Undiagnosed Cobalamin Deficiency in the Face of COVID-19: An unrecognized comorbidity and silent killer.

Undiagnosed Cobalamin Deficiency in the Face of COVID-19:  An unrecognized comorbidity and silent killer. 

People with undiagnosed vitamin B12 deficiency may be at a higher risk of dying from COVID-19.   Not only does low B12 suppress one’s immune system making it harder to fend off infection and produce antibodies, but B12 deficiency also causes hyperhomocysteinemia, which in turn can cause dangerous blood clots (i.e. deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction).

Hyperhomocysteinemia is a significant and an independent risk factor for vascular disease. Experts believe severe COVID-19 is more a disease of the vascular system striking the endothelium affecting its cells and lining verses solely being a respiratory virus that kills.  Hyperhomocysteinemia (HHcy) causes thrombosis, vascular and endothelial injury, as well as inflammation in blood vessels.

Low B12 afflicts over 15% (1 in 6) Americans or 49.8 million.  There are a variety of causes which is why the incidence is higher than one might expect (Table 1). B12 deficiency strikes all ages, races, and socioeconomic classes.

Untreated B12 deficiency is a major medical and public health problem owing to its increasing prevalence and unappreciated association with morbidity and mortality.  B12 deficiency has been completely overlooked in severe COVID-19 causing death.  Silently, it can take its toll on the public, striking older-adults harder.  This is not only because clinicians fail to screen symptomatic or at-risk patients, as well as blaming low B12 symptoms on “normal aging,” but because the prevalence in geriatrics is even higher (> 20% or at least 1 in 5).

Failing to address B12 deficiency in America by health care leaders is a chronic problem.   Clinicians’ knowledge deficit, loose screening, poor protocols and an absent awareness campaign has added to the overall mortality, and it may have even spiked the death toll during this current COVID-19 pandemic.

The Centers for Disease Control (CDC) admits that B12 deficiency is “simple to prevent and simple to treat, but the diagnosis is easy to miss and is often overlooked,” yet the CDC as well as the World Health Organization have not created a B12 Awareness campaign to educate practicing clinicians, healthcare and extended care facilities, nor the public.

How many COVID-19 deaths have been complicated by untreated or improperly treated B12 deficiency?  Clinicians should be aware of risk factors causing thrombosis, and B12 deficiency is just such a risk factor. Low B12 causes poor and debilitating health and is a multi-system metabolic disease like diabetes.  Low B12 causes a host of other medical problems besides thrombosis affecting the neurologic and hematologic systems causing depression, mental illness, suicidal ideations, cognitive impairment or dementia, neuropathy, gait and balance disturbances, fall-related trauma, demyelination, anemia, neutropenia, and intellectual disabilities in children, costing millions of healthcare dollars each year.

Healthcare leaders and administrators need to be updated and educated about the consequences of B12 deficiency to prevent injury, disability, and deadly outcomes.  It is incomprehensible as well as negligent to fail to diagnose it early.  There has been an inexpensive treatment known for over seven decades which costs less than $50.00 per year.

Could more blacks die from severe COVID-19 due to underlying conditions causing HHcy?  Could this be compounded by clinicians wrongly assuming B12 deficiency is primarily in whites, making lack of testing even more scarce in this race?  Certain disorders such as lupus, diabetes, renal failure and sickle cell disease as well as antiepileptic drugs and methotrexate are all risk factors for B12 deficiency. Blacks are more prone to these disorders which is even more reason they need proper B12 screening by using homocysteine and methylmalonic acid testing.

Doctors report that younger COVID-19 patients in their 30’s and 40’s without risk factors developed strokes and other blood clots.  Are some of these cases made worse or even caused by undiagnosed B12 deficiency causing HHcy?  Misdiagnosed B12 deficiency stems from the medical community not being educated about this disorder, not knowing the signs, symptoms, risk factors, nor the proper diagnostic tests and treatment.  Therefore, clinicians may wrongly conclude their patients are not at risk, nor understand that B12 deficiency is a comorbidity. (Table 2).

Debilitated elderly as well as Veterans in hospitals, nursing homes, assisted living, and rehabilitation centers are notoriously not properly screened for B12 deficiency.  B12 deficiency has been reported to impact up to 43% of long-term care residents.  Delayed diagnosis or treatment can cause bad outcomes and even death, which is why B12 deficiency certainly needs to be added as a Never Event in hospitalizations and extended care facilities.

Investigation of underlying B12 deficiency with COVID-19 needs to be immediately addressed to know the true incidence.  COVID-19 and B12 deficiency are a deadly combination.   Reports of the elderly dropping like dominoes in nursing homes makes me wonder how many elders had untreated B12 deficiency decreasing their chances of survival.   In New York, more than 4,500 COVID-19 patients were wrongly discharged from hospitals back to nursing homes, spreading the virus to more of their community.    Especially vulnerable is the untreated or misdiagnosed B12-deficient resident.

