Fully vaccinated individuals with existing comorbidities have an increased risk of breakthrough COVID-19 infections and hospitalization


A new study by researchers from Truveta Inc, a clinical data analytics company based in Washington-USA has found that fully vaccinated individuals with existing comorbidities such as diabetes, chronic kidney disease (CKD), chronic lung disease, or those with immunocompromising conditions have increased risk of COVID-19 breakthrough infections and also hospitalization.

The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2022.04.26.22271727v1

Here we found that the incidence of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization following breakthrough infection were significantly greater among patients with select comorbid medical conditions when compared to the general population. Specifically, people with diabetes, chronic lung disease, or CKD have increased incidence of breakthrough infection compared to the general population after adjusting for age, sex, race, and ethnicity.

These conditions are thought to lead to impaired immune function (32–34). This is consistent with studies in unvaccinated people showing higher risk of infection in these populations as well as a study in mostly male U.S. veterans which showed reduced vaccine effectiveness in patients with a high Charlson comorbidity index (9).

In our study, patients with comorbidities had nearly twice the odds of being hospitalized than the general vaccinated population. Overall, these findings add to prior studies showing worse outcomes following COVID-19 infection in people who are immunocompromised, with diabetes, CKD, or with chronic lung disease (5–7) and adds additional support for recommendations of booster vaccines given these groups continue to fare worse than the general vaccinated population.

One study in an unvaccinated population reported ORs of greater than 2 for in-hospital mortality following COVID-19 infection in patients with diabetes, CKD, or pulmonary disease when compared with the general population (6).

We identified CKD as the highest risk comorbidity for hospitalization, even after adjustment for age and demographic factors. Notably, a large study in male U.S. veterans did not show an elevated risk of severe outcomes in breakthrough infections in patients with diabetes, chronic lung disease, or CKD (10).

This was possibly due to their study design which matched patients by comorbidity burden thereby reducing any differences between groups. In contrast our study compared patients with identified comorbidities to a control group without these comorbidities and did not exclude or match patients with multiple comorbidities.

We found that the immunocompromised group had the smallest increased risk of breakthrough infection compared to the other comorbidities. This is possibly due to a higher adoption of protective behaviors such as social distancing and mask wearing in this group than other groups and the general population.

Additionally, while we found that those with chronic lung disease had the highest rate of breakthrough infection (2.63%) it had the lowest rate of hospitalization (10.23%). This might be due to those with COPD having supplemental oxygen and steroids readily available, or that COPD may capture a broad range of disease from very mild asthma to end-stage COPD, therefore attenuating overall risk of hospitalization in our data; though future research is necessary.

Like all studies, ours is subject to limitations. First, there are multiple confounding features which are difficult to address with the available data including the timing of patient vaccination, precedent undiagnosed COVID-19 infection, and the timing of infections in relation to SARS-CoV-2 variants of concern. Future studies should correct for these potential confounders.

Secondly, our current data definitions rely heavily on ICD-10-CM codes, except for CKD which incorporates lab tests. This limits the scope and may limit the accuracy of our comorbidity groups and COVID-19 diagnoses. For example, adding labs would improve sensitivity for COVID-19 cases. As more data become available, we plan to include SARS-CoV-2 variants of concern, geography, and more comorbidities.

Our current outcome models consider only the effect of a single comorbidity on our outcomes of interest. Future iterations of this analysis should consider the effect of multiple simultaneous comorbidities on outcomes as well as their interaction effects. Currently, we treat each comorbidity as purely independent, but it is known that patients can have multiple comorbidities (e.g., diabetes and CKD).

Future research could consider the interaction effects of patients having multiple comorbidities on probabilities of outcome events; specifically, models of breakthrough infection and hospitalization outcomes should consider how the interactions among these comorbidities may contribute to differences in odds of breakthrough infection and hospitalization.

As vaccinated individuals continue to make decisions about booster vaccinations, they will be looking for information regarding their personal risk of breakthrough COVID-19 infection and severe outcomes like hospitalization. The FDA and CDC both made recommendations to include high-risk groups, such as those we studied, as groups who should receive booster vaccinations.

While there is robust data showing increased risk to unvaccinated groups with comorbidities, both the FDA and CDC cited limited data in vaccinated groups with comorbidities.

The findings of this study improve the evidence and support recommendations for people with comorbidities such as chronic kidney disease, chronic lung disease, diabetes or people who are immunocompromised to receive the primary vaccination sequence as well as a booster dose.

This page summarises important considerations for the care of people with co-existing medical conditions during the COVID-19 pandemic. Key points from guidance and position statements are summarised for each condition, and there is a link to the main BMJ Best Practice topic. This overview topic is continually reviewed and updated, and more conditions will be added to this list.

Our full topic on Coronavirus disease 2019 (COVID-2019) includes information on diagnosis and management, as well as prevention, differential diagnosis, epidemiology, aetiology, prognosis, and complications.

