key: cord-1040706-7ohso8hl
authors: Stochino, Claudia; Villa, Simone; Zucchi, Patrizia; Parravicini, Pierpaolo; Gori, Andrea; Raviglione, Mario Carlo
title: Clinical characteristics of COVID-19 and active tuberculosis co-infection in an Italian reference hospital
date: 2020-06-01
journal: Eur Respir J
DOI: 10.1183/13993003.01708-2020
sha: ef4c0ad1310ec0aa74526d9109f06db55cd87a97
doc_id: 1040706
cord_uid: 7ohso8hl

The COVID-19 infection rate was high in patient with active tuberculosis. Major clinical complications were seen only in two patients thus requiring ex novo oxygen supply, one of whom with advanced tuberculosis died. Nasal swab viral clearance was rapid.

Risk factors such as advanced age and some co-morbidities, such as diabetes and chronic respiratory diseases, are associated with poor outcomes in both TB and COVID-19. 3 However, only limited information about COVID-19 and active TB co-infection has been reported so far. [4] [5] [6] Concerns remain that COVID-19 could have a negative impact on the clinical course of TB and its ultimate outcome. 7, 8 This study describes clinical, radiological, and laboratory characteristics of a series of COVID-19 patients with concurrent active TB in a hospital in Sondrio province, Region Lombardy in northern Italy.

Patients with active TB admitted to the hospital were analysed to assess the impact of COVID-19 on their clinical course as well as radiologic and laboratory consequences of the co-infection. TB diagnosis relied mainly on Xpert MTB/RIF and chest radiography (CXR) followed by culture confirmation and phenotypic and genotypic drug susceptibility testing (DST). At the time of TB diagnosis, patients were also tested for human immunodeficiency virus (HIV). COVID-19 diagnosis was based on the results of the real-time, reverse transcriptase-polymerase chain reaction (rRT-PCR) for SARS-CoV-2 from nasopharyngeal swabs. Radiological results at COVID-19 diagnosis were compared with the most recent radiographs available prior to the onset of COVID-19 to assess any change in pulmonary TB (PTB)-related lesions. A patient was considered COVID-19 laboratory-negative if two consecutive swabs, ≥24 hours apart, were negative. Follow-up swabs were performed after 14 days from diagnosis and then every 7 days. 9 Clinical data were recorded during a followup period of 6-41 days following the first positive swab. The study was approved by the Nineteen patients (95%) had PTB and, among them, three (P11,P13-14) had also extrapulmonary involvement: two patients (P11 and P13) had renal and neurological (P11 with TB meningeal abscess and small brain granulomas; P13 with TB meningitis and encephalitis) localization; whereas one (P14) patient had a disseminated form with pericardial, pleural, splenic, and bone TB. TB was diagnosed using Xpert MTB/RIF (18/19;95%); in 14 patients, the diagnosis was confirmed by culture. In one case diagnosis was confirmed by bone biopsy (1/19;5%). At admission, CXR showed a multilateral involvement in 12/19 (63%) cases. Only one patient (P19) had an exclusively extrapulmonary TB (abdominal lymph nodes) that was diagnosed through needle aspiration.

Five patients (P07,P10,P17-18,P20) were infected with a drug-resistant strain: three were isoniazid resistant (through genotypic DST in P10) and two were multidrug-resistant. The standard anti-TB treatment regimen (isoniazid, rifampicin, ethambutol, and pyrazinamide) was used in 14 cases, while in six patients therapy was tailored based on clinical characteristics and DST results. Hydroxychloroquine (200 mg twice a day) was administered to all patients with COVID-19 co-infection and was well tolerated. No antiviral therapy was administered since no patient met the condition of intensive case admission for its use.

Patients requiring second-line anti-TB drugs (pretomanid, linezolid, terizidone, and clofazimine) for treatment of multidrug-resistant forms (P18 and P20) were monitored through electrocardiogram and no QT interval prolongation was observed.

The median time from TB diagnosis and SARS-CoV-2 detection was 30 (range 19-69) days.

The comparison of CXR after COVID-19 diagnosis with the latest available one (on average 32 [range 7-88] days earlier) showed that in 12 patients (63%) TB lesions were reduced (on average 30 [range 7-88] days before), whereas seven patients (35%) had worsening TB lesions (on average 32 [range 14-57] days earliest) and in one with EPTB there was no change. At CXR, three patients (15%) (P02, P06, P20) had mild-to-moderate interstitial thickening associated with COVID-19, and one (P13) had ground glass pattern compatible with COVID-19 on computed tomography (CT) scan.

A general lymphocytopenia (total lymphocyte count <1,500/mm 3 ) was detected in 13 patients (65%) and one patient (P18) had thrombocytopenia (platelet count <150x10 3 /mm 3 ).

Increased serum levels of transaminase (both aspartate aminotransaminase and alanine aminotransaminase) was observed in two cases (P19 and P20) who were known to have previously suffered from anti-TB drug-induced hepatitis. Nineteen (95%) patients high Ddimer levels (>250 ng/mL)-but only five (P01, P04, P06-07, P11) more than 2,000 ng/mLand 11 of them (58%) had an increased ferritin concentration (>300 ng/mL). One patient, P19, affected by sickle cell anaemia, had a level of 5,036 ng/mL attributed to frequent blood transfusions.

Oxygen supplementation was required in four patients at admission (P02, P05, P08, P17); in three patients (P02,P08,P17) it was soon discontinued and in one reduced from 2 to 1 L/min (P05). During hospitalization, three patients required ex novo oxygen supply (P06, P11, P13) due haemoglobin desaturation below 95%. Among them, two had respiratory complications: one had a pneumothorax due to subpleural blebs rupture (P11) which required temporary oxygen supplementation until thoracic drainage, and one elderly patient (P06), with advanced PTB and cachexia, developed COVID-19 pneumonia and severe hypoxia (requiring 10L/min oxygen supplementation) dying 6 days after COVID-19 diagnosis. Our study requires some final comments. First, the low rate of clinical and radiological deterioration in our series may be associated to the young age of most patients, low frequency of other co-morbidities including HIV infection, low prevalence of MDR-TB, and the quality of healthcare services. Second, clinical symptoms may have been partly underestimated due to cultural and linguistic barriers as the vast majority of patients were recent immigrants. Third, lung lesions caused by COVID-19 might have been over-looked due to the use of portable CXR at patient's bed instead of CT scan given the decision to prevent further nosocomial. 10 Finally, the duration of follow-up was limited to a few weeks thus not allowing assessment of longer-term outcomes which will be, however, assessed later.

In conclusion, the impact of COVID-19 on active TB appears to be clinically manageable with proper care. Rigorous infection control practices and personal protection devices are fundamental to prevent the risk of in-hospital transmission especially when dealing with a highly vulnerable population. $ at COVID-19 diagnosis compared to the last available CXR result; ^ isoniazid-resistance was detected only through genotypic drugsusceptibility test; * lung pattern at chest radiography; ** lung pattern at chest computed tomography scan; £ ferritin was n ot routinely assessed but was part of a set of exams to perform only in patients affected by COVID-19, however, due to the lag obtaining the swab results for SARS-CoV-2 it was not included; & Frequent blood transfusions to treat severe anaemia due to sickle cell disease; ‡ O2 supply ex novo; § O2 supply at admission ad then stopped; # oxygen supply was required temporarily due to pleural blebs rupture and consequent pneumothorax.

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