Background: Risk factors for developing long COVID are not clearly established. The present study was designed to determine if any sign, symptom, or treatment of the acute phase, or personal characteristics of the patient, is associated with the development of long COVID. Methods: A cohort study was carried out, randomly selecting symptomatic COVID-19 patients and not vaccinated. The severity of the acute illness was assessed through the number of compatible COVID-19 symptoms, hospitalizations, and the symptom severity score using a 10-point visual analog scale. Results: After multivariate analysis, a severity score ≥8 (RR 2.0, 95%CI 1.1–3.5, p = 0.022), hospitalization (RR 2.1, 95%CI 1.0–4.4, p = 0.039), myalgia (RR 1.9, 95%CI 1.08–3.6, p = 0.027), tachycardia (RR 10.4, 95%CI 2.2–47.7, p = 0.003), and use of antibiotics (RR 2.0, 95%CI 1.1–3.5, p = 0.022), was positively associated with the risk of having long COVID. Higher levels of education (RR 0.6, 95%CI 0.4–0.9, p = 0.029) and type positive B blood group (B + AB, RR 0.44, 95%CI 0.2–0.9, p = 0.044) were protective factors. The most important population attributable fractions (PAFs) for long COVID were myalgia (37%), severity score ≥8 (31%), and use of antibiotics (27%). Conclusions: Further studies in diverse populations over time are needed to expand the knowledge that could lead us to prevent and/or treat long COVID.

Coronavirus disease 2019 (COVID‑19) is currently the major public health problem worldwide. Neutral electrolyzed saline solution that contains reactive chlorine and oxygen species may be an effective therapeutic. In the present study, the treatment efficacy of intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care vs. usual medical care alone was evaluated in ambulatory patients with COVID‑19. A prospective, 2‑arm, parallel‑group, randomized, open‑label, multi‑center, phase I‑II clinical trial including 214 patients was performed. The following two outcomes were evaluated during the 20‑day follow‑up: i) The number of patients with disease progression; and ii) the patient acceptable symptom state. Serial severe acute respiratory syndrome coronavirus 2 naso/oro‑pharyngeal detection by reverse transcription‑quantitative (RT‑q) PCR was performed in certain patients of the experimental group. Biochemical and hematologic parameters, as well as adverse effects, were also evaluated in the experimental group. The experimental treatment decreased the risk of hospitalization by 89% [adjusted relative risk (RR)=0.11, 95% confidence interval (CI): 0.03‑0.37, P<0.001] and the risk of death by 96% (adjusted RR=0.04, 95% CI: 0.01‑0.42, P=0.007) and also resulted in an 18‑fold higher probability of achieving an acceptable symptom state on day 5 (adjusted RR=18.14, 95% CI: 7.29‑45.09, P50% were negative for the virus as detected by RT‑qPCR in naso/oro‑pharyngeal samples on day 4, with only a small number of positive patients on day 6. Clinical improvement correlated with a decrease in C‑reactive protein, aberrant monocytes and increased lymphocytes and platelets. Cortisol and testosterone levels were also evaluated and a decrease in cortisol levels and an increase in the testosterone‑cortisol ratio were observed on days 2 and 4. The experimental treatment produced no serious adverse effects. In conclusion, neutral electrolyzed saline solution markedly reduced the symptomatology and risk of progression in ambulatory patients with COVID‑19. The present clinical trial was registered in the Cuban public registry of clinical trials (RPCEC) database (May 5, 2020; no. TX‑COVID19: RPCEC00000309).

