Chloroquine (CQ) is a 4-aminoquinoline drug used for the treatment of diverse diseases. It inhibits lysosomal acidification and therefore prevents autophagy by blocking autophagosome fusion and degradation. In cancer treatment, CQ is often used in combination with chemotherapeutic drugs and radiation because it has been shown to enhance the efficacy of tumor cell killing. Since CQ and its derivatives are the only inhibitors of autophagy that are available for use in the clinic, multiple ongoing clinical trials are currently using CQ or hydroxychloroquine (HCQ) for this purpose, either alone, or in combination with other anticancer drugs. Here we show that in the mouse breast cancer cell lines, 67NR and 4T1, autophagy is induced by the DNA damaging agent cisplatin or by drugs that selectively target autophagy regulation, the PtdIns3K inhibitor LY294002, and the mTOR inhibitor rapamycin. In combination with these drugs, CQ sensitized to these treatments, though this effect was more evident with LY294002 and rapamycin treatment. Surprisingly, however, in these experiments CQ sensitization occurred independent of autophagy inhibition, since sensitization was not mimicked by Atg12, Beclin 1 knockdown or bafilomycin treatment, and occurred even in the absence of Atg12. We therefore propose that although CQ might be helpful in combination with cancer therapeutic drugs, its sensitizing effects can occur independently of autophagy inhibition. Consequently, this possibility should be considered in the ongoing clinical trials where CQ or HCQ are used in the treatment of cancer, and caution is warranted when CQ treatment is used in cytotoxic assays in autophagy research.

Autophagy is a protein and organelle degradation pathway that is involved in diverse diseases including cancer. Recent evidence suggests that autophagy is a cell survival mechanism in tumor cells and that its inhibition especially in combination with other therapy could be beneficial but it remains unclear if all cancer cells behave the same way when autophagy is inhibited. We inhibited autophagy in a panel of breast cancer cell lines and found that some of them are dependent on autophagy for survival even in nutrient rich conditions without any additional stress while others need autophagy only when stressed. Survival under unstressed conditions is due to cell type specific autophagy regulation of STAT3 activity and this phenotype is enriched in triple negative cell lines. This autophagy-dependency affects response to therapy because autophagy inhibition reduced tumor growth in vivo in autophagy-dependent but not in autophagy-independent breast tumors while combination treatment with autophagy inhibitors and other agent was preferentially synergistic in autophagy-dependent cells. These results imply that autophagy-dependence represents a tumor cell specific characteristic where autophagy inhibition will be more effective. Moreover, our results suggest that autophagy inhibition might be a potential therapeutic strategy for triple negative breast cancers, which currently lack an effective targeted treatment.

Background. Antibody titer and the life span of antibodies against SARS-CoV-2 have been found to be associated with the clinical presentation in individuals. The extent of exposure of healthcare workers and the general public to SARS-CoV-2 needs to be assessed to monitor the COVID-19 pandemic. Thus, this study is an attempt in assessing the anti-SARS-CoV-2 antibody in health care workers. Methods. This laboratory-based cross-sectional study was performed in Manmohan Memorial Medical College and Teaching Hospital, Kathmandu from November 2020 to January 2021. A total of 185 HCWs were enrolled in this study. Their serum samples were screened for anti-SARS-CoV-2 antibodies, and a structured questionnaire was administered to collect further information. Anti-SARS-CoV-2 antibody screening was performed using lateral flow immunoassay. The data were analyzed using SPSS version 20. Results. Among 185 HCWs that participated in the study, 41 (22.2%) tested positive for the anti-SARS-CoV-2 antibody. Of these 41 HCWs, 37 tested positive for IgG only and 4 of them tested positive for both IgM and IgG antibodies. The presence of the previous history of SARS-CoV-2 infection ( p < 0.001 ), the presence of flu-like symptoms within the last 6 months ( p < 0.001 ), and the presence of positive contact history ( p = 0.002 ) were statistically significant with the presence of the antibody among HCWs. Conclusion. Healthcare workers carry a high burden of SARS-CoV-2 infection and are at risk of acquiring infection from their workplace. Anti-SARS-CoV-2 antibody screening among healthcare workers is highly recommended in multiple healthcare settings as it can help in monitoring transmission dynamics and evaluation of infection control policies.

Introduction The post-coronavirus disease 2019 (COVID-19) syndrome is defined as the persistence of symptoms after viral clearance and the emergence of new symptoms after a few months following recovery from COVID-19. This study aimed to assess the prevalence of post-COVID-19 syndrome and the risk factors that contribute to its development. Methods This study was conducted prospectively in Tribhuvan University Teaching Hospital (TUTH), located in Maharajgunj, Kathmandu. The patients were followed up for three months. Results The post-COVID status of 300 patients admitted to the COVID emergency of TUTH was studied. The mean age of the patients was 46.6±15.7 years, and the proportion of male (56%) was slightly higher than female (44%). Most of the patients (81.7%) had fever on their presentation to the emergency which was followed by fatigue (81.3%) and cough (78.3%). During the post-COVID phase, fatigue was the most common persistent symptom, with 34% experiencing fatigue after 60 days and 28.3% even after 90 days from the onset of symptoms. Univariate logistic regression showed sore throat (OR 4.6; 95% CI (2.8–7.6)), rhinitis (OR 3.6; 95% CI (2.1–5.9)), fatigue (OR 3.7; 95% CI (1.8–7.6)), diarrhea (OR 4.1; 95% CI (2.4–6.9)), anosmia (OR 6.7; 95% CI (3.9–11.3)), ageusia (OR 7.8; 95% CI (4.5–13.4)) and shortness of breath (OR 14.9; 95% CI (1.8–119.6)) at admission were all predictors of post-COVID syndrome after three months. Conclusion Even after recovering from COVID-19, people with COVID-19 may develop symptoms. As a result, COVID-19’s long-term consequences should not be neglected, as they may lead to increased morbidity among patients, consumption of financial resources, and added burden on the health system.

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