Considerations for perinatal care
Severity of COVID-19 in pregnant women

Pregnant women are at risk of more severe COVID-19 infection and should take extra precautions, especially those above 28 weeks’ gestation.[1][2][3][4][5]

Pregnancy increases the risk of hospitalisation, intensive care admission, and receipt of mechanical ventilation. MBRRACE-UK (Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK) advises that all pregnant or post-partum women who have COVID-19 receive multidisciplinary team care and obstetric leadership with daily review and are given advice about when to seek urgent medical attention.[6][7]

Risk factors for hospital admission with COVID-19 infection during pregnancy include: being unvaccinated; being from a black, Asian, or other minority ethnic group; having a BMI of 25 or more; pre-pregnancy comorbidity (such as diabetes or hypertension); age 35 or older; increased socioeconomic deprivation.[8][9] In the US, Hispanic and non-Hispanic black women also seem to be disproportionately affected by SARS-CoV-2 infection during pregnancy.[10]

Maternal COVID-19 is associated with a higher risk of pre-eclampsia/eclampsia, preterm birth, birth by emergency caesarean section, prolonged maternal admission following birth, venous thromboembolism, myocardial infarction, and maternal mortality or serious morbidity from obstetric complications.[11][12][13][14][15][16][17][18][8] Pre-existing comorbidities, high maternal age, pre-pregnancy obesity, gestational diabetes, pre-gestational diabetes, pre-eclampsia, and non-white ethnicity are associated with more severe COVID-19 disease during pregnancy.[2][13][19][18]

Disease severity is associated with higher rates of preterm birth, caesarean delivery, maternal intensive care admission, neonatal intensive care admission, and maternal death.[2][20][21] Maternal SARS-CoV-2 status does not appear to affect postnatal haemorrhage, infant 5-minute APGAR score, or birth weight for gestational age.[11][22]

A study conducted in the UK reported that the risks of pneumonia, needing respiratory support, and requiring intensive care admission were higher during the periods of Alpha and Delta variant predominance compared with the period of wildtype SARS-CoV-2 predominance.[23]

Impact of maternal COVID-19 infection on the neonate

Infants born to mothers who test positive for SARS-CoV-2 have an increased risk of admission for neonatal care, prolonged neonatal admission, hyperbilirubinaemia, respiratory distress syndrome, and any other respiratory disorder.[14][22][24] A US study found that risk for stillbirth was higher among women who had COVID-19 at delivery hospitalisation compared with those without COVID-19; association was higher during period of Delta-variant predominance compared with the period before Delta.[25]

Fewer than 2% of babies born to mothers with COVID-19 have confirmed SARS-CoV-2 infection. Transmission may occur in utero, perinatally, or in the early postnatal period. Severe maternal infection, maternal death, maternal admission to an intensive care unit, and postnatal maternal infection were associated with an increased risk of SARS-CoV-2 positivity in the newborn.[26]

Vaccination of pregnant and lactating women

Pregnant women should be advised to take up the influenza vaccine.[8] Guidance is available on use of COVID-19 vaccines during pregnancy.[27] In the US, the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend COVID-19 vaccination for all people who are pregnant, breastfeeding, trying to get pregnant now, or might become pregnant in the future.[28][29] In the UK, guidance advises that pregnant women should be offered vaccination at the same time as non-pregnant women, based on their age and clinical risk group.[8][30] Unvaccinated women are more likely to be admitted to hospital with COVID-19 compared with vaccinated women.[23][31] Women who are breastfeeding may also be offered any suitable COVID-19 vaccine.[30] Local guidance should be followed.

There is no association between COVID-19 vaccination during pregnancy and spontaneous abortion, postpartum haemorrhage, chorioamnionitis, caesarean delivery, neonatal intensive care admission, 5-minute APGAR score <7, stillbirth, preterm birth, or small for gestational age infant.[32][33][34][35][36][37][38][39]

Analysis of pregnancies occurring during clinical trials of the AZD1222 (AstraZeneca) vaccine demonstrated no difference in rates of conception between women who received the SARS-CoV-2 vaccine and women who received the control vaccine.[40] Cohort data have also suggested that administration of COVID-19 mRNA vaccines is not associated with oocyte or embryo development, implantation, or early pregnancy loss in patients undergoing IVF.[41]

The number needed to vaccinate (NNV) to prevent one symptomatic case of COVID-19 has been calculated as between 41 and 206 pregnant women. The NNV to prevent severe COVID-19 is between 412 and 2058. Numbers needed to harm are 37,037 for vaccine-related myocarditis and 48,780 for vaccine-related thrombosis with thrombocytopenia syndrome.[42] Transfer of SARS-CoV-2 antibodies to cord blood and breast milk after maternal vaccination has been described.[43][44][45] One case-control study in the US found that maternal completion of a 2-dose mRNA COVID-19 vaccination series during pregnancy might help prevent COVID-19 hospitalisation among infants aged <6 months.[46]

Considerations for mental health of pregnant women

Pregnant women have reported higher levels of distress and psychiatric symptoms during the COVID-19 pandemic.[47] A report from the UK’s Centre for Mental Health and the Maternal Mental Health Alliance completed a rapid evidence review of the impact of COVID-19 on mental health during pregnancy and after birth, and found that women experiencing financial insecurity or racial inequality had a higher risk of poor mental health.[48]

Routine antenatal care

Some elements of routine perinatal care may be amended during the COVID-19 pandemic.

