Evolving mortality and clinical outcomes of hospitalized subjects during successive COVID-19 waves in Catalonia, Spain.

BACKGROUND: The changes in shield strategies, treatments, emergence variants, and healthcare pathways might shift the profile and outcome of patients hospitalized with COVID-19 in successive waves of the outbreak. METHODS: We retrospectively analysed the characteristics and in-hospital outcomes of all patients admitted with COVID-19 in eight university hospitals of Catalonia (North-East Spain) between Feb 28, 2020 and Feb 28, 2021. Using a 7-joinpoint regression analysis, we split admissions into four waves. The main hospital outcomes included 30-day mortality and admission to intensive care unit (ICU). FINDINGS: The analysis included 17,027 subjects admitted during the first wave (6800; 39.9%), summer wave (1807; 10.6%), second wave (3804; 22.3%), and third wave (4616; 27.1%). The highest 30-day mortality rate was reported during the first wave (17%) and decreased afterwards, remaining stable at 13% in the second and third waves (overall 30% reduction); the lowest mortality was reported during the summer wave (8%, 50% reduction). ICU admission became progressively more frequent during successive waves. In Cox regression analysis, the main factors contributing to differences in 30-day mortality were the epidemic wave, followed by gender, age, diabetes, chronic kidney disease, and neoplasms. INTERPRETATION: Although in-hospital COVID-19 mortality remains high, it decreased substantially after the first wave and is highly dependent of patient's characteristics and ICU availability. Highest mortality reductions occurred during a wave characterized by younger individuals, an increasingly frequent scenario as vaccination campaigns progress. FUNDING: This work did not receive specific funding.

Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial.

BACKGROUND: No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. METHODS: Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. RESULTS: A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (-1.41 vs -1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (-3.37 vs -3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. CONCLUSIONS: In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care.

Divergences on expected pneumonia cases during the COVID-19 epidemic in Catalonia: a time-series analysis of primary care electronic health records covering about 6 million people.

BACKGROUND: Pneumonia is one of the complications of COVID-19. Primary care electronic health records (EHR) have shown the utility as a surveillance system. We therefore analyse the trends of pneumonia during two waves of COVID-19 pandemic in order to use it as a clinical surveillance system and an early indicator of severity. METHODS: Time series analysis of pneumonia cases, from January 2014 to December 2020. We collected pneumonia diagnoses from primary care EHR, a software system covering > 6 million people in Catalonia (Spain). We compared the trend of pneumonia in the season 2019-2020 with that in the previous years. We estimated the expected pneumonia cases with data from 2014 to 2018 using a time series regression adjusted by seasonality and influenza epidemics. RESULTS: Between 4 March and 5 May 2020, 11,704 excess pneumonia cases (95% CI: 9909 to 13,498) were identified. Previously, we identified an excess from January to March 2020 in the population older than 15 years of 20%. We observed another excess pneumonia period from 22 october to 15 november of 1377 excess cases (95% CI: 665 to 2089). In contrast, we observed two great periods with reductions of pneumonia cases in children, accounting for 131 days and 3534 less pneumonia cases (95% CI, 1005 to 6064) from March to July; and 54 days and 1960 less pneumonia cases (95% CI 917 to 3002) from October to December. CONCLUSIONS: Diagnoses of pneumonia from the EHR could be used as an early and low cost surveillance system to monitor the spread of COVID-19.

A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19.

BACKGROUND: Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. METHODS: We conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. RESULTS: The analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. CONCLUSIONS: Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.).