We pretend to care for our elders, but do we really?  Why has B12 deficiency been allowed to flourish in America and especially attack the elderly causing severe debilitation and early death?

Time is of the essence.  Our healthcare system and governmental leaders, often funded by Big Pharma, must stop being blind or complacent to this negligent practice and need to be held accountable.  I call on the Surgeon General of the United States to implement a Call for Action to combat B12 deficiency and stop bad practice. Perhaps COVID-19 will get B12 deficiency back into the spotlight and on all clinicians’ and healthcare facilities’ radar screens.

In 1934, three great Americans (Minot, Murphy, & Whipple) won the Nobel Prize in Medicine and Physiology for their life-saving discovery—cobalamin (vitamin B12). They proved the disease to be no longer “pernicious,” but today their teachings have been forgotten, harming the public, making it once again pernicious, yet silently pernicious.  Our seniors are the poster children of this mismanaged disease.

Hopefully something positive can come out of COVID-19, and finally addressing B12 deficiency once and for all and thereby protecting the public, may be just what America needs as a silver lining in this deadly pandemic.

Table 2: Cobalamin Deficiency Criteria List & Score

Cobalamin Deficiency Risk (CDR) Score

Low Risk:                 0—1

At Risk:                    2—4

High Risk:                5 or greater

I.     NEUROLOGIC MANIFESTATIONS  (+2)

• Paresthesias
• Weakness of legs, arms, or trunk
• Unsteady gait, balance problems
• Ataxia
• Dizziness or light-headedness
• Tremors
• Restless legs
• Lhermitte’s sign
• Romberg’s sign
• Abnormal Babinski reflex
• Visual disturbances
• Forgetfulness, short-term memory loss, or dementia
• Mental status changes
• Impotence, erectile dysfunction
• Urinary or fecal incontinence
• Impaired vibration, position sense
• Abnormal reflexes
• Seizures
• Paralysis

II.    NEUROPSYCHIATRIC MANIFESTATIONS  (+2)

• Depression, suicidal ideations
• Diagnosis of mental illness or on psychiatric medications
• Post-partum depression or psychosis
• Anxiety
• Poor concentration or foggy thinking
• ADD/ADHD
• Personality changes
• Irritability
• Paranoia
• Mania
• Hallucinations
• Psychosis
• Violent behavior
• Homicidal ideations

III.   HEMATOLOGIC MANIFESTATIONS  (+2)

• Anemia
• Macrocytosis
• Hypersegmented neutrophils
• Anisocytosis
• Leukopenia
• Thrombocytopenia
• Pancytopenia

IV.  GENERAL SIGNS/SYMPTOMS  (+1)

• Generalized weakness or fatigue
• Shortness of breath
• Pallor or jaundice
• Frequent falls or near falls
• Loss of appetite/weight loss
• Frequent infections, poor wound healing
• Orthostatic hypotension
• Postural orthostatic tachycardia
• Occlusive vascular disorder or thrombotic events  (e.g., PE, DVT, CVA, MI, portal vein thrombosis)
• Cervical dysplasia
• Malnutrition
• Glossitis
• Tinnitus
• Skin hyperpigmentation or hypopigmentation
• Hepatomegaly or splenomegaly

V.   GASTROINTESTINAL RISKS  (+2)

• Decreased stomach acid or atrophic gastritis
• Gastroparesis
• Helicobacter pylori infection
• Giardiasis
• GERD or ulcer disease
• Gastrectomy (partial or complete), bariatric surgery
• Ileal resection (partial or complete)
• Malabsorption syndromes (e.g., Crohn’s disease, IBS, celiac disease)
• Pancreatitis, pancreatic exocrine insufficiency
• Small intestinal bacterial overgrowth
• Diphyllobothrium latum (fish tapeworm)
• Liver disease (e.g., cirrhosis, hepatitis C)

VI. (a) POPULATION AT RISK  (+2)

• Vegans, vegetarians, macrobiotic diets
• MTHFR, MTR, MTRR gene mutation
• Nitrous oxide administration or abuse
• Eating disorders

     (b) POPULATION AT RISK (+1)

• Age 50 or over
• Diabetes
• Autoimmune disorders (e.g., thyroid, IDDM, lupus)
• Family history of pernicious anemia
• Proton pump inhibitor or H2-blocker use
• Metformin use
• Alcoholism
• Dialysis patients
• AIDS
• Pregnancy
• Intrauterine growth retardation
• Chemo- or radiation therapy
• Phenylketonuria (PKU)
• Down syndrome