Antenatal care:

Women are advised to continue routine antenatal care, and the nationally recommended schedule of antenatal care should be offered in full wherever possible.[8] Ideally, antenatal appointments should be offered in-person, particularly to women from BAME communities, with communication difficulties, or whose medical, social, or psychological conditions put them at higher risk of complications or adverse outcomes during pregnancy.[8]

If there is concern about the patient or fetus, a face-to-face appointment should be advised. Women should be encouraged to attend pregnancy assessment services if they have any concerns for their or their baby’s well being.[8]
Before face-to-face consultations, patients should be contacted to screen for symptoms of COVID-19. Patients who report symptoms of COVID-19 should be assessed to determine if an urgent antenatal appointment is needed, or if the appointment can be delayed.[1][49] A home appointment may be offered instead.[49]
Investigations such as blood tests and ultrasound scans should be arranged with other in-person maternity appointments to limit repeat clinic attendance.[8]

Remote consultations by telephone or video call may replace some face-to-face appointments in low-risk pregnancies.[1] Women may be advised to check their blood pressure at home if possible, and given advice on when to seek medical assistance.[1]
Intrapartum care:

Women should be offered SARS-CoV-2 testing on admission to the maternity unit.[8]
Birth partners should be screened for symptoms of COVID-19 on contact or attendance of the maternity unit.[8][50]
Scheduled induction and caesarean delivery may continue if indicated, but if the patient screens positive for suspected COVID-19 infection, individual assessment should be made to determine if it is safe to reschedule.[8][51] COVID-19 status alone is not an indication for caesarean delivery.[52]

Continuous fetal monitoring using cardiotocography during labour is not indicated for asymptomatic women who test positive for SARS-CoV-2, unless there is another indication for monitoring (e.g. previous caesarean delivery). Women with confirmed or suspected symptomatic COVID-19 should be offered continuous fetal monitoring during labour and vaginal birth.[8]
Home birth may still be considered for low-risk pregnancies, where appropriate support can be provided.[8]
Postnatal care:

As with antenatal care, the number of postnatal visits may be limited, and some may be done remotely rather than face-to-face, depending on the needs of mother and baby.[49][51] The first visit after birth and the day 5 blood spot should be prioritised for a face-to-face visit.[49]
Long-acting contraception should be offered.
Considerations for newborn care
The American Academy of Pediatrics has published guidance on the care of babies born to mothers who have COVID-19. Clinicians should wear airborne, droplet, and contact precautions-level personal protective equipment to attend deliveries from mothers with COVID-19. Suctioning, positive pressure ventilation, and intubation may all generate infant virus aerosols.[53]

Observational cohort studies have found that the risk of the newborn acquiring SARS-CoV-2 infection is low when contact and droplet precautions are taken to protect the newborn from maternal respiratory secretions.[54][55][56] A mask should be worn, and meticulous breast and hand hygiene performed, for direct skin-to-skin contact between mother and child.[1][53] The mother should maintain a reasonable distance from the infant where possible; an isolette may be used to facilitate distancing and provide additional protection from respiratory droplets.[53] A cohort study has shown that maternal SARS-CoV-2 immunoglobulin G antibodies can transfer across the placenta. Antibody transfer increases as time between maternal infection and delivery increases. Transfer is independent of disease severity.[57]

Breastfeeding is encouraged. Mothers may also express breast milk after appropriate hand hygiene for uninfected carers to feed the infant. [53]

Infants requiring neonatal intensive care and respiratory support optimally should be admitted to a single patient room with the potential for negative room pressure.[53]

Healthy newborns should be tested for SARS-CoV-2 at least once before hospital discharge.[53]

Where testing capacity is available, newborns should be tested for SARS-CoV-2 infection at 24 hours and 48 hours after birth. Infants should be bathed after birth to remove virus particles potentially present on the skin surface.[53]

In the UK, the Royal College of Paediatrics and Child Health and the Resuscitation Council have published guidelines for neonatal settings during the COVID-19 pandemic. Suctioning of the lower respiratory tract, bag-valve-mask ventilation, and intubation of the newborn are considered aerosol-generating procedures. Clinicians should don PPE if the mother is clinically suspected or confirmed to have SARS-CoV-2 infection.[58]

Clinicians should attend deliveries according to their normal institutional policies; maternal COVID-19 infection alone is not an indication to attend. If possible, the neonatal team should be in a separate room and the baby brought to them, to avoid exposure of the neonatal team to the mother.[59] Neonatal resuscitation should follow current national and European guidelines. Where possible, use of a video-laryngoscope should be considered for intubation, because this may help to reduce exposure to the virus, if it is present, by reducing the clinician’s proximity to the baby’s airway. Uncuffed tracheal tubes should be used.[59] The newborn can be dried as usual while the cord is still intact. Deferred cord clamping is recommended in the absence of other contraindications.[53]

Well babies born to mothers with suspected or confirmed COVID-19 and who do not require medical intervention may remain with their mother in their designated room.[4][53] Babies should only be tested for SARS-CoV-2 if unwell. Early discharge should be facilitated where possible, in conjunction with community midwifery services. Neonatal and infant physical examination screening (NIPE), including visualisation of the soft palate, should be completed before discharge. NIPE is not considered an aerosol-generating procedure.[58]

Breastfeeding should be encouraged; the benefits substantially outweigh the risks of transmission.[4][52] There is currently no evidence that COVID-19 can be transmitted through breast milk.[8][51][60][61] A mask should be worn, and meticulous hand hygiene performed, for breast or formula feeding. For babies born to mothers with suspected or confirmed COVID-19 who require to be admitted to a neonatal unit, clinical investigations should be minimised while maintaining standards of care. Babies requiring respiratory support should be nursed in an incubator if the mother has clinically suspected or confirmed COVID-19.[58]

