Doxycycline for the prevention of progression of COVID-19 to severe disease requiring intensive care unit (ICU) admission: a randomized, controlled, open-label, parallel group trial (DOXPREVENT.ICU)

BackgroundAfter admission to hospital, COVID-19 progresses in a substantial proportion of patients to critical disease that requires intensive care unit (ICU) admission. MethodsIn a pragmatic, non-blinded trial, 387 patients aged 40-90 years were randomised to receive treatment with SoC plus doxycycline (n=192) or SoC only (n=195). The primary outcome was the need for ICU admission as judged by the attending physicians. Three types of analyses were carried out for the primary outcome: "Intention to treat" (ITT) based on randomisation; "Per protocol" (PP), excluding patients not treated according to randomisation; and "As treated" (AT), based on actual treatment received. The trial was undertaken in six hospitals in India with high-quality ICU facilities. An online application serving as the electronic case report form was developed to enable screening, randomisation and collection of outcomes data. ResultsAdherence to treatment per protocol was 95.1%. Among all 387 participants, 77 (19.9%) developed critical disease needing ICU admission. In all three primary outcome analyses, doxycycline was associated with a relative risk reduction (RRR) and absolute risk reduction (ARR): ITT 31.6% RRR, 7.4% ARR (P=0.063); PP 40.7% RRR, 9.6% ARR (P=0.017); AT 43.2% RRR, 10.8% ARR (P=0.007), with numbers needed to treat (NTT) of 13.4 (ITT), 10.4 (PP), and 9.3 (AT), respectively. Doxycycline was well tolerated with not a single patient stopping treatment due to adverse events. ConclusionsIn hospitalized COVID-19 patients, doxycycline, a safe, inexpensive, and widely available antibiotic with anti-inflammatory properties, reduces the need for ICU admission when added to SoC.

Tuberculous mediastinal lymphadenopathy presenting with left vocal cord palsy: A rare entity.

A 23-year-old-male student, never-smoker presented to our hospital outpatient department with complaints of loss of appetite, unintentional weight loss, fatigue and low-grade fever for two months, hoarseness of voice (HOV) for two weeks. He was evaluated for HOV with video laryngoscopy which demonstrated left vocal cord palsy. Contrast enhanced CT Chest (CECT) was performed for evaluation of mediastinal lesions which revealed multiple peripheral enhancing conglomerate mediastinal lymph nodes. EBUS-trans bronchial needle aspiration (TBNA) and endobronchial biopsy were performed and specimens sent for smear and culture for AFB, Xpert MTB/RIF assay and histopathology. Results were consistent with Mycobacterium tuberculosis (MTB) infection and culture was positive for M. tuberculosis complex. Patient had been started on anti tubercular therapy (ATT) and during his 4th month follow up he showed clinicoradiological improvement without recovery of recurrent laryngeal nerve palsy.