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      Clinical characteristics, outcomes, & mortality in pregnant women with COVID-19 in Maharashtra, India: Results from PregCovid registry

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          Abstract

          Background & objectives:

          The PregCovid registry was established to document the clinical presentations, pregnancy outcomes and mortality of pregnant and post-partum women with COVID-19.

          Methods:

          The PregCovid registry prospectively collects information in near-real time on pregnant and post-partum women with a laboratory-confirmed diagnosis of SARS-CoV-2 from 19 medical colleges across the State of Maharashtra, India. Data of 4203 pregnant women collected during the first wave of the COVID-19 pandemic (March 2020-January 2021) was analyzed.

          Results:

          There were 3213 live births, 77 miscarriages and 834 undelivered pregnancies. The proportion of pregnancy/foetal loss including stillbirths was six per cent. Five hundred and thirty-four women (13%) were symptomatic, of which 382 (72%) had mild, 112 (21%) had moderate, and 40 (7.5%) had severe disease. The most common complication was preterm delivery (528, 16.3%) and hypertensive disorders in pregnancy (328, 10.1%). A total of 158 (3.8%) pregnant and post-partum women required intensive care, of which 152 (96%) were due to COVID-19 related complications. The overall case fatality rate (CFR) in pregnant and post-partum women with COVID-19 was 0.8 per cent (34/4203). Higher CFR was observed in Pune (9/853, 1.1%), Marathwada (4/351, 1.1%) regions as compared to Vidarbha (9/1155, 0.8%), Mumbai Metropolitan (11/1684, 0.7%), and Khandesh (1/160, 0.6%) regions. Comorbidities of anaemia, tuberculosis and diabetes mellitus were associated with maternal deaths.

          Interpretation & conclusions:

          The study demonstrates the adverse outcomes including severe COVID-19 disease, pregnancy loss and maternal death in women with COVID-19 in Maharashtra, India.

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          Most cited references27

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          WHO Declares COVID-19 a Pandemic