Background: A promising novel cell-free bioactive formulation for articular cartilage regeneration, called BIOF2, has recently been tested in pre-clinical trials. The aim of the present study was to evaluate the efficacy and safety of BIOF2 for intra-articular application in patients with severe osteoarthritis of the knee.Methods: A prospective, randomized, 3-arm, parallel group clinical trial was conducted. It included 24 patients with severe osteoarthritis of the knee (WOMAC score 65.9 ± 17). Before they entered the study, all the patients were under osteoarthritis control through the standard treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed by their family physician. Patients were distributed into three groups of 8 patients each (intra-articular BIOF2, total joint arthroplasty, or conservative treatment with NSAIDs alone). The WOMAC score, RAPID3 score, and Rasmussen clinical score were evaluated before treatment and at months 3, 6, and 12. BIOF2 was applied at months 0, 3, and 6. Complete blood count and blood chemistry parameters were determined in the BIOF2 group before treatment, at 72 h, and at months 1, 3, 6, and 12. In addition, articular cartilage volume was evaluated (according to MRI) at the beginning of the study and at month 12.Results: The NSAID group showed no improvement at follow-up. Arthroplasty and BIOF2 treatments showed significant improvement in all the scoring scales starting at month 3. There were no statistically significant differences between the BIOF2 group and the arthroplasty group at month 6 (WOMAC score: 19.3 ± 18 vs 4.3 ± 5;P = 0.24) or month 12 (WOMAC score: 15.6 ± 15 vs 15.7 ± 17;P = 1.0). Arthroplasty and BIOF2 were successful at month 12 (according to a WOMAC score: ≤ 16) in 75% of the patients and the daily use of NSAIDs was reduced, compared with the group treated exclusively with NSAIDs (RR = 0.33, 95% CI 0.12–0.87,P = 0.02. This result was the same for BIOF2 vs NSAIDs and arthroplasty vs NSAIDs). BIOF2 significantly increased the articular cartilage by 22% (26.1 ± 10 vs 31.9 ± 10 cm²,P < 0.001) and produced a significant reduction in serum lipids. BIOF2 was well tolerated, causing slight-to-moderate pain only upon application.Conclusions: The intra-articular application of the new bioactive cell-free formulation (BIOF2) was well tolerated and showed no significative differences with arthroplasty for the treatment of severe osteoarthritis of the knee. BIOF2 can regenerate articular cartilage and is an easily implemented alternative therapy for the treatment of osteoarthritis.Trial registrationCuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000250. Registered 08/15/2017—Retrospectively registered,http://rpcec.sld.cu/en/trials/RPCEC00000250-En.

The worldwide efforts that healthcare professionals are making in the COVID‑19 pandemic is well known, and the high risk of illness and death that front‑line staff experience on a daily basis is a reality, despite well‑defined protocols for the use of personal protective equipment. In addition, it is well known that vaccination is still faraway to be achieved worldwide and that new variants are emerging, thus additional protective measures must be explored. A prospective open‑label randomized controlled clinical trial was performed on front‑line medical staff from the Dr. Enrique Cabrera General Hospital in México City to evaluate the effectiveness of nasopharyngeal and oropharyngeal rinses with a neutral electrolyzed water, known as SES, to reduce the risk of COVID‑19 disease among front‑line, not vaccinated medical staff. A total of 170 volunteers were enrolled and equally divided in a control group and SES group. All members of the trial wore the adequate personal protection equipment at all times while performing their duties, as required by standard COVID‑19 safety protocols. Additionally, the SES group participants followed a prophylactic protocol with SES (oral and nasal rinses, three times a day for 4 weeks). All participants were monitored for COVID‑19 symptoms and disease in a time‑frame of 4 weeks and the incidence of illness per group was registered. The relative risk of disease, associated with each treatment was calculated. The presence of COVID‑19‑positive cases, in the group that received the nasal and oral rinses with SES was 1.2%, while in the group that did not do the SES rinses (control group), it was 12.7% (P=0.0039 and RR=0.09405; 95% CI of 0.01231‑0.7183). The prophylactic protocol was demonstrated as a protective factor, in more than 90%, for developing the disease, and without adverse effects. Nasal and oral rinses with SES may be an efficient alternative to reinforce the protective measures against COVID‑19 disease and should be further investigated. The present clinical trial was retrospectively registered in the Cuban public registry of clinical trials (RPCEC) database (March 16, 2021; PREVECOVID‑19: RPCEC00000357).

