Long COVID-19 may be defined as patients who, four weeks after the diagnosis of SARS-Cov-2 infection, continue to have signs and symptoms not explainable by other causes. The estimated frequency is around 10% and signs and symptoms may last for months. The main long-term manifestations observed in other coronaviruses (Severe Acute Respiratory Syndrome (SARS), Middle East respiratory syndrome (MERS)) are very similar to and have clear clinical parallels with SARS-CoV-2: mainly respiratory, musculoskeletal, and neuropsychiatric. The growing number of patients worldwide will have an impact on health systems. Therefore, the main objective of these clinical practice guidelines is to identify patients with signs and symptoms of long COVID-19 in primary care through a protocolized diagnostic process that studies possible etiologies and establishes an accurate differential diagnosis. The guidelines have been developed pragmatically by compiling the few studies published so far on long COVID-19, editorials and expert opinions, press releases, and the authors’ clinical experience. Patients with long COVID-19 should be managed using structured primary care visits based on the time from diagnosis of SARS-CoV-2 infection. Based on the current limited evidence, disease management of long COVID-19 signs and symptoms will require a holistic, longitudinal follow up in primary care, multidisciplinary rehabilitation services, and the empowerment of affected patient groups.

Rationale: Antimicrobial therapy remains a controversial issue in nonsevere exacerbations of chronic obstructive pulmonary disease (COPD). Objectives: To evaluate the efficacy of antibiotic therapy in moderate exacerbations of mild-to-moderate COPD. Methods: This study involved a multicenter, parallel, double-blind, placebo-controlled, randomized clinical trial. Patients aged 40 years or older, smokers, or ex-smokers of 10 pack-years or more with spirometrically confirmed mild-to-moderate COPD (FEV1 > 50% predicted and FEV1/FVC ratio < 0.7) and diagnosed with an exacerbation were enrolled in the study. The patients were randomized to receive amoxicillin/clavulanate 500/125 mg three times a day or placebo three times a day for 8 days. Measurements and Main Results: The primary outcome measure was clinical cure at end of therapy visit (EOT) at Days 9 to 11. A total of 310 subjects fulfilled all the criteria for efficacy analysis. A total of 117 patients with amoxicillin/clavulanate (74.1%) and 91 with placebo (59.9%) were considered cured at EOT (difference, 14.2%; 95% confidence interval, 3.7–24.3). The median time to the next exacerbation was significantly longer in patients receiving antibiotic compared with placebo (233 d [interquartile range, 110–365] compared with 160 d [interquartile range, 66–365]; P < 0.05). The best C-reactive protein serum cut-off for predicting clinical failure with placebo was 40 mg/L, with an area under the curve of 0.732 (95% confidence interval, 0.614–0.851). Conclusions: Treatment of ambulatory exacerbations of mild-to-moderate COPD with amoxicillin/clavulanate is more effective and significantly prolongs the time to the next exacerbation compared with placebo. Clinical trial registered with www.clinical.gov (NCT00495586).

Objective To evaluate the efficacy of oral anti-inflammatory or antibiotic treatment compared with placebo in the resolution of cough in patients with uncomplicated acute bronchitis and discoloured sputum. Design Multicentre, parallel, single blinded placebo controlled, randomised clinical trial. Setting Nine primary care centres in Spain. Participants Adults aged 18 to 70 presenting symptoms associated with respiratory tract infection of less than one week’s duration, with cough as the predominant symptom, the presence of discoloured sputum, and at least one other symptom of lower respiratory tract infection (dyspnoea, wheezing, chest discomfort, or chest pain). Interventions Patients were randomised to receive either ibuprofen 600 mg three times daily, amoxicillin-clavulanic acid 500 mg/125 mg three times daily, or placebo three times daily for 10 days. The duration of symptoms was measured with a diary card. Main outcome measure Number of days with frequent cough after the randomisation visit. Results 416 participants were randomised (136 to ibuprofen, 137 to antibiotic, and 143 to placebo) and 390 returned their symptom diaries fully completed. The median number of days with frequent cough was slightly lower among patients assigned to ibuprofen (9 days, 95% confidence interval 8 to 10 days) compared with those receiving amoxicillin-clavulanic acid (11 days, 10 to 12 days) or placebo (11 days, 8 to 14 days), albeit without statistically significant differences. Neither amoxicillin-clavulanic acid nor ibuprofen increased the probability of cough resolution (hazard ratio 1.03, 95% confidence interval 0.78 to 1.35 and 1.23, 0.93 to 1.61, respectively) compared with placebo. Adverse events were observed in 27 patients, and were more common in the antibiotic arm (12%) than ibuprofen or placebo arms (5% and 3%, respectively; P<0.01). Conclusion No significant differences were observed in the number of days with cough between patients with uncomplicated acute bronchitis and discoloured sputum treated with ibuprofen, amoxicillin-clavulanic acid, or placebo. Trial registration Current Controlled Trials ISRCTN07852892.

To assess the drug compliance observed among patients with lower respiratory tract infection treated with once-daily, twice-daily and thrice-daily antibiotic regimens. We performed a prospective study in the primary care setting including patients with suspected bacterial lower respiratory tract infections, not allergic to β-lactam antimicrobials, macrolides or quinolones, treated with several antibiotic regimens. Patient compliance was assessed by electronic monitoring. A total of 251 patients were enrolled (136 in the thrice-daily group, 70 in the twice-daily group and 45 in the once-daily group). The mean container openings ranged from 94.3 ± 12.6% with once-daily antibiotics to 74.8 ± 17.7% with thrice-daily drugs (P < 0.001). Seventy-five patients in the thrice-daily group took at least 80% of the medications (55.1%), being significantly less than those receiving twice-daily (71.4%) or once-daily (86.7%; P < 0.001) drugs. Only 20.6% of the patients assigned to the thrice-daily regimens opened the container every 8 ± 4 h during at least 80% of the course. Among the patients assigned the same number of doses daily, compliance was better with the shortest antibiotic courses, being worse with schedules of 7 days or more. The percentage of patients who opened the MEMS container the satisfactory number of times a day was lower among the thrice-daily regimens. Moreover, the thrice-daily group more frequently forgot the afternoon dose. The rate of compliance was very low, mainly when antibiotics were administered thrice daily and in regimens of 7 days or more. New strategies addressed to improve antibiotic drug compliance are, therefore, necessary.