          The World Health Organization (WHO) on March 11, 2020, has declared the novel coronavirus (COVID-19) outbreak a global pandemic (1). At a news briefing, WHO Director-General, Dr. Tedros Adhanom Ghebreyesus, noted that over the past 2 weeks, the number of cases outside China increased 13-fold and the number of countries with cases increased threefold. Further increases are expected. He said that the WHO is “deeply concerned both by the alarming levels of spread and severity and by the alarming levels of inaction,” and he called on countries to take action now to contain the virus. “We should double down,” he said. “We should be more aggressive.” Among the WHO’s current recommendations, people with mild respiratory symptoms should be encouraged to isolate themselves, and social distancing is emphasized and these recommendations apply even to countries with no reported cases (2). Separately, in JAMA, researchers report that SARS-CoV-2, the virus that causes COVID-19, was most often detected in respiratory samples from patients in China. However, live virus was also found in feces. They conclude: “Transmission of the virus by respiratory and extrarespiratory routes may help explain the rapid spread of disease.”(3). COVID-19 is a novel disease with an incompletely described clinical course, especially for children. In a recente report W. Liu et al described that the virus causing Covid-19 was detected early in the epidemic in 6 (1.6%) out of 366 children (≤16 years of age) hospitalized because of respiratory infections at Tongji Hospital, around Wuhan. All these six children had previously been completely healthy and their clinical characteristics at admission included high fever (>39°C) cough and vomiting (only in four). Four of the six patients had pneumonia, and only one required intensive care. All patients were treated with antiviral agents, antibiotic agents, and supportive therapies, and recovered after a median 7.5 days of hospitalization. (4). Risk factors for severe illness remain uncertain (although older age and comorbidity have emerged as likely important factors), the safety of supportive care strategies such as oxygen by high-flow nasal cannula and noninvasive ventilation are unclear, and the risk of mortality, even among critically ill patients, is uncertain. There are no proven effective specific treatment strategies, and the risk-benefit ratio for commonly used treatments such as corticosteroids is unclear (3,5). Septic shock and specific organ dysfunction such as acute kidney injury appear to occur in a significant proportion of patients with COVID-19–related critical illness and are associated with increasing mortality, with management recommendations following available evidence-based guidelines (3). Novel COVID-19 “can often present as a common cold-like illness,” wrote Roman Wöelfel et al. (6). They report data from a study concerning nine young- to middle-aged adults in Germany who developed COVID-19 after close contact with a known case. All had generally mild clinical courses; seven had upper respiratory tract disease, and two had limited involvement of the lower respiratory tract. Pharyngeal virus shedding was high during the first week of symptoms, peaking on day 4. Additionally, sputum viral shedding persisted after symptom resolution. The German researchers say the current case definition for COVID-19, which emphasizes lower respiratory tract disease, may need to be adjusted(6). But they considered only young and “normal” subjecta whereas the story is different in frail comorbid older patients, in whom COVID 19 may precipitate an insterstitial pneumonia, with severe respiratory failure and death (3). High level of attention should be paid to comorbidities in the treatment of COVID-19. In the literature, COVID-19 is characterised by the symptoms of viral pneumonia such as fever, fatigue, dry cough, and lymphopenia. Many of the older patients who become severely ill have evidence of underlying illness such as cardiovascular disease, liver disease, kidney disease, or malignant tumours. These patients often die of their original comorbidities. They die “with COVID”, but were extremely frail and we therefore need to accurately evaluate all original comorbidities. In addition to the risk of group transmission of an infectious disease, we should pay full attention to the treatment of the original comorbidities of the individual while treating pneumonia, especially in older patients with serious comorbid conditions and polipharmacy. Not only capable of causing pneumonia, COVID-19 may also cause damage to other organs such as the heart, the liver, and the kidneys, as well as to organ systems such as the blood and the immune system. Patients die of multiple organ failure, shock, acute respiratory distress syndrome, heart failure, arrhythmias, and renal failure (5,6). What we know about COVID 19? In December 2019, a cluster of severe pneumonia cases of unknown cause was reported in Wuhan, Hubei province, China. The initial cluster was epidemiologically linked to a seafood wholesale market in Wuhan, although many of the initial 41 cases were later reported to have no known exposure to the market (7). A novel strain of coronavirus belonging to the same family of viruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as the 4 human coronaviruses associated with the common cold, was subsequently isolated from lower respiratory tract samples of 4 cases on 7 January 2020. On 30 January 2020, the WHO declared that the SARS-CoV-2 outbreak constituted a Public Health Emergency of International Concern, and more than 80, 000 confirmed cases had been reported worldwide as of 28 February 2020 (8). On 31 January 2020, the U.S. Centers for Disease Control and Prevention announced that all citizens returning from Hubei province, China, would be subject to mandatory quarantine for up to 14 days. But from China COVID 19 arrived to many other countries. Rothe C et al reported a case of a 33-year-old otherwise healthy German businessman :she became ill with a sore throat, chills, and myalgias on January 24, 2020 (9). The following day, a fever of 39.1°C developed, along with a productive cough. By the evening of the next day, he started feeling better and went back to work on January 27. Before the onset of symptoms, he had attended meetings with a Chinese business partner at his company near Munich on January 20 and 21. The business partner, a Shanghai resident, had visited Germany between January 19 and 22. During her stay, she had been well with no signs or symptoms of infection but had become ill on her flight back to China, where she tested positive for 2019-nCoV on January 26. This case of 2019-nCoV infection was diagnosed in Germany and transmitted outside Asia. However, it is notable that the infection appears to have been transmitted during the incubation period of the index patient, in whom the illness was brief and nonspecific. The fact that asymptomatic persons are potential sources of 2019-nCoV infection may warrant a reassessment of transmission dynamics of the current outbreak (9). Our current understanding of the incubation period for COVID-19 is limited. An early analysis based on 88 confirmed cases in Chinese provinces outside Wuhan, using data on known travel to and from Wuhan to estimate the exposure interval, indicated a mean incubation period of 6.4 days (95% CI, 5.6 to 7.7 days), with a range of 2.1 to 11.1 days. Another analysis based on 158 confirmed cases outside Wuhan estimated a median incubation period of 5.0 days (CI, 4.4 to 5.6 days), with a range of 2 to 14 days. These estimates are generally consistent with estimates from 10 confirmed cases in China (mean incubation period, 5.2 days [CI, 4.1 to 7.0 days] and from clinical reports of a familial cluster of COVID-19 in which symptom onset occurred 3 to 6 days after assumed exposure in Wuhan (10-12). The incubation period can inform several important public health activities for infectious diseases, including active monitoring, surveillance, control, and modeling. Active monitoring requires potentially exposed persons to contact local health authorities to report their health status every day. Understanding the length of active monitoring needed to limit the risk for missing infections is necessary for health departments to effectively use resources. A recent paper provides additional evidence for a median incubation period for COVID-19 of approximately 5 days (13). Lauer et al suggest that 101 out of every 10 000 cases will develop symptoms after 14 days of active monitoring or quarantinen (13). Whether this rate is acceptable depends on the expected risk for infection in the population being monitored and considered judgment about the cost of missing cases. Combining these judgments with the estimates presented here can help public health officials to set rational and evidence-based COVID-19 control policies. Note that the proportion of mild cases detected has increased as surveillance and monitoring systems have been strengthened. The incubation period for these severe cases may differ from that of less severe or subclinical infections and is not typically an applicable measure for those with asymptomatic infections In conclusion, in a very short period health care systems and society have been severely challenged by yet another emerging virus. Preventing transmission and slowing the rate of new infections are the primary goals; however, the concern of COVID-19 causing critical illness and death is at the core of public anxiety. The critical care community has enormous experience in treating severe acute respiratory infections every year, often from uncertain causes. The care of severely ill patients, in particular older persons with COVID-19 must be grounded in this evidence base and, in parallel, ensure that learning from each patient could be of great importance to care all population,
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            Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection : The INTERCOVID Multinational Cohort Study

