectious complications of Tocilizumab in patients affected by COVID-19 pneumonia. Results A total of 913 patients who were diagnosed with COVID-19 were included. The overall superinfection infection rate among the COVID-19 patients was 6%. Superinfection in patients who received the Tocilizumab was 17.2% and in the non-Tocilizumab group was 4.8%. The superinfection rate among severe and critically ill patients was even higher at 41.8% and 69.9% (Tocilizumab group) and 2.1% and 11.8% (non-Tocilizumab group), respectively (p < 0.001). There was no difference in mortality observed between the groups (p = 0.846). Infection among HIV co-infection was very low at 2.3%. Conclusion Contrary to some studies, a higher rate of infection was observed among the Tocilizumab group, and no difference in mortality was observed between Tocilizumab and the non-Tocilizumab group. Infection among patients with HIV remains low in this susceptible population.

EPIDEMIOLOGICAL AND CLINICAL CHARACTERISTICS OF COVID-19 PATIENTS IN KENYA (preprint)

Abstract Background More than 49,000 cases of infection and 900 deaths from COVID-19 have been recorded in the Kenya. However, the characteristics and risk factors for severe outcomes among hospitalized COVID-19 patients in this setting have not been described. Methods We extracted demographic, laboratory, clinical and outcome data from medical records of RT-PCR confirmed SARS-CoV2 patients admitted in six hospitals in Kenya between March and September, 2020. We used Cox proportional hazards regressions to determine factors related to in-hospital mortality. Results Data from 787 COVID-19 patients was available. The median age was 43 years (IQR 30-53), with 505 (64%) males. At admission, 455 (58%) were symptomatic. The commonest symptoms were cough (337, 43%), loss of taste or smell (279, 35%), and fever (126, 16%). Co-morbidities were reported in 340 (43%), with cardiovascular disease, diabetes and HIV documented in 130 (17%), 116 (15%), 53 (7%) respectively. 90 (11%) were admitted to ICU for a mean of 11 days, 52 (7%) were ventilated with a mean of 10 days, 107 (14%) died. The risk of death increased with age [hazard ratio (HR) 1.57 (95% CI 1.13-2.19)] for persons >60 years compared to those <60 years old; having co-morbidities [HR 2.34 (1.68-3.25)]; and among males [HR 1.76 (1.27, 2.44)] compared to females. Elevated white blood cell count and aspartate aminotransferase were associated with higher risk of death. Conclusions We identify the risk factors for mortality that may guide stratification of high risk patients.

Tocilizumab in nonventilated patients hospitalized with Covid-19 pneumonia (preprint)

BackgroundCoronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Safety and efficacy of the anti-interleukin-6 receptor antibody tocilizumab was evaluated in patients hospitalized with Covid-19 pneumonia. MethodsNonventilated patients hospitalized with Covid-19 pneumonia were randomized (2:1) to tocilizumab (8 mg/kg intravenous) or placebo plus standard care. Sites enrolling high-risk and minority populations were emphasized. The primary endpoint was cumulative proportion of patients requiring mechanical ventilation or who had died by Day 28. ResultsOf 389 randomized patients, 249 patients received tocilizumab and 128 received placebo in the modified intent-to-treat population (Hispanic/Latino, 56.0%; Black/African American, 14.9%; American Indian/Alaska Native, 12.7%; White, 12.7%; other/unknown, 3.7%). The cumulative proportion (95% confidence interval [CI]) of patients requiring mechanical ventilation or who had died by Day 28 was 12.0% (8.52% to 16.86%) and 19.3 % (13.34% to 27.36%) for the tocilizumab and placebo arms, respectively (log-rank P=0.0360; hazard ratio, 0.56 [95% CI, 0.33 to 0.97]). Median time to clinical failure up to Day 28 favored tocilizumab over placebo (hazard ratio 0.55 [95% CI, 0.33 to 0.93]). All-cause mortality by Day 28 was 10.4% with tocilizumab and 8.6% with placebo (weighted difference, 2.0% [95% CI, - 5.2% to 7.8%). In the safety population, serious adverse events occurred in 15.2% of tocilizumab patients (38/250 patients) and 19.7% of placebo patients (25/127). ConclusionsThis trial demonstrated the efficacy and safety of tocilizumab over placebo in reducing the likelihood of progression to requiring mechanical ventilation or death in nonventilated patients hospitalized with Covid-19 pneumonia. Trial registrationClinicalTrials.gov NCT04372186