The World Health Organization recommends that mothers and their infants room in together and practise skin-to-skin contact, especially immediately after birth and when establishing breastfeeding. Babies should not wear face masks or other face coverings because this may risk suffocation.[8]

Considerations for patients with dermatological conditions receiving drugs that affect the immune response
A cohort study of 500,000 people in the UK found that autoimmune disease and history of oral corticosteroid were associated with increased risk of fatal COVID-19.[62] Guidelines recommend that non-essential face-to-face consultations with patients with dermatological conditions should be avoided, with appointments either rescheduled or done using telemedicine.[63][64]

Patients taking drugs that affect the immune response may have atypical presentations of COVID-19: for example, they may not develop a fever.[64]

UK guidelines recommend that patients with known or suspected COVID-19 infection continue on topical treatments and that new-onset dermatological conditions are treated with topical treatments if possible, rather than systemic treatments that act on the immune system.[64] If the patient is already taking systemic treatment, they should be advised they can continue hydroxychloroquine, chloroquine, mepacrine, dapsone, and sulfasalazine, and advised that they should not suddenly stop taking oral corticosteroids. All other oral immunosuppressive therapies, biologicals, and monoclonal antibodies could be temporarily stopped during COVID-19 infection.

The risks and benefits of stopping should be carefully considered with the patient or their carer, including considering the effect that stopping treatment may have on other comorbid conditions; guidelines highlight the importance of patients not stopping their medications without first speaking with their providers.[64][65][66]

The half-life of some drugs means that immunosuppression will continue for some time after stopping treatment. The International Psoriasis Council, the European Association of Dermatology and Venereology (EADV), and the International Eczema Council recommend discontinuing or postponing the use of immunosuppressive medications in patients diagnosed with COVID-19.[67][68][69] UK guidelines recommend that for patients not known to have COVID-19 infection, the risks and benefits of starting or continuing a drug that affects the immune system need to be carefully considered, including considering whether the required monitoring is possible, whether the patient has had COVID-19 vaccination, and whether there are changes that could make hospital attendance or admission less likely.[64]

Advice on COVID-19 vaccination for patients having or scheduled to have immunosuppressive therapy is available and should be consulted.[30][70] The International Psoriasis Council advises that the benefits and risks of using immunosuppressive therapy should be carefully weighed for each patient who is at higher risk of severe illness because of their age or comorbidities.[67] The US National Psoriasis Foundation COVID-19 Task Force does not recommend that patients stop their biological or oral therapies for psoriasis and/or psoriatic arthritis; any decision to start or stop a biological or oral systemic therapy should be individualised and involve a healthcare provider.[71]

Expert recommendations are available for the management of autoimmune bullous disease (pemphigus, pemphigoid, dermatitis herpetiformis) and atopic dermatitis (eczema) during the pandemic.[72][73]

The British Association of Dermatologists has produced a risk stratification table, for help in identifying patients for whom, due to their disease and treatment, COVID-19 poses a higher risk.[74]

Considerations for patients with dermatological conditions receiving oral retinoids
The UK Medicines and Healthcare products Regulatory Agency has published guidance to assist safe prescribing of oral retinoids during the pandemic. Consultations for considering a first prescription of oral retinoids should take place face-to-face, where possible. If this is not possible, a remote appointment must include the same full risk-benefit discussion as a face-to-face appointment. If the patient is <18 years, a parent or guardian should be involved for part of the initial consultation. Advice is given for home pregnancy testing to fulfil the requirements of the Pregnancy Prevention Programme, and for monitoring blood tests and psychiatric symptoms.[75]

Considerations for patients with gastrointestinal or liver conditions treated with drugs that affect the immune response
Clinicians should be aware that deteriorating liver function tests and gastrointestinal symptoms could be associated with COVID-19. Patients with decompensated liver disease may be at higher risk of severe COVID-19 when taking drugs that affect the immune response. A cohort study of 500,000 people in the UK found that autoimmune disease and history of oral corticosteroid were associated with increased risk of fatal COVID-19.[62]

Patients taking drugs that affect the immune response may have atypical presentations of COVID-19: for example, they may not develop a fever.[76]

UK guidelines recommend that patients should not stop or change their medication without discussion with their gastroenterology or hepatology team, to reduce the risk of a disease flare. Similarly, the American Association for the Study of Liver Diseases (AASLD) and the European Association for Study of the Liver (EASL) advise against making anticipatory adjustments to immunosuppressive drugs in patients without COVID-19.[77][78]

Patients may continue taking aminosalicylates; these drugs do not affect the immune response.[76] Dosage, route of administration, and mode of delivery should be considered for patients who take drugs that affect the immune response, with the aim of minimising face-to-face contact. The risks and benefits of starting a new drug, including need to start treatment during the COVID-19 pandemic, risk profile, feasibility of monitoring and review, route of administration, and whether the patient has had a COVID-19 vaccination should be considered.[76] Advice on COVID-19 vaccination for patients having or scheduled to have immunosuppressive therapy is available and should be consulted.[30][70]

The AASLD advises that immunosuppressive therapy should be commenced in patients with liver disease, with or without COVID-19, if there is a strong indication for treatment, (e.g., graft rejection, autoimmune hepatitis).[77] Patients with symptoms of COVID-19 should not suddenly stop oral or rectal corticosteroids. Urgent specialist advice should be sought before stopping or changing medications that affect the immune response in patients with COVID-19.[76] The AASLD advises that clinicians consider reducing doses of immunosuppressants, particularly azathioprine and mycophenolate, based on general principles for managing infections in immunosuppressed patients and to decrease the risk of superinfection.[77]