            This cohort study assesses the association between COVID-19 and maternal and neonatal outcomes in pregnant women with COVID-19 diagnosis compared with concomitantly enrolled pregnant women without COVID-19 diagnosis. Question To what extent does COVID-19 in pregnancy alter the risks of adverse maternal and neonatal outcomes compared with pregnant individuals without COVID-19? Findings In this multinational cohort study of 2130 pregnant women in 18 countries, women with COVID-19 diagnosis were at increased risk of a composite maternal morbidity and mortality index. Newborns of women with COVID-19 diagnosis had significantly higher severe neonatal morbidity index and severe perinatal morbidity and mortality index compared with newborns of women without COVID-19 diagnosis. Meaning This study indicates a consistent association between pregnant individuals with COVID-19 diagnosis and higher rates of adverse outcomes, including maternal mortality, preeclampsia, and preterm birth compared with pregnant individuals without COVID-19 diagnosis. Importance Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, Setting, and Participants In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. Exposures COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. Main Outcomes and Measures The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. Results A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. Conclusions and Relevance In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.
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              Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study

              Abstract Objectives To describe a national cohort of pregnant women admitted to hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, identify factors associated with infection, and describe outcomes, including transmission of infection, for mothers and infants. Design Prospective national population based cohort study using the UK Obstetric Surveillance System (UKOSS). Setting All 194 obstetric units in the UK. Participants 427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020. Main outcome measures Incidence of maternal hospital admission and infant infection. Rates of maternal death, level 3 critical care unit admission, fetal loss, caesarean birth, preterm birth, stillbirth, early neonatal death, and neonatal unit admission. Results The estimated incidence of admission to hospital with confirmed SARS-CoV-2 infection in pregnancy was 4.9 (95% confidence interval 4.5 to 5.4) per 1000 maternities. 233 (56%) pregnant women admitted to hospital with SARS-CoV-2 infection in pregnancy were from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth. Conclusions Most pregnant women admitted to hospital with SARS-CoV-2 infection were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes, and transmission of SARS-CoV-2 to infants was uncommon. The high proportion of women from black or minority ethnic groups admitted with infection needs urgent investigation and explanation. Study registration ISRCTN 40092247.
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                Author and article information

