A Review on the Effect of COVID-19 in Pregnant Women

Coronavirus Disease 2019 (COVID-19) is an emerging disease with a rapid increase in cases and deaths since its first discovery in December 2019, in Wuhan, China. Limited data are available on COVID-19 effects during pregnancy;however, information on diseases associated with other highly pathogenic coronaviruses (i.e. Severe Acute Respiratory Syndrome [SARS] and the Middle East respiratory syndrome [MERS]) may provide insight into the effects of COVID-19 during pregnancy. Coronaviruses cause illnesses ranging from the common cold to severe respiratory disease and death. The data indicate an average of 5 days incubation period (range: 2-14 days). The average age range of the hospitalized patients was 49-56 years, and a third to half of them have an underlying illness. Children were rarely mentioned. Within hospitalized cases, men were more frequent (54%-73%). Fever, cough, myalgia, vomiting, and diarrhea are common symptoms. This review aims at giving an in-depth understanding of COVID-19 by comparing its effects with SARS and MERS to evaluate its severity in pregnant women1. The results of varied studies show that COVID-19 affects pregnant women seriously and there is an alarming need to look into this aspect to prevent its harmful effects on the fetus.Copyright © 2020

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review.

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.

Pharmacokinetic evaluation of drug-drug interactions in the treatment of COVID-19.

Objective: The COVID-19 pandemic, which started in Wuhan, China and affected the whole world, still represents a unique global challenge with its contagiousness and lethality. The symptoms of COVID-19 patients may differ depending on the severity of the disease. According to the report published by the Ministry of Health Coronavirus Research Advisory Board on the diagnosis, treatment and control of COVID-19, drug combination therapy (hydroxychloroquine, lopinavir / ritonavir and favipiravir) is recommended by health authorities. Drug-drug interaction is a possible situation as a result of simultaneous use of these drugs, which are metabolized by cytochrome P 450 enzymes (CYP), which are mostly found in the liver, with some other drugs. In this review, we aimed to show the pharmacokinetic drug-drug interactions of the drugs used in the treatment of COVID-19, especially by indicating the metabolism pathways. Result and Discussion: The COVID-19 pandemic adversely affects social life, economic and financial markets worldwide. Appropriate treatment protocols are of great importance but taking drug-drug interactions into account in treatment practices prevents unwanted results in patient treatment.Copyright © 2021 University of Ankara. All rights reserved.

Audiovestibular and vaccination complications of COVID-19

Objectives: Since its first appearance in Wuhan December 2019, SARS-CoV2 virus received great attention due to its severe symptoms and high spread causing COVID-19 disease which spread all over the world like a pandemic. The causative virus is capable of human-to-human transmission via droplet and direct contact suggesting that upper respiratory tract is the main site to virus manifestations. There is a great diversity in its clinical picture, although the severe respiratory and neurological symptoms are commonly present;however, other symptoms are present. Although otological manifestations are reported in many COVID-19 patients even in asymptomatic cases, they did not receive much attention compared with other critical manifestations. In this article, we paid our attention specifically to the otological manifestations of COVID-19 and their relevance either to the virus infection, treatment, or vaccination through literature review. Conclusion(s): COVID-19 disease has a deleterious effect on the inner ear. This effect is not only due to SARS-Cov-2 infection, but it could be also due to the ototoxic drugs used for treatment. The COVID-19 vaccinations are found to be implicated in the otological symptoms in some cases.Copyright © 2022, The Author(s).

Study on the risk signal mining related to lopinavir/ritonavir based on the US FDA Adverse Event Reporting System.