Considerations for patients with lower gastrointestinal symptoms UK guidance on the investigation and triage of patients with suspected colorectal cancer has been published. Patients should undergo urgent colonoscopy or computed tomography if they:[79][80] have early signs of large bowel obstruction are aged 40 or over with unexplained weight loss and abdominal pain, a faecal immunochemical test (FIT) result >100 micrograms/gram and they have not had a colonoscopy in the last 3 years are aged 50 or over with unexplained rectal bleeding, FIT >100 micrograms/gram and they have not had a colonoscopy in the last 3 years are aged 60 or over with iron deficiency anaemia or changes in bowel habit, FIT >100 micrograms/gram and they have not had a colonoscopy in the last 3 years have symptoms that a specialist considers to need urgent investigation.

Quantitative FIT should be offered to adults without rectal bleeding who are aged 50 and over with either unexplained abdominal pain or weight loss, are aged under 60 with changes in their bowel habit or with iron-deficiency anaemia, or are aged 60 and over and have anaemia even in the absence of iron-deficiency.[80]

If patients have symptoms of weight loss, abdominal pain, changes to bowel habit or iron deficiency anaemia, and either FIT 10-100 micrograms/gram or FIT >100 micrograms/gram and a colonoscopy requiring no further investigation within the last 3 years, they should undergo prioritised colonoscopy or computed tomography.

Patients with lower gastrointestinal symptoms and FIT <10 micrograms/gram are suitable for deferred evaluation and should receive clear advice on who to contact for further clinical assessment should their symptoms change or worsen.

Considerations for endoscopy
Upper gastrointestinal (GI) endoscopy is a high-risk procedure for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Lower GI endoscopy also carries a risk of SARS-CoV-2 infection. European and Asia-Pacific guidelines make recommendations for upper and lower GI endoscopy during the COVID-19 pandemic.[81][82][83]

Patients should be triaged as high or low risk one day before endoscopy and the triage assessment should be repeated on the day of the procedure. High-risk patients include those with symptoms of COVID-19 (particularly cough, fever, shortness of breath, or diarrhoea), or travel/residence in an area reporting high community transmission of COVID-19 during the previous 14 days, or contact with an individual confirmed, or very likely, to have COVID-19.

Relatives and carers should not accompany the patient in the endoscopy unit. During endoscopic pre-assessment, clinicians and patients should wear surgical masks, maintain a distance of at least 1 to 2 metres, and if possible use a physical barrier (e.g., face shield). The patient’s temperature should be checked before endoscopy. Separate recovery areas or time slots should be available for patients at particularly high risk of COVID-19.

During the endoscopy procedure, only essential personnel should be present and they should use full personal protective equipment. This should always include shoe coverings, a disposable hairnet, protective eyewear, and a waterproof disposable gown. For low-risk patients, gloves and a surgical mask should be used. For high-risk patients, two pairs of gloves and a filtering face mask should be used.

GI endoscopy should only be performed for patients with suspected or confirmed COVID-19 where medically necessary, ideally in a negative pressure room.

GI endoscopy should always be performed for:

Acute upper/lower GI bleeding with haemodynamic instability
Anaemia with haemodynamic instability
Capsule endoscopy/enteroscopy for urgent or emergent bleeding
Foreign body in oesophagus
High-risk foreign body in stomach
Obstructive jaundice
Acute ascending cholangitis.
The guidance advises on prioritisation and deferral of procedures for other indications.

The American Gastroenterological Association (AGA) Institute have published a rapid review and recommendations on the role of SARS-CoV-2 testing prior to endoscopy.[84] The AGA Institute suggests pre-procedure testing where there is an intermediate prevalence of asymptomatic SARS-CoV-2 infection (0.5%-2%). They recommend against testing where the prevalence of asymptomatic infection is low (<0.5%) due to the high number of false positives and suggest that availability of personal protective equipment (PPE) may drive decision-making. In areas of high prevalence, pre-procedure testing is not recommended due to the number of false negatives, and again, availability of PPE may drive decision-making. In areas with a surge in COVID-19 patients, endoscopy may be reserved for emergency or time-sensitive procedures.[84]

The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) recommend that all paediatric endoscopic procedures are done in a negative pressure room with all staff using airborne, contact, and droplet precautions regardless of patient risk stratification. To optimise healthcare delivery and minimise risk, NASPGHAN have proposed stratifying procedures as emergent, urgent (assess benefits and risks before proceeding), or elective.[85]

Transient elastography may reduce the need for endoscopic screening for varices in some patients with cirrhosis. Non-invasive assessments including the Baveno VI criteria, platelet-to-liver stiffness measurement ratio, liver stiffness measurement and spleen stiffness measurement have good predictive value for clinically significant varices and to identify patients at risk of bleeding. Screening for varices should balance the risks of SARS-CoV-2 transmission from endoscopy against the risk of bleeding. Elective upper GI endoscopy to screen for varices in patients with no history of bleeding can be deferred until the COVID-19 outbreak is controlled. Endoscopic eradication of oesophageal varices should be performed following a variceal bleed.[86]

