Objective This study aimed to define the clinical course of anosmia in relation to other clinical symptoms. Methods 135 patients with COVID-19 were reached by phone and subsequently included in the study. Olfactory functions were evaluated using a questionnaire for assessment of self-reported olfactory function. Patients were divided into four subgroups according to the presence of olfactory symptoms and temporal relationship with the other symptoms: group1 had only olfactory complaints (isolated, sudden-onset loss of smell); group2 had sudden-onset loss of smell, followed by COVID-19 related complaints; group3 initially had COVID-19 related complaints, then gradually developed olfactory complaints; and group4 had no olfactory complaints. Results In total, 59.3% of the patients interviewed had olfactory complaints during the disease course. The olfactory dysfunction severity during COVID-19 infection was significantly higher in group1 compared to groups 2 and 3. In groups1-3, the odor scores after recovery from COVID-19 disease were significantly lower compared to the status prior to disease onset. The residual olfactory dysfunction was similar between groups1 and 2, but was more evident than group3. Mean duration for loss of smell was 7.8 ± 3.1 (2-15) days. Duration of loss of smell was longer in groups1 and 2 than in group3. Odor scores completely returned back to the pre-disease values in 41 (51.2%) patients with olfactory dysfunction. Rate of complete olfactory dysfunction recovery was higher in group3 compared to groups1 and 2. Conclusion In isolated anosmia cases, anosmia is more severe, and complete recovery rates are lower compared to the patients who have other clinical symptoms. Level of evidence Level 4.

BACKGROUND The characteristics of COVID-19 outbreak and high fatality rate of COVID-19 infection have attracted the attention of scientists due to the strong interactions between components of metabolic syndrome, metabolic abnormalities, and viral pathobiology of COVID-19. Combined metabolic cofactors supplementation (CMCS) consisting of L-serine, N-acetyl-L-cysteine (NAC), nicotinamide riboside (NR), and L-carnitine tartrate is being studied for the treatment of patients with COVID-19. METHODS We conducted a placebo-controlled, phase-2 clinical trial involving ambulatory COVID-19 patients. A total of 100 patients were randomly assigned on a 3:1 basis to hydroxychloroquine plus CMCS or hydroxychloroquine plus placebo. The total treatment period for the hydroxychloroquine was 5 days, and for the CMCS/placebo was 14 days. Clinical status was evaluated daily by phone, using a binomial scale for subject reported presence or absence for multiple COVID-19 related symptoms. Plasma samples for clinical chemistry analyses were collected on day 0 and day 14. RESULTS A total of 93 patients completed the trial. The combination of CMCS and hydroxychloroquine significantly reduced the average complete recovery time compared with hydroxychloroquine and placebo (6.6 days vs 9.3 days, respectively). Moreover, there was a significant reduction in ALT, AST and LDH levels on day 14 compared to day 0 in the hydroxychloroquine plus CMCS group. The adverse effects were uncommon and self-limiting. CONCLUSIONS In patients with mild-to-moderate COVID-19, CMCS resulted in a significant reduction in recovery time and liver enzymes associated with hepatic function compared to placebo. We observed that CMSC is associated with a low incidence of adverse events.

This study demonstrates that vitamin D deficiency is associated with tear hyperosmolarity and tear film dysfunction. Patients with vitamin D deficiency may be prone to dry eye.

Aim: Disorders in the metabolism of homocysteine and B vitamins, which are involved in a one-carbon transfer reaction and important for DNA synthesis and methylation, have been hypothesized to be associated with carcinogenesis. The purpose of this study is to evaluate the levels of homocysteine, vitamin B12 and folic acid in patients with newly diagnosed lung cancer and determines whether they might be used as an accurate tumor marker for monitoring the patients if they are found to be elevated in lung cancer. Materials and Methods: Forty male patients with lung cancer were included in this study. Age-matched forty healthy males who had not malignant disease or had not received any drug affecting plasma homocysteine levels were selected as control group. Homocysteine, vitamin B12 and folate levels were measured in the samples obtained from the patients and controls. Results: Mean age of the patients with lung cancer was 58.7 ± 9.9 years. All the patients were cigarettes smokers. Mean daily consumption of cigarettes was 2.0±0.7 packs and mean duration of smoking was 30 ± 11 years. Histologic type of carcinoma was found to be squamous cell carcinoma in 55%, adenocarcinoma — in 35%, and small cell carcinoma — in 10% of the cases. Clinical stage was stage IA in 20%, stage IB — in 20%, stage IIA — in 2.5%, stage IIB — in 10%, stage IIIA — in 12.5%, stage IIIB — in 20%, and stage IV — in 15% of the cases. Mean homocysteine level was 15.3 ± 7.3 μmol/l in the patients with lung cancer while 9.8 ± 2.6 μmol/l in controls. Homocysteine level was significantly higher in the patients with lung cancer compared to control group (p < 0.001). Mean folate level was 4.3 ± 1.8 pg/ml in cancer cases while 6.1 ± 2.3 pg/ml in controls. That is to say, plasma folate levels were significantly lower in cases of lung cancer compared to controls (p < 0.001). There was no significantly difference between groups with regard to B12 levels (mean B12 level was 234 ± 99 and 240 ± 104 ng/ml in the patients with lung cancer and controls, respectively, p = 0.78). Plasma homocysteine, vitamin B12 and folate levels did not show significant difference with respect to histologic type of carcinoma. No significant correlation was found between plasma homocysteine, vitamin B12, folate levels and number of cigarettes smoked per day, duration of smoking, age of the patient, and clinical stage of carcinoma. There was also no correlation between number of cigarettes smoked per day, duration of smoking, age of the patient and clinical stage of carcinoma. A possible inverse correlation between plasma homocysteine, vitamin B12 and folate levels was not observed. Conclusion: In conclusion, high plasma homocysteine and low folate levels could be associated with lung cancer. However, further studies performed on large patient population are needed.

COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD + ) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.