Objective: To explore the clinical safety of lopinavir/ritonavir (LPV/r) by mining the risk signals of adverse events (AEs) related to LPV/r for the safe application of the drug in the treatment of novel coronavirus pneumonia (COVID-19). Method(s): The risk signals related to LPV/r in AE reports of US FDA Adverse Event Reporting System (FAERS) from the first quarter of 2010 to the third quarter of 2019 were mined by reporting odds ratio (ROR). An AE with reports more than 3 and 95% confidence interval (CI) lower limit of ROR greater than 1 was defined as a positive signal. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA). The PTs of top 50 adverse event reports and signal strength were selected and analyzed. Result(s): From the first quarter of 2010 to the third quarter of 2019, a total of 13 335 AE reports with LPV/r as the primary suspicious drug were reported in the FAERS database. Four hundred and fifty-five AE risk signals with reports more than 3 and the 95%CI lower limit of ROR greater than 1 were detected, involving 7 718 AE reports. The top 2 system organs involved in AE reports were "injury, poisoning and procedural complications" [13.6% (1 051/7 718)] and "pregnancy, puerperium and perinatal conditions" [11.7% (899/7 718)]. However, 998 (95.0%) of 1051 AE reports involved in "injury, poisoning and procedural complications" were related to drug exposure during pregnancy. The system organ with the highest signals was "congenital, familial and genetic disorders" [16.3% (74/455)]. In addition, 144 AEs caused by drug interactions were detected, which ranked the 7th in the AE reports. Conclusion(s): The risk signals of fetal, neonatal and infant abnormalities related to LPV/r during pregnancy were detected, suggesting that attention should be paid to the risk of using LPV/r in pregnant women and infants. The interaction between LPV/r and other drugs was also worthy of attention.Copyright © 2020 by the Chinese Medical Association.

Safety application of novel coronavirus pneumonia antiviral drugs.

Three antiviral drugs, including interferon alpha (aerosol inhalation), lopinavir/ritonavir (oral medication), and ribavirin (intravenous infusion), are recommended by Diagnosis and Treatment of Novel Coronavirus Pneumonia (revised version, the 5th ed), which was issued by the National Health Commission of People's Republic of China and National Administration of traditional Chinese Medicine. In addition, clinical trials on a new antiviral drug-remdesivir which is not yet on the market has also been launched in China. Medication safety related data on treatment for infections of severe acute respiratory syndrome coronavirus, middle respiratory syndrome coronavirus, human immunodeficiency virus, lopinavir/ritonavir, and ribavirin, safety data of remdesivir in animal experiment, phase I clinical trials and clinical trials of treating Ebola virus infection, and preliminary reports of treatment in novel coronavirus pneumonia were briefly reviewed, aiming to provide evidence for clinical safety medication.Copyright © 2020 by the Chinese Medical Association.

Rashes caused by arbidol in a patient with novel coronavirus pneumonia.

A 50-year-old male patient with agitated depression and hyperlipemia received oral amoxicillin and clavulanate potassium 0.5 g once daily and 2 lopinavir and ritonavir tablets twice daily for novel coronavirus infection, based on previous drugs including quetiapine, clonazepam, and atorvastatin calcium. After 3 days, lopinavir and ritonavir was changed to oral arbidol 200 mg, thrice daily due to suspicious drug interaction. After taking arbidol for 3 days, the patient developed red papules on the whole body. Considering that it might be related to amoxicillin and clavulanate potassium, the drug was stopped and loratadine was given. But the rashes were aggravated. Considering that the drug eruption was caused by arbidol, arbidol was discontinued and the rashes subsided in a large area the next day. Then vitamin C injection, calcium gluconate injection, and ribavirin were added. After 5 days, the rashes subsided completely. After 17 days, the patient recovered from pneumonia.Copyright © 2020 by the Chinese Medical Association.

Antiviral agents for COVID-19.

In December 2019, the endemic of COVID-19 broke out in Wuhan, China. The disease is highly contagious and quickly spreads at home and abroad, causing great concern. However, there are no definite effective antiviral drugs in clinical use. Given the urgency of the COVID-19 outbreak, based on the diagnosis and treatment recommendation and relavant researches, this article describes the optional antiviral drugs such as remdesivir, oseltamivir, arbidol, lopinavir/ritonavir, ribavirin, and interferon-alpha to provide a reference for treatment of COVID-19.Copyright © 2020 by the Chinese Medical Association.