Considerations for patients receiving systemic anti-cancer therapy
Patients with cancer are at higher risk of severe disease and death than patients with no comorbid conditions.[87][88] An observational study of patients referred to oncology services in Europe reported that mortality from COVID-19 was 33.6% and was associated with male sex, age ≥65 years, ≥2 comorbidities and active malignancy. Nearly 60% of patients developed acute respiratory failure. Delivery of cancer therapy (chemotherapy, immunotherapy and targeted therapy) was not associated with case severity or mortality.[89] An observational study from the US also found that administration of cytotoxic chemotherapy was not associated with severe or critical COVID-19. Patients with active lung or haematological malignancies, baseline neutropenia, or lymphopenia at COVID-19 diagnosis had worse outcomes.[90] Another cohort study found that patients who had received cancer treatment within 3 months before COVID-19 diagnosis had a significantly higher risk of adverse outcomes compared with patients without cancer, and patients with no recent cancer treatment had similar outcomes to those without cancer.[91] Data from the UK Coronavirus Cancer Monitoring Project (UKCCMP) found that patients with haematological malignancies had increased susceptibility to severe acute respiratory syndrome coronavirus 2 and also had more severe COVID-19 disease compared with patients with solid organ tumours; recent chemotherapy conferred an additional risk.[92] A US case-control study found that patients with cancer and COVID-19 were at significantly increased risk of hospitalisation and death than patients without cancer.[93] Non-Hodgkin’s lymphoma, lung cancer, and recent diagnosis of leukaemia were most associated with an increased risk of COVID-19 infection. Analysis of US health-insurance claims data found that lung cancer, leukaemias, and lymphomas were significant risk factors for fatal COVID-19 in patients <70 years.[94] Among patients with a recent cancer diagnosis, African-American patients had a significantly higher risk of COVID-19 than white patients.[93] In Europe, day 14 case fatality rate for patients with solid or haematological malignancies and confirmed severe acute coronavirus 2 (SARS-CoV-2) infection decreased over the course of the pandemic, from 25.6% in the first major outbreak (February to June 2020) to 16.2% in the second major outbreak (July 2020 to February 2021). Risk of complications requiring hospitalisation and/or antiviral therapy also decreased during the second major outbreak compared with the first.[95]

The most common presenting symptoms of COVID-19 in patients with cancer are fever, cough, and acute dyspnoea.[89] However, patients may present with atypical symptoms of COVID-19, and other conditions, notably neutropenic sepsis and pneumonitis, can mimic COVID-19.[96][97] Patients with a fever or other symptoms of infection should have a comprehensive evaluation.[97]

UK guidelines recommend that systemic anti-cancer treatment should be deferred, if possible, in patients who have COVID-19 until at least 10 days have elapsed since a positive test for SARS-CoV-2 and any significant symptoms have resolved.[96] Systemic anti-cancer treatment may be continued if necessary for urgent control of the cancer; a shared decision should be reached with the patient.[96]

UK guidelines recommend that the highest priority for systemic anti-cancer treatments should be:[96]

Curative treatment with a high (more than 50%) chance of success
Adjuvant or neoadjuvant treatment that adds at least 50% chance of cure to surgery or radiotherapy alone or treatment given at relapse.
NHS England has made recommendations for treatment change options for systemic anti-cancer therapy (SACT). These take into account the degree of immunosuppression caused by the treatment, the ability to administer treatment in a setting that reduces exposure to COVID-19, resource availability, feasibility, and capacity.[98]

The European Society for Medical Oncology (ESMO) has published guidance on management of cancer patients during the COVID-19 pandemic and recommends that the benefit/risk ratio may need to be reconsidered in some patients. ESMO considers patients receiving chemotherapy and those who have received chemotherapy in the last 3 months to be at risk. ESMO suggests that decisions for starting or continuing cancer therapy are discussed for both patients who do not have COVID-19 infection, and those who do have COVID-19 infection but are asymptomatic or paucisymptomatic, and are still fit and willing to be treated after explanation of the risks and benefits.[99] Cancer care prioritisation and intensity should be adapted to the pandemic scenario.[100]

ESMO suggests the following patient prioritisation:[99]

High priority: patient condition is immediately life threatening, clinically unstable, and/or the magnitude of benefit qualifies the intervention as high priority (e.g., significant overall survival gain and/or substantial improvement in quality of life [QoL])
Medium priority: patient situation is non-critical but delay beyond 6 weeks could potentially impact overall outcome and/or the magnitude of benefit qualifies for intermediate priority
Low priority: patient’s condition is stable enough that services can be delayed for the duration of the COVID-19 pandemic and/or the intervention is non-priority based on the magnitude of benefit (e.g., no survival gain with no change nor reduced QoL).
ESMO advise that where feasible, all cancer patients admitted to hospital for cancer treatment should be tested for SARS-CoV-2, irrespective of chest radiographic findings or symptoms, if considered at high risk of mortality from SARS-CoV-2 infection. Clinicians should rapidly review the patient’s clinical presentation, their clinical, travel and epidemiological history and planned procedures to ascertain their risk of infectiousness. Healthcare professionals should use personal protective equipment meticulously. Clinicians should consider giving granulocyte colony stimulating factor to elderly patients with comorbidities and patients with an intermediate or high risk of febrile neutropenia, to reduce the risk of febrile neutropenia. Prophylaxis against venous thromboembolism is recommended for patients with cancer and COVID-19. Immune checkpoint inhibitors should not be delayed or withheld in the adjuvant/neoadjuvant setting where there is a significant survival benefit. If a patient receiving immune checkpoint inhibitor therapy for an approved indication tests positive for SARS-CoV-2, the immune checkpoint inhibitor therapy should be withheld until recovery. Tyrosine kinase inhibitors may be withheld until recovery in patients who develop COVID-19 and have oncologically stable disease.[100]

