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

BackgroundGiven 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. MethodsWe 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. ResultsRates 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. ConclusionMost 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

BackgroundHealthcare 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. MethodsThis 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. ResultsOne thousand six hundred thirty-one (1631) staff enrolled, totalling 60% of the workforce. The overall crude seroprevalence was 18.4% and the adjusted value (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], and a prior positive SARS-CoV-2 PCR result OR 11.0 (CI: 7.2-18.0, p<0.001). Age, sex, comorbidities or working in a COVID-19 designated area 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). ConclusionsThe 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.

EPIDEMIOLOGICAL AND CLINICAL CHARACTERISTICS OF COVID-19 PATIENTS IN KENYA

BackgroundMore 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. MethodsWe 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. ResultsData 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. ConclusionsWe identify the risk factors for mortality that may guide stratification of high risk patients.

Tocilizumab in nonventilated patients hospitalized with Covid-19 pneumonia

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

Fanconi syndrome and lactic acidosis associated with stavudine and lamivudine therapy.

We report a case of the nucleoside reverse transcriptase inhibitors, stavudine and lamivudine inducing Fanconi syndrome in a patient. The presence of simultaneous lactic acidosis suggests mitochondrial toxicity within the proximal renal tubular cells as the likely pathogenesis. We recommend that both the above nucleosides be added to the list of antiretroviral drugs that can induce Fanconi syndrome and that patients on stavudine and lamivudine be monitored carefully for early signs of Fanconi syndrome.

HIV, hepatitis B and hepatitis C coinfection in Kenya.

There are few data regarding hepatitis and HIV coinfection in Africa. In 378 HIV seropositive individuals in Nairobi, 23 (6%) were hepatitis B virus (HBV) and HIV coinfected, four (1%) were hepatitis C virus (HCV) and HIV coinfected and one patient was infected with all three viruses. Coinfected individuals were more likely to be men and older; a lack of HBV vaccination was a risk factor for HIV/HBV coinfection (P = 0.001) and tenofovir containing regimens appeared most effective at reducing HBV viral load.