Herbal medicines in the treatment of coronavirus disease 2019 (Covid-19)

Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, started in livestock within the markets of Wuhan, China and was consequently spread around the world. The virus has been rapidly spread worldwide due to the outbreak. COVID-19 is the third serious coronavirus outbreak in less than 20 years after Severe Acute Respiratory Syndrome (SARS) in 2003 and Middle East Respiratory Syndrome (MERS) in 2012. The novel virus has a nucleotide identity closer to that of the SARS coronavirus than that of the MERS coronavirus. Since there is still no vaccine, the main ways to improve personal immunity against this disease are prophylactic care and self-resistance including an increased personal hygiene, a healthy lifestyle, an adequate nutritional intake, a sufficient rest, and wearing medical masks and increasing time spent in well ventilated areas. There is a need for novel antivirals that are highly efficient and economical for the management and control of viral infections when vaccines and standard therapies are absent. Herbal medicines and purified natural products have the potential to offer some measure of resistance as the development of novel antiviral drugs continues. In this review, we evaluated 41 articles related to herbal products which seemed to be effective in the prevention or treatment of COVID-19.Copyright © 2021 The Author(s).

Safety profile assessment of drug products used for the pathogenetic treatment of COVID-19.

Objective. To review and summarize literature data in studies of safety of the drug products used for the pathogenetic treatment of COVID-19. Materials and methods. As the first stage of monitoring the drug's safety, which are used in the treatment of COVID-19 in Russia, a systematic review of studies of the drug's safety profiles was carried out: Mefloquine, hydroxychloroquine, azithromycin, lopinavir/ritonavir, favipiravir, tocilizumab, olokizumab, baricitinib in the international databases Medline, PubMed, ClinicalTrials.gov and Cochrane Library for the period 2019-2021. Results. The review included 51 articles that met the selection criteria. Based on the results of the review, it can be concluded that the safety profile (frequency, severity and severity) of most drugs repurposed for COVID-19 corresponds to those for the registered indications. At the same time, according to world experience, there is an increase in the number of reports of adverse drug reactions of hydroxychloroquine and azithromycin, which is provoked by the active use of these drugs for combination therapy. Conclusions. According to the literature, a high incidence of adverse events was noted in hydroxychloroquine, chloroquine and azithromycin. Subsequent analysis and comparison of the safety profiles of hydroxychloroquine, chloroquine and azithromycin with data from the national automated information system (AIS) database of Roszdravnadzor is a necessary component of effective and safe pharmacotherapy for COVID-19.Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Efficacy of N-acetyl Cysteine in Severe COVID-19 Patients: A Randomized Controlled Phase III Clinical Trial

Background: Today, various drugs have been investigated as the primary or complementary treatment for coronavirus disease 2019 (COVID-19). N-acetylcysteine (NAC) has been used as a mucolytic in pulmonary diseases. This drug apparently contributes to the retrieval of the intracellular antioxidant system. Objective(s): This study aimed to determine the efficacy of NAC in severe COVID-19 patients admitted to the intensive care unit (ICU). Method(s): This single-blinded randomized controlled phase III clinical trial included 40 patients with confirmed COVID-19 (based on polymerase chain reaction) admitted to the Shahid Mohammadi Hospital's ICU, Bandar Abbas, Iran, in 2020. All cases had severe COVID-19. They were allocated randomly to two equal groups. Patients in the control group received standard drug therapy based on the treatment protocol of the national COVID-19 committee, while those in the NAC group received a single dose of intravenous NAC (300 mg/kg) upon admission to the ICU in addition to standard drug treatment. Clinical status and laboratory tests were done on admission to the ICU and then 14 days later or at discharge without knowing the patient grouping. Result(s): The two groups were comparable regarding age, gender, and other baseline laboratory and clinical parameters. At the final evaluation, respiratory rate (21.25 +/- 4.67 vs. 27.37 +/- 6.99 /min) and D-dimer (186.37 +/- 410.23 vs. 1339.04 +/- 2183.87 ng/mL) were significantly lower in the NAC group (P = 0.004 and P = 0.030, respectively). Also, a lower percentage of patients in the NAC group had lactate dehydrogenase (LDH) <= 245 U/L (0% vs. 25%, P = 0.047). Although the length of ward and ICU stay was shorter in the NAC group than in controls, the difference was statistically insignificant (P = 0.598 and P = 0.629, respectively). Mortality, on the other hand, was 75% in the control group and 50% in the NAC group, with no statistically significant difference (P = 0.102). Concerning the change in the study parameters, only the decrease in diastolic blood pressure (DBP) was significantly higher with NAC (P = 0.042). The intubation and mechanical ventilation rates were higher, while oxygen with mask and nasal oxygen rates were lower with NAC, but the difference was statistically insignificant. Conclusion(s): Based on the current research, NAC is related to a significant decrease in RR, D-dimer, and DBP in severe COVID-19. Also, LDH was significantly lower in the NAC group than in the controls. More research with larger sample sizes is needed to validate the current study results.Copyright © 2023, Author(s).