The American Society for Clinical Oncology (ASCO) has published recommendations for oncologists regarding ethics and resource scarcity. ASCO advises that allocation of scarce resources should be based on health benefits and that a fair and consistent allocation policy should be developed before allocation becomes necessary. Given that cancer is a heterogeneous disease that differs in its prognosis, progression, and treatment between individuals, patients with cancer should not unconditionally be denied access to scarce resources. Cancer diagnoses and prognoses should be considered individually, with input from the treating oncologist, and the oncologist caring for a patient should not make scarce resource allocation decisions about that patient. Allocation plans and decisions should be communicated honestly and compassionately to patients. Oncologists and patients should discuss advance care planning, including care goals and end-of-life treatment preferences.[101]

The US National Institutes of Health Coronavirus Disease (COVID-19) Treatment Guidelines provide recommendations for treatment of COVID-19 in adults and children with cancer.[102] The recommendations for treating COVID-19 in patients with cancer are the same as for the general population; however, clinicians should be aware of potential drug interactions and overlapping toxicities. A haematologist or oncologist should be consulted before adjusting cancer-directed medications. Molecular diagnostic testing for SARS-CoV-2 is recommended in patients who develop signs and symptoms of COVID-19 and in asymptomatic patients prior to procedures that require anaesthesia and before initiating cytotoxic chemotherapy and long-acting biologic therapy.

The American College of Cardiology has made recommendations for alterations to routine cardiac surveillance for patients with breast cancer receiving SACT who are at low risk for cardiotoxicity. Patients at higher risk should receive usual care.[103]

One cohort study reported outcomes for children and adolescents (<19 years) with cancer and COVID-19 infection. Almost 20% of patients had severe or critical COVID-19 infection, and 3.8% died from COVID-19. Residence in a low, lower-middle, or upper-middle income country, age 15-18 years, lymphopenia, neutropenia, and intensive treatment were associated with increased risk of severe or critical illness.[104] Outcomes of patients with cancer may be affected by post-COVID-19 sequelae.[105]

Guidelines for SARS-CoV-2 vaccination for patients receiving SACT are available.[106][107] A study conducted in Israel prospectively examined the immunogenicity of the BNT162b2 mRNA vaccine in patients with solid organ tumours who were receiving SACT. After the first dose of vaccine, 29% of patients receiving SACT were seropositive for SARS-CoV-2 compared with 84% of controls. After the second dose of vaccine, 86% of patients receiving SACT were seropositive for SARS-CoV-2. The vaccine was not associated with a higher rate of adverse events in people receiving SACT.[108] A prospective cohort study conducted in the UK reported that SACT was not associated with reduced neutralising antibody titre following SARS-CoV-2 vaccination. Seroconversion of patients with solid organ malignancies was 39% after the first vaccine dose and 85% after the second dose. Seroconversion of patients with haematological malignancies was 29% after the first vaccine dose and 59% after the second dose.[109] A prospective, multi-centre, non-inferiority study of the mRNA-1273 COVID-19 vaccine found that most patients with cancer who received chemotherapy, immunotherapy, or both for a solid tumour developed an adequate antibody response to vaccination.[110] International registry data have shown that patients with cancer who develop breakthrough COVID-19 infection after full vaccination continue to be at risk from severe outcomes.[111] Among the patients who had a breakthrough infection, those with haematological malignancies were over-represented.

Considerations for patients receiving radiotherapy
The National Institute for Health and Care Excellence in the UK has issued guidelines for the delivery of radiotherapy during the COVID-19 pandemic. Patients with known or suspected COVID-19 may still receive radiotherapy, provided that national guidance on infection prevention and control can be followed. Patients who are immunosuppressed and develop a fever, with or without respiratory symptoms, should be assessed in secondary or tertiary care for neutropenic sepsis.[112]

When prioritising radiotherapy treatments, clinicians should take into account patient-specific risk factors (including comorbidities and risk of immunosuppression), the risk of untreated cancer versus the risk of severe illness caused by COVID-19, and service capacity issues.

The highest-priority treatments are:[112]

Radical radiotherapy or chemoradiotherapy with curative intent, if the patient has a rapidly proliferating tumour and treatment has already started and there is little or no possibility of compensating for treatment gaps
External beam radiotherapy with subsequent brachytherapy, if the patient has a rapidly proliferating tumour and external beam radiotherapy treatment has already started
Radiotherapy that has not started yet, if the patient has a rapidly proliferating tumour and they would normally start treatment
Urgent palliative radiotherapy for patients with malignant spinal cord compression who have salvageable neurological function.
The European Society for Medical Oncology (ESMO) has published guidance on management of cancer patients during the COVID-19 pandemic and recommends that the benefit/risk ratio may need to be reconsidered in some patients. ESMO considers patients receiving extensive radiotherapy to be at risk. ESMO suggests that decisions for starting or continuing cancer therapy are discussed for both patients who do not have COVID-19 infection, and those who do have COVID-19 infection, are asymptomatic or paucisymptomatic, and are still fit and willing to be treated after explanation of the risks and benefits.[99][100]