Objectives: Helicobacter pylori gastric infection strongly correlates with gastric diseases such as chronic gastritis, functional dyspepsia, and complications such as peptic ulcers and gastric cancer. In developing countries, systemic therapies are not usually successful due to elevated antibiotic resistance. Additionally, oral H. pylori infection and periodontal disease correlate with gastric treatment failures. This study aimed to explore the effect of an integral therapy, comprising oral hygiene and concomitant systemic treatment, to increase the eradication of gastric infection and recurrences.Materials and Methods: A prospective, randomized, four‐arm, parallel‐group, open‐label clinical trial was conducted to investigate the efficacy of integral therapy to eradicate gastric H. pylori infection and avoid recurrences in double‐positive (real‐time PCR oral and gastric infection) patients. Oral hygiene involved mouthwash with neutral electrolyzed water (NEW), with or without periodontal treatment. One hundred patients were equally distributed into four groups: NS, NS‐PT, NEW, and NEW‐PT. All patients had concomitant systemic therapy and additionally, the following oral treatments: mouthwash with normal saline (NS), periodontal treatment and mouthwash with normal saline (NS‐PT), mouthwash with NEW (NEW), and periodontal treatment and mouthwash with NEW (NEW‐PT). Gastric and oral infection and symptoms were evaluated one and four months after treatments.Results: Integral therapy with NEW‐PT increased gastric eradication rates compared with NS or NS‐PT (84%−96% vs. 20%−56%; p < 0.001). Even more, a protective effect of 81.2% (RR = 0.1877; 95% CI: 0.0658−0.5355; p = 0.0018) against recurrences and 76.6% (RR = 0.2439; 95% CI: 0.1380−0.4310; p < 0.001) against treatment failure (eradication of infection and associated symptoms) was observed in patients from the NEW and NEW‐PT groups.Conclusions: Implementation of oral hygiene and systemic treatment can increase the eradication of gastric infection, associated symptoms, and recurrences. NEW is recommended as an antiseptic mouthwash due to its efficacy and short‐ and long‐term safety.

Background: Coronavirus disease (COVID-19) is currently the main public health problem worldwide. The administration of neutral electrolyzed saline, a solution that contains reactive species of chlorine and oxygen (ROS), may be an effective therapeutic alternative due to its immunomodulating characteristics, in systemic inflammation control, as well as in immune response improvement, promoting control of the viral infection. The present study evaluated the efficacy of treatment with intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care versus usual medical care alone, in ambulatory patients with COVID-19.Methods: A prospective, 2-arm, parallel group, randomized, open-label, phase I-II clinical trial included 39 patients in the control group (usual medical care alone) and 45 patients in the experimental group (usual medical care + intravenous and/or nebulized electrolyzed saline, with dose escalation). Two aspects were evaluated during the twenty-day follow-up: i) the number of patients with disease progression (hospitalization or death); and ii) the Patient Acceptable Symptom State (PASS), a single-question outcome that determines patient well-being thresholds for pain and function. Biochemical and hematologic parameters, as well as adverse effects, were evaluated in the experimental group. Results: The experimental treatment decreased the risk for hospitalization by 92% (adjusted RR=0.08, 95% CI: 0.01-0.50, P=0.007), with a 43-fold increase in the probability of achieving an acceptable symptom state on day 5 (adjusted RR= 42.96, 95% CI: 9.22-200.0, P<0.001). Intravenous + nebulized administration was better than nebulized administration alone, but nebulized administration was better than usual medical care alone. Clinical improvement correlated with a decrease in C-reactive protein, and aberrant monocytes and an increase of lymphocytes, and platelets. Cortisol and testosterone levels were also evaluated, observing a decrease in cortisol levels and an increment of testosterone-cortisol ratio, on days 2 and 4. Conclusions: The experimental treatment produced no serious adverse effects. In conclusion, intravenous and/or nebulized neutral electrolyzed saline importantly reduced the symptomatology and risk of progression (hospitalization and death), in ambulatory patients with COVID-19.Trial registration: Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000309. Registered: 05. May 2020. https://rpcec.sld.cu/en/trials/RPCEC00000309-En