Perinatal Care during the COVID-19 Pandemic

Background: Following the pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and considering its capacity for rapid mutation, there have been many studies and articles on this novel coronavirus over the past three years. Therefore, providing knowledge and directions for management of SARS-CoV-2, for hospital staff is crucial. Hence, we collected the research information from different perspectives and summarized the guidelines for perinatal care on the topic of SARS-CoV-2, and for possible future viral pandemics. Method(s): A systematic review aimed at assessing the publications written in English and Chinese, offering different perspectives on the topic of perinatal care concerning SARS-CoV-2, was conducted using PubMed and Google Scholar from 2020 to 2022. In addition, we summarized the guidelines from the Taiwan Association of Obstetrics and Gynecology, American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine, Maternal Immunization Task Force and Partners, and Academy of Breastfeeding Medicine. Result(s): Due to physiological changes, pregnant patients may be prone to have complications, especially pre-eclampsia, affecting morbidity and mortality. Most neonates of coronavirus disease (COVID-19) infected mothers did not show any clinical abnormalities due to the infection. However, compared to the general population, infected neonates needed more invasive ventilation care, while the proportion of asymptomatic neonates was less than that in the general population. Further, long term complications are still under investigation. Evidence of vertical transmission via the placenta and umbilical cord is rare but not absent. Paxlovid (nirmatrelvir/ritonavir) can be administered to patients with comorbidities, and indications for cesarean delivery does not include COVID-19 infection. Vaccination against COVID-19 should not be delayed during pregnancy and lactation. Conclusion(s): Obstetricians and gynecologists should pay more attention to pregnant women with SARS-CoV-2 because of the physiological changes and higher risks of complications, morbidity, and mortality. Early prevention with vaccination in pregnant women is the key to controlling the COVID-19 pandemic, from which we can learn how to manage the next pandemic.Copyright © 2023 The Author(s).

Analysis of adverse reactions of lopinavir/ritonavir in the treatment of coronavirus disease 2019.

Objective: To explore the occurrence of adverse reactions of lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19). Method(s): The medical records of patients with COVID-19 who received LPV/r treatment in the Fourth People's Hospital of Nanning from January 24th to February 6th, 2020 were collected and the occurrence of adverse events during the treatment was retrospectively analyzed. According to the 5 principles of adverse drug reaction correlation evaluation proposed in the Handbook of Adverse Drug Reaction Reporting and Monitoring in China, adverse events that were certainly related, probably related, and possibly related to LPV/r were defined as LPV/r-related adverse reactions. The incidence of adverse reactions was calculated and the main clinical manifestations and severity of adverse reactions [grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), and grade 5 (death);grade 3-5 was defined as severe adverse reaction] were analyzed. Result(s): A total of 28 patients were enrolled in the analysis, including 13 males and 15 females, aged from 18 to 70 years with an average age of 44 years. The courses of treatment with LPV/r of patients ranged from 2 to 12 days, with a median course of 6 days. Of the 28 patients, 18 developed LPV/r related adverse reactions, with an incidence of 64.3%. The LPV/r-related adverse reactions in 18 patients included gastrointestinal reactions in 14 patients (grade 1 in 13 patients and grade 2 in 1 patient), bradycardia in 2 patients (grade 2 in both patients), and acute hemolysis in 1 patient (grade 3), and liver injury in 1 patient (grade 3), and no grade 4 or 5 adverse reactions occurred. The incidence of severe adverse reactions was 7.1%. Thirteen patients with grade 1 adverse reactions did not affect the treatment, and the symptoms were relieved after 2-7 days of continuous medication. LPV/r was discontinued in 5 patients with grade 2 or 3 adverse reactions, 4 of whom received symptomatic treatment, and the symptoms disappeared 2-10 days later. Conclusion(s): The incidence of adverse reactions in COVID-19 patients treated with LPV/r in our hospital was 64.3%. LPV/r mainly leads to mild gastrointestinal reactions and can also lead to bradycardia, acute hemolysis, and liver injury. Blood routine, liver function, and electrocardiogram need to be monitored during the treatment.Copyright © 2020 by the Chinese Medical Association.

Hyperkalemia caused by Qingfei Paidu decoction() in a patient with novel coronavirus pneumonia.

A 23-year-old male patient received moxifloxacin, recombinant human interferon alpha-2b for injection, and lopinavir and ritonavir for 7 days for novel coronavirus pneumonia. There was no abnor-malityof serum potassium. Moxifloxacin was stopped, Qingfei Paidu decoction() was given, and then the patient's serum potassium began to rise. On day 10 after taking the decoction, laboratory tests showed serum potassium 5.7 mmol/L and the patient was diagnosed with hyperkalemia. Insulin injection 4 U diluted to 5% glucose injection 250 ml was given once by IV infusion, and then the serum potassium decreased to 5.0 mmol/L 6 hours later and 4.6 mmol/L 2 days later. After 5 days, the serum potassium rose again and finally to 5.4 mmol/L on day 17 after taking the decoction. Insulin was given once that day and 2 days later once daily according to the previous method. Then the serum potassium decreased and did not rise again. The patient recovered from novel coronavirus pneumonia and was discharged on day 28 after hospitalization.Copyright © 2020 by the Chinese Medical Association.

Acute hemolytic reaction in patients with novel coronavirus pneumonia induced by high-dose ribavirin injection: report of 2 cases.

Two female patients (patient 1, 22-year-old;patient 2, 50-year-old) received IV infusion of ribavirin injection (4 g in the first dose and the next day 1.2 g thrice daily), oral 2 lopinavir and ritonavir tablets twice daily, and aerosol inhalation of recombinant human interferon alpha2b for injection for novel coronavirus pneumonia. There was no obvious abnormality in blood routine and liver function before treatment. Laboratory tests showed red blood cell count (RBC) 2.89x1012/L, hemoglobin (Hb) 75 g/L, alanine aminotransferase (ALT) 22.8 U/L, aspartate aminotransferase (AST) 33.9 U/L, total bilirubin (TBil) 71.2 mumol/L, and indirect bilirubin (IBil) 63.5 mumol/L in patient 1 on the 2nd day of treatment, and RBC 3.46x1012/L, Hb 95 g/L, ALT 17.7 U/L, AST 21.3 U/L, TBil 86.1 mumol/L, and IBil 67.1 mumol/L in patient 2 on the 3rd day of treatment. The direct antiglobulin test was positive, indirect antiglobulin test was negative, and antinuclear antibody test was negative in both patients. They were diagnosed as having acute hemolytic anemia. Con-sidering the relationship to ribavirin, ribavirin was given in reduced dose and then finally discontinued in patient 1, and was discontinued directly in patient 2. On the basis of continued use of the other 2 drugs, both of them were treated with ursodeoxycholic acid. The Hb and bilirubin level of the 2 patients gradually returned to normal.Copyright © 2020 by the Chinese Medical Association.

Effect of low-to-moderate dose glucocorticoids on viral clearance in COVID-19: a retrospective study.

Objective: To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19. Methods: A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg.kg-1.d-1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results: The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years (chi2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days (P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups (P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group (P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively (P>0.05). Conclusion(s): Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.Copyright © 2020 by the Chinese Medical Association.