ESMO suggests the following patient prioritisation:[99]

High priority: patient condition is immediately life threatening, clinically unstable, and/or the magnitude of benefit qualifies the intervention as high priority (e.g., significant overall survival gain and/or substantial improvement in quality of life [QoL])
Medium priority: patient situation is non-critical but delay beyond 6 weeks could potentially impact overall outcome and/or the magnitude of benefit qualifies for intermediate priority
Low priority: patient’s condition is stable enough that services can be delayed for the duration of the COVID-19 pandemic and/or the intervention is non-priority based on the magnitude of benefit (e.g., no survival gain with no change nor reduced QoL).
The International Lymphoma Radiation Oncology Group has published emergency guidelines for radiotherapy in haematological malignancies, should radiotherapy be necessary. Alternative dose fractionations may be given.[113]

The European Society for Radiotherapy and Oncology (ESTRO) and the American Society for Radiation Oncology (ASTRO) have published guidance on radiotherapy for lung cancer in the current COVID-19 pandemic.[114] They highlight that the prognosis of lung cancer patients should not be compromised by departing from guideline-recommended radiotherapy practice; however, delaying or interrupting treatment is generally recommended for patients with COVID-19. An international group of experts in the management of lung cancer have also published recommendations for optimising lung cancer radiotherapy during the pandemic.[115]

Further oncology resources are available at:

Considerations for patients with head and neck cancer
A European observational study reported an unadjusted mortality rate of 44.8% for patients with head and neck cancer and COVID-19. Overall mortality was higher in male patients, patients ≥ 65 years and patients with ≥2 comorbidities.[89]

An international consensus has made recommendations for head and neck surgical oncology practice in the context of the COVID-19 pandemic. Flexible nasendoscopy should be performed for patients with symptoms or signs suggestive of new cancer or recurrence, or patients with concern for critical airway obstruction, only if adequate personal protective equipment (PPE) is available. Suspicious findings on imaging are not sufficient to confirm a diagnosis of cancer; a core biopsy or fine needle aspiration of a suspicious lymph node is also required. Panendoscopy is not required if a biopsy can be performed under local anaesthesia. Non-emergent surgery should be deferred in patients with confirmed or strongly suspected COVID-19. Tracheostomies should be avoided in patients with oral cancer undergoing transoral surgery; tracheostomies should not be avoided in patients with advanced T2 or T3 oral cancer requiring a free flap. Treatment protocols are given for oral, laryngeal and differentiated thyroid cancer.[116]

Considerations for patients with neuromuscular diseases
The World Muscle Society has published advice for management of patients with neuromuscular disease during the COVID-19 pandemic. Patients with neuromuscular diseases are likely to be at high or very high risk of a severe course of illness if they develop COVID-19. Patients should follow government advice on infection prevention and control measures in their country. Patients should make sure they have enough medication and ventilatory support for at least one month. Patients on ventilatory support should be contacted to ensure they have adequate equipment and information. Patients should continue taking corticosteroids and may require a dose increase if they become unwell. Corticosteroids should not be stopped if a patient becomes ill. Immunosuppressive treatment should not be stopped preemptively unless advised otherwise by a specialist. If a patient taking immunosuppressive medication becomes ill, an individual decision regarding temporary withdrawal or a change of immunosuppressive agent should be made with their neuromuscular specialist. When initiating immunosuppressants, the risk of becoming severely ill with COVID-19 should be balanced against the risk of deferring treatment.[117]

Where possible, treatments for neuromuscular diseases should be given in a non-hospital setting and subcutaneous immunoglobulin used instead of intravenous immunoglobulin. Intravenous immunoglobulin, plasma exchange and complement inhibitor treatment is not expected to affect the risk of COVID-19 infection or of severe disease. Chloroquine and azithromycin should not be given to patients with myasthenia gravis unless ventilatory support is available.[117]

In the UK, people aged 12 years or above with specific underlying health conditions that put them at risk of severe COVID-19 should be offered vaccination; this currently includes those with severe neuro-disability and/or neuromuscular conditions that compromise respiratory function.[30]

Use of ACE inhibitors and angiotensin-II receptor antagonists
People with cardiovascular disease are at higher risk of severe complications and death from COVID-19; however, meta-analyses have found no association between ACE inhibitor or angiotensin-II receptor antagonist use and mortality from COVID-19, need for mechanical ventilation, or adverse cardiac events.[118][119][120] Use of ACE inhibitors or angiotensin-II receptor antagonists has been associated with increased survival in patients with COVID-19 who do not require intensive care admission.[121]

British, European, American, and Asian heart groups advise that patients should continue to take ACE inhibitors and angiotensin-II receptor antagonists as prescribed.[122][123][124][125] Any change in medication should be based on individual patient risk assessment.

Use of proton-pump inhibitors
Two meta-analyses have found an association between current use of proton-pump inhibitors (PPIs) and severe clinical outcomes of COVID-19.[126][127] In one meta-analysis, past use of PPIs was not associated with more severe outcomes from COVID-19 infection.[126] Neither current nor past PPI use was associated with increased risk of severe acute respiratory syndrome coronavirus 2 infection.[126][127] Researchers recommend that clinicians reassess the risks and benefits of PPI use and exercise caution when treating patients taking PPIs during the pandemic.[126][127]

refere: https://bestpractice.bmj.com/topics/en-gb/3000190



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