                Journal
                Indian J Med Res
                Indian J Med Res
                IJMR
                The Indian Journal of Medical Research
                Wolters Kluwer - Medknow (India )
                0971-5916
                0975-9174
                May-Jun 2021
                : 153
                : 5-6
                : 629-636
                Affiliations
                [1 ]Department of Clinical Research Lab, ICMR-National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India
                [2 ]Department of Obstetrics & Gynecology, Topiwala National Medical College & BYL Nair Charitable Hospital, Mumbai, Maharashtra, India
                [3 ]Medical Education & Drugs Department, Government of Maharashtra, Mumbai, Maharashtra, India
                [4 ]Department of Molecular Immunology & Microbiology, ICMR-National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India
                [5 ]Department of Clinical Research, ICMR-National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India
                [6 ]Department of Molecular & Cellular Biology Laboratory, ICMR-National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India
                []ICMR-National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India
                Author notes
                For correspondence: Dr Rahul K. Gajbhiye, Clinical Research Lab, ICMR-National Institute for Research in Reproductive Health, Parel, Mumbai 400 012, Maharashtra, India e-mail: gajbhiyer@ 123456nirrh.res.in
                [≠]

                Equal contribution

                [#]

                PregCovid Registry Network:

                Shyamkumar Sirsam, Government Medical College, Akola; Ganesh Tondge, Swati Kagne, Government Medical College, Ambejogai; Shrinivas Gaddappa, Government Medical College, Aurangabad; Uma Wankhede, Government Medical College, Baramati; Sarika Wankhede, Government Medical College, Chandrapur; Arun Morey, Government Medical College, Dhule; Rajeshree Patil, Government Medical College, Gondia; Narendra Patil, Sanjay Bansode, Government Medical College, Jalgaon; Shirish Dattatray Shanbhag, Rajarshi Chhatrapati Shahu Maharaj Government Medical College, Kolhapur; Mangal Ashok Shinde, Vilasrao Deshmukh Government Institute of Medical Sciences, Latur; Jyoti Rokade, Government Medical College, Miraj; Akash Khobragade, Saint George Hospital, Ashok Anand, Grant Medical College and J J Group of Hospitals, Ganesh Shinde, TNMC and BYL Nair Hospital, Tushar Palve, Cama & Albless Hospital, Mumbai; Anil Humane, Jitendra Deshmukh, Manjushri Waikar, Government Medical College, Nagpur; Monika Akare, Prashant Uikey, Indira Gandhi Government Medical College, Nagpur; Fasiha Tasneem Abdul Aziz, S R. Wakode, Government Medical College, Nanded; Ramesh Bhosale, Shilpa Naik, Byramjee Jeejeebhoy Medical College, Pune; Vidya Tirankar, Vaishampayan Memorial Government Medical College, Solapur; Rohidas Chavan, Vasantrao Naik Government Medical College, Yavatmal, Maharashtra, India

                Article
                IJMR-153-629
                10.4103/ijmr.ijmr_1938_21
                8555584
                34596595
                7fc2f4a6-7312-4415-9336-0009bab93bb4
                Copyright: © 2021 Indian Journal of Medical Research

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

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                Original Article

                Medicine
                covid-19,maternal deaths,miscarriage,pregnancy complications,pre-term birth,severe disease
                Medicine
                covid-19, maternal deaths, miscarriage, pregnancy complications, pre-